FN Thomson Reuters Web of Science™ VR 1.0 PT S AU Baumann, MH Pablo, JP Ali, SF Rothman, RB Mash, DC AF Baumann, MH Pablo, JP Ali, SF Rothman, RB Mash, DC BE Ali, SF TI Noribogaine (12-hydroxyibogamine): A biologically active metabolite of the antiaddictive drug ibogaine SO NEUROBIOLOGICAL MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Neurobiological Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY AUG 04-06, 1999 CL COPENHAGEN, DENMARK SP Int Soc Neurochem, Neuroresearch, Sevier Amer, Bie & Berntsen AS, Parke Davis, Neurosci Res Div, USDA, Natl Ctr Toxicol Res ID INDUCED LOCOMOTOR-ACTIVITY; ANTI-ADDICTIVE DRUG; NUCLEUS-ACCUMBENS; RADIOLIGAND-BINDING; ALKALOID IBOGAINE; RATS; MORPHINE; SEROTONIN; MECHANISMS; DOPAMINE AB lbogaine (IBO) is a plant-derived alkaloid that is being evaluated as a possible medication for substance use disorders. When administered peripherally to monkeys and humans, IBO is rapidly converted to an o-demethylated metabolite, 12-hydroxyibogamine (NORIBO). We have found in rats that peak blood levels of NORIBO can exceed those of the parent compound, and NORIBO persists in the bloodstream for at least 24 h. Surprisingly few studies have examined the in vivo biological activity of NORIBO. In the present series of experiments, we compared the effects of intravenous (iv) administration of IBO and NORIBO (1 and 10 mg/kg) on unconditioned behaviors, circulating stress hormones, and extracellular levels of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens of male rats. IBO caused dose-related increases in tremors and forepaw treading, whereas NORIBO did not. Both IBO and NORIBO produced significant elevations in plasma corticosterone and prolactin, but IBO was more potent as a stimulator of corticosterone secretion. Neither drug affected extracellular DA levels in the nucleus accumbens. However, both IBO and NORIBO increased extracellular 5-HT levels, and NORIBO was more potent in this regard. The present data demonstrate that NORIBO is biologically active and undoubtedly contributes to the in vivo pharmacological profile of IBO in rats. Most importantly, NORIBO appears less likely to produce the adverse effects associated with IBO (i.e., tremors and stress-axis activation), suggesting that the metabolite may be a safer alternative for medication development. C1 NIDA, IRP, Clin Psychopharmacol Sect, NIH, Baltimore, MD 21224 USA. Univ Miami, Sch Med, Dept Neurol, Miami, FL USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Baumann, MH (reprint author), NIDA, IRP, Clin Psychopharmacol Sect, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 40 TC 15 Z9 16 U1 1 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-279-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 914 BP 354 EP 368 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BT09R UT WOS:000171939100033 PM 11085335 ER PT S AU Binienda, Z Beaudoin, MA Thorn, BT Sadovova, N Skinner, RD Slikker, W Ali, SF AF Binienda, Z Beaudoin, MA Thorn, BT Sadovova, N Skinner, RD Slikker, W Ali, SF BE Ali, SF TI Application of electrophysiological method to study interactions between ibogaine and cocaine SO NEUROBIOLOGICAL MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Neurobiological Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY AUG 04-06, 1999 CL COPENHAGEN, DENMARK SP Int Soc Neurochem, Neuroresearch, Sevier Amer, Bie & Berntsen AS, Parke Davis, Neurosci Res Div, USDA, Natl Ctr Toxicol Res ID NUCLEUS-ACCUMBENS; SPECTRAL-ANALYSIS; D-AMPHETAMINE; RATS; RESPONSES; STRIATUM; DRUG; EEG AB The psychoactive indole alkaloid, ibogaine (IBO), has been investigated for over a decade concerning its reported anti-addictive properties for opioids as well as psychomotor stimulants. The mechanism for the anti-addictive action of IBO is still unclear. IBO interactions with opioid, NMDA, nicotinic, adrenergic, and serotonergic receptor sites have been suggested. The involvement of the dopaminergic system in IBO action is well documented. Increased or decreased levels of dopamine (DA) in specific brain regions following IBO pretreatment have been seen concomitantly with increased or decreased motor activity after subsequent amphetamine or cocaine administration. In this report, in vivo electrophysiological measures were monitored in awake adult male rats in order to investigate alterations of the electrocorticogram (ECoG) resulting from interactions between IBO and cocaine (COC). Rats were implanted bilaterally with bipolar ECoG electrodes. They were either injected with saline, COC alone (20 mg/kg, i.p.) or IBO (50 mg/kg, i.p.) and COC 1 hr later. The concentrations of DA, 5-HT, and their metabolites DOPAC, HVA, and 5-HIAA were assessed in the caudate nucleus in separate groups of saline-, COC-, and IBO/COC-treated rats. An alpha, power increase was observed within 10 min after COC injection, which lasted for less than 20 min. A desynchronization over alpha(2) and both beta power bands was observed throughout the recording. In IBO/COC-treated rats, a significant increase in delta, theta, and alpha, power occurred within 20 min after COC injection (p < 0.05). This effect lasted for up to an hour. DA levels significantly increased after COC only and decreased after IBO administration. A further decrease in levels of DA was observed in IBO/COC-treated rats. DA turnover increased significantly after IBO alone but was not observed after IBO/COC treatment. The alterations in ECoG and neurotransmitter levels suggest a decreased response to COC following IBO pretreatment. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, ROW Sci, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Anat, Little Rock, AR 72205 USA. RP Binienda, Z (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 17 TC 2 Z9 2 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-279-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 914 BP 387 EP 393 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BT09R UT WOS:000171939100035 PM 11085337 ER PT S AU Paule, MG Gillam, MP Allen, RR Chelonis, JJ AF Paule, MG Gillam, MP Allen, RR Chelonis, JJ BE Ali, SF TI Effects of chronic in utero exposure to cocaine on behavioral adaptability in rhesus monkey offspring when examined in adulthood SO NEUROBIOLOGICAL MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Neurobiological Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY AUG 04-06, 1999 CL COPENHAGEN, DENMARK SP Int Soc Neurochem, Neuroresearch, Sevier Amer, Bie & Berntsen AS, Parke Davis, Neurosci Res Div, USDA, Natl Ctr Toxicol Res ID PRENATAL EXPOSURE; INFANT OUTCOMES; PREGNANCY; RABBITS; EXPRESSION C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Behav Toxicol Lab, Jefferson, AR 72079 USA. Arkansas Childrens Hosp, Ctr Appl Res & Evaluat, Complex Brain Funct Lab, Little Rock, AR 72202 USA. Peak Stat Serv, Evergreen, CO 80439 USA. RP Paule, MG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Behav Toxicol Lab, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 15 TC 10 Z9 10 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-279-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 914 BP 412 EP 417 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BT09R UT WOS:000171939100038 PM 11085340 ER PT J AU Mayorga, AJ Popke, EJ Fogle, CM Paule, MG AF Mayorga, AJ Popke, EJ Fogle, CM Paule, MG TI Adaptation of a primate operant test battery to the rat: effects of chlorpromazine SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE operant; learning; timing; motivation ID BEHAVIORAL-TEST BATTERY; RHESUS-MONKEYS; PERFORMANCE; COMPLEX; DRUGS; POTENCY AB The National Center for Toxicological Research (NCTR) Operant Test Battery (OTB) has been used extensively in rhesus monkeys to characterize the effects of drugs and toxicants on the performance of tasks designed to model several cognitive functions. Recently, the majority of the OTB tasks have been adapted for use in rats. The current study is the first to examine the effects of a prototypic pharmacological agent previously assessed in monkeys on rat OTB performance. The effects of the dopamine antagonist chlorpromazine (0.56-5.6 mg/kg, i.p.) were assessed in rats performing tasks designed to model auditory-visual-position discrimination, learning, time estimation, and appetitive motivation. All four tasks were equally sensitive to the behavioral effects of chlorpromazine. This pattern of sensitivity was very similar to that obtained when chlorpromazine was tested in monkeys performing the OTB. These data thus suggest that operant tasks designed to model cognitive functions in monkeys can also be used in rats, and that the effects of chlorpromazine on the performance of these tasks may be predictive of results obtained with monkeys. Further characterization of the rat OTB using prototypic pharmacological agents will further determine the extent to which drug effects on rat OTB performance can be generalized to primates. Published by Elsevier Science Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Mayorga, AJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132, Jefferson, AR 72079 USA. NR 22 TC 9 Z9 9 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JAN-FEB PY 2000 VL 22 IS 1 BP 31 EP 39 DI 10.1016/S0892-0362(99)00045-8 PG 9 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 272DH UT WOS:000084634900005 PM 10642112 ER PT J AU Jenkins, MY Mitchell, GV Grundel, E AF Jenkins, MY Mitchell, GV Grundel, E TI Natural tocopherols in a dietary supplement of lutein affect tissue distribution of tocopherols in young rats SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID VITAMIN-E; ALPHA-TOCOPHEROL; GAMMA-TOCOPHEROL; BETA-CAROTENE; MARIGOLD EXTRACT; MACULAR DEGENERATION; BALB/C MICE; IN-VITRO; CANCER; CELLS AB The effects of graded levels of Flora GLO (FG), a dietary supplement containing lutein derived from marigold flowers, on tissue concentrations of lutein and alpha- and gamma -tocopherol were determined. Six groups of male weanling Fischer 344 vats (15/group) were fed ad libitum modified AIN-93G diets containing 0%, 0.30%, 0.60%, 1.20%, 2.40%, or 4.80% FG for eight weeks. FG provided 0%, 0.015%, 0.030%, 0.060%, 0.120%, or 0.240% lutein, corresponding levels of tocopherols were similar to0%, 0.006%, 0.012%, 0.023%, 0.046%, and 0.092%, respectively. Maximal up-takes of lutein in plasma, spleen, and liver were observed with 4.8% FG. Lutein was not detectable in brain, heart, lung, testes, and kidney. Concentrations of alpha -tocopherol in the plasma (mug/mg triglycerides) were reduced in all rats fed FG (p < 0.05). -Tocopherol increased nonlinearly in lung, heart, and spleen with increased FG level. alpha -Tocopherol in liver increased with increased dietary FC; rr-tocopherol in kidney, testes, and brain did not increase. At each dietary level of FG, the spleen had a higher percentage of gamma -tocopherol, and testes and brain had a lower percentage of gamma -tocopherol than all other tissues. For all tissues, the concentrations of alpha -tocopherol were always higher than those of gamma -tocopherol. Tocopherols added to the dietary supplement for functional purposes appeared to have a significant effect on tissue levels of tocopherols. Therefore, changes in alpha- and gamma -tocopherol levels in tissues of rats fed FG cannot be attributed solely to Effects of lutein. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Nutr Prod Labeling & Dietary Supplements, Laurel, MD 20708 USA. RP Jenkins, MY (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Nutr Prod Labeling & Dietary Supplements, Laurel, MD 20708 USA. NR 49 TC 13 Z9 14 U1 0 U2 2 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2000 VL 37 IS 2 BP 207 EP 214 DI 10.1207/S15327914NC372_14 PG 8 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 383ND UT WOS:000165888100014 PM 11142095 ER PT J AU Desai, VG Aidoo, A Li, J Lyn-Cook, LE Casciano, DA Feuers, RJ AF Desai, VG Aidoo, A Li, J Lyn-Cook, LE Casciano, DA Feuers, RJ TI Effects of bleomycin on liver antioxidant enzymes and the electron transport system from ad libitum-fed and dietary-restricted female and male Fischer 344 rats SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID MITOCHONDRIAL-DNA DAMAGE; CALORIC RESTRICTION; LIPID-PEROXIDATION; SKELETAL-MUSCLE; BETA-CAROTENE; HUMAN-CELLS; VITAMIN-C; DISEASE; AGE; TOXICOLOGY AB Dietary restriction (DR) is the only known intervention that delays aging and age-related diseases. Mechanisms proposed to explain this DR effect include a decline in free radical production and an increase in free radical detoxification. In the present study the effect of bleomycin (BLM) as a reactive oxygen species-generating antitumor drug has been evaluated on antioxidant enzymes and the electron transport system in different cellular fractions of liver in female and male Fischer 344 rats. Animals were fed ad libitum (AL) or 60% of the AL intake (DR) and were given a single intraperitoneal injection of 2.5, 5, or 10 mg BLM/kg body wt. After four weeks, BLM significantly increased glutathione peroxidase and lactate dehydrogenase activities in liver cytosol of female AL rats and increased activity even more in male rats. Similar changes were also noted for glutathione reductase and glucose 6-phosphate dehydrogenase activities in BLM-treated AL rats. In liver mitochondria, glutathione peroxidase was increased in female and male AL rats but was increased more in female rats. Drug treatment had no significant effect on these enzyme activities in cytosolic or mitochondrial fractions of DR animals. Profound effects of BLM were noted in activities of complexes I, III, and IV of the electron transport system in AL and DR female and male rats; however, complex II demonstrated no significant diet or treatment effect. Induced antioxidant enzyme activities in BLM-treated AL rats may be a response to excessive free radical generation due to BLM metabolism in AL animals that is mitigated by DR. Furthermore, dysfunction of the electron transport system might suggest its role in a secondary generation of free radicals during BLM metabolism contributing to its toxicity. C1 US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Dept Hlth & Human Serv, Jefferson, AR 72079 USA. RP Feuers, RJ (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Dept Hlth & Human Serv, HFT-120, Jefferson, AR 72079 USA. NR 33 TC 9 Z9 9 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2000 VL 36 IS 1 BP 42 EP 51 DI 10.1207/S15327914NC3601_7 PG 10 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 308FH UT WOS:000086699500007 PM 10798215 ER PT J AU Mitchell, GV Grundel, E Jenkins, MY Satchithanandam, S AF Mitchell, GV Grundel, E Jenkins, MY Satchithanandam, S TI Reduced fat diets influence alpha-tocopherol concentrations in plasma lipoproteins and tissues of male and female rats SO NUTRITION RESEARCH LA English DT Article DE vitamin E; alpha-tocopherol; reduced-fat; lipoproteins; gender; rat ID VITAMIN-E; REPLACEMENT; HUMANS; ABSORPTION; TRANSPORT AB This study examined the effects of feeding low-fat diets containing comparable levels of vitamin E and a fat source rich in unsaturated fatty acids (sunflower oil blend). Weanling male and female Sprague Dawley rats were used in the study. Three groups of each gender (15 rats/group) were fed, for six weeks, diets containing 5.6% fat or 2.8% fat in which the dietary fat was replaced by cornstarch or a commercially available fat-free margarine product The diets were a modification of the AIN-76 diet. Food intake was significantly increased in male and female rats fed the reduced fat diet containing the fat-free margarine. Caloric intakes and body and tissue weights of the animals were not affected by the dietary treatments. Rats fed the reduced-fat diets had higher concentrations of plasma alpha-tocopherol, liver alpha.-tocopherol, and plasma HDL alpha-tocopherol,than did rats fed the 5.6% fat diet. Female rats receiving the reduced-fat diet containing the fat-free margarine had significantly lower concentrations of total plasma and HDL alpha-tocopherol compared with the group fed the diet in which the fat was replaced by cornstarch. Reductions in the fat level of diets rich in unsaturated fatty acids can enhance vitamin E transport and storage when dietary vitamin E levels are maintained. The magnitude of the changes in alpha-tocopherol metabolism in the rat depends on gender and the dietary components used as a substitute for the fat. Published by Elsevier Science Inc. C1 US FDA, Off Food Labeling, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Mitchell, GV (reprint author), US FDA, Off Food Labeling, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 30 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 0271-5317 J9 NUTR RES JI Nutr. Res. PD JAN PY 2000 VL 20 IS 1 BP 69 EP 78 DI 10.1016/S0271-5317(99)00139-6 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 267YW UT WOS:000084387700009 ER PT J CA Comm Infect Dis TI Varicella vaccine update SO PEDIATRICS LA English DT Article ID HEALTHY-CHILDREN; UNITED-STATES; FOLLOW-UP; INFECTIONS; CHICKENPOX; VIRUS; EFFICACY AB Recommendations for routine varicella vaccination were published by the American Academy of Pediatrics in May 1995, but many eligible children remain unimmunized. This update provides additional information on the varicella disease burden before the availability of varicella vaccine, potential barriers to immunization, efforts to increase the level of coverage, new safety data, and new recommendations for use of the varicella vaccine after exposure and in children with human immunodeficiency virus infections. Pediatricians are strongly encouraged to support public health officials in the development and implementation of varicella immunization requirements for child care and school entry. C1 AAP Council Pediat Practice, Elk Grove Village, IL 60007 USA. Amer Thorac Soc, New York, NY 10019 USA. Canadian Paediat Soc, Ottawa, ON, Canada. Ctr Dis Control & Prevent, Atlanta, GA USA. US FDA, Rockville, MD 20857 USA. NIH, Bethesda, MD 20892 USA. Natl Vaccine Program Off, Rockville, MD USA. Columbia Univ, New York, NY 10027 USA. RP AAP Council Pediat Practice, Elk Grove Village, IL 60007 USA. NR 32 TC 2 Z9 8 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 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD JAN PY 2000 VL 105 IS 1 BP 136 EP 141 PG 6 WC Pediatrics SC Pediatrics GA 273KL UT WOS:000084706400024 ER PT J CA Comm Infect Dis TI Prevention of Lyme disease SO PEDIATRICS LA English DT Article ID OUTER-SURFACE PROTEIN; BORRELIA-BURGDORFERI TRANSMISSION; NEW-YORK STATE; TICK BITES; ANTIBIOTIC-PROPHYLAXIS; RISK-FACTORS; NEW-JERSEY; VACCINE; OSPA; ARTHRITIS AB Lyme disease is currently the most frequently reported vector-borne illness in the United States, accounting for more than 95% of such cases. The purpose of this report is to provide recommendations for preventing Lyme disease, including the use of Lyme disease vaccine. Individuals can reduce their risk of Lyme disease by avoiding tick-infested habitats when in endemic areas. If exposure to tick-infested habitats cannot be avoided, individuals may reduce their risk of infection by using repellents, wearing protective clothing, and regularly checking for and removing attached ticks. Morbidity from Lyme disease can be reduced significantly by detecting and treating the infection in its early stages; early and appropriate treatment almost always results in a prompt and uncomplicated cure. A Lyme disease vaccine (LYMErix, SmithKline Beecham, Collegeville, PA) was licensed by the US Food and Drug Administration on December 21, 1998, for persons 15 to 70 years of age. This vaccine seems to be safe and effective, but whether its use is cost-effective has yet to be clearly established. Use of this vaccine causes false-positive enzyme immunoassay results for Lyme disease. Lyme disease can be diagnosed in vaccinated persons by immunoblot testing. Decisions about the use of this vaccine should be based on an assessment of a person's risk as determined by activities and behaviors relating to tick exposure in endemic areas. This vaccine should be considered an adjunct to, not a replacement for, the practice of personal protective measures against tick exposure and the early diagnosis and treatment of Lyme disease. C1 AAP Council Pediat Practice, Elk Grove Village, IL 60007 USA. Amer Thorac Soc, New York, NY 10019 USA. Canadian Paediat Soc, Ottawa, ON, Canada. Natl Vaccine Program Off, Rockville, MD USA. Ctr Dis Control & Prevent, Atlanta, GA USA. US FDA, Rockville, MD 20857 USA. NIH, Bethesda, MD 20892 USA. RP Comm Infect Dis (reprint author), AAP Council Pediat Practice, Elk Grove Village, IL 60007 USA. NR 46 TC 0 Z9 0 U1 0 U2 1 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 JAN PY 2000 VL 105 IS 1 BP 142 EP 147 PG 6 WC Pediatrics SC Pediatrics GA 273KL UT WOS:000084706400025 ER PT J CA Comm Infect Dis TI Recommended Childhood Immunization Schedule - United States, January-December 2000 SO PEDIATRICS LA English DT Article C1 Comm Infect Dis, Elk Grove Village, IL 60007 USA. Red Book, New York, NY 10019 USA. Pediat Practice Act Grp, Elk Grove Village, IL 60007 USA. Amer Thorac Soc, New York, NY 10019 USA. Canadian Paediat Soc, Ottawa, ON, Canada. Ctr Dis Control & Prevent, Atlanta, GA USA. US FDA, Rockville, MD 20857 USA. NIH, Bethesda, MD 20892 USA. Natl Vaccine Program Off, Rockville, MD USA. RP Comm Infect Dis, Elk Grove Village, IL 60007 USA. NR 6 TC 0 Z9 0 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 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD JAN PY 2000 VL 105 IS 1 BP 148 EP 151 PG 4 WC Pediatrics SC Pediatrics GA 273KL UT WOS:000084706400026 ER PT J AU Pichichero, ME Edwards, KM Anderson, EL Rennels, MB Englund, JA Yerg, DE Blackwelder, WC Jansen, DL Meade, BD AF Pichichero, ME Edwards, KM Anderson, EL Rennels, MB Englund, JA Yerg, DE Blackwelder, WC Jansen, DL Meade, BD TI Safety and immunogenicity of six acellular pertussis vaccines and one whole-cell pertussis vaccine given as a fifth dose in four- to six-year-old children SO PEDIATRICS LA English DT Article DE acellular; adverse reactions; antibody; diphtheria-tetanus-pertussis vaccine; pertussis vaccine; whole cell; whooping cough ID LINKED IMMUNOSORBENT-ASSAY; TOXIN NEUTRALIZATION TEST; ADVERSE REACTIONS; HUMAN-SERA; IMMUNIZATIONS; ANTITOXIN; ELISA AB Objective. To evaluate the safety and immunogenicity of 6 different acellular pertussis vaccines combined with diphtheria and tetanus toxoids (DTaP) and with 1 licensed whole-cell pertussis vaccine (DTwP) as a fifth dose in children who had previously received the same DTaP, a different DTaP, or DTwP as primary and fourth-dose vaccinations. Methods. Healthy 4- to 6-year-old children were enrolled at 5 National Institute of Allergy and Infectious Diseases Vaccine Treatment and Evaluation Units to receive a fifth dose of a DTaP or DTwP vaccine. All had been randomly assigned to receive 3 primary doses of DTaP or DTwP at 2, 4, and 6 months and a fourth-dose booster at 15 to 20 months of age as part of earlier National Institutes of Health multicenter acellular pertussis vaccine trials. Parents recorded the occurrence and magnitude of fever, irritability, and injection site redness, swelling, and pain for 3 days after vaccination. Sera obtained before and 1 month after the booster vaccination were analyzed by enzyme-linked immunosorbent assay for antibody to pertussis toxin, filamentous hemagglutinin, fimbriae, pertactin, and diphtheria and tetanus toxoid. Safety and/or immunogenicity data are reported for 317 children who received DTaP and 10 children who received DTwP. Results. Fever and moderate or severe irritability were uncommon following the fifth dose of DTaP vaccine and were generally less frequent than following the fourth dose. However, for the DTaP vaccine groups, redness, swelling, and pain increased in prevalence compared with the fourth dose. The time course and frequency of reactions following DTaP vaccination were generally similar in children who received the same DTaP, a different DTaP, or DTwP for previous doses in the 5- dose series. No significant differences among the DTaP vaccines were detected in the occurrence of reactions, but the statistical power to detect differences was limited by sample size. Significant increases in antibodies directed against the included antigens were observed for all DTaP vaccines in paired pre- and post-fifth dose sera. Post-fifth dose antibody concentrations differed significantly among the DTaP vaccines. Some children in the study showed an antibody response to an antigen not reported to be in the DTaP vaccine. Conclusion. All the studied DTaP vaccines performed similarly with regard to reactions, whether given as a fifth sequential dose of the same vaccine, a mix of different DTaP vaccines in the 5-dose sequence, or after 3 DTwP and 1 DTaP vaccinations. Large injection site reactions occurred more frequently after the fifth dose of DTaP than after the previous 4 doses. A fifth dose of all DTaP vaccines induced an antibody response to those antigens contained in the vaccine. No DTaP was consistently most or least reactogenic or immunogenic. C1 Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Sch Med, Rochester, NY 14642 USA. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. St Louis Univ, Sch Med, Dept Med, St Louis, MO 63104 USA. Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. Baylor Coll Med, Dept Microbiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. NIAID, Div Microbiol & Infect Dis, Bethesda, MD 20892 USA. Ctr Biol Evaluat & Res, Div Bacterial Prod, Rockville, MD USA. RP Pichichero, ME (reprint author), Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Sch Med, 601 Elmwood Ave,POB 672, Rochester, NY 14642 USA. FU NIAID NIH HHS [N01-AI05051, N01-AI02645, N01-AI05049] NR 22 TC 42 Z9 42 U1 0 U2 2 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 JAN PY 2000 VL 105 IS 1 BP art. no. EP e11 DI 10.1542/peds.105.1.e11 PG 8 WC Pediatrics SC Pediatrics GA 273KL UT WOS:000084706400038 PM 10617748 ER PT J AU Rennels, MB Deloria, MA Pichichero, ME Losonsky, GA Englund, JA Meade, BD Anderson, EL Steinhoff, MC Edwards, KM AF Rennels, MB Deloria, MA Pichichero, ME Losonsky, GA Englund, JA Meade, BD Anderson, EL Steinhoff, MC Edwards, KM TI Extensive swelling after booster doses of acellular pertussis-tetanus-diphtheria vaccines SO PEDIATRICS LA English DT Article; Proceedings Paper CT Meeting of the Academic-Pediatric-Societies CY MAY 03, 1998 CL NEW ORLEANS, LOUISIANA SP Acad Pediat Societies DE pertussis; reactions; vaccine; diphtheria; toxoid ID WHOLE-CELL; ADVERSE REACTIONS; CHILDREN; IMMUNOGENICITY; IMMUNIZATION; TOXOIDS; JAPAN; REACTOGENICITY; VACCINATION; RESPONSES AB Background. Diphtheria and tetanus toxoid combined with acellular pertussis (DTaP) vaccines are less reactogenic than diphtheria and tetanus toxoid combined with whole cell pertussis (DTwP) vaccines. However, local reactions increase in rate and severity with each successive DTaP dose, and swelling of the entire injected limb has been reported after booster doses. Methods. We reviewed reports of swelling of the entire thigh or upper arm after the fourth and fifth dose, respectively, of DTaP vaccines administered in the National Institutes of Health multicenter comparative DTaP studies. Relationships were explored among reports of severe swelling, rates of other reactions, quantity of vaccine contents, and prevaccination and postvaccination antibody levels to pertussis toxin, tetanus toxin, and diphtheria toxin. Results. Entire thigh swelling was an unsolicited reaction reported in 20 (2%) of the 1015 children who received 4 consecutive doses of the same DTaP vaccine. The reaction was associated with 9 of the 12 DTaP vaccines evaluated. Although there were no reports of swelling of the entire upper arm in 121 children given a fifth dose of the same DTaP, 4 (2.7%) of 146 recipients of 5 doses of a mixed schedule of DTaP vaccines experienced such swelling. Rates of other reactions were higher in children with entire thigh swelling than in those without. Of the children with entire thigh swelling, 60% had local pain, and 60% had erythema. All swelling subsided spontaneously without sequelae. There was a significant linear association between the rates of entire thigh swelling after dose 4 and diphtheria toxoid content in the DTaP products. Lesser degrees of swelling (> 50 mm but less than entire limb) correlated with pertussis toxoid content after dose 4 and aluminum content after dose 5. No relationship was established between levels of serum antibody to diphtheria, tetanus, or pertussis toxin and rates of swelling of the whole thigh. Conclusions. Booster doses of DTaP vaccines can cause entire limb swelling, which is usually associated with redness and pain. Our data suggest that this extensive swelling reaction may be more common with vaccines containing high diphtheria toxoid content. C1 Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Rochester, Sch Med, Rochester, NY USA. Baylor Coll Med, Houston, TX 77030 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. St Louis Univ, Sch Med, St Louis, MO USA. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. RP Rennels, MB (reprint author), 22 S Greene St, Baltimore, MD 21201 USA. FU NIAID NIH HHS [N01-AI15096, N01-AI02645, N01-AI05049] NR 27 TC 81 Z9 81 U1 1 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 JAN PY 2000 VL 105 IS 1 BP art. no. EP e12 DI 10.1542/peds.105.1.e12 PG 6 WC Pediatrics SC Pediatrics GA 273KL UT WOS:000084706400039 PM 10617749 ER PT J AU Boykins, RA Joshi, M Syin, C Dhawan, S Nakhasi, H AF Boykins, RA Joshi, M Syin, C Dhawan, S Nakhasi, H TI Synthesis and construction of a novel multiple peptide conjugate system: strategy for a subunit vaccine design SO PEPTIDES LA English DT Article DE linear peptide; peptide sequence with N-terminal haloacetyl; base peptide; peptide sequence synthesized on core template ID DIFFICULT SEQUENCES; ANTIGEN; PROTECTION; PROTEINS; HYDROLYSIS; EPITOPES AB We describe the design and synthesis of a novel well characterized multi-peptide conjugate (MPC) system containing antigens from human malaria parasite and the Tar protein of HIV type-1 (HIV-1-Tat). Construction of the MPC utilizes Fmoc solid-phase peptide synthesis coupled with solution chemistry. In the first phase, a core template that serves as primary anchor for the synthesis and attachment of multiple antigens is synthesized. Serine(trityl) and multiple lysine branches with epsilon groups blocked during chain assembly are incorporated forming a tetrameric core. Cysteine whose side chain thiol serves to couple haloacetyl or S-protected haloacetyl peptides is added to complete assembly of the cure template. Modification to the coupling solvent, addition of key amino acid derivatives (N-[1-hydroxy-4-methoxybenzyl]) in the peptide sequence allows the synthesis of base peptides on the core template with molecular mass greater than 7500 kDa. Base peptides are then reacted with high performance liquid chromatography purified haloacetyl peptides to generate multiple peptide conjugates with molecular masses of 10 to 13 kDa. MPC constructs thus formed are further characterized by matrix assisted laser desorption-time of Eight mass spectroscopy (MALDI-MS), amino acid analysis, size exclusion chromatography, and SDS-polyacrylamide gel electrophoresis (PAGE). To our knowledge, this is the first report describing a chemically well defined multiple conjugate system with potential For development of synthetic subunit vaccines. (C) 2000 Elsevier Science Inc. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Div Emerging Transfus Transmitted Dis, Mol Virol Lab,Immunopathogenesis Sect, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Allergen Prod & Parasitol, Lab Parasit Biol & Biochem, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Blood Applicat, Bethesda, MD 20892 USA. RP Dhawan, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Emerging Transfus Transmitted Dis, Mol Virol Lab,Immunopathogenesis Sect, 1401 Rockville Pike, Bethesda, MD 20892 USA. NR 32 TC 14 Z9 15 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD JAN PY 2000 VL 21 IS 1 BP 9 EP 17 DI 10.1016/S0196-9781(99)00172-2 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 291LH UT WOS:000085735300002 PM 10704714 ER PT J AU Avdeef, A Berger, CM Brownell, C AF Avdeef, A Berger, CM Brownell, C TI pH-metric solubility. 2: Correlation between the acid-base titration and the saturation shake-flask solubility-pH methods SO PHARMACEUTICAL RESEARCH LA English DT Article DE solubility; dissolution; solubility-pH profile; potentiometric; oral absorption ID DRUG; PARTITION; SALTS AB Purpose. The objective of this study was to compare the results of a normal saturation shake-flask method to a new potentiometric acid-base titration method for determining the intrinsic solubility and the solubility-pH profiles of ionizable molecules, and to report the solubility constants determined by the latter technique. Methods. The solubility-pH profiles of twelve generic drugs (atenolol, diclofenac. Na, famotidine, flurbiprofen, furosemide, hydrochlorothiazide, ibuprofen, ketoprofen, labetolol. HCl, naproxen, phenytoin, and propranolol. HCl), with solubilities spanning over six orders of magnitude, were determined both by the new pH-metric method and by a traditional approach (24 hr shaking of saturated solutions, followed by filtration, then HPLC assaying with UV detection). Results. The 212 separate saturation shake-flask solubility measurements and those derived from 65 potentiometric titrations agreed well. The analysis produced the correlation equation: log(1/S)titration = -0.063(+/- 0.032) + 1.025(+/-0.011) log(1/S)(shake-flask), s = 0.20, r(2) = 0.978. The potentiometrically-derived intrinsic solubilities of the drugs were: atenolol 13.5 mg/mL, diclofenac. Na 0.82 mu g/mL, famotidine 1.1 mg/mL, flurbiprofen 10.6 mu g/mL, furosemide 5.9 mu g/mL, hydrochlorothiazide 0.70 mg/mL, ibuprofen 49 mu g/mL, ketoprofen 118 mu g/mL, labetolol. HCl 128 mu g/mL, naproxen 14 mu g/mL, phenytoin 19 mu g/mL, and propranolol. HCl 70 mu g/mL. Conclusions. The new potentiometric method was shown to be reliable for determining the solubility-pH profiles of uncharged ionizable drug substances. Its speed compared to conventional equilibrium measurements, its sound theoretical basis, its ability to generate the full solubility-pH profile from a single titration, and its dynamic range (currently estimated to be seven orders of magnitude) make the new pi-I-metric method an attractive addition to traditional approaches used by preformulation and development scientists. It may be useful even to discovery scientists in critical decision situations (such as calibrating computational prediction methods). C1 PION INC, Cambridge, MA 02138 USA. US FDA, CDER, Rockville, MD 20850 USA. RP Avdeef, A (reprint author), PION INC, 127 Smith Pl, Cambridge, MA 02138 USA. NR 19 TC 153 Z9 156 U1 5 U2 62 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD JAN PY 2000 VL 17 IS 1 BP 85 EP 89 DI 10.1023/A:1007526826979 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 288CG UT WOS:000085543800014 PM 10714613 ER PT J AU Lumpkin, MM AF Lumpkin, MM TI International pharmacovigilance: Developing cooperation to meet the challenges of the 21st century SO PHARMACOLOGY & TOXICOLOGY LA English DT Article; Proceedings Paper CT Symposium on Drug Safety in the 21st Century CY OCT 29, 1999 CL UNIV COPENHAGEN, COPENHAGEN, DENMARK SP PHARMACOLGY & TOXICOLOGY, Dept Pharmacology, Univ Copenhagen HO UNIV COPENHAGEN AB Much has been accomplished internationally in the past decade to harmonise the much of the process of postmarketing drug risk detection. However, formidable challenges exist in harmonising analytical approaches to such data and in leveraging international database resources to improve the quality of such data. In addition, international challenges continue in the arena of drug risk management once a specific risk has been detected. Especially problematic are the questions of appropriate methodology and metrics to assess the public health impact of our risk management techniques. Finally, international challenges remain in the world of drug risk communication to practitioners, dispensers, and patients. The primary challenge confronting us is that of providing easily accessible, understandable, unbiased information on drug risk to these communities so that truly informed decisions about medicines can be made at the individual patient level. Only by meeting internationally these challenges in drug risk detection, management, and communication can our citizens know how to best use these wonderful pharmacological gifts to which we nom have access. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Lumpkin, MM (reprint author), US FDA, Ctr Evaluat & Res, 5600 Fishers Lane,Room HFD-2, Rockville, MD 20857 USA. NR 2 TC 5 Z9 5 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0901-9928 J9 PHARMACOL TOXICOL JI Pharmacol. Toxicol. PY 2000 VL 86 SU 1 BP 20 EP 22 DI 10.1034/j.1600-0773.2000.d01-6.x PG 3 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 334BN UT WOS:000088165400006 PM 10905749 ER PT S AU Dominguez, K Bertolli, J Fowler, M Peters, V Ortiz, I Melville, S Rakusan, T Frederick, T Hsu, H D'Almada, P Maldonado, Y Wilfert, C AF Dominguez, K Bertolli, J Fowler, M Peters, V Ortiz, I Melville, S Rakusan, T Frederick, T Hsu, H D'Almada, P Maldonado, Y Wilfert, C CA PSD Consortium Perinatal Safety Review Working Gr BE Ammann, AJ Rubinstein, A TI Lack of definitive severe mitochondrial signs and symptoms among deceased HIV-uninfected and HIV-indeterminate children <= 5 years of age, pediatric spectrum of HIV disease project (PSD), USA SO PREVENTION AND TREATMENT OF HIV INFECTION IN INFANTS AND CHILDREN SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd Conference on Global Strategies for the Prevention of HIV Transmission from Mothers to Infants CY SEP 01-06, 1999 CL MONTREAL, CANADA SP Glaxo Welcome ID HUMAN-IMMUNODEFICIENCY-VIRUS AB Background: In response to recent reports of mitochondrial dysfunction in HIV-uninfected infants exposed to antiretroviral (ARV) prophylaxis., the Perinatal Safety Review Working Group reviewed deaths in five large HIV-exposed perinatal cohorts in the United States to determine if similar cases of severe mitochondrial toxicity could be detected. We describe the results of this review for the PSD cohort. Methods: Hospitalization, clinic and death records for deceased HIV-uninfected and HIV-indeterminate children who were less than 5 years of age were reviewed. Standard definitions were used to classify HIV infection status and the likelihood that signs and symptoms were related to mitochondrial dysfunction. Children were classified as having signs and symptoms that were considered (1) unrelated, (2) unlikely, (3) consistent with, or (4) likely related to mitochondrial disease. SIDS deaths were put into a separate category. Results: 8,465 of 13,125 HIV-exposed children were either HIV-uninfected or HIV-indeterminate. Among the 84 deaths in the subgroup of 8,465 children, 9 were considered in Class 2 (unlikely), 4 were considered in Class 3 (consistent with), and none were considered in Class 4 (likely). 97% of those children who received ARV prophylaxis received zidovudine alone. None of the HIV-uninfected deaths were classified in 2, 3, or 4; and only one of these was exposed to ARV prophylaxis. Among the 3 HIV-indeterminate children who were classified in 3 (consistent with), 2 had no or unknown ARV exposure before 1994 when use of ZDV prophylaxis became the standard of care. Both HIV-uninfected and HIV-indeterminate children with ARV exposure or unknown exposure had lower mortality rates than children without ARV exposure. Conclusion: Monoprophylaxis with ZDV was not associated with higher death rates in the cohort of 8,465 children or with any findings likely consistent with mitochondrial dysfunction among the 85 deaths. Ongoing monitoring of drug safety in large multi-site prospective cohort studies of HIV-exposed children is essential in the era of highly active antiretroviral therapy. C1 Ctr Dis Control & Prevent, Mother Child Transmiss Pediat & Adolescent Studie, Epidemiol Branch, Div HIV AIDS Prevent, Atlanta, GA 30333 USA. New York City Dept Hlth, Off AIDS Surveillance, New York, NY 10012 USA. Puerto Rico Dept Hlth, AIDS Surveillance Program, Rio Piedras, PR 00921 USA. Texas Dept Hlth, Div HIV AIDS, Austin, TX 78756 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Los Angeles Cty Dept Hlth Serv, Pediat AIDS Surveillance Study, Los Angeles, CA 90012 USA. State Labs Inst, Pediat AIDS Surveillance Project, Boston, MA 02130 USA. Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. NIAID, Pediat Med Branch, Div Aids, NIH, Bethesda, MD 20892 USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. Bristol Myers Squibb Pharmaceut Res Inst, Wallingford, CT USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Clin Trials & Surveys Corp, Baltimore, MD USA. Glaxo Wellcome Res & Dev Ltd, Res Triangle Pk, NC USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pediat, Newark, NJ 07103 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Childrens Hosp, Los Angeles, CA 90027 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pediat, Newark, NJ 07103 USA. Ctr Dis Control & Prevent, Stat & Data Management Branch, Div HIV AIDS Prevent, Atlanta, GA 30333 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. NIAID, Pediat Med Branch, Div Aids, NIH, Bethesda, MD 20892 USA. US FDA, CDER, Div Antiviral Drug Prod, Rockville, MD 20857 USA. RP Dominguez, K (reprint author), Ctr Dis Control & Prevent, Mother Child Transmiss Pediat & Adolescent Studie, Epidemiol Branch, Div HIV AIDS Prevent, 1600 Clifton Rd,Mailstop E-45, Atlanta, GA 30333 USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 7 TC 32 Z9 33 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-267-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 918 BP 236 EP 246 PG 11 WC Infectious Diseases; Multidisciplinary Sciences; Pediatrics SC Infectious Diseases; Science & Technology - Other Topics; Pediatrics GA BT09V UT WOS:000171939500028 PM 11131710 ER PT S AU Horwitz, W AF Horwitz, W BE Fajgelj, A Ambrus, A TI The potential use of quality control data to validate pesticide residue method performance SO PRINCIPLES AND PRACTICE OF METHOD VALIDATION SE ROYAL SOCIETY OF CHEMISTRY SPECIAL PUBLICATIONS LA English DT Proceedings Paper CT Joint AOAC/FAO/IAEA/IUPAC International Workshop on the Principles and Practices of Method Validation CY NOV 04-06, 1999 CL BUDAPEST, HUNGARY SP AOAC, IDF, FAO, WHO, ISO, IUPAC AB Full scale interlaboratory (collaborative) studies are becoming too expensive and time consuming to support their use as the only way to validate methods of analysis. Furthermore, reliable estimates of method performance parameters, such as accuracy, precision, and limits of applicability, cannot be achieved by individual collaborative studies at the concentration levels of 0.01-1 mg.kg(-1), the region of interest for residue analysis, when the expected random error among laboratories is of the order of 20-30% of the mean. Performance data from proficiency studies of tens of thousands of control determinations accumulated over the past decade from individual and multiple laboratories are being examined to determine their potential as a substitute for interlaboratory performance data. An analysis of variance indicates that as much as 80% of the total variability of pesticide residue analysis is "random error." If this is the case, proficiency data may be substituted for method-performance data, when recovery is acceptable, because the individual factors of analyte, method, matrix, laboratory, and time contribute little to overall variability. C1 US FDA, Ctr Food Safety & Appl Nutr HFS500, Washington, DC 20204 USA. RP Horwitz, W (reprint author), US FDA, Ctr Food Safety & Appl Nutr HFS500, Washington, DC 20204 USA. NR 10 TC 6 Z9 6 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 0260-6291 BN 0-85404-783-2 J9 ROY SOC CH PY 2000 IS 256 BP 1 EP 8 DI 10.1039/9781847551757-00001 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA BR51Y UT WOS:000166706000001 ER PT S AU Ciarkowski, AA AF Ciarkowski, AA GP AACC AACC AACC TI FDA regulatory requirements for medical devices with control algorithms SO PROCEEDINGS OF THE 2000 AMERICAN CONTROL CONFERENCE, VOLS 1-6 SE PROCEEDINGS OF THE AMERICAN CONTROL CONFERENCE LA English DT Proceedings Paper CT 2000 American Control Conference (ACC 2000) CY JUN 28-30, 2000 CL CHICAGO, IL SP Amer Automat Control Council, IFAC, US Natl Member Org, Int Federat Automat Control C1 US FDA, HFZ450, Rockville, MD 20850 USA. RP Ciarkowski, AA (reprint author), US FDA, HFZ450, 9200 Corp Blvd, Rockville, MD 20850 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0743-1619 BN 0-7803-5520-2 J9 P AMER CONTR CONF PY 2000 BP 3497 EP 3500 PG 4 WC Automation & Control Systems SC Automation & Control Systems GA BR32L UT WOS:000166106200718 ER PT B AU Hinson, WG Pipkin, JL Wu, J Young, JF AF Hinson, WG Pipkin, JL Wu, J Young, JF BE Wang, PP TI Using visualization to confirm mathematical analysis SO PROCEEDINGS OF THE FIFTH JOINT CONFERENCE ON INFORMATION SCIENCES, VOLS 1 AND 2 LA English DT Proceedings Paper CT 5th Joint Conference on Information Sciences (JCIS 2000) CY FEB 27-MAR 03, 2000 CL ATLANTIC CITY, NJ SP Assoc Intelligent Machinery, Machine Intelligent & Fussy Log Lab, Elsevier Publishing Co, Inc, Informat Sci Journal, USA Res Off AB Automated analysis of, two-dimensional gel autoradiographs brought to the forefront the importance of the researcher in providing judgmental decisions concerning quantitation of subjective and non-conclusive data. Here we discuss one example of how. the use of visualization techniques provide the information needed to properly assess values determined by the automated system. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Hinson, WG (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ASSOC INTELLIGENT MACHINERY PI DURHAM PA PO BOX 90291, DURHAM, NC 27708-0291 USA BN 0-9643456-9-2 PY 2000 BP 931 EP 933 PG 3 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BV66Q UT WOS:000179698300233 ER PT S AU Arciniega, JL AF Arciniega, JL BE Balls, M VanZeller, AM Halder, ME TI What's in a name? The meaning of the term "potency", as applied to immunobiologicals for human use, and its implications for alternatives and validation SO PROGRESS IN THE REDUCTION, REFINEMENT AND REPLACEMENT OF ANIMAL EXPERIMENTATION SE DEVELOPMENTS IN ANIMAL AND VETERINARY SCIENCES LA English DT Proceedings Paper CT 3rd World Congress on Alternatives and Animal Use in the Life Science CY AUG 29-SEP 02, 1999 CL BOLOGNA, ITALY SP Colgate Palmolive Co, European Commiss, Environm DIrector Gen, European Commiss, Joint Res Ctr, Toiletry & Perfumery Assoc, European Cosmet, Gillette Co, Glaxo Wellcome, Int Fdn Eth Res, Kimberly Clark Corp, L Oreal, Procter & Gamble Co, Unilever Res, Utrecht Congress AB US law requires that biologicals meet defined criteria for potency. For this purpose, the US Code of Federal Regulations sanctions the use of laboratory surrogates of efficacy in humans, with no specific mention of acceptable experimental designs. Some experts believe that the term "potency" should be reserved for those assays involving challenge of actively immunised animals with bacteria, viruses or toxins, on the assumption that such tests might be more-specific predictors of the efficacy of a product for humans. However, due to the inherent limitations of modelling human disease in animals, the superiority of this approach has not always been demonstrated. Indeed, some vaccines have achieved disease eradication or control in the absence of traditional animal surrogates. Therefore, the use of a large number of animals to validate a bioassay of high variability and limited predictive value might be difficult to justify. Fortunately, an evolution of thinking based on improved analytical procedures and reliance on Good Manufacturing Practice has led to the wider acceptance of the view that a laboratory surrogate of human efficacy is only one of the tools which can be used to ensure that a manufacturing process yields immunobiologicals of consistent quality. Thus, many assays, including those that do not directly measure protective immune mechanisms, can serve as potency tests, if they are well-controlled and carefully chosen to predict, within the limits of current knowledge and resources, the protective behaviour of an immunobiological in man. The expanded use of this approach should lead to a reduced and more humane use of animals. C1 US FDA, Lab Methods Dev & Qual Control, CBER, Rockville, MD 20852 USA. RP Arciniega, JL (reprint author), US FDA, Lab Methods Dev & Qual Control, CBER, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 10 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-5168 BN 0-444-50529-6 J9 DEV AN VET PY 2000 VL 31 BP 979 EP 986 PN A & B PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BS42Q UT WOS:000169797500095 ER PT J AU Junod, SW AF Junod, SW TI Diethylene glycol deaths in Haiti SO PUBLIC HEALTH REPORTS LA English DT Article ID EPIDEMIC C1 US FDA, Hist Off, Rockville, MD 20857 USA. RP Junod, SW (reprint author), US FDA, Hist Off, HFC-24,Rm 1351,5600 Fishers Lane, Rockville, MD 20857 USA. NR 8 TC 12 Z9 14 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JAN-FEB PY 2000 VL 115 IS 1 BP 78 EP 86 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 293DD UT WOS:000085835500019 PM 10968588 ER PT J AU Bajic, S Doerge, DR Lu, L Hansen, EB AF Bajic, S Doerge, DR Lu, L Hansen, EB TI Analysis of erythromycin by liquid chromatography/mass spectrometry using involatile mobile phases with a novel atmospheric pressure ionization source SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID SALMON TISSUE AB A critical limitation of electrospray ionization (ESI) liquid chromatography/mass spectrometry (LC/MS) sources is the susceptibility to blockage of interface orifices due to the deposition of involatile components from the sample and/or mobile phase, These components, including salts, buffers, and ion-pairing agents, can be essential to the performance of the chosen analytical method. We report here the performance enhancements provided by a novel atmospheric pressure ionization (API) source in the analysis of erythromycin A (ERY) using mobile phases that contain involatile components. The enhanced robustness of the new source is derived from the use of a continuous Row of aqueous solvent at the sampling cone orifice that maintains unobstructed ion transmission. The ESI mass spectral responses measured for ERY, using an LC separation that incorporates 10 mM sodium phosphate with and without 10 mM octane sulfonate, were monitored by repeated injections over 13-15 h total analysis time, Minimal effects on ESI mass spectral responses (integrated peak area) or chromatographic performance (peak shape, retention time) were observed during these studies. In the absence of the aqueous cleaning flow, complete loss of mass spectral responses and total blocking of the sampling cone was observed in less than 30 min. Responses for ERY spiked into chicken and beef liver, and catfish muscle at or below the regulatory level of interest (100 ppb), were quantified by internal standard calibration using this procedure. These results demonstrate the ability of a novel API-MS ion source to perform analyses that require the use of involatile mobile phase additives. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Finnigan MassLab, Manchester M23 9BE, Lancs, England. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 6 TC 15 Z9 15 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2000 VL 14 IS 3 BP 156 EP 160 DI 10.1002/(SICI)1097-0231(20000215)14:3<156::AID-RCM850>3.0.CO;2-K PG 5 WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 280NE UT WOS:000085108200006 PM 10637421 ER PT J AU Doerge, DR Fogle, CM Paule, MG McCullagh, M Bajic, S AF Doerge, DR Fogle, CM Paule, MG McCullagh, M Bajic, S TI Analysis of methylphenidate and its metabolite ritalinic acid in monkey plasma by liquid chromatography/electrospray ionization mass spectrometry SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID CAPILLARY AB Methylphenidate (MP, Ritalin(R)) is a psychotropic drug widely prescribed to children for treating the symptoms of attention deficit disorder with and without hyperactivity, Because little information exists about the effects of chronic MP administration on cognitive function in children, measures of behavior changes in non-human primates are important surrogates. An essential component of such studies is the determination of MP plasma levels under chronic and acute dosing conditions, An analytical method was developed that provided sufficient sensitivity to measure low levels of the active parent drug (lower limit of quantitation = 0.25 ng/mL) and the inactive metabolite, ritalinic acid (RA), in monkey plasma as well as the ability to conveniently analyze large numbers of samples. The method uses a polymeric reversed-phase sorbent for solid phase extraction, an efficient reverse-phase high performance liquid chromatography (HPLC) separation, deuterated internal standards for isotope dilution quantification of MP and RA, and detection by sensitive electrospray ionization mass spectrometry (ES-MS) with a single quadrupole instrument. The method responses are linear over the range of plasma concentrations of MP and RA observed in monkeys, gives respective analyte recoveries of 75 and 60% with reasonable precision and accuracy, and demonstrates robust MS performance for rapid determination of MP/RA plasma levels, The average peak MP concentration (ca. 16 ng/mL) and half-lives for MP and RA elimination in monkeys (1.79 and 2.31 h, respectively) were not significantly different under acute vs. chronic dosing conditions and were comparable to values previously reported from human studies. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Finnigan MassLab, Manchester M23 9BE, Lancs, England. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 7 TC 28 Z9 28 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2000 VL 14 IS 8 BP 619 EP 623 DI 10.1002/(SICI)1097-0231(20000430)14:8<619::AID-RCM916>3.0.CO;2-2 PG 5 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 305RV UT WOS:000086554800001 PM 10786896 ER PT J AU Doerge, DR Churchwell, MI Delclos, KB AF Doerge, DR Churchwell, MI Delclos, KB TI On-line sample preparation using restricted-access media in the analysis of the soy isoflavones, genistein and daidzein, in rat serum using liquid chromatography electrospray mass spectrometry SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article AB Soy isoflavones are the subject of many investigations in experimental animals and humans regarding possible modulation of endocrine activity and chemoprevention of carcinogenesis. Genistein and daidzein, the principal biologically active isoflavones in soy, were measured using on-line solid-phase extraction (SPE) and liquid chromatography electrospray mass spectrometry (LC/ES-MS) detection in serum of rats consuming a common open-formula (NIH 31) chow that contained approximately 30 mu g each of genistein and daidzein per gram of feed and a specially designed 'soy-free' chow that contained approximately 60-fold lower isoflavones. The use of a restricted-access/reverse phase trap cartridge and automated column switching permitted rapid and robust analytical performance with many injections of plasma onto a reverse phase LC column, Enzymatic deconjugation and a single centrifugation step were the only sample preparation steps required, The limit of detection for the isoflavones, based on the MS responses observed in serum from male and female rats consuming the soy-free chow, was 0.020 mu M The method, which uses deuterated isoflavones as internal standards, was determined to be accurate using spiked control serum (102-110% of added amounts) and precise using spiked control serum and incurred serum (<6% relative standard deviation), The average genistein and daidzein levels were determined in female (0.62 and 0.25 mu M, respectively) and male rats (0.35 and 0.20 mu M, respectively) consuming the standard diet. The sex difference observed for serum genistein concentrations was statistically significant (p < 0.0001). These results underscore the potential impact of standard open-formula diets on the results from rodent bioassays of biological activity, Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 9 TC 50 Z9 51 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2000 VL 14 IS 8 BP 673 EP 678 DI 10.1002/(SICI)1097-0231(20000430)14:8<673::AID-RCM935>3.3.CO;2-6 PG 6 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 305RV UT WOS:000086554800011 PM 10786906 ER PT J AU Holland, RD Rafii, F Heinze, TM Sutherland, JB Voorhees, KJ Lay, JO AF Holland, RD Rafii, F Heinze, TM Sutherland, JB Voorhees, KJ Lay, JO TI Matrix-assisted laser desorption/ionization time-of-flight mass spectrometric detection of bacterial biomarker proteins isolated from contaminated water, lettuce and cotton cloth SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID RAPID IDENTIFICATION; SHIGELLA-FLEXNERI; WHOLE CELLS; SURVIVAL; VEGETABLES AB Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectra of bacterial proteins were obtained from water, lettuce and cloth samples contaminated with Shigella flexneri, Escherichia coli, and Aeromonas hydrophila. Spectra were obtained using proteins directly isolated from water (or water used for rinsing samples) without culturing the bacteria. For S, flexneri and E, coli, two marker ions for specific proteins associated with a virulence-related property (acid resistance) were easily detected. For A, hydrophila, ions from two specifically selected marker proteins, as well as ions from the larger group of proteins isolated from pure cultures, all matched spectra from a contaminated water sample, providing strong evidence that A. hydrophila was the bacterial contaminant, Rinse water from contaminated lettuce and cloth samples showed the same marker ions as the contaminated water samples, Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Colorado Sch Mines, Golden, CO 80401 USA. RP Lay, JO (reprint author), Div Chem, 3900 NCTR Rd, Jefferson, AR 72079 USA. RI Lay, Jackson/G-1007-2011 OI Lay, Jackson/0000-0003-3789-2527 NR 17 TC 23 Z9 26 U1 1 U2 9 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2000 VL 14 IS 10 BP 911 EP 917 DI 10.1002/(SICI)1097-0231(20000530)14:10<911::AID-RCM965>3.3.CO;2-3 PG 7 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 319NL UT WOS:000087348000014 PM 10825256 ER PT J AU Kohane, DS Lu, NT Gokgol-Kline, AC Shubina, M Kuang, Y Hall, S Strichartz, GR Berde, CB AF Kohane, DS Lu, NT Gokgol-Kline, AC Shubina, M Kuang, Y Hall, S Strichartz, GR Berde, CB TI The local anesthetic properties and toxicity of saxitonin homologues for rat sciatic nerve block in vivo SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article DE ED50; LD50; local anesthetic; peripheral nerve; saxitoxin; sciatic; tetrodotoxin ID SODIUM-CHANNELS; EXCITABLE-MEMBRANES; TETRODOTOXIN; MECHANISM; DURATION AB Background and objectives. Saxitoxin and its homologues are naturally occurring compounds that block the sodium channel with high potency. They have the potential for providing prolonged duration local anesthesia when coinjected with vasoconstrictors or conventional local anesthetics and are devoid of local neurotoxicity. Here, we compare sciatic nerve block with saxitoxin to those with neosaxitoxin, decarbamoyl saxitoxin, and tetrodotoxin (TTX), in a search for even safer compounds. Methods. Rats received percutaneous sciatic nerve block with toxins. The compounds were compared in terms of lethality, onset and duration of action for thermal analgesia (hot-plate testing), and motor block (weight-bearing). Data were expressed as medians with 25th and 75th percentiles, and median effective concentrations were determined. Results. The median concentrations at which analgesia of 60 minutes duration was achieved were neosaxitoxin, 34 +/- 2 mu mol/L; saxitoxin, 58 +/- 3 mu mol/L; TTX, 92 +/- 5 mu mol/L; and decarbamoyl saxitoxin, 268 +/-; 8 mu mol/L. Similar trends were observed for other measures of effectiveness (block duration of 90 minutes, maximal block), and for lethality so thar the therapeutic indices were similar. No toxin had a marked predominance of sensory or motor block. The potency of TTX was intermediate between those of the saxitoxins, and its therapeutic index was slightly better. No difference was observed in time to onset of nerve blockade among the toxins. Conclusions. Substitutions on the saxitoxin nucleus result in large differences in incidence and duration of block, and toxicity. The therapeutic indices of the saxitoxins are similar; that of TTX is slightly better. C1 Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. US FDA, Off Seafood, Washington Seafood Lab Branch, Washington, DC 20204 USA. Brigham & Womens Hosp, Dept Anesthesia & Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Childrens Hosp, Dept Anesthesia, 300 Longwood Ave,Room 555, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM 35647] NR 24 TC 38 Z9 39 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1098-7339 EI 1532-8651 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD JAN-FEB PY 2000 VL 25 IS 1 BP 52 EP 59 DI 10.1016/S1098-7339(00)80011-5 PG 8 WC Anesthesiology SC Anesthesiology GA 276RW UT WOS:000084892000010 PM 10660241 ER PT J AU Godar, DE AF Godar, DE TI Singlet oxygen-triggered immediate preprogrammed apoptosis SO SINGLET OXYGEN, UV-A, AND OZONE SE METHODS IN ENZYMOLOGY LA English DT Review ID PROGRAMMED CELL-DEATH; UV-INDUCED IMMEDIATE; ULTRAVIOLET-LIGHT; DELAYED APOPTOSIS; SUPEROXIDE ANION; FLOW-CYTOMETRY; CYTOCHROME-C; RADIATION; ACTIVATION; INDUCTION C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Godar, DE (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. OI GODAR, DIANNE/0000-0002-7690-5223 NR 33 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2000 VL 319 BP 309 EP 330 PG 22 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQ66A UT WOS:000089101100030 PM 10907523 ER PT J AU Shacter, E AF Shacter, E TI Protein oxidative damage SO SINGLET OXYGEN, UV-A, AND OZONE SE METHODS IN ENZYMOLOGY LA English DT Review ID LOW-DENSITY-LIPOPROTEIN; TRITIATED SODIUM-BOROHYDRIDE; BOVINE SERUM-ALBUMIN; AMINO-ACID-RESIDUES; CATALYZED OXIDATION; PLASMA-PROTEINS; LYSINE RESIDUES; CARBONYL GROUPS; S-THIOLATION; MECHANISM C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Immunol Lab, Bethesda, MD 20892 USA. RP Shacter, E (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Immunol Lab, Bethesda, MD 20892 USA. NR 56 TC 84 Z9 87 U1 2 U2 12 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2000 VL 319 BP 428 EP 436 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQ66A UT WOS:000089101100038 PM 10907531 ER PT J AU Schmued, LC Hopkins, KJ AF Schmued, LC Hopkins, KJ TI Fluoro-Jade: Novel fluorochromes for detecting toxicant-induced neuronal degeneration SO TOXICOLOGIC PATHOLOGY LA English DT Article DE neuronal death; fluorescent probe; kainic acid; methamphetamine; d-fenfluramine; ibogaine; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; (MPTP); dizocilpine maleate (MK-801) ID CENTRAL-NERVOUS-SYSTEM; 3-NITROPROPIONIC ACID; CEREBRAL-CORTEX; DOMOIC ACID; RAT-BRAIN; METHAMPHETAMINE; LOCALIZATION; TERMINALS; IBOGAINE; HYPOXIA AB Two anionic fluorescein derivatives can be used for the simple and definitive localization of neuronal degeneration in brain tissue sections. Initial work on the first generation fluorochrome, Fluoro-Jade, demonstrated the utility of this compound for the detection of neuronal degeneration induced by a variety of well-characterized neurotoxicants, including kainic acid, 3-nitropropionic acid, isoniazid, ibogaine, domoic acid, and dizocilpine maleate (MK-801). After validation, the tracer was used to reveal previously unreported sites of neuronal degeneration associated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyri (MPTP), methamphetamine, and d-fenfluramine. Preliminary findings with a second generation fluorescein derivative, Fluoro-Jade B, suggest that this tracer results in staining of optimal contrast and resolution in animals dosed with kainic acid. These 2 tracers can be combined with other histologic methods, including immunofluoresence and fluorescent Nissl stains. Recent preliminary findings on a number of specialized applications of Fluoro-Jade include the detection of apoptosis, amyloid plaques, astrocytes, and dead cells in tissue culture. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Schmued, LC (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. FU PHS HHS [7013.01] NR 34 TC 185 Z9 189 U1 0 U2 3 PU SOC TOXICOLOGIC PATHOLOGISTS PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN-FEB PY 2000 VL 28 IS 1 BP 91 EP 99 DI 10.1177/019262330002800111 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA 279HV UT WOS:000085039100011 PM 10668994 ER PT J AU Lester, DS Pine, PS Delnomdedieu, M Johannessen, JN Johnson, GA AF Lester, DS Pine, PS Delnomdedieu, M Johannessen, JN Johnson, GA TI Virtual neuropathology: Three-dimensional visualization of lesions due to toxic insult SO TOXICOLOGIC PATHOLOGY LA English DT Article DE magnetic resonance imaging (MRI); neurotoxicity; histology; microscopy; rat brain; drug effects ID MAGNETIC-RESONANCE MICROSCOPY; NEUROTOXIC LESION; RAT; HISTOLOGY AB A first-pass approach incorporating high-field magnetic resonance imaging (MRI) was used for rapid detection of neuropathologic lesions in fixed rat brains. This inherently 3-dimensional and nondestructive technique provides high-resolution, high-contrast images of fixed neuronal tissue in the absence of sectioning or staining. This technique, magnetic resonance microscopy (MRM), was used to identify diverse lesions in 2 well-established rat neurotoxicity models. The intrinsic contrast in the images delineated lesions that were identified using a battery of histologic stains, some of which would nut be used in routine screening. Furthermore, the MRM images provided the locations of lesions, which were verified upon subsequent sectioning and staining of the same samples. The inherent contrast generated by water properties is exploited in MRM by choosing suitable pulse sequences, or proton stains. This approach provides the potential for a comprehensive initial MRM screen for neurotoxicity in preclinical models with the capability for extrapolation to clinical analyses using classical MRI. C1 US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Laurel, MD 20708 USA. RP Lester, DS (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Room 2009,8301 Muirkirk Rd, Laurel, MD 20708 USA. OI Johnson, G.Allan/0000-0002-7606-5447 FU PHS HHS [P41 05959] NR 14 TC 15 Z9 15 U1 0 U2 1 PU SOC TOXICOLOGIC PATHOLOGISTS PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN-FEB PY 2000 VL 28 IS 1 BP 100 EP 104 DI 10.1177/019262330002800112 PG 5 WC Pathology; Toxicology SC Pathology; Toxicology GA 279HV UT WOS:000085039100012 PM 10668995 ER PT J AU Epstein, J AF Epstein, J TI Hepatitis C virus lookback: emerging science and public policy SO TRANSFUSION LA English DT Editorial Material C1 US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Dept Hlth & Human Serv, Rockville, MD 20852 USA. RP Epstein, J (reprint author), US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Dept Hlth & Human Serv, Rockville, MD 20852 USA. NR 9 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JAN PY 2000 VL 40 IS 1 BP 3 EP 5 DI 10.1046/j.1537-2995.2000.40010003.x PG 3 WC Hematology SC Hematology GA 274ZE UT WOS:000084794300003 PM 10644804 ER PT J AU Hardegen, NJ Toro, LA Muller, J Wahl, LM Hewlett, IK Dhawan, S AF Hardegen, NJ Toro, LA Muller, J Wahl, LM Hewlett, IK Dhawan, S TI HIV-1 infects and alters immune function of a monocyte subset expressing low CD14 surface phenotype SO VIRAL IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MONONUCLEAR PHAGOCYTES; MACROPHAGE; DIFFERENTIATION; PATHOGENESIS; CELLS; RECEPTOR AB Monocytes represent a leukocyte subset that express high levels of CD14 on their surface (CD14-high), These cells play a critical role in the pathogenesis of HIV-1 infection. In the present study, we have identified a monocyte subset expressing an extremely low level of CD14 (CD14-low), and examined their susceptibility to HIV-1 infection. Phenotypic analysis by flow cytometry of these cells revealed a low level of CD4, but the absence of CD3, CD14, CD19, and CD83 surface markers. Both CD14-low and CD14-high cell populations expressed CD13 and CD33 markers on their surface, suggesting these cells to be of myeloid origin, Morphologically, CD14-low cells were indistinguishable from CD14-high cells. CD14-low cells were susceptible to infection with a monocytotropic strain of HIV-1 (HIVADA) However, like CD14-high monocytes, CD14-low cells could not be productively infected with a T cell tropic strain of HIV-1 (H9/HTLVIIIB) Similar to CD14-high monocytes, CD14-low cells were capable of inducing antigen-stimulated CD4(+) T-cell proliferation. HIV-1 infection substantially reduced their ability to induce antigen-stimulated T-cell proliferation. These data indicate that CD14-low cells belong to the monocyte lineage and may play an important role in the immunopathogenesis of HIV-1 infection. C1 US FDA, Immunopathogenesis Sect, Mol Virol Lab,Ctr Biol Evaluat & Res, Div Transfus Transmitted Dis, Rockville, MD 20852 USA. Nat Inst Dent & Craniofacial Res, Immunopathol Sect, NIH, Bethesda, MD USA. EntreMed Inc, Rockville, MD USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Dhawan, S (reprint author), US FDA, Immunopathogenesis Sect, Mol Virol Lab,Ctr Biol Evaluat & Res, Div Transfus Transmitted Dis, 1401 Rockville Pike,HFM-315, Rockville, MD 20852 USA. NR 23 TC 1 Z9 1 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0882-8245 J9 VIRAL IMMUNOL JI Viral Immunol. PY 2000 VL 13 IS 1 BP 19 EP 26 DI 10.1089/vim.2000.13.19 PG 8 WC Immunology; Virology SC Immunology; Virology GA 293RF UT WOS:000085866300005 PM 10733165 ER PT J AU Saldanha, J Heath, A Lelie, N Pisani, G Nubling, M Yu, M AF Saldanha, J Heath, A Lelie, N Pisani, G Nubling, M Yu, M CA Collaborative Study Grp TI Calibration of HCV working reagents for NAT assays against the HCV international standard SO VOX SANGUINIS LA English DT Article ID RNA; TECHNOLOGY AB Background and Objectives: Five HCV RNA reference reagents, the Paul Ehrlich Institut (PEI) reference 75, the National Institute for Biological Standards and Control (NIBSC) reagent 96/586, the Central Laboratory of the Netherlands Red Cross Blood Transfusion Service (CLB) Pelispy HCV RNA run control S2001, the Istituto Superiore di Sanita (ISS) reagent 0498 and the CBER panel member No. 1,were calibrated against the WHO International Standard, 96/790. Materials and Methods: The reference materials were calibrated in a collaborative study organised by NIBSC. Nineteen laboratories, using a range of qualitative and quantitative assays returned results. Results: The concentrations of the reagents were: 25,000 IU/ml for the PEI material, 710 IU/ml for the NIBSC material 96/586, 1,000 IU/ml for the CLB material, 1,700 IU/ml for the ISS material 0498 and 250 IU/ml for the CBER panel member No. 1. Conclusions: The calibration of these five reference reagents for HCV RNA nucleic acid amplification technology (NAT) assays enables them to be used for standardisation and validation of assays. Such calibrants are essential for meeting the requirements of the European Medicinal Evaluation Agency (EMEA) for the testing of plasma pools and donations for HCV RNA for the release of blood products and the PEI requirements for the release testing of erythrocyte and thrombocyte concentrates. Copyright (C) 2000 S. Karger AG, Basel. C1 Natl Inst Biol Stand & Controls, Div Virol, S Mimms EN6 3QG, Herts, England. Natl Inst Biol Stand & Controls, Div Informat, S Mimms EN6 3QG, Herts, England. Netherlands Blood Transfus Serv, Cent Lab, Amsterdam, Netherlands. Ist Super Sanita, Immunol Lab, I-00161 Rome, Italy. Paul Ehrlich Inst, D-6070 Langen, Germany. US FDA, CBER, Div Hematol, Rockville, MD 20857 USA. RP Saldanha, J (reprint author), Natl Inst Biol Stand & Controls, Div Virol, Blanche Lane, S Mimms EN6 3QG, Herts, England. NR 9 TC 63 Z9 67 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PY 2000 VL 78 IS 4 BP 217 EP 224 DI 10.1159/000031184 PG 8 WC Hematology SC Hematology GA 340LX UT WOS:000088536600002 PM 10895094 ER PT J AU Arakawa, Y Armstrong, D Barrowcliffe, T Griffiths, E Hardegree, MC Padilla, AM Reigel, F Roberts, H Schild, G van Aken, WG Wood, D AF Arakawa, Y Armstrong, D Barrowcliffe, T Griffiths, E Hardegree, MC Padilla, AM Reigel, F Roberts, H Schild, G van Aken, WG Wood, D CA WHO Expert Comm Biol Standard TI WHO Expert Committee on Biological Standardization SO WHO EXPERT COMMITTEE ON BIOLOGICAL STANDARIZATION SE WHO TECHNICAL REPORT SERIES LA English DT Article ID INFLUENZAE TYPE-B; POLYSACCHARIDE CONJUGATE VACCINES; GUINEA-PIG MODEL; HEMOPHILUS-INFLUENZAE; CAPSULAR POLYSACCHARIDE; NEISSERIA-MENINGITIDIS; OROPHARYNGEAL CARRIAGE; MECKLENBURG COUNTY; MEMBRANE-PROTEIN; NORTH-CAROLINA C1 Natl Inst Infect Dis, Dept Bacterial & Blood Prod, Tokyo, Japan. Natal Bioprod Inst, Pinetown, South Africa. WHO, Int Lab Biol Stand, Natl Inst Biol Stand & Controls, Potters Bar, Herts, England. WHO, CH-1211 Geneva, Switzerland. US FDA, Off Vaccine Res & Rev, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Swiss Fed Off Publ Hlth, Div Biol, Bern, Switzerland. Univ N Carolina, Sch Med, Chapel Hill, NC USA. WHO, Int Lab Biol Stand, Cent Lab, Netherlands Red Cross Blood Transfus Serv, Amsterdam, Netherlands. RP Arakawa, Y (reprint author), Natl Inst Infect Dis, Dept Bacterial & Blood Prod, Tokyo, Japan. NR 74 TC 0 Z9 0 U1 1 U2 1 PU WORLD HEALTH ORGANIZATION PI GENEVA PA 1211 27 GENEVA, SWITZERLAND SN 0512-3054 J9 WHO TECH REP SER PY 2000 VL 897 BP 1 EP 106 PG 106 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BS75F UT WOS:000171051600001 ER PT J AU Buyse, M George, SL Evans, S Geller, NL Ranstam, J Scherrer, B Lesaffre, E Murray, G Edler, L Hutton, J Colton, T Lachenbruch, P Verma, BL AF Buyse, M George, SL Evans, S Geller, NL Ranstam, J Scherrer, B Lesaffre, E Murray, G Edler, L Hutton, J Colton, T Lachenbruch, P Verma, BL CA ISCB Subcommittee Fraud TI The role of biostatistics in the prevention, detection and treatment of fraud in clinical trials SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Joint Meeting of the International-Society-for-Clinical-Biostatistics/Society-for-Clinical-Tr ials CY JUL 07-10, 1997 CL BOSTON, MA SP Int Soc Clin Biostatist, Soc Clin Trial ID PUBLISHING SENSITIVE DATA; BREAST-CANCER TRIALS; SCIENTIFIC MISCONDUCT; ELIGIBILITY CRITERIA; MEDICAL-RESEARCH; DIGIT PHENOMENON; INTEGRITY; SCIENCE; QUALITY; DISTRIBUTIONS AB Recent cases of fraud in clinical trials have attracted considerable media attention, but relatively little reaction from the biostatistical community. In this paper we argue that biostatisticians should be involved in preventing fraud las well as unintentional errors), detecting it, and quantifying its impact on the outcome of clinical trials. We use the term 'fraud' specifically to refer to data fabrication (making up data values) and falsification (changing data values), Reported cases of such fraud involve cheating on inclusion criteria so that ineligible patients can enter the trial, and fabricating data so that no requested data are missing. Such types of fraud are partially preventable through a simplification of the eligibility criteria and through a reduction in the amount of data requested. These two measures are feasible and desirable in a surprisingly large number of clinical trials, and neither of them in any way jeopardizes the validity of the trial results. With regards to detection of fraud, a brute force approach has traditionally been used, whereby the participating centres undergo extensive monitoring involving up to 100 per cent verification of their case records. The cost-effectiveness of this approach seems highly debatable, since one could implement quality control through random sampling schemes, as is done in fields other than clinical medicine. Moreover, there are statistical techniques available (but insufficiently used) to detect 'strange' patterns in the data including, but no limited to, techniques for studying outliers, inliers, overdispersion, underdispersion and correlations or lack thereof. These techniques all rest upon the premise that it is quite difficult to invent plausible data, particularly highly dimensional multivariate data. The multicentric nature of clinical trials also offers an opportunity to check the plausibility of the data submitted by one centre by comparing them with the data from all other centres. Finally, with fraud detected, it is essential to quantify its likely impact upon the outcome of the clinical trial. Many instances of fraud in clinical trials, although morally reprehensible, have a negligible impact on the trial's scientific conclusions. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Int Inst Drug Dev, B-1050 Brussels, Belgium. Limburgs Univ Ctr, Diepenbeek, Belgium. Duke Univ, Med Ctr, Durham, NC USA. Med Control Agcy, London, England. NHLBI, Off Biostat Res, Bethesda, MD USA. Lund Univ, Lund, Sweden. Inst Rech Jouveinal, Fresnes, France. Univ Hosp St Raphael, Biostat Ctr Clin Trials, B-3000 Louvain, Belgium. Univ Edinburgh, Med Stat Unit, Edinburgh EH8 9YL, Midlothian, Scotland. German Canc Res Ctr, Dept Biostat, D-6900 Heidelberg, Germany. Newcastle Univ, Dept Math & Stat, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. US FDA, Rockville, MD 20857 USA. Med Coll & Hosp, Jhansi, Uttar Pradesh, India. RP Int Inst Drug Dev, 430 Ave Louise B14, B-1050 Brussels, Belgium. EM mbuyse@id2.be RI Ranstam, Jonas/A-4386-2009 OI Ranstam, Jonas/0000-0002-8287-7273 NR 115 TC 84 Z9 84 U1 3 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD DEC 30 PY 1999 VL 18 IS 24 BP 3435 EP 3451 DI 10.1002/(SICI)1097-0258(19991230)18:24<3435::AID-SIM365>3.3.CO;2-F PG 17 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 273PQ UT WOS:000084716400008 PM 10611617 ER PT J AU Henry, SH Bosch, FX Troxell, TC Bolger, PM AF Henry, SH Bosch, FX Troxell, TC Bolger, PM TI Public health - Reducing liver cancer - Global control of aflatoxin SO SCIENCE LA English DT Article ID HEPATITIS-B VACCINATION; METABOLISM; RISK; B-1 C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Inst Catala Oncol, Unitat Epidemiol, Barcelona, Spain. RP Henry, SH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RI BOSCH JOSE, FRANCESC XAVIER/J-6339-2012 OI BOSCH JOSE, FRANCESC XAVIER/0000-0002-7172-3412 NR 19 TC 112 Z9 123 U1 1 U2 18 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 24 PY 1999 VL 286 IS 5449 BP 2453 EP 2454 DI 10.1126/science.286.5449.2453 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 268RQ UT WOS:000084429700026 PM 10636808 ER PT J AU Friedman, MA Woodcock, J Lumpkin, MM Shuren, JE Hass, AE Thompson, LJ AF Friedman, MA Woodcock, J Lumpkin, MM Shuren, JE Hass, AE Thompson, LJ TI Safety of FDA-Approved drugs - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Friedman, MA (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 22 PY 1999 VL 282 IS 24 BP 2297 EP 2298 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 265TK UT WOS:000084261700012 ER PT J AU Rundlof, T Venable, RM Pastor, RW Kowalewski, J Widmalm, G AF Rundlof, T Venable, RM Pastor, RW Kowalewski, J Widmalm, G TI Distinguishing anisotropy and flexibility of the pentasaccharide LNF-1 in solution by carbon-13 NMR relaxation and hydrodynamic modeling SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; MOLECULAR-DYNAMICS SIMULATIONS; LIQUID-CRYSTALLINE MEDIUM; SPIN RELAXATION; MOTIONAL PROPERTIES; OVERHAUSER ENHANCEMENT; ROTATIONAL DIFFUSION; C-13-NMR RELAXATION; CROSS-CORRELATION; OLIGOSACCHARIDES AB Carbon-13 spin-lattice (T-1) and spin-spin (T-2) relaxation times and H-1-C-13 NOEs have been measured at four magnetic field strengths (7.0, 9.4, 11.7, and 14.1 T) for a 30 degrees C D2O solution of lacto-N-fucopentaose-1, a pentasaccharide from human milk. There are significant differences between the residues, with the largest T-1, T-2, and NOE values for carbons with axial C-H bonds of the 4-substituted glucose unit (E) at the reducing end. The data were fit using model free formalism, first with overall rotation assumed to be isotropic and then with rotational anisotropy taken into account. Somewhat improved fits were obtained with the latter, which yielded an anisotropy D-parallel to/D-perpendicular to = 1.35-1.5. The generalized order parameters, S-2, for ring carbons of residues A-D were similar in the two models, and approximately equal to 0.7, though significant differences in both order parameters and internal relaxation times were obtained for residue E. As supported by Langevin dynamics simulations, the experimentally derived S-2 for the ring carbons of residue E, 0.68 for Cl (alpha-anomeric configuration) and 0.43 for C2 and C3, are best explained by large fluctuations within the minimum of a single dominant conformation. The translational diffusion coefficient, D-t, obtained from NMR measurements equaled 1.8 x 10(-6) cm(2) s(-1). Hydrodynamic calculations on the energy minimized dominant conformation yielded D-parallel to/D-perpendicular to = 1.8 and D-t = 2.0 x 10(-6) cm(2) s(-1), assuming one bound water per hydroxyl group and rigid geometry. The difference between the anisotropy fitted from relaxation data and that calculated by hydrodynamics is proposed to be associated with the substantial flexibility at the reducing end. C1 Univ Stockholm, Arrhenius Lab, Dept Organ Chem, Div Phys Chem, S-10691 Stockholm, Sweden. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Bethesda, MD 20892 USA. RP Widmalm, G (reprint author), Univ Stockholm, Arrhenius Lab, Dept Organ Chem, Div Phys Chem, S-10691 Stockholm, Sweden. NR 74 TC 40 Z9 40 U1 2 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD DEC 22 PY 1999 VL 121 IS 50 BP 11847 EP 11854 DI 10.1021/ja992675b PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 270AF UT WOS:000084512700031 ER PT J AU Casciano, DA Aidoo, A Chen, T Mittelstaedt, RA Manjanatha, MG Heflich, RH AF Casciano, DA Aidoo, A Chen, T Mittelstaedt, RA Manjanatha, MG Heflich, RH TI Hprt mutant frequency and molecular analysis of Hprt mutations in rats treated with mutagenic carcinogens SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE Hprt; rat lymphocyte assay; DNA sequencing; mutation frequency; mutational spectra; thiotepa; N-ethyl-N-nitrosourea; 7,12-dimethylbenzp[a]anthracene ID ETHYL-N-NITROSOUREA; EXPOSED IN-VIVO; T-LYMPHOCYTES; 6-THIOGUANINE-RESISTANT LYMPHOCYTES; FISCHER-344 RATS; PERIPHERAL-BLOOD; 7,12-DIMETHYLBENZANTHRACENE; ETHYLNITROSOUREA; INDUCTION; ASSAY AB Much of the progress in the field of cancer research has come from the increased understanding of the molecular events associated with the initiation and accumulation of mutational events associated with carcinogenesis. Genetic toxicologists have developed a number of in vitro and in vivo non-mammalian and mammalian systems to predict those genetic events required to induce the cancer process. Several model rodent systems have been proposed that have the ability to detect and quantify in vivo somatic mutation in endogenous genes and transgenes and relate the nature of the mutation to the specific type of chemical damage. One such system, the rat lymphocyte hypoxanthine guanine phosphoribosyl transferase (Hprt) assay is described in this review. Data are presented that describe mutant induction and mutational spectra in N-ethyl-N-nitrosourea (ENU), 7,12-dimethylbenzo[a]anthracene (DMBA) and thiotepa (TEPA) treated rats. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Genet & Reproduct Toxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. US EPA, Div Environm Carcinogenesis, NHEERL, Res Triangle Pk, NC 27711 USA. RP Casciano, DA (reprint author), Natl Ctr Toxicol Res, Div Genet & Reproduct Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 20 TC 9 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD DEC 17 PY 1999 VL 431 IS 2 BP 389 EP 395 DI 10.1016/S0027-5107(99)00181-5 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 270LY UT WOS:000084538200021 PM 10636003 ER PT J AU Mittelstaedt, RA Smith, BA Chen, T Beland, FA Heflich, RH AF Mittelstaedt, RA Smith, BA Chen, T Beland, FA Heflich, RH TI Sequence specificity of Hprt lymphocyte mutation in rats fed the hepatocarcinogen 2-acetylaminofluorene SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE F344 rat; denaturing gradient gel electrophoresis; polymerase chain reaction; DNA sequencing ID ETHYL-N-NITROSOUREA; IN-VIVO MUTATION; LIVER-TUMORS; FISCHER-344 RATS; T-LYMPHOCYTES; DNA-SEQUENCE; B6C3F1 MOUSE; RAS GENES; HA-RAS; INDUCTION AB Rats fed the hepatocarcinogen 2-acetylaminofluorene (2-AAF) have a low, but significantly increased, frequency of lymphocyte Hprt mutants. In this study, mutants from 2-AAF-fed and control F344 rats were examined for mutations in the Hprt gene in order to determine if the 2-AAF treatment resulted in an agent-specific mutation profile. The most common mutation from 2-AAF-treated rats was G:C --> T:A transversion (32% of all mutations) followed by 1-basepair (bp) deletion (19%); there were very few (5%) G:C --> A:T transitions. Among mutations from control rats, G:C --> A:T transition was the most common (43%), and there were very few G:C --> T:A transversions (5%) and no l-bp deletions. The profile of mutations from 2-AAF-fed rats was significantly different from control rats (P = 0.003) and was consistent with the types of mutations produced by 2-AAF in vitro. The results of this study indicate that even weak mutational responses in the lymphocyte Hprt assay are capable of producing mutation profiles that reflect the DNA damage inducing them. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Mittelstaedt, RA (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. NR 31 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD DEC 16 PY 1999 VL 431 IS 1 BP 167 EP 173 DI 10.1016/S0027-5107(99)00204-3 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 274WG UT WOS:000084787600016 PM 10656495 ER PT J AU Aoki, Y Tosato, G AF Aoki, Y Tosato, G TI Role of vascular endothelial growth factor/vascular permeability factor in the pathogenesis of Kaposi's sarcoma-associated herpesvirus-infected primary effusion lymphomas SO BLOOD LA English DT Article; Proceedings Paper CT 3rd National AIDS Malignancy Conference CY MAY 27, 1999 CL BETHESDA, MARYLAND ID ASCITES TUMOR-GROWTH; EPSTEIN-BARR-VIRUS; CELL-LINE; TYROSINE KINASE; CASTLEMANS-DISEASE; FLUID ACCUMULATION; PERIPHERAL-BLOOD; FACTOR RECEPTOR; DNA-SEQUENCES; ANGIOGENESIS AB primary effusion lymphomas (PELs), which are rare lymphomas associated with Kaposi's sarcoma-associated herpesvirus (or human herpesvirus-8) infection, present as malignant lymphomatous effusions in body cavities. Because PELs prefer liquid growth, we hypothesized that increased vascular permeability would be required for effusions to form. We found that the PEL cell lines BC-1, BCP-1, and BCBL-1 produce high levels of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), Reverse transcriptase-polymerase chain reaction analysis of RNA from the PEL cell lines amplified the 3 VEGF-secreted isoforms: VEGF/VPF121, VEGF/VPF145, and VEGF/VPF165, Two of the PEL cell lines expressed the VEGF/VPF receptor Flt-1, but VEGF/VPF did not stimulate proliferation in these cells, Most (13/14) control SCID/beige mice inoculated intraperitoneally with BCBL-1 cells and subsequently observed or treated with control antibodies developed effusion lymphoma of human cell origin with prominent bloody ascites. In contrast, none (0/9) of the mice treated with a neutralizing antihuman VEGF/VPF antibody developed ascites and effusion lymphoma. These results demonstrate that VEGF/VPF is critical to BCBL-1 growth as effusion lymphoma in mice and suggest that VEGF/VPF stimulation of vascular permeability may be critical to the pathogenesis of PELs, (C) 1999 by The American Society of Hematology. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. RP Aoki, Y (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bldg 29A,Room 2D06,HFM-535,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 53 TC 71 Z9 74 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 1999 VL 94 IS 12 BP 4247 EP 4254 PG 8 WC Hematology SC Hematology GA 263TD UT WOS:000084140600031 PM 10590069 ER PT J AU Chang, HC Holland, RD Bumpus, JA Churchwell, MI Doerge, DR AF Chang, HC Holland, RD Bumpus, JA Churchwell, MI Doerge, DR TI Inactivation of Coprinus cinereus peroxidase by 4-chloroaniline during turnover: comparison with horseradish peroxidase and bovine lactoperoxidase SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE Coprinus cinereus peroxidase; 4-chloroaniline; suicide substrate; inactivation; covalent binding; heme; peptide mapping; electrospray/MS; MALDI-TOF/MS ID MACRORHIZUS PEROXIDASE; FUNGAL PEROXIDASES; PROSTHETIC GROUP; CDNA SEQUENCE; SODIUM-AZIDE; HEME EDGE; OXIDATION; TRANSFORMATIONS; METABOLISM; OLIGOMERS AB The peroxidase from Coprinus cinereus (CPX) catalyzed oxidative oligomerization of 4-chloroaniline (4-CA) forming several products: N-(4-chlorophenyl)-benzoquinone monoamine (dimer D), 4,4'-dichloroazobenzene (dimer E); 2-(4-chloroanilino)-N-(4-chlorophenyl)-benzoquinone (trimer F); 2-amino-5-chlorobenzoquinone-di-4-chloroanil (trimer G); 2-(4-chloroanilino)-5-hydroxybenzoquinone-di-4-chloroanil (tetramer H) and 2-amino-5-(-4-chlroanilino)-benzoquinone (tetramer I). In the presence of 4-CA and H2O2, CPX was irreversibly inactivated within 10 min. Inactivation of CPX in the presence of H2O2 was a time-dependent, first-order process when the concentration of 4-CA was varied between 0 and 2.5 mM. The apparent dissociation constant (K-j) for CPX and 4-CA was 0.71 mM. The pseudo-first order rate constant for inactivation (k(inact)), was 1.15 x 10 (- 2) s(-1). Covalent incorporation of 20 mole C-14-4-CA per mole of inactivated CPX was observed. The partition ratio was about 2200 when either 4-CA or H2O2 was used as the limiting substrate. These results shrew that 4-CA is a metabolically activated inactivator (i.e. a suicide substrate). Unmodified heme and hydroxymethyl heme were isolated from native, 4-CA-inactivated and H2O2-incubated CPX. Inactivation resulted in significant losses in both heme contents. Analysis of tryptic peptides from 4-CA-inactivated CPX by. MALDI-TOF/ MS and UV-VIS spectrophotometry suggested that trimer G and tetramer H were the major 4-CA derivatives that were covalently bound, including to apeptide (MCDAGFSPDEVVDLLAAHSLASQEGLNSAIFR) containing the heme binding site. These studies show that heme destruction and covalent modification of the polypeptide chain art: both important for the inactivation of CPX. These results were compared with similar studies on 4-CA-inactivated horseradish peroxidase (HRP) and bovine lactoperoxidase (LPO) during the oxidation of 4-CA. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Univ No Iowa, Dept Chem, Cedar Falls, IA 50614 USA. RP Chang, HC (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. OI Bumpus, John/0000-0002-9222-7979 FU NIEHS NIH HHS [ESO 4492] NR 33 TC 24 Z9 24 U1 1 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD DEC 15 PY 1999 VL 123 IS 3 BP 197 EP 217 DI 10.1016/S0009-2797(99)00136-2 PG 21 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 273TA UT WOS:000084722400002 PM 10654839 ER PT J AU Datta, AR Benjamin, MM AF Datta, AR Benjamin, MM TI Cell density dependent acid sensitivity in stationary phase cultures of enterohemorrhagic Escherichia coli O157 : H7 SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE acid sensitivity; cell density; Escherichia coli ID HEMOLYTIC-UREMIC-SYNDROME; SIGMA-FACTOR KATF; SALMONELLA-TYPHIMURIUM; TOLERANCE RESPONSE; LISTERIA-MONOCYTOGENES; APPLE CIDER; RPOS; PH; RESISTANCE; VIRULENCE AB Escherichia coli O157:H7, the causative agent of hemorrhagic colitis and hemolytic uremic syndrome, can survive in a highly acidic environment. The acid resistance of this organism, as measured by its ability to survive in low pH, depended on the density of the cells present during the assay. At low cell densities (less than or equal to 2 x 10(7) ml(-1)), about 100% of the stationary phase cells survived in Luria broth pH 2.5 at 37 degrees C For at least 7 h. The same cultures at high cell densities (2-5 x 10(9) ml(-1)) were about 1000-fold more sensitive under identical conditions. Exponential phase cultures did not exhibit the cell density effect, The increased acid sensitivity at high cell densities was absent in the stationary phase cultures of a rpoS mutant (rpoS::pRR10) of an E. coli O157:H7 strain. Cell density dependent acid sensitivity of the stationary phase cultures was also observed in other enterohemorrhagic E. coli and Shigella strains. The increased acid sensitivity at high cell densities was absent in Gram-positive organisms. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Datta, AR (reprint author), US FDA, Div Field Sci, HFC-141,Room 1241,5600 Fishers Lane, Rockville, MD 20857 USA. EM Adatta@ora.fda.gov NR 31 TC 16 Z9 16 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0378-1097 EI 1574-6968 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD DEC 15 PY 1999 VL 181 IS 2 BP 289 EP 295 DI 10.1111/j.1574-6968.1999.tb08857.x PG 7 WC Microbiology SC Microbiology GA 263LZ UT WOS:000084127300014 PM 10585551 ER PT J AU Poirier, MC Patterson, TA Slikker, W Olivero, OA AF Poirier, MC Patterson, TA Slikker, W Olivero, OA TI Incorporation of 3 '-azido-3 '-deoxythymidine (AZT) into fetal DNA and fetal tissue distribution of drug after infusion of pregnant late-term rhesus macaques with a human-equivalent AZT dose SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE transplacental; zidovudine; monkey; DNA incorporation; pharmacokinetics ID HUMAN-IMMUNODEFICIENCY-VIRUS; MATERNAL VIRAL LOAD; ZIDOVUDINE PHARMACOKINETICS; TRANSPLACENTAL TRANSFER; TRANSMISSION; MICE; 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE; AZIDOTHYMIDINE; INFANTS; MICRONUCLEI AB In the United States, the nucleoside analogue drug 3'-azido-3'-deoxythymidine (AZT; also called zidovudine or ZDV) is given to most pregnant women who produce a positive test result for HIV-1. To investigate transplacental distribution and genotoxicity of AZT, near-term pregnant rhesus (Macaca mulatta) monkeys and their fetuses were studied. Four pregnant monkeys were continuously infused with 8 mg AZT/kg body weight for the 4 hours just prior to hysterotomy at term. This short-term AZT exposure resulted in AZT incorporation into DNA of fetal liver, lung, heart, skeletal muscle, brain, testis, and placenta, which varied between 29 and 1944 molecules of AZT/10(6) nucleotides. In contrast, values for AZT and combined metabolites, determined by radioactivity, varied between 0.94 and 5.20 mu g AZT equivalents/g tissue. A fifth animal, (H076), was infused with 17.3 mg AZT/kg body weight for similar to 3 hours, followed by 1 hour without drug before hysterotomy. Similar to the 4 other monkeys, variable levels of AZT (16-147 molecules of AZT/10(6) nucleotides) were incorporated into organ DNA of H076, whereas organ tissues contained less-variable levels of AZT and metabolites (0.86-2.05 mu g AZT equivalents/g tissue). For H076, at hysterotomy 1 hour after discontinuation of drug, values for AZT and the 3'-azido-3'-deoxythymidine-beta-D-glucuronide (AZTG) in fetal blood and amniotic fluid were twofold and threefold higher than those in maternal blood. Most AZT pharmacokinetic parameters in the fifth monkey were similar to those previously reported for the first 4 monkeys and those observed in a similar study of pregnant women. These data show that a short-term AZT infusion in pregnant rhesus monkeys, which have similar AZT pharmacokinetics to those present in a pregnant human, results in incorporation of drug into the DNA of placenta and most fetal organs. Data imply that the human fetus may also be subject to incorporation of AZT into DNA even after short-term AZT infusion to the mother just before delivery. C1 NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Poirier, MC (reprint author), NCI, Div Basic Sci, NIH, Bldg 37,Room 2A05,37 Convent Dr,MSC-4255, Bethesda, MD 20892 USA. FU NIEHS NIH HHS [Y01-ES-10187] NR 33 TC 43 Z9 43 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD DEC 15 PY 1999 VL 22 IS 5 BP 477 EP 483 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 284MR UT WOS:000085336600008 PM 10961609 ER PT J AU Brorson, K Thompson, C Wei, G Krasnokutsky, M Stein, KE AF Brorson, K Thompson, C Wei, G Krasnokutsky, M Stein, KE TI Mutational analysis of avidity and fine specificity of anti-levan antibodies SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLUENZAE TYPE-B; MONOCLONAL-ANTIBODY; IMMUNE-RESPONSE; CAPSULAR POLYSACCHARIDE; SOMATIC MUTATION; FAB FRAGMENT; REPERTOIRE SHIFT; VL USAGE; VH-GENE; BINDING AB Using the polyfructose, bacterial levan, as a model polysaccharide, we analyzed how V regions affect binding in anti-polysaccharide mAbs. Previously, panels of mAb were constructed from bacterial levan-immunized BALB/c and CBA/Ca mice. The BALB/c mAb were mostly germline V(H)J606:V(kappa)11, and a subset contained presumed somatic mutations in the complementarity-determining regions (CDRs) that correlated with increases in avidity for the beta(2-->1) inulin linkage of levan, The CBA/Ca mAb were more heterogeneous in V gene usage, but a subset of inulin-nonreactive mAb were V(H)J60G:V-A and had V-H sequence differences in the CDRs from the V(H)J606 regions of the BALB/c mAb, In this report, V(H)J606 Abs containing various combinations of specifically mutated H and L chains were produced by engineered transfectants and tested for inulin avidity and levan binding. Two presumed somatic mutations seen in CDRs of the BALB/c hybridomas were shown to directly cause marked increases in avidity for inulin (V-H N53H, 9-fold; V-L N53I, 20-fold; together, 46-fold) but not for beta(2-->6) levan, Exchange of either positions 50 or 53 in V-H or the H3 loop between the BALB/c and CBA/Ca mAb resulted in either fine specificity shift or total loss of bacterial levan binding, Three-dimensional models of the V regions suggested that residues that affect binding to inulin alone are near the edge of the CDR surface, while residues involved with binding both forms of levan and affecting fine specificity are in the V-H:V-L junctional area. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. RP Brorson, K (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 65 TC 5 Z9 6 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1999 VL 163 IS 12 BP 6694 EP 6701 PG 8 WC Immunology SC Immunology GA 263PJ UT WOS:000084134200044 PM 10586066 ER PT J AU Itzhak, Y Martin, JL Ali, SF AF Itzhak, Y Martin, JL Ali, SF TI Methamphetamine- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity in inducible nitric oxide synthase-deficient mice SO SYNAPSE LA English DT Article DE dopamine; striatum; iNOS knockout mice; locomotor activity; behavioral sensitization ID INDUCED BEHAVIORAL SENSITIZATION; TYROSINE-HYDROXYLASE ACTIVITY; EXCITATORY AMINO-ACIDS; STRIATAL DOPAMINE; BODY-TEMPERATURE; FREE-RADICALS; CAUDATE-NUCLEUS; RAT STRIATUM; IN-VIVO; BRAIN AB Previous studies have suggested a role for the retrograde messenger, nitric oxide (NO), in methamphetamine (METH)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- induced dopaminergic neurotoxicity. Since evidence supported the involvement of the neuronal nitric oxide synthase (nNOS) isoform in the dopaminergic neurotoxicity, the present study was undertaken to investigate whether the inducible nitric oxide synthase (iNOS) isoform is also associated with METH- and MPTP-induced neurotoxicity. The administration of METH (5mg/kg x 3) to iNOS deficient mice [homozygote iNOS(-/-)] and wild type mice (C57BL/6) resulted in significantly smaller depletion of striatal dopaminergic markers in the iNOS(-/-) mice compared with the wild-type mice. METH-induced hyperthermia was also significantly lower in the iNOS(-/-) mice than in wild-type mice. In contrast to the outcome of METH administration, MPTP injections (20 mg/kg x 3) resulted in a similar decrease in striatal dopaminergic markers in iNOS(-/-) and wild-type mice. In the set of behavioral experiments, METH-induced locomotor sensitization was investigated. The acute administration of METH (1.0 mg/kg) resulted in the same intensity of locomotor activity in iNOS(-/-) and wild-type mice. Moreover, 68 to 72 h after the exposure to the high-dose METH regimen (5 mg/kg x 3), a marked sensitized response to a challenge injection of METH (1.0 mg/kg) was observed in both the iNOS(-/-) and wild-type mice. The finding that iNOS(-/-) mice were unprotected from MPTP-induced neurotoxicity suggests that the partial protection against METH-induced neurotoxicity observed was primarily associated with the diminished hyperthermic effect of METH seen in the iNOS(-/-) mice. Moreover, in contrast to nNOS deficiency, iNOS deficiency did not affect METH-induced behavioral sensitization. (C) 1999 Wiley-Liss, Inc. C1 Univ Miami, Sch Med, Dept Psychiat & Behav Sci R629, Miami, FL 33136 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Itzhak, Y (reprint author), Univ Miami, Sch Med, Dept Psychiat & Behav Sci R629, Gautier Bldg,1011 NE 15th St, Miami, FL 33136 USA. FU NIDA NIH HHS [DA08584] NR 55 TC 35 Z9 36 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD DEC 15 PY 1999 VL 34 IS 4 BP 305 EP 312 DI 10.1002/(SICI)1098-2396(19991215)34:4<305::AID-SYN6>3.0.CO;2-# PG 8 WC Neurosciences SC Neurosciences & Neurology GA 252XM UT WOS:000083527600006 PM 10529724 ER PT J AU Rezapkin, GV Douthitt, M Dragunsky, E Chumakov, KM AF Rezapkin, GV Douthitt, M Dragunsky, E Chumakov, KM TI Reevaluation of nucleotide sequences of wild-type and attenuated polioviruses of type 3 SO VIRUS RESEARCH LA English DT Article DE oral poliovirus vaccine (OPV); attenuation; vaccine safety; neurovirulence ID CENTRAL-NERVOUS-SYSTEM; NEUROVIRULENCE TEST; SABIN-3 POLIOVIRUS; TRANSGENIC MICE; VACCINE; STRAIN; MICROEVOLUTION; POLIOMYELITIS; VIRUS; PCR AB Published sequences of wild-type and attenuated Sabin strains of type 3 poliovirus (Leon/37 and Leon 12a(1)b) were derived from cDNA clones. Recent direct sequencing of Sabin 3 RNA showed that it differed from the published sequence in at least two sites. Here results of direct sequencing of genomes of three independently re-derived sub-strains of attenuated Sabin 3 poliovirus used for oral poliovirus vaccine (OPV) production in addition to the most widely used Pfizer sub-strain are reported. The results showed that all four sub-strains of attenuated type 3 poliovirus contain unique patterns of mutations. Two stocks of the wild-type progenitor Leon/37 strain were also sequenced. Analysis of the two samples of Leon/37 virus showed that one of them is much closer to the Sabin 3 strain, and is an intermediate product of the attenuation process. In addition, we created genetically engineered constructs which contained some of the mutations suspected for their possible role in neurovirulence, and tested them in monkeys and in transgenic mice sensitive to poliovirus. The results suggested that none of them increased neurovirulence of the virus, but some may improve virus replication. Therefore the only mutation occurring in Sabin 3 under vaccine production conditions that appears to affect neurovirulence of the virus is the well known U-->C reversion at nucleotide 472. Published by Elsevier Science B.V. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Chumakov, KM (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-470,1401 Rockville Pike, Rockville, MD 20852 USA. EM chumakov@cber.fda.gov NR 32 TC 5 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD DEC 15 PY 1999 VL 65 IS 2 BP 111 EP 119 DI 10.1016/S0168-1702(99)00108-2 PG 9 WC Virology SC Virology GA 269WZ UT WOS:000084501600003 PM 10581384 ER PT J AU Ali, SF Thiriet, N Zwiller, J AF Ali, SF Thiriet, N Zwiller, J TI Acute ibogaine injection induces expression of the immediate early genes, egr-1 and c-fos, in mouse brain SO MOLECULAR BRAIN RESEARCH LA English DT Article DE ibogaine; egr-1; c-fos; early gene expression; neurotoxicity ID NMDA RECEPTOR COMPLEX; ANTI-ADDICTIVE DRUG; MK-801 BINDING; RAT-BRAIN; COCAINE; MORPHINE; STRIATUM; ACTIVATION; INDUCTION; TOLERANCE AB The aim of the present study was to evaluate if an acute injection of ibogaine (IBO) induces immediate early gene expression in different regions of mouse brain. Adult male C57 mice received a single injection of IBO and were perfused transcardially with 1% paraformaldehyde 30 min after the drug administration. A single injection of IBO produced a significant increase of egr-1 messenger RNA induction in nucleus accumbens (NAc), caudate-putamen (CPu), frontal cortex (FCx), septum, dentate gyrus (DG) and CA3 region of hippocampus, whereas c-fos gene was induced in CPu, FCx, DG, septum and CA1 region of hippocampus. This gene expression may be due, in part, to the stimulant properties of IBO, as we found with other psychostimulants. (C) 1999 Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Ctr Neurochim, INSERM, U338, F-67084 Strasbourg, France. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 37 TC 9 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD DEC 10 PY 1999 VL 74 IS 1-2 BP 237 EP 241 DI 10.1016/S0169-328X(99)00283-1 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 269WA UT WOS:000084499500027 ER PT J AU Hu, WG Chen, J Collins, FM Gu, XX AF Hu, WG Chen, J Collins, FM Gu, XX TI An aerosol challenge mouse model for Moraxella catarrhalis SO VACCINE LA English DT Article DE aerosol challenge; animal model; M-catarrhalis ID OUTER-MEMBRANE PROTEIN; BRANHAMELLA-CATARRHALIS; PULMONARY CLEARANCE; OTITIS-MEDIA; IMMUNE-RESPONSE; ANIMAL-MODEL; IMMUNIZATION; PATHOGEN; VACCINE; CHINCHILLA AB A simple, reproducible, and non-invasive mouse pulmonary clearance model for Moraxella catarrhalis via aerosol challenge was established. All of eight tested strains could be inoculated into mice at more than 10(5) colony-forming units (CFU)/lung with a challenge concentration of 1 x 10(9)-6 x 10(9) CFU/ml in a nebulizer. The number of bacteria retained at 6 h postchallenge was more than 10(4) CFU/lung while at 24 h postchallenge, approximate 10(3) CFU/ml or less remained in the lungs. A maximum of 100 mice could be challenged per aerosol exposure. The number of bacteria inoculated in the lungs could be adjusted by the bacterial challenge concentration, the exposure time, and the negative pressure. Lung tissue sections revealed that bacteria were evenly distributed in the lungs. Passive immunization significantly enhanced pulmonary clearance of the homologous strain in this model. These data indicate that this model will be useful for evaluating M. catarrhalis vaccine candidates and studying roles of immunity against M, catarrhalis. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Natl Inst Deafness & Commun Disorders, Immunol Lab, NIH, Rockville, MD 20850 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Gu, XX (reprint author), Natl Inst Deafness & Commun Disorders, Immunol Lab, NIH, 5 Res Court, Rockville, MD 20850 USA. NR 23 TC 12 Z9 12 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 DEC 10 PY 1999 VL 18 IS 9-10 BP 799 EP 804 DI 10.1016/S0264-410X(99)00335-7 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 262RA UT WOS:000084079200007 PM 10580192 ER PT J AU Misbin, RI AF Misbin, RI TI Should the declaration of Helsinki be revised? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Misbin, RI (reprint author), US FDA, Rockville, MD 20857 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 9 PY 1999 VL 341 IS 24 BP 1852 EP 1853 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 262NU UT WOS:000084074000019 PM 10610463 ER PT J AU Henney, JE Shuren, JE Nightingale, SL McGinnis, TJ AF Henney, JE Shuren, JE Nightingale, SL McGinnis, TJ TI Internet purchase of prescription drugs: Buyer beware SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Shuren, JE (reprint author), US FDA, HF-11,Room 14-101,5600 Fishers Lane, Rockville, MD 20857 USA. NR 3 TC 22 Z9 22 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 7 PY 1999 VL 131 IS 11 BP 861 EP 862 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 262ET UT WOS:000084053200010 PM 10610633 ER PT J AU Masur, H Kaplan, JE Holmes, KK Alston, BL Ampel, N Anderson, JR Baker, AC Barr, D Bartlett, JG Bennett, JE Benson, CA Bozzette, SA Chaisson, RE Crumpacker, CS Currier, JS Deyton, L Drew, WL Duncan, WR Eisinger, RW El-Sadr, W Feinberg, J Freedberg, KA Furrer, H Gnann, JW Goldberger, MJ Goldie, S Goosby, EP Gross, PA Hafner, R Havlir, D Hooton, TM Jabs, DA Jacobson, MA Janoff, E Kitahata, M Kovacs, JV Leport, C Levin, MJ Lopez, JC Marco, M Mayers, DL Melnick, DA Mofenson, LM Montaner, JSG Moore, R Neaton, J Nelson, C O'Neill, JF Palefsky, J Pau, A Phair, JP Piscitelli, S Polis, MA Quinn, TC Reiss, P Rimland, D Sears, CL Seeff, L Sepkowitz, KA Slama, TG Sloand, EM Spector, SA Thomas, DL Van Dyke, RB Watts, DH Wheat, LJ Whitcup, SM Williams, P Wright, TC Castro, KG DeCock, KM Dowell, SF Dworkin, MS Dykewicz, C Ellerbrock, T Hajjeh, R Holmberg, S Holtgrave, DR Jaffe, HW Jones, JL Juranek, DD Mast, E Navin, T Pellett, PE Reeves, WC Stewart, JA Villarino, ME Kaplan, JE AF Masur, H Kaplan, JE Holmes, KK Alston, BL Ampel, N Anderson, JR Baker, AC Barr, D Bartlett, JG Bennett, JE Benson, CA Bozzette, SA Chaisson, RE Crumpacker, CS Currier, JS Deyton, L Drew, WL Duncan, WR Eisinger, RW El-Sadr, W Feinberg, J Freedberg, KA Furrer, H Gnann, JW Goldberger, MJ Goldie, S Goosby, EP Gross, PA Hafner, R Havlir, D Hooton, TM Jabs, DA Jacobson, MA Janoff, E Kitahata, M Kovacs, JV Leport, C Levin, MJ Lopez, JC Marco, M Mayers, DL Melnick, DA Mofenson, LM Montaner, JSG Moore, R Neaton, J Nelson, C O'Neill, JF Palefsky, J Pau, A Phair, JP Piscitelli, S Polis, MA Quinn, TC Reiss, P Rimland, D Sears, CL Seeff, L Sepkowitz, KA Slama, TG Sloand, EM Spector, SA Thomas, DL Van Dyke, RB Watts, DH Wheat, LJ Whitcup, SM Williams, P Wright, TC Castro, KG DeCock, KM Dowell, SF Dworkin, MS Dykewicz, C Ellerbrock, T Hajjeh, R Holmberg, S Holtgrave, DR Jaffe, HW Jones, JL Juranek, DD Mast, E Navin, T Pellett, PE Reeves, WC Stewart, JA Villarino, ME Kaplan, JE CA USPHS IDSA Prevention Oportunisti TI 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; MYCOBACTERIUM-AVIUM COMPLEX; PLACEBO-CONTROLLED TRIAL; ACTIVE ANTIRETROVIRAL THERAPY; TRIMETHOPRIM-SULFAMETHOXAZOLE; CYTOMEGALOVIRUS RETINITIS; RANDOMIZED TRIAL; TOXOPLASMIC ENCEPHALITIS; AEROSOLIZED PENTAMIDINE; MAINTENANCE THERAPY C1 NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Washington, Seattle, WA 98195 USA. Univ Arizona, Tucson, AZ USA. Johns Hopkins Univ, Baltimore, MD USA. Natl Assoc People AIDS, Washington, DC USA. Forum Collaborat HIV Res, Washington, DC USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Harvard Univ, Med Ctr, Boston, MA 02115 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. US Dept Vet Affairs, Washington, DC USA. Univ Calif San Francisco, Mt Zion Med Ctr, San Francisco, CA 94120 USA. Harlem Hosp, New York, NY USA. Holmes Hosp, Cincinnati, OH USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Hosp Bern, CH-3010 Bern, Switzerland. Univ Alabama, Birmingham, AL USA. US FDA, Rockville, MD 20857 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. US Dept Hlth & Human Serv, Washington, DC USA. Hackensack Med Ctr, Hackensack, NJ 07604 USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. Vet Adm Med Ctr, Minneapolis, MN 55417 USA. Univ Washington, Seattle, WA 98195 USA. Hop Bichat Claude Bernard, F-75877 Paris 18, France. Hosp Univ Gregorio Maranon, Madrid, Spain. Treatment Act Grp, New York, NY USA. Henry Ford Hosp, Detroit, MI 48202 USA. Kaiser Permanente, Springfield, VA USA. St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. Univ Minnesota, Minneapolis, MN USA. US Hlth Resources & Serv Adm, Rockville, MD 20857 USA. Northwestern Univ, Chicago, IL 60611 USA. Johns Hopkins Hosp, Baltimore, MD 21287 USA. Univ Amsterdam, Amsterdam, Netherlands. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Natl Fdn Infect Dis, Indianapolis, IN USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. RP Masur, H (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. RI Furrer, Hansjakob/G-6768-2013 OI Furrer, Hansjakob/0000-0002-1375-3146 NR 90 TC 19 Z9 19 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 7 PY 1999 VL 131 IS 11 BP 873 EP 908 PG 36 WC Medicine, General & Internal SC General & Internal Medicine GA 262ET UT WOS:000084053200019 ER PT J AU Cornish, K Lytle, CD AF Cornish, K Lytle, CD TI Viral impermeability of hypoallergenic, low protein, guayule latex films SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article DE hypoallergenic latex; latex allergy; latex prototypes; Parthenium argentatum; viral barrier properties ID HEVEA-BRASILIENSIS LATEX; CROSS-REACTIVITY; VIRUS AB Guayule latex proteins do not cross-react with antibodies raised against latex proteins in commercially available products manufactured from Hevea brasiliensis latex. Thus guayule latex is a promising raw material for the manufacture of hypoallergenic latex products, safe for use by people suffering from IgE-mediated Type I "latex allergy." Also, guayule latex is a low protein material and therefore unlikely to cause widespread sensitization. Latex products commonly are used as essential barriers against the transmission of disease, and so guayule hypoallergenic latex medical products would be a viable alternative only if they possess effective viral barrier properties. To address this question, fingers of prototype hand-dipped guayule latex examination gloves were tested for their permeability to a surrogate challenge virus, phi X174. This virus has a diameter of 27 nm and is similar in size to the smallest human pathogenic viruses. Prototype guayule latex condom films were tested using synthetic blood over a range of pressures and, after 4 years of storage, with synthetic blood and with the phi X174 virus. We concluded that guayule latex films taken from prototype hand-dipped gloves and condoms provide effective barriers to virus transmission and that they remain effective (at least in condoms) after long-term storage. (C) 1999 John Wiley & Sons, Inc. C1 ARS, USDA, Western Reg Res Ctr, Albany, CA 94710 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Cornish, K (reprint author), ARS, USDA, Western Reg Res Ctr, Albany, CA 94710 USA. RI Cornish, Katrina/A-9773-2013 NR 20 TC 15 Z9 15 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD DEC 5 PY 1999 VL 47 IS 3 BP 434 EP 437 DI 10.1002/(SICI)1097-4636(19991205)47:3<434::AID-JBM20>3.0.CO;2-N PG 4 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 239UV UT WOS:000082788800020 PM 10487897 ER PT J AU Powell, AJ Darmon, AJ Gonos, ES Lam, EWF Peden, KWC Jat, PS AF Powell, AJ Darmon, AJ Gonos, ES Lam, EWF Peden, KWC Jat, PS TI Different functions are required for initiation and maintenance of immortalization of rat embryo fibroblasts by SV40 large T antigen SO ONCOGENE LA English DT Article DE SV40 T antigen; immortalization; REFs ID VIRUS-40 LARGE-T; SIMIAN-VIRUS-40 LARGE-T; LARGE TUMOR-ANTIGEN; SIMIAN VIRUS-40; ADENOVIRUS E1A; J-DOMAIN; TRANSFORMING FUNCTION; CELLULAR PROTEIN-P53; HYDROPHOBIC REGION; P53 BINDING AB We have used two different, but complementary assays to characterize functions of SV40 T antigen that are necessary for its ability to immortalize rat embryo fibroblasts. In accordance with previous work, we found that several functions were required. These include activities that map to the p53 binding domain and the amino terminal 176 amino acids which contain the J domain as well as the CR1 and CR2 domain required for binding and sequestering the RE family of pocket proteins. Moreover, we found that even though activities dependent only upon the amino terminus were sufficient for immortalization they were unable to maintain it. This suggests that immortalization by these amino terminal functions requires either additional events or immortalization of a subset of cells within the heterogeneous rat embryo fibroblast population, We further found that an activity dependent upon amino acids 17-27 which remove a portion of the CR1 domain and the predicted alpha-1 helix of the J domain was not necessary to maintain growth but was required for direct immortalization suggesting that at least one of the functions required initially was not required to maintain the immortal state. This represents the first demonstration that some of the functions required for maintenance of the immortal state differ from those required for initiation of immortalization. C1 Royal Free & Univ Coll Med Sch, Sch Med, Ludwig Inst Canc Res, London W1P 8BT, England. Univ London Imperial Coll Sci Technol & Med, Sch Med, Ludwig Inst Canc Res, London W2 1PG, England. Univ London Imperial Coll Sci Technol & Med, Sch Med, Sect Cell Biol & Virol, London W2 1PG, England. US FDA, Ctr Biol Evaluat & Res, Lab Retrovirus Res, Bethesda, MD 20892 USA. UCL, Dept Biochem & Mol Biol, London WC1E 6BT, England. RP Jat, PS (reprint author), UCL, Dept Biochem & Mol Biol, Gower St, London WC1E 6BT, England. NR 56 TC 19 Z9 19 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 2 PY 1999 VL 18 IS 51 BP 7343 EP 7350 DI 10.1038/sj.onc.1203154 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 263HN UT WOS:000084119400020 PM 10602490 ER PT J AU Alpert, S AF Alpert, S TI Implementing the final rule - Commentary SO ACADEMIC EMERGENCY MEDICINE LA English DT Editorial Material DE Final Rule; Food and Drug Administration; waiver; informed consent; research; emergency medicine C1 US FDA, Off Device Evaluat, Rockville, MD 20857 USA. RP Alpert, S (reprint author), US FDA, Off Device Evaluat, Rockville, MD 20857 USA. NR 2 TC 6 Z9 6 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD DEC PY 1999 VL 6 IS 12 BP 1188 EP 1189 DI 10.1111/j.1553-2712.1999.tb00130.x PG 2 WC Emergency Medicine SC Emergency Medicine GA 268EZ UT WOS:000084402500002 PM 10609918 ER PT J AU Pauken, CM LaBorde, JB Bolon, B AF Pauken, CM LaBorde, JB Bolon, B TI Retinoic acid acts during peri-implantational development to alter axial and brain formation SO ANATOMY AND EMBRYOLOGY LA English DT Article DE exencephaly; neural tube defects; RT-PCR; RARs; RXRs; implantation ID MOUSE EMBRYONIC-DEVELOPMENT; NEURAL-TUBE DEFECTS; VITAMIN-A; MESSENGER-RNA; CREST CELLS; EXPRESSION; HINDBRAIN; RECEPTORS; IDENTITY; RAT AB All-trans retinoid acid (RA) induces a stereotypic spectrum of stage-specific malformations in vertebrate conceptuses. The present work evaluated the anatomic and biochemical effects of exposure to RA in mouse embryos at a peri-implantational stage of development - gestational day (GD) 5. The RA receptors (RARs) beta and gamma, the retinoid X receptors (RXRs) alpha and beta, and the cellular retinoid acid binding proteins (CRABPs) I and II were detected by RT-PCR in both control and treated individual GD 5 decidua/embryo complexes 3 h after RA injection, indicating the presence of the mRNAs coding for the proteins that mediate the effects of RA. In contrast, the RAR alpha mRNA was detected in some but not all decidua/embryo complexes, both control and treated, suggesting that its expression is initiated at approximately GD 5, while RXR gamma mRNA was not detected. Examination of the control and RA-exposed embryos on GD 10, 12, or 17 showed that greater than 50% of the RA-exposed embryos were adversely affected, many with defects found only after serial histopathological examination. The malformations were localized primarily in the central nervous system, the branchial arches, and their derivatives. These terata included excessive folding and elevation of the neural tube floor plate, exencephaly (with detachment of the cephalic neuroepithelium and rarefied cephalic mesenchyme), persistent patency of Rathke's pouch, small trigeminal ganglia, neural diverticula (chiefly from the spinal cord), and/or various optic and otic defects. Unexpectedly, limb reduplications were not apparent in RA-exposed fetuses. Those litters examined on GD 17 had a high percentage of resorbed or malformed implantations, and the few apparently normal fetuses were developmentally delayed with repect to bone ossification. These data confirm that the development of neural- and neural crest-derived structures are severely disrupted by RA exposure prior to initial specification of the neural plate and suggest that many of the proteins that regulate RA signaling are available in early vertebrate embryos at this developmental stage. C1 Pathol Associates Int Corp, NCTR, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. RP Pauken, CM (reprint author), Arizona State Univ, Dept Biol, Tempe, AZ 85287 USA. NR 60 TC 11 Z9 13 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-2061 J9 ANAT EMBRYOL JI Anat. Embryol. PD DEC PY 1999 VL 200 IS 6 BP 645 EP 655 DI 10.1007/s004290050311 PG 11 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 259DF UT WOS:000083878100008 PM 10592067 ER PT J AU Schwieterman, WD AF Schwieterman, WD TI FDA perspective on anti-TNF treatments SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article C1 Food & Drug Adm, Immunol & Infect Dis Branch, Div Clin Trial Design & Anal, Rockville, MD 20852 USA. RP Schwieterman, WD (reprint author), Food & Drug Adm, Immunol & Infect Dis Branch, Div Clin Trial Design & Anal, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD DEC PY 1999 VL 58 SU 1 BP 90 EP 91 PG 2 WC Rheumatology SC Rheumatology GA 265JM UT WOS:000084239700016 ER PT J AU Bass, L Liebert, CA Lee, MD Summers, AO White, DG Thayer, SG Maurer, JJ AF Bass, L Liebert, CA Lee, MD Summers, AO White, DG Thayer, SG Maurer, JJ TI Incidence and characterization of integrons, genetic elements mediating multiple-drug resistance, in avian Escherichia coli SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SITE-SPECIFIC INTEGRATION; CONJUGATIVE R-PLASMIDS; GRAM-NEGATIVE BACTERIA; ANTIBIOTIC-RESISTANCE; STREPTOMYCIN-SPECTINOMYCIN; TRIMETHOPRIM RESISTANCE; MERCURY RESISTANCE; SEQUENCE-ANALYSIS; ENTERO-TOXIN; TN21 AB Antibiotic resistance among avian bacterial isolates is common and is of great concern to the poultry industry. Approximately 36% (n = 100) of avian, pathogenic Escherichia coli isolates obtained from diseased poultry exhibited multiple-antibiotic resistance to tetracycline, oxytetracycline, streptomycin, sulfonamides, and gentamicin, Clinical avian E. coli isolates were further screened for the presence of markers for class 1 integrons, the integron recombinase intI1 and the quaternary ammonium resistance gene qacE Delta 1, in order to determine the contribution of integrons to the observed multiple-antibiotic resistance phenotypes, Sixty-three percent of the clinical isolates were positive for the class 1 integron markers infI1 and qacE Delta 1. PCR analysis with the conserved class 1 integron primers yielded amplicons of approximately 1 kb from E. coli isolates positive for intI7 and qacE Delta 1. These PCR amplicons contained the spectinomycin-streptomycin resistance gene aadA1. Further characterization of the identified integrons revealed that many were part of the transposon Tn21, a genetic element that encodes both antibiotic resistance and heavy-metal resistance to mercuric compounds. Fifty percent of the clinical isolates positive for the integron marker gene intI1 as well as for the qacE Delta 1 and aadA1 cassettes also contained the mercury reductase gene merA. The correlation between the presence of the merA gene with that of the integrase and antibiotic resistance genes suggests that these integrons are located in Tn21, The presence of these elements among avian E. coli isolates of diverse genetic makeup as well as in Salmonella suggests the mobility of Tn21 among pathogens in humans as well as poultry. C1 Univ Georgia, Dept Avian Med, Athens, GA 30602 USA. Univ Georgia, Dept Microbiol, Athens, GA 30602 USA. Univ Georgia, Dept Med Microbiol & Parasitol, Athens, GA 30602 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Maurer, JJ (reprint author), Univ Georgia, Dept Avian Med, Athens, GA 30602 USA. OI Summers, Anne/0000-0003-4258-9696 FU NIGMS NIH HHS [GM28211] NR 63 TC 168 Z9 183 U1 1 U2 21 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 1999 VL 43 IS 12 BP 2925 EP 2929 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 261YE UT WOS:000084037900018 PM 10582884 ER PT J AU Niu, MT Salive, ME Ellenberg, SS AF Niu, MT Salive, ME Ellenberg, SS TI Neonatal deaths after hepatitis B vaccine - The vaccine adverse event reporting system, 1991-1998 SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID CLINICAL-EXPERIENCE; MORTALITY RATES; SAFETY; VAERS AB Objective: To evaluate reports of neonatal deaths (aged 0-28 days), after hepatitis B (HepB) immunization reported to: the national Vaccine Adverse Event Reporting System (VAERS). Design: Case series; review of autopsy reports. Setting: Voluntary reports submitted to VAERS, a pas- surveillance system, from the US population, Patients: All US neonates (0-28 days of age) whose deaths after HepB vaccination given alone were reported to VAERS, occurring from January 1, 1991, through October 5, 1998. Intervention: None (observational database). Results: Of 1771 neonatal reports, there were 18 deaths in 8 boys and 9 girls (1 patient unclassified). The mean age at vaccination for these 18 cases was 12 days (range, 1-27 days): median time from vaccination to onset of symptoms was 2 days (range, 0-20 days); and I : median time from symptoms to death was 0 days I (range, 0-15 days). The mean birth weight of the neonates (n = 15) was 3034 g (range, 1828-4678 g). The The causes of death for the 17 autopsied cases were sudden infant death syndrome for 12, infection for 3, and 1 case each of intracerebral hemorrhage, accidental suffocation, and congenital heart disease. Conclusion: Few neonatal deaths following HepB vaccination have been reported, despite the use of at least 86 million doses of pediatric vaccine given in the united 1 States since 1991. While the limitations of passive surveillance systems do not permit definitive inference, these data suggest that HepB immunization is not causing a clear increase in neonatal deaths. C1 US FDA, Ctr Biol Evaluat & Res, Div Biostat & Epidemiol, Rockville, MD 20852 USA. RP Niu, MT (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Biostat & Epidemiol, 1401 Rockville Pike,HFM-210, Rockville, MD 20852 USA. NR 20 TC 17 Z9 18 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD DEC PY 1999 VL 153 IS 12 BP 1279 EP 1282 PG 4 WC Pediatrics SC Pediatrics GA 261HK UT WOS:000084003600012 PM 10591306 ER PT J AU Kues, HA D'Anna, SA Osiander, R Green, WR Monahan, JC AF Kues, HA D'Anna, SA Osiander, R Green, WR Monahan, JC TI Absence of ocular effects after either single or repeated exposure to 10 mW/cm(2) from a 60 GHz CW source SO BIOELECTROMAGNETICS LA English DT Article DE ocular exposure; millimeter wave; rabbit; nonhuman primate; hazard assessment ID PRIMATE EYE AB This study was designed to examine ocular effects associated with exposure to millimeter waves (60 GHz). Rabbits served as the primary experimental subjects. To confirm the results of the rabbit experiments in a higher species, the second phase of the study used nonhuman primates (Macaca mulatta). First, this study used time-resolved infrared radiometry to assess the field distribution patterns produced by different antennas operating at 60 GHz. These results allowed us to select an antenna that produced a uniform energy distribution and the best distance at which to expose our experimental subjects, The study then examined ocular changes after exposure at an incident power density of 10 mW/cm(2). Acute exposure of both rabbits and nonhuman primates consisted of a single 8h exposure, and the repeated exposure protocol consisted of five separate 4h exposures on consecutive days. One eye in each animal was exposed and the contralateral eye served as the sham-exposed control. After postexposure diagnostic examinations, animals were euthanized and the eyes were removed. Ocular tissue was examined by both light and transmission electron microscopy. Neither microscopic examinations nor the diagnostic procedures performed on the eyes of acute and repeatedly exposed rabbits found any ocular changes that could be attributed to millimeter-wave exposure at 10 mW/cm(2). Examination of the primates after comparable exposures also failed to detect any ocular changes due to exposure. On the basis of our results, we conclude that single or repeated exposure to 60 GHz CW radiation at 10 mW/cm(2) does not result in any detectable ocular damage. (C) 1999 Wiley-Liss, Inc. C1 Johns Hopkins Univ, Appl Phys Lab, Laurel, MD 20723 USA. Johns Hopkins Univ, Sch Med, Wilmer Ophthalmol Inst, Baltimore, MD 21205 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Kues, HA (reprint author), Johns Hopkins Univ, Appl Phys Lab, 11100 Johns Hopkins Rd, Laurel, MD 20723 USA. RI Osiander, Robert/J-5781-2015 OI Osiander, Robert/0000-0001-9672-5513 NR 7 TC 21 Z9 23 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0197-8462 J9 BIOELECTROMAGNETICS JI Bioelectromagnetics PD DEC PY 1999 VL 20 IS 8 BP 463 EP 473 DI 10.1002/(SICI)1521-186X(199912)20:8<463::AID-BEM1>3.0.CO;2-T PG 11 WC Biology; Biophysics SC Life Sciences & Biomedicine - Other Topics; Biophysics GA 262YD UT WOS:000084095100001 PM 10559768 ER PT J AU Gail, MH Kessler, L Midthune, D Scoppa, S AF Gail, MH Kessler, L Midthune, D Scoppa, S TI Two approaches for estimating disease prevalence from population-based registries of incidence and total mortality SO BIOMETRICS LA English DT Article DE bias of prevalence estimate; cancer registry; chronic disease prevalence; Lexis diagram; precision of prevalence estimate; prevalence estimation ID CANCER AB Two approaches are described for estimating the prevalence of a disease that may have developed in a previous restricted age interval among persons of a given age at a particular calendar time. The prevalence for all those who ever developed disease is treated as a special case. The counting method (CM) obtains estimates of prevalence by dividing the estimated number of diseased persons by the total population size, taking loss to follow-up into account. The transition rate method (TRM) uses estimates of transition rates and competing risk calculations to estimate prevalence. Variance calculations are described for CM and TRM as well as for a variant of CM, called counting method times 10 (CM10), that is designed to yield more precise estimates than Chi. We compare these three estimators in terms of precision and in terms of the underlying assumptions required to justify the methods. CM makes fewer assumptions but is typically less precise than TRM or CM10. For common diseases such as breast cancer, CM may be preferred because its precision is excellent even though not as high as for TRM or CM10. For less common diseases, such as brain cancer, however, TRM or CM10 and other methods that make stabilizing assumptions may be preferred to CM. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20855 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Informat Management Serv, Silver Spring, MD 20904 USA. RP Gail, MH (reprint author), NCI, Div Canc Epidemiol & Genet, Execut Plaza S,Room 8032,6120 Execut Blvd,MSC 724, Bethesda, MD 20892 USA. NR 13 TC 28 Z9 28 U1 0 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 1999 VL 55 IS 4 BP 1137 EP 1144 DI 10.1111/j.0006-341X.1999.01137.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 265BB UT WOS:000084218000020 PM 11315059 ER PT J AU Meyer, MC Jarvi, EJ Straughn, AB Pelsor, FR Williams, RL Shah, VP AF Meyer, MC Jarvi, EJ Straughn, AB Pelsor, FR Williams, RL Shah, VP TI Bioequivalence of immediate-release theophylline capsules SO BIOPHARMACEUTICS & DRUG DISPOSITION LA English DT Article DE theophylline; bioequivalence; dissolution; human; Biopharmaceutics Classification System AB A three-way crossover study in 18 healthy male volunteers was conducted to evaluate the bioequivalence of three different 200 mg anhydrous theophylline immediate-release (IR) capsules. The products had not. been rated as therapeutically equivalent by the US Food and Drug Administration (FDA) owing to a lack of bioequivalence data. Serum samples were obtained from 0 to 34 h after dosing. Mean time of maximum serum concentration (T-max) ranged from 1.3 to 1.4 h. Mean values for the maximum serum concentration (C-max) and the area under the serum concentration-time curves (AUC) differed by <5% for the three products. The confidence limits for Ln-transformed C-max and AUC ranged from greater than or equal to 89 to less than or equal to 113%. It was concluded that the three products were bioequivalent. in addition, the rapid in vitro dissolution of these formulations, as well as the reported high solubility and high permeability of theophylline, was predictive of the lack of any bioavailability differences among the three products. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Univ Tennessee, Coll Pharm, Dept Pharmaceut Sci, Memphis, TN 38163 USA. Idaho State Univ, Coll Pharm, Dept Pharmaceut Sci, Pocatello, ID 83209 USA. US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Meyer, MC (reprint author), Univ Tennessee, Coll Pharm, Dept Pharmaceut Sci, 874 Union Ave, Memphis, TN 38163 USA. NR 8 TC 1 Z9 1 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0142-2782 J9 BIOPHARM DRUG DISPOS JI Biopharm. Drug Dispos. PD DEC PY 1999 VL 20 IS 9 BP 417 EP 419 DI 10.1002/1099-081X(199912)20:9<417::AID-BDD205>3.0.CO;2-W PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 353AJ UT WOS:000089251300003 PM 10951430 ER PT J AU Miller, MA AF Miller, MA TI Quality control and safety of animal products SO CANADIAN JOURNAL OF ANIMAL SCIENCE LA English DT Article DE animal drug; food safety; antibiotic AB This paper discusses the new animal drug approval process regulated by the Center for Veterinary Medicine (CVM), Food and Drug Administration (FDA) of the United States. The Center for Veterinary Medicine of FDA considers two criteria in ensuring the human food safety of edible animal products: i) safety of the chemical residues and ii) for antimicrobial products, microbiological safety including changes in bacterial pathogen load and resistance pattern. The hazard associated with animal drug products of non-carcinogenic compounds is assessed by conducting a standard battery of toxicology test, whereas the hazard from the carcinogenic potential of compounds is evaluated based on structure, results of genetic toxicity tests, and toxicology studies. Post approval monitoring is carried out to ensure that the animal drugs are being used properly after their approval. Particular concern is given to those eliciting an "acute" toxic reaction at relatively low levels. The other aspect of food safety regulated by CVM of FDA is microbiological safety, especially to antimicrobial drugs used at subtherapeutic levels in feeds. The studies are designed by FDA to ensure that antibiotic treatment of food-producing animals does not alter pathogen load or resistance pattern of pathogens. Two studies are generally performed: i) the salmonella shedding study, which addresses the effect of drug treatment on feces of animals artificially infected with salmonella; and ii) the coliform resistance study, which monitors the effect of the drug on the resistance pattern of E. coli present in the endogenous fetal flora. After a retrospective study of the microbiological safety over past 20 yr, CVM of FDA is planning to revise some microbiological safety studies with focuses on: i) pathogen load, pathogen excretion and microorganism resistance pattern at the time of slaughter; and ii) susceptibility studies on products that have utility in human medicine. C1 US FDA, Human Food Safety & Consultat Serv, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20857 USA. RP Miller, MA (reprint author), US FDA, Human Food Safety & Consultat Serv, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20857 USA. NR 9 TC 2 Z9 2 U1 2 U2 6 PU AGR INST CANADA PI OTTAWA PA SUITE 907 151 SLATER ST, OTTAWA, ONTARIO K1P 5H4, CANADA SN 0008-3984 J9 CAN J ANIM SCI JI Can. J. Anim. Sci. PD DEC PY 1999 VL 79 IS 4 BP 533 EP 538 PG 6 WC Agriculture, Dairy & Animal Science SC Agriculture GA 283TK UT WOS:000085291700016 ER PT J AU Englert, CR Petricoin, EF Krizman, DB Emmert-Buck, MR AF Englert, CR Petricoin, EF Krizman, DB Emmert-Buck, MR TI Molecular profiling of human cancer: New opportunities SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Article DE genomics; Human Genome Project; microdissection; microarrays; molecular profiling; tissue proteomics ID LASER CAPTURE MICRODISSECTION; GENE-EXPRESSION PROFILES; HUMAN-GENOME; SERIAL ANALYSIS; SINGLE CELLS; TISSUE; MICROARRAYS; PROTEOMICS; PROJECT; BIOLOGY AB The Human Genome Project will be completed in the near future, providing new opportunities for researchers to better understand human biology. In order to maximize the value of the genetic data, high-throughput molecular analyses will become an essential experimental methodology, allowing global views of gene expression to be produced and examined. As an example, this approach will permit investigators studying cancer to comprehensively examine the genes and gene products whose alterations underlie tumor development and progression. This information will be essential in determining the fundamental causes of human neoplasms as well as having immediate practical value in the development of clinically useful diagnostic markers and therapeutic targets. C1 NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. NCI, Pathogenet Unit, Pathol Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biolog & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. NCI, Ctr Adv Technol, Gaithersburg, MD 20877 USA. RP Englert, CR (reprint author), NIH, Howard Hughes Med Inst, Res Scholars Program, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU Howard Hughes Medical Institute NR 39 TC 1 Z9 1 U1 0 U2 0 PU PHARMAPRESS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD DEC PY 1999 VL 1 IS 6 BP 712 EP 719 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 342HL UT WOS:000088639100007 PM 19629868 ER PT J AU Rahman, MM Gu, XX Tsai, CM Kolli, VSK Carlson, RW AF Rahman, MM Gu, XX Tsai, CM Kolli, VSK Carlson, RW TI The structural heterogeneity of the lipooligosaccharide (LOS) expressed by pathogenic non-typeable Haemophilus influenzae strain NTHi 9274 SO GLYCOBIOLOGY LA English DT Article DE HTHi; lipooligosaccharide; characterization; otitis media ID HEMOPHILUS-INFLUENZAE; DETOXIFIED LIPOOLIGOSACCHARIDE; LIPOPOLYSACCHARIDE; OLIGOSACCHARIDE; DUCREYI; POLYSACCHARIDE; GLYCOFORMS; PROTEINS AB Nontypeable Haemophilus influenzae (NTHi) is an important pathogen responsible for otitis media in children and of pneumonitis in adults with depressed resistance. NTHi is acapsular and, therefore, capsular polysaccharide-based vaccines are ineffective for preventing infections by this pathogen, Recently it was found that a detoxified lipooligosaccharide (LOS) conjugate from NTHi 9274 induced bactericidal antibodies effective against a large number of NTHi isolates, and conferred protection against NTHi otitis media in chinchillas (X,-X,Gu et al, 1996, Infect, Immun., 64, 4047-4053; X.-X.Gu et al,, 1997,, Infect. Immun., 65, 4488-4493), In this paper we report the chemical characterization of the LOS from NTHi 9274 LOS, NTHi is capable of expressing a heterogenous population of LOS exhibited by multiple oligosaccharide (OS) epitopes, OSs released from the LOS of NTHi 9274 by mild acid hydrolysis were purified using Bio-Gel P4 gel permeation chromatography. The OSs were characterized by glycosyl composition analysis, glycosyl linkage analysis, nuclear magnetic resonance spectroscopy (NMR), fast atom bombardment mass spectrometry (FAB-MS), matrix-assisted laser desorption time of flight mass spectrometry (MALDITOF-MS), and tandem MS/MS. At least 17 different OS molecules were observed. These contained variable glycosyl residues, phosphate (P), and phosphoethanolamine (PEA) substituents, These molecules contained either three, four, or five hexoses, and all contained four heptosyl residues. The four heptosyl residues consisted of one D,D-Hep and three L,D-Hep, Dephosphorylation of the OSs with aqueous 48% hydrofluoric acid (HF) reduced the number of molecules to about to seven; Hex(1-7)Hep(4)Kdo(1). Of these seven, Hex(2)Hep(4)Kdo(1), Hex(3)Hep(4)Kdo(1), and Hex(4)Hep(4)Kdo(1) were the major constituents, Thus, this NTHi LOS preparation is very heterogeneous, and contains structures different from those previously published for Haemophilus influenzae. The tandem MS/MS analysis and glycosyl linkage data suggest that the LOS oligosaccharides have the following structures: [GRAPHICS] where Hex is either a Glc or Gal residue. C1 Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. Natl Inst Deafness & Other Commun Disorders, Immunol Lab, Rockville, MD 20850 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Carlson, RW (reprint author), Univ Georgia, Complex Carbohydrate Res Ctr, 220 Riverbend Rd, Athens, GA 30602 USA. NR 31 TC 41 Z9 43 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD DEC PY 1999 VL 9 IS 12 BP 1371 EP 1380 DI 10.1093/glycob/9.12.1371 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 262AU UT WOS:000084044200010 PM 10561462 ER PT J AU Aoki, I Itoh, S Yokota, S Tanaka, SI Ishii, N Okuda, K Minami, M Klinman, DM AF Aoki, I Itoh, S Yokota, S Tanaka, SI Ishii, N Okuda, K Minami, M Klinman, DM TI Contribution of mast cells to the T helper 2 response induced by simultaneous subcutaneous and oral immunization SO IMMUNOLOGY LA English DT Article ID PROMPTLY PRODUCE INTERLEUKIN-4; CELLULAR IMMUNE-RESPONSES; PARASITE TRICHURIS-MURIS; CONNECTIVE-TISSUE-TYPE; CYTOKINE PRODUCTION; INTERFERON-GAMMA; TH2 CELLS; B-CELLS; FC-RECEPTORS; IFN-GAMMA AB This work examines the contribution of mast cells to the synergistic enhancement of the T helper 2 (Th2) immune response elicited following simultaneous oral and subcutaneous (s.c.) immunization. The s.c. route induced a Th1-biased immune response, characterized by increased interferon-gamma (IFN-gamma) and immunoglobulin G2a (IgG2a) antibody production. In contrast, oral immunization stimulated a primarily Th2-type response in which interleukin-4 (IL-4) and IgG1 antibody production were dominant. Simultaneous immunization also triggered a Th2-biased response, the magnitude of which exceeded the additive effects of s.c. and oral immunization alone by greater than threefold. To analyse whether mast cells in gut-associated lymphoid tissue contributed to this synergistic response, mast cell-deficient mice WBB6F(1)-w/w(v) were studied. Whereas the primary response following simultaneously antigen administration was reduced only twofold in these animals compared with wild type controls WBB6F(1)-+/+ (suggesting that mast cells were not needed to initiate Th2 immunity), reconstitution with bone-marrow-derived mast cells from WBB6F1-+/+ mice resulted in a superoptimal response (suggesting that mast cells contribute to the magnitude and perpetuation of these Th2-biased responses). C1 Yokohama City Univ, Sch Med, Dept Pathol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. Yokohama City Univ, Sch Med, Dept Pediat, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. Yokohama City Univ, Sch Med, Dept Internal Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. Yokohama City Univ, Sch Med, Dept Dermatol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. Yokohama City Univ, Sch Med, Dept Bacteriol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. Yokohama City Univ, Sch Med, Dept Parasitol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. US FDA, Sect Retroviral Immunol, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Aoki, I (reprint author), Yokohama City Univ, Sch Med, Dept Pathol, Kanazawa Ku, 3-9 Fuku Ura, Yokohama, Kanagawa 2360004, Japan. NR 38 TC 9 Z9 10 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 1999 VL 98 IS 4 BP 519 EP 524 DI 10.1046/j.1365-2567.1999.00878.x PG 6 WC Immunology SC Immunology GA 268UQ UT WOS:000084434400006 PM 10594683 ER PT J AU Huang, LY Krieg, AM Eller, N Scott, DE AF Huang, LY Krieg, AM Eller, N Scott, DE TI Induction and regulation of Th1-inducing cytokines by bacterial DNA, lipopolysaccharide, and heat-inactivated bacteria SO INFECTION AND IMMUNITY LA English DT Article ID CD4+ T-CELLS; IFN-GAMMA PRODUCTION; INTERFERON-GAMMA; IN-VITRO; IL-12 PRODUCTION; CPG MOTIFS; IMMUNE REGULATION; BRUCELLA-ABORTUS; P40 HOMODIMER; INTERLEUKIN-12 AB Th1 immune responses, characterized by production of gamma interferon (IFN-gamma), are associated with protective immunity to viruses and intracellular bacteria. Heat-killed Brucella; abortus promotes secretion of Th1-inducing cytokines such as interleukin-12 (IL-12) and IFN-gamma and has been used as a carrier to induce Th1 responses to vaccines. To explore which bacterial constituents could mediate this response and how it is regulated, murine spleen cells were cultured with B. abortus derived DNA, lipopolysaccharide (LPS), or whole killed organisms. Each constituent induced similar, substantial amounts of IL-10. However, only B. abortus and B. abortus DNA induced high levels of IFN-gamma and IL-12. B. abortus and B. abortus DNA-stimulated IL-12 production was maximal by 6 to 18 h, while IL-10 production steadily accumulated over this time period. These kinetics suggested that IL-10 may eventually downmodulate the Th1-like cytokine response to B. abortus and B. abortus DNA, which was confirmed by using neutralizing antibody. In the absence of IL-10, B. abortus LPS induced strong IFN-gamma responses, but IL-12 p70 levels were still undetectable from BALB/c spleen cells. LPS induced IL-12 if the spleen cells were primed with IFN-gamma and IL-10 was neutralized, indicating that LPS can stimulate IL-12 production under the most favorable conditions. Responses to Escherichia coli LPS and DNA mirrored the responses to B. abortus components, suggesting that immune effects observed with these constituents may be generalizable to many microbial species. In vivo experiments demonstrated the same hierarchy of responses for IL-12 production. These findings support the likelihood that microbial components, if used as carriers or adjuvants, can differ substantially in their ability to effect a Th1 response. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. RP Scott, DE (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29,Rm 232,8800 Rockville Pike, Bethesda, MD 20892 USA. EM scottd@cber.fda.gov NR 58 TC 61 Z9 64 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1999 VL 67 IS 12 BP 6257 EP 6263 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 257DW UT WOS:000083768000005 PM 10569735 ER PT J AU Meyer, RJ AF Meyer, RJ TI A United States regulator's perspective on the ongoing chlorofluorocarbon transition SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE chlorofluorocarbons; metered dose inhalers; phaseout; FDA AB The Food and Drug Administration (FDA) put in place a general ban on the use of chlorofluorocarbons for the products it regulates (medical devices, drugs, and foods) in 1978, exempting those products where chlorofluorocarbon use was determined to be essential for the public health, In the intervening years, as the international commitment to a full transition away from all chlorofluorocarbon use took shape under the Montreal Protocol the FDA has worked with industry to facilitate the development and testing of alternative technologies and products for inhalation drug products. As these alternative products begin to move from testing through the approval process and into marketing, the FDA is working collaboratively with the Environmental Protection Agency, other governmental agencies, and nongovernmental stakeholders to develop a transition policy for the United States. The transition policy for metered dose inhalers must be one that achieves the dual aims of first protecting the patients who rely on these vital medical products, while also achieving the public health need of protecting the ozone laver, As a part of developing such a transition strategy, the FDA published an advance notice of proposed rulemaking (ANPRM) in March 1997. The ANPRM proposed mechanisms by which the FDA could determine when chlorofluorocarbon use in a drug product could no longer be considered essential. The ANPRM resulted in a large amount of valuable public debate and input. The FDA is now working to incorporate the knowledge gained from these public comments as it continues the rule-making process. C1 US FDA, Div Pulm & Allergy Drug Prod, Rockville, MD 20857 USA. US FDA, CFC Work Grp, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Meyer, RJ (reprint author), US FDA, Div Pulm & Allergy Drug Prod, HFD-570,5600 Fishers Lane, Rockville, MD 20857 USA. NR 0 TC 2 Z9 3 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 1999 VL 104 IS 6 BP S236 EP S238 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 266FD UT WOS:000084289200037 PM 10588981 ER PT J AU Thompson, J Ruvinov, SB Freedberg, DI Hall, BG AF Thompson, J Ruvinov, SB Freedberg, DI Hall, BG TI Cellobiose-6-phosphate hydrolase (CelF) of Escherichia coli: Characterization and assignment to the unusual family 4 of glycosylhydrolases SO JOURNAL OF BACTERIOLOGY LA English DT Article ID MULTIPLE SEQUENCE ALIGNMENT; BETA-GLUCOSIDE UTILIZATION; BGL OPERON; GLYCOSYL HYDROLASES; CELLOBIOSE UTILIZATION; NUCLEOTIDE-SEQUENCE; AMINO-ACID; PHOSPHOTRANSFERASE SYSTEM; FUSOBACTERIUM-MORTIFERUM; STAPHYLOCOCCUS-AUREUS AB The gene celF of the cryptic cel operon of Escherichia coli has been cloned, and the encoded 6-phospho-beta-glucosidase (cellobiose-6-phosphate [6P] hydrolase; CelF [EC 3.2.1.86]) has been expressed and purified in a catalytically active state. Among phospho-beta-glycosidases, CelF exhibits unique requirements for a divalent metal ion and NAD(+) for activity and, by sequence alignment, is assigned to family 4 of the glycosylhydrolase superfamily. CelF hydrolyzed a variety of P-beta-glucosides, including cellobiose-6P, salicin-6P, arbutin-6P, gentiobiose-6P, methyl-beta-glucoside-6P, and the chromogenic analog, p-nitrophenyl-beta-D-glucopyranoside-6P. In the absence of a metal ion and NAD(+), purified CelF was rapidly and irreversibly inactivated. The functional roles of the cofactors have not been established, but NAD(+) appears not to be a reactant and there is no evidence for reduction of the nucleotide during substrate cleavage. In solution, native CelF exists as a homotetramer (M-w, similar to 200,000) composed of noncovalently linked subunits, and this oligomeric structure is maintained independently of the presence or absence of a metal ion. The molecular weight of the CelF monomer (M-r, similar to 50,000), estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, is in agreement with that calculated from the amino acid sequence of the polypeptide (450 residues; M-r = 50,512). Comparative sequence alignments provide tentative identification of the NAD(+)-binding domain (residues 7 to 40) and catalytically important glutamyl residues (Glu(112) and Glu(356)) of CelF. C1 NIDCR, Oral Infect & Immun Branch, Microbial Biochem & Genet Unit, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Bethesda, MD 20892 USA. Univ Rochester, Dept Biol, Rochester, NY 14627 USA. RP Thompson, J (reprint author), NIDCR, Oral Infect & Immun Branch, Microbial Biochem & Genet Unit, Bldg 30,Room 528,Covent Dr 4350, Bethesda, MD 20892 USA. NR 51 TC 42 Z9 47 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 1999 VL 181 IS 23 BP 7339 EP 7345 PG 7 WC Microbiology SC Microbiology GA 259FV UT WOS:000083884600026 PM 10572139 ER PT J AU Delogu, G Brennan, MJ AF Delogu, G Brennan, MJ TI Functional domains present in the mycobacterial hemagglutinin, HBHA SO JOURNAL OF BACTERIOLOGY LA English DT Article ID HEPARIN-BINDING HEMAGGLUTININ; PREDICTING COILED COILS; FILAMENTOUS HEMAGGLUTININ; COMPLEMENT COMPONENT-C3; PROTEOGLYCAN DECORIN; BORDETELLA-PERTUSSIS; BACTERIAL ADHERENCE; SEQUENCE-ANALYSIS; EPITHELIAL-CELLS; PROTEIN AB Identification and characterization of mycobacterial adhesins and complementary host receptors required for colonization and dissemination of mycobacteria in host tissues are needed for a more complete understanding of the pathogenesis of diseases caused by these bacteria and for the development of effective vaccines, Previous investigations have demonstrated that a 28-kDa heparin-binding mycobacterial surface protein, HBHA, can agglutinate erythrocytes and promote mycobacterial aggregation in vitro. In this study, further molecular and biochemical analysis of HBHA demonstrates that it has three functional domains: a transmembrane domain of 18 amino acids residing near the N terminus, a large domain of 81 amino acids consistent with an or-helical coiled-coil region, and a Lys-Pro-Ala-rich C-terminal domain that mediates binding to proteoglycans. Using His-tagged recombinant HBHA proteins and nickel chromatography we demonstrate that HBHA polypeptides which contain the coiled-coil region form multimers, This tendency to oligomerize may be responsible for the induction of mycobacterial aggregation since a truncated N-terminal HBHA fragment containing the coiled-coil domain promotes mycobacterial aggregation. Conversely, a truncated C-terminal HBHA fragment which contains Lys-Pro-Ala-rich repeats binds to the proteoglycan decorin, These results indicate that HBHA contains at least three distinct domains which facilitate intercalation into surface membranes, promote bacterium bacterium interactions, and mediate the attachment to sulfated glycoconjugates found in host tissues. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Brennan, MJ (reprint author), US FDA, Ctr Biol Evaluat & Res, 29 Lincoln Dr,HFM-431, Bethesda, MD 20892 USA. RI Delogu, Giovanni/I-3701-2012 OI Delogu, Giovanni/0000-0003-0182-8267 NR 39 TC 52 Z9 59 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 1999 VL 181 IS 24 BP 7464 EP 7469 PG 6 WC Microbiology SC Microbiology GA 263QZ UT WOS:000084137900009 PM 10601202 ER PT J AU LeClerc, JE Li, BG Payne, WL Cebula, TA AF LeClerc, JE Li, BG Payne, WL Cebula, TA TI Promiscuous origin of a chimeric sequence in the Escherichia coli O159 : H7 genome SO JOURNAL OF BACTERIOLOGY LA English DT Article ID HEMOLYTIC UREMIC SYNDROME; NUCLEOTIDE-SEQUENCE; STRUCTURAL GENES; O157-H7; STRAINS; OUTBREAK; DIARRHEA; BACTERIA AB A novel sequence of 2.9 Mb in the intergenic region between the mutS and rpoS genes of Escherichia call O157:H7 and closely related strains replaces a sequence of 6.1 kb in E. coli K-12 strains. At the same locus in Shigella dyscnteriae type 1, a sequence identical to that in O157:H7 is bounded by the ISI insertion sequence element. Extensive polymorphism in the mutS-rpoS chromosomal region is indicative of horizontal transfer events. C1 US FDA, Ctr Food Safety & Appl Nutr, Mol Biol Branch, Washington, DC 20204 USA. RP Cebula, TA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Mol Biol Branch, HFS-235,200 C St SW, Washington, DC 20204 USA. NR 25 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 1999 VL 181 IS 24 BP 7614 EP 7617 PG 4 WC Microbiology SC Microbiology GA 263QZ UT WOS:000084137900028 PM 10601221 ER PT J AU Reddy, NR Solomon, HM Fingerhut, GA Rhodehamel, EJ Balasubramaniam, VM Palaniappan, S AF Reddy, NR Solomon, HM Fingerhut, GA Rhodehamel, EJ Balasubramaniam, VM Palaniappan, S TI Inactivation of Clostridium botulinum type E spores by high pressure processing SO JOURNAL OF FOOD SAFETY LA English DT Article ID HIGH HYDROSTATIC-PRESSURE; PHOSPHATE-BUFFERED SALINE; LISTERIA-MONOCYTOGENES; ESCHERICHIA-COLI; STRAINS; HEAT; SALMONELLA; RESISTANT; BACILLUS; FOODS AB The effect of high pressure treatments at various temperature combinations on the inactivation of Clostridium botulinum type E spores of strains, Alaska and Beluga in phosphate buffer (0.067 M, pH 7.0) was investigated No reduction of spores was observed at any pressurization (Maximum = 827 MPa) for temperatures below 35C. At pressurization of 827 MPa for 5 min, log unit reduction of spores increased as temperatures increased from 35 to 55C. An increase in the processing time from 5 to 10 min at a combination of high pressure (827 MPa) and low temperature (40C) resulted in a 5-log reduction of Alaska spores. About 5-log reductions for strains Alaska and Beluga occurred at 50 and 55C, respectively, after processing at pressures of 827 MPa for 5 min. C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. US FDA, Div Microbiol Studies, Washington, DC 20204 USA. IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. Cryovac, Sealed Air Corp, Duncan, SC 29334 USA. Tetra Rex Packaging Syst, Buffalo Grove, IL 60089 USA. RP Reddy, NR (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM RNR@CFSAN.FDA.GOV RI Balasubramaniam, VM Bala/A-2576-2008 OI Balasubramaniam, VM Bala/0000-0002-1540-4273 NR 32 TC 56 Z9 60 U1 1 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0149-6085 J9 J FOOD SAFETY JI J. Food Saf. PD DEC PY 1999 VL 19 IS 4 BP 277 EP 288 DI 10.1111/j.1745-4565.1999.tb00252.x PG 12 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 269ZQ UT WOS:000084511000005 ER PT J AU Weisz, A Ito, Y AF Weisz, A Ito, Y TI Standardization of biological dyes and stains through use of pH-zone-refining countercurrent chromatography SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Meeting Abstract C1 US FDA, Off Cosmet & Colors, Washington, DC 20204 USA. NHLBI, NIH, Biophys Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC PY 1999 VL 47 IS 12 MA 12 BP 1645 EP 1645 PG 1 WC Cell Biology SC Cell Biology GA 263RX UT WOS:000084140000028 ER PT J AU Wang, JH Guan, EN Roderiquez, G Norcross, MA AF Wang, JH Guan, EN Roderiquez, G Norcross, MA TI Inhibition of CCR5 expression by IL-12 through induction of beta-chemokines in human T lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL STIMULATORY FACTOR; INTERFERON-GAMMA PRODUCTION; MACROPHAGE-TROPIC HIV-1; MOLECULAR-CLONING; HUMAN MONOCYTES; IFN-GAMMA; IN-VITRO; RECEPTOR; INTERLEUKIN-12; MIP-1-ALPHA AB IL-12 induces initiation of the differentiation of naive CD4(+) T lymphocytes into Thl cells and is important for the control of cell-mediated immunity, beta-Chemokines serve to attract various types of blood leukocytes to sites of infection and inflammation. The specific receptor for the beta-chemokines (macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and RANTES), CCR5, also functions as the primary coreceptor for macrophage-tropic isolates of HIV-1, IL-12, but not IL-4, IL-10, or IL-13, now has been shown to down-modulate the surface expression of CCR5 induced by IL-2 on both CD4(+) and CD8(+) T lymphocytes, Decreased CCR5 surface expression was not secondary to transcriptional inhibition, given that CCR5 mRNA was enhanced in cells cultured in IL-12/IL-2 compared with those cultured in IL-2 only. The effect of IL-12 in down-modulation of CCR5 surface expression was shown to be mediated by soluble factors secreted from the T cells. Rapid and transient intracellular Ca2+ mobilization was induced in monocytes by IL-12-induced supernatants, which desensitized the response of monocytes to MIP-1 alpha, but not their response to stromal cell-derived factor-1 alpha. Neutralization with specific Abs identified these factors as MIP-1 alpha and MIP-1 beta from most donors. IL-4, IL-10, IFN-gamma, and IL-18 primarily inhibited MIP-1 beta secretion and also weakly suppressed MIP-1 alpha secretion. HIV-1 replication was inhibited in IL-2/IL-12-containing cultures that correlated with chemokine and chemokine-receptor levels. These data suggest that the effects of IL-12 on beta-chemokine production and chemokine-receptor expression may contribute to the immunomodulatory activities of IL-12 and may have potential therapeutic relevance in controlling HIV-1 replication. C1 US FDA, Ctr Biol Evaluat & Res, Lab Cell & Viral Regulat, Div Therapeut Prot,NIH, Bethesda, MD 20892 USA. RP Wang, JH (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Cell & Viral Regulat, Div Therapeut Prot,NIH, Bldg 29B,Room 4E12,HFM 525,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 43 TC 42 Z9 42 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1999 VL 163 IS 11 BP 5763 EP 5769 PG 7 WC Immunology SC Immunology GA 258MT UT WOS:000083843500003 PM 10570258 ER PT J AU Machado, SG Murray, GD Teasdale, GM AF Machado, SG Murray, GD Teasdale, GM TI Evaluation of designs for clinical trials of neuroprotective agents in head injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE clinical trial design; head injury; prognostic models; statistical power ID MULTICENTER; NIMODIPINE; EFFICACY; SEPSIS AB In a study involving the statistical modeling of potential head injury trials, we explore approaches to trial design that could enhance their power to detect treatment-related effects on clinical outcome. The study uses a survey organized by the European Brain Injury Consortium of over 1,000 head-injured patients to characterize the population from which trial participants can be selected. A variety of models are postulated for the effects of "neuroprotective" treatment on outcome, and their interaction with a range of strategies for targeting patients for inclusion in the trial is evaluated. A very simple strategy of targeting patients with an intermediate prognosis was found to allow a reduction in sample size by 30%, with no reduction in statistical power. This paper illustrates an important methodology for studying the characteristics of competing trial designs. C1 Univ Edinburgh, Sch Med, Edinburgh EH8 9AG, Midlothian, Scotland. US FDA, Off Biostat, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ Glasgow, Dept Neurosurg, Inst Neurol Sci, So Gen Hosp, Glasgow, Lanark, Scotland. RP Murray, GD (reprint author), Univ Edinburgh, Sch Med, Teviot Pl, Edinburgh EH8 9AG, Midlothian, Scotland. NR 15 TC 46 Z9 46 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD DEC PY 1999 VL 16 IS 12 BP 1131 EP 1138 DI 10.1089/neu.1999.16.1131 PG 8 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 266WC UT WOS:000084322400001 PM 10619192 ER PT J AU Wear, KA AF Wear, KA TI Frequency dependence of ultrasonic backscatter from human trabecular bone: Theory and experiment SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID HIP FRACTURE; OLDER WOMEN; ATTENUATION; DENSITY; VELOCITY; OSTEOPOROSIS; PREDICTION; COEFFICIENTS; CALCANEUS; SITES AB A model describing the frequency dependence of backscatter coefficient from trabecular bone is presented. Scattering is assumed to originate from the surfaces of trabeculae, which are modeled as long thin cylinders with radii small compared with the ultrasonic wavelength. Experimental ultrasonic measurements at 500 kHz, 1 MHz, and 2.25 MHz from a wire target and from trabecular bone samples from human calcaneus in vitro are reported. In both cases, measurements are in good agreement with theory. For mediolateral insonification of calcaneus at low frequencies, including; the typical diagnostic range (near 500 kHz), backscatter coefficient is proportional to frequency cubed. At higher frequencies, the frequency response flattens out. The data also suggest that at diagnostic frequencies, multiple scattering effects on the average are relatively small for the samples investigated. Finally, at diagnostic frequencies, the data suggest that absorption is likely to be a larger component of attenuation than scattering. [S0001-4966(99)02612-0]. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP US FDA, Ctr Devices & Radiol Hlth, HFZ-142,12720 Twinbrook Pkwy, Rockville, MD 20852 USA. EM kaw@cdrh.fda.gov NR 38 TC 127 Z9 133 U1 2 U2 9 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD DEC PY 1999 VL 106 IS 6 BP 3659 EP 3664 DI 10.1121/1.428218 PG 6 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 266YW UT WOS:000084328700064 PM 10615704 ER PT J AU Teruya-Feldstein, J Setsuda, J Yao, X Kingma, DW Straus, S Tosato, G Jaffe, ES AF Teruya-Feldstein, J Setsuda, J Yao, X Kingma, DW Straus, S Tosato, G Jaffe, ES TI MIP-1 alpha expression in tissues from patients with hemophagocytic syndrome SO LABORATORY INVESTIGATION LA English DT Article ID EPSTEIN-BARR-VIRUS; T-CELL LYMPHOMA; TUMOR-NECROSIS-FACTOR; INTERFERON-GAMMA; MALIGNANT HISTIOCYTOSIS; INDUCIBLE PROTEIN-10; HUMAN MONOCYTES; LYMPHOHISTIOCYTOSIS; HYPERCYTOKINEMIA; PATHOGENESIS AB Hemophagocytic syndrome (HPS) is a clinicopathologic syndrome that can be precipitated by a variety of causes and is characterized by a systemic activation of macrophages, which are induced to undergo phagocytosis. Chemokines play an important role in the inflammatory cell recruitment into tissues. We examined the expression of chemokines and cytokines in tissues exhibiting histologic evidence of HPS in a variety of settings: peripheral T-cell lymphoma, three patients; nasal T/NK cell lymphoma, one patient; subcutaneous panniculitis-like T-cell lymphoma, one patient; and chronic EBV infection, one patient. Compared with control tissues, we found elevated macrophage inflammatory protein-alpha (MIP-1 alpha) and interferon-gamma (IFN-gamma) expression, but not macrophage-derived chemotactic factor (MDC) or TNF-alpha, in tissues of patients with HPS irrespective of the cause or setting. MIP-1 alpha can promote macrophage chemotaxis and IFN-gamma promotes macrophage activation. Elevated expression of IP-10 and monokine induced by IFN-gamma (Mig) was also detected in tissues exhibiting features of HPS, providing an explanation for the occurrence of chemoattraction of T-cells and NK cells. Immunohistochemical analysis of tissues with evidence of phagocytic activity in that site showed MIP-1 alpha characteristically localized to endothelial cells of blood vessels and splenic sinuses, lymphocytes, and macrophages. These results provide evidence for MIP-1 alpha chemokine expression in tissues from patients with HPS and suggest that MIP-1 alpha may play an important role in the pathogenesis of the hemophagocytic syndrome. C1 NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH, Bldg 10,Room 2N202,10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. NR 36 TC 28 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD DEC PY 1999 VL 79 IS 12 BP 1583 EP 1590 PG 8 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 268YM UT WOS:000084448200016 PM 10616208 ER PT J AU Gutman, S Richter, K AF Gutman, S Richter, K TI New directions in the FDA regulation of in vitro diagnostic devices SO LABORATORY MEDICINE LA English DT Article AB Since 1976, the Food and Drug Administration has been involved activity in the regulation of in vitro diagnostic devices. Regulation involves a series of premarket and postmarket controls designed to assure that tests meet minimum thresholds of performance and are labeled properly. The review program for medical devices recently has undergone a variety of changes to produce more effective use of its regulatory tools. C1 US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Rockville, MD 20852 USA. RP Gutman, S (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, HFZ-440,2098 Gaither Rd, Rockville, MD 20852 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LAB MED JI Lab. Med. PD DEC PY 1999 VL 30 IS 12 BP 782 EP 784 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 259ZN UT WOS:000083924000016 ER PT J AU Satchithanandam, S Flynn, TJ Calvert, RJ Kritchevsky, D AF Satchithanandam, S Flynn, TJ Calvert, RJ Kritchevsky, D TI Effect of peanut oil and randomized peanut oil on cholesterol and oleic acid absorption, transport, and distribution in the lymph of the rat SO LIPIDS LA English DT Article ID EXPERIMENTAL ATHEROSCLEROSIS; VEHICLE AB Peanut oil was shown to be atherogenic in cholesterol-fed rats, rabbits, and monkeys. However, after randomization, a process in which the fatty acids in peanut oil are randomly rearranged, its atherogenicity was significantly reduced in cholesterol-fed rabbits and monkeys. The mechanism for this effect remains unknown; This study was designed to investigate whether the absorption, transport and distribution of dietary cholesterol and oleic and in the lymph were altered in the presence of peanut oil or randomized peanut oil. Previous Investigators collected lymph through the mesenteric duct for 6 h and analyzed lymph for cholesterol. In the present study, lymph fluids were collected at timed intervals for up to 8h and then at 24 h via the thoracic duct. Cholesterol and oleic acid (fatty acid) were estimated not only in the whole lymph but also in lymph lipoprotein fractions and in major lipid fractions. A 24-h lymph lipid absorption will not affect the results. Thoracic duct lymph collection is quantitative compared to mesenteric duct lymph collection, which provides only a fraction of the total lymph. Rats were given a lipid emulsion containing either peanut oil or randomized peanut oil. The emulsion also contained cholesterol, oleic acid, and sodium taurocholate in saline and was given through a duodenal catheter. Results show that absorption, transport, and distribution of cholesterol and oleic acid in the lymph fluids were similar in both dietary groups. These results suggest that the atherogenicity of peanut oil may be due to other events taking place subsequent to the release of cholesterol-containing chylomicrons and very low density lipoprotein by the small intestinal epithelial cells into the blood or may be due to the triglyceride structure itself. C1 US FDA, Div Sci & Appl Technol, Laurel, MD 20708 USA. US FDA, Div Toxicol Res, Laurel, MD 20708 USA. US FDA, Div Clin Res & Review Staff, Laurel, MD 20708 USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. RP Satchithanandam, S (reprint author), US FDA, Off Special Nutr, HFS-465,200 C St SW, Washington, DC 20204 USA. OI Flynn, Thomas/0000-0002-7248-0643 FU NHLBI NIH HHS [HL-00734] NR 23 TC 3 Z9 3 U1 1 U2 5 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PD DEC PY 1999 VL 34 IS 12 BP 1305 EP 1311 DI 10.1007/s11745-999-0482-5 PG 7 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 275NZ UT WOS:000084827400006 PM 10652990 ER PT J AU Chan, HP Sahiner, B Wagner, RF Petrick, N AF Chan, HP Sahiner, B Wagner, RF Petrick, N TI Classifier design for computer-aided diagnosis: Effects of finite sample size on the mean performance of classical and neural network classifiers SO MEDICAL PHYSICS LA English DT Article DE computer-aided diagnosis; classifier design; linear classifier; quadratic classifier; neural network; sample size; feature space dimensionality; ROC analysis ID VARIANCE AB Classifier design is one of the key steps in the development of computer-aided diagnosis (CAD) algorithms. A classifier is designed with case samples drawn from the patient population. Generally, the sample size available for classifier design is limited, which introduces variance and bias into the performance of the trained classifier, relative to that obtained with an infinite sample size. For CAD applications, a commonly used performance index for a classifier is the area, A(z), under the receiver operating characteristic (ROC) curve. We have conducted a computer simulation study to investigate the dependence of the mean performance, in terms of A(z), on design sample size for a linear discriminant and two nonlinear classifiers, the quadratic discriminant and the backpropagation neural network (ANN). The performances of the classifiers were compared for four types of class distributions that have specific properties: multivariate normal distributions with equal covariance matrices and unequal means, unequal covariance matrices and unequal means, and unequal covariance matrices and equal means, and a feature space where the two classes were uniformly distributed in disjoint checkerboard regions. We evaluated the performances of the classifiers in feature spaces of dimensionality ranging from 3 to 15, and design sample sizes from 20 to 800 per class. The dependence of the resubstitution and hold-out performance on design (training) sample size (N-t) was investigated. For multivariate normal class distributions with equal covariance matrices, the linear discriminant is the optimal classifier. It was found that its A(z)-versus-1/N-t curves can be closely approximated by linear dependences over the range of sample sizes studied. In the feature spaces with unequal covariance matrices where the quadratic discriminant is optimal, the linear discriminant is inferior to the quadratic discriminant or the ANN when the design sample size is large. However, when the design sample is small, a relatively simple classifier, such as the linear discriminant or an ANN with very few hidden nodes, may be preferred because performance bias increases with the complexity of the classifier. In the regime where the classifier performance is dominated by the 1/N-t term, the performance in the limit of infinite sample size can be estimated as the intercept (1/N-t = 0) of a linear regression of A(z) versus 1/N-t. The understanding of the performance of the classifiers under the constraint of a finite design sample size is expected to facilitate the selection of a proper classifier for a given classification task and the design of an efficient resampling scheme. (C) 1999 American Association of Physicists in Medicine. [S0094-2405(99)00212-6]. C1 Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Chan, HP (reprint author), Univ Michigan, Dept Radiol, 1500 E Med Ctr Dr,UHB1 F510B, Ann Arbor, MI 48109 USA. FU NCI NIH HHS [CA 48129] NR 17 TC 92 Z9 92 U1 1 U2 6 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 1999 VL 26 IS 12 BP 2654 EP 2668 DI 10.1118/1.598805 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 267LJ UT WOS:000084359200020 PM 10619251 ER PT J AU Yu, L Bridgers, A Polli, J Vickers, A Long, S Roy, A Winnike, R Coffin, M AF Yu, L Bridgers, A Polli, J Vickers, A Long, S Roy, A Winnike, R Coffin, M TI Vitamin E-TPGS increases absorption flux of an HIV protease inhibitor by enhancing its solubility and permeability SO PHARMACEUTICAL RESEARCH LA English DT Article; Proceedings Paper CT 13th Annual Meeting of the American-Association-of-Pharmaceutical-Scientists CY NOV 15-19, 1998 CL SAN FRANCISCO, CALIFORNIA SP Amer Assoc Pharmaceut Scientists, GlaxoWellcome Inc, R&D DE amprenavir; vitamin E-TPGS; solubility; permeability; absorption flux ID CACO-2 CELL MONOLAYERS; P-GLYCOPROTEIN; CYCLOSPORINE; SURFACTANTS; SAQUINAVIR; TRANSPORT; SUCCINATE; CHILDREN; EFFLUX AB Purpose. To investigate the effect of vitamin E-TPGS, d-alpha-tocopheryl polyethylene glycol 1000 succinate, on the solubility and permeability of amprenavir, a potent HIV protease inhibitor. Methods. The aqueous solubility of amprenavir was measured as a function of vitamin E-TPGS concentration. Directional transport through Caco-2 cell monolayers was determined in the presence and absence of vitamin E-TPGS and P-glycoprotein inhibitors. Absorption flux was estimated from Caco-2 cell permeability and aqueous solubility. Results. The solubility of amprenavir in a pH 7 buffer at 37 degrees C was 0.036 +/- 0.007 mg/mL. The solubility linearly increased with increasing vitamin E-TPGS concentration (above 0.2 mg/mL). Polarized transport was demonstrated in the basolateral to apical direction, exceeding apical to basolateral transport by a factor of 6. The active efflux system was inhibited by vitamin E-TPGS and known P-glycoprotein inhibitors verapamil and GF120918. Conclusions. The solubility of amprenavir was improved in the presence of vitamin E-TPGS through micelle solubilization. Vitamin E-TPGS inhibits the efflux system and enhances the permeability of amprenavir. Overall. vitamin E-TPGS enhanced the absorption flux of amprenavir by increasing its solubility and permeability. The enhancement is essential to the development of the novel soft gelatin capsule formulation of amprenavir for use in the clinic. C1 Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. RP Yu, L (reprint author), US FDA, Div Prod Qual Res, 5600 Fishers Lane, Rockville, MD 20857 USA. RI Yu, Lawrence/L-6280-2016 NR 18 TC 150 Z9 161 U1 4 U2 17 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD DEC PY 1999 VL 16 IS 12 BP 1812 EP 1817 DI 10.1023/A:1018939006780 PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 272XB UT WOS:000084675300006 PM 10644067 ER PT J AU Yu, LX AF Yu, LX TI An integrated model for determining causes of poor oral drug absorption SO PHARMACEUTICAL RESEARCH LA English DT Article DE small intestinal transit; dissolution; permeation; absorption; modeling ID DISSOLUTION RATE; PARTICLE-SIZE; GRISEOFULVIN; BIOAVAILABILITY; HUMANS AB Purpose. To develop an integrated absorption model for estimating the fraction of dose absorbed and determining the causes of poor oral drug absorption. Methods. Both analytical and numerical methods were used to estimate the fraction of dose absorbed. Results. An integrated absorption model was developed by considering transit flow, dissolution, and permeation processes, simultaneously. A framework was proposed to determine permeability-, dissolution- and solubility-limited absorption. Digoxin, griseofulvin, and panadiplon were employed to illustrate the applications of the integrated model in identifying the causes of poor absorption and guiding formulation development Conclusions. The integrated absorption model was successfully applied to digoxin, griseofulvin, and panadiplon to estimate the fraction dose absorbed and to roughly determine the causes of poor oral drug absorption. C1 Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. RP Yu, LX (reprint author), US FDA, Div Prod Qual Res, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 19 TC 104 Z9 108 U1 2 U2 9 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD DEC PY 1999 VL 16 IS 12 BP 1883 EP 1887 DI 10.1023/A:1018911728161 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 272XB UT WOS:000084675300017 PM 10644078 ER PT J AU Poirier, LA Doerge, DR Gaylor, DW Miller, MA Lorentzen, RJ Casciano, DA Kadlubar, FF Schwetz, BA AF Poirier, LA Doerge, DR Gaylor, DW Miller, MA Lorentzen, RJ Casciano, DA Kadlubar, FF Schwetz, BA TI An FDA review of sulfamethazine toxicity SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Review ID RATS; LIVER; INITIATION; PROMOTION; INDUCTION; TUMORS AB Recently, changes have been proposed in the criteria historically used in the evaluation of the applicability to humans of some of the results obtained from the rodent carcinogenicity bioassay data, These questions center on the suitability of the rodent model for agents that exert their toxic effects via specific enzyme interactions and endocrine mechanisms which appear to be inoperative within humans. Within the U.S. Food and Drug Administration (FDA), this issue has been brought to the forefront of concern with the recent application for a New Animal Drug Application for sulfamethazine (SMZ). A panel of FDA experts from the National Center for Toxicological Research (NCTR), the Center for Veterinary Medicine (CVM), and the Center for Food Safety and Applied Nutrition has reviewed the sum of the scientific evidence available on the toxicology of SMZ. They noted that, in previous feeding studies at NCTR, high doses of SMZ were associated with significant incidences of thyroid tumors in mice and rats. The panel also notes that the tumorigenic activity of SMZ in rodents was due to its goitrogenic activity, resulting in constant stimulation of the thyroid by TSH, Humans, on the other hand, mere found to be insensitive to the SMZ-like inhibition of thyroid function. Further, apart from X-irradiation and radioactive iodine, there are no other physical or chemical agents known to cause thyroid tumors in humans. Thus, the expert panel concludes that the best scientific information available indicates that elevated levels of TSH and the consequent thyroid tumors would not be produced under approved use conditions of SMZ. This conclusion is in agreement with recommendations made by three other panels, viz. the World Health Organization, the U.S. Environmental Protection Agency, and CVM, which also evaluated the public health risk of SMZ. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Off Director, Jefferson, AR 72079 USA. Ctr Vet Med, Rockville, MD 20855 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Poirier, LA (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. NR 24 TC 34 Z9 34 U1 1 U2 6 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD DEC PY 1999 VL 30 IS 3 BP 217 EP 222 DI 10.1006/rtph.1999.1348 PG 6 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 275CK UT WOS:000084801700006 PM 10620471 ER PT J AU Gaylor, DW Kodell, RL Chen, JJ AF Gaylor, DW Kodell, RL Chen, JJ TI Human cancer risk estimates are reduced when based on relative risk for common rodent tumors SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Letter C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Gaylor, DW (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 4 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 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD DEC PY 1999 VL 30 IS 3 BP 283 EP 284 DI 10.1006/rtph.1999.1355 PG 2 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 275CK UT WOS:000084801700012 PM 10620477 ER PT J AU Hwang, JS Chen, JJ AF Hwang, JS Chen, JJ TI An evaluation of risk estimation procedures for mixtures of carcinogens SO RISK ANALYSIS LA English DT Article DE upper confidence limit; likelihood-based confidence limit; multistage carcinogenesis model; Monte Carlo simulation AB The estimation of health risks from exposure to a mixture of chemical carcinogens is generally based on the combination of information from several available single compound studies. The current practice of directly summing the upper bound risk estimates of individual carcinogenic components as an upper bound on the total risk of a mixture is known to be generally too conservative. Gaylor and Chen (1996, Risk Analysis) proposed a simple procedure to compute an upper bound on the total risk using only the upper confidence limits and central risk estimates of individual carcinogens. The Gaylor-Chen procedure was derived based on an underlying assumption of the normality for the distributions of individual risk estimates. In this paper we evaluated the Gaylor-Chen approach in terms of the coverage probability. The performance of the Gaylor-Chen approach in terms the coverages of the upper confidence limits on the true risks of individual carcinogens. In general, if the coverage probabilities for the individual carcinogens are all approximately equal to the nominal level, then the Gaylor-Chen approach should perform well. However, the Gaylor-Chen approach can be conservative or anti-conservative if some or all individual upper confidence limit estimates are conservative or anti-conservative, C1 Acad Sinica, Inst Stat Sci, Taipei 115, Taiwan. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Hwang, JS (reprint author), Acad Sinica, Inst Stat Sci, Taipei 115, Taiwan. NR 7 TC 8 Z9 8 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD DEC PY 1999 VL 19 IS 6 BP 1071 EP 1076 DI 10.1023/A:1007074426128 PG 6 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 266HZ UT WOS:000084295700004 PM 10765447 ER PT J AU Barlow, S Kavlock, RJ Moore, JA Schantz, SL Sheehan, DM Shuey, DL Lary, JM AF Barlow, S Kavlock, RJ Moore, JA Schantz, SL Sheehan, DM Shuey, DL Lary, JM TI Teratology society public affairs committee position paper: Developmental toxicity of endocrine disruptors to humans SO TERATOLOGY LA English DT Review ID DOSE-RESPONSE ANALYSIS; FALLING SPERM QUALITY; CD BR RATS; SEMEN QUALITY; BREAST-CANCER; POLYCHLORINATED-BIPHENYLS; REPRODUCTIVE DEVELOPMENT; IN-UTERO; 5-ALPHA-REDUCTASE INHIBITOR; ORGANOCHLORINE COMPOUNDS C1 Ctr Dis Control & Prevent, Div Birth Defects & Pediat Genet, Atlanta, GA 30341 USA. US EPA, Reprod Toxicol Div, Res Triangle Pk, NC 27711 USA. Inst Evaluat Hlth Risks, Washington, DC 20006 USA. Univ Illinois, Coll Vet Med, Dept Vet Biosci, Urbana, IL 61802 USA. Natl Ctr Toxicol Res, Genet & Reprod Toxicol Div, Jefferson, AR 72079 USA. Dupont Pharmaceut Co, Stine Haskell Res Ctr, Newark, DE 19714 USA. RP Ctr Dis Control & Prevent, Div Birth Defects & Pediat Genet, MS F-45,4770 Buford Highway, Atlanta, GA 30341 USA. EM jm12@cdc.gov NR 126 TC 27 Z9 30 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0040-3709 J9 TERATOLOGY JI Teratology PD DEC PY 1999 VL 60 IS 6 BP 365 EP 375 DI 10.1002/(SICI)1096-9926(199912)60:6<365::AID-TERA9>3.0.CO;2-6 PG 11 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 262DQ UT WOS:000084050700009 PM 10590398 ER PT J AU Hart, RW Dixit, R Seng, J Turturro, A Leakey, JEA Feuers, R Duffy, P Buffington, C Cowan, G Lewis, S Pipkin, J Li, SY AF Hart, RW Dixit, R Seng, J Turturro, A Leakey, JEA Feuers, R Duffy, P Buffington, C Cowan, G Lewis, S Pipkin, J Li, SY TI Adaptive role of caloric intake on the degenerative disease processes SO TOXICOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Society-of-Toxicology Symposium on Contemporary Concepts in Toxicology CY OCT 26-28, 1998 CL RESTON, VIRGINIA SP Soc Toxicol ID DIETARY RESTRICTION; DNA-REPAIR; LIFE-SPAN; METABOLIC-ACTIVATION; HEPATIC-ENZYMES; B6C3F1 MICE; CANCER; RATS; AGE; HYPOTHALAMUS AB Carcinogenicity and aging are characterized by a set of complex endpoints, which appear as a series of molecular events, Many of these events can be modified by caloric intake, Since most of these processes determine an organism's ability to cope with various environmental stressors, it is not surprising that a relationship tin the presence of a constant nutrient density) exists between caloric intake and time-to-tumor and/or life span. Our studies have clearly shown that generally, the greater the caloric intake, the greater the body weight, the higher the incidence of spontaneous tumor occurrence, the greater the susceptibility to chemical carcinogens, and the shorter the life span. It is also recognized that variables other than body weight influence the life span and carcinogenesis. We have focused our attention on the questions of how and to what extent caloric intake modifies those homeostatic processes believed to be critical in determining the ability of an organism to cope with endogenous and exogenous stresses such as chemical, physical, and biological carcinogens. The response of an organism to its environment can be divided into four categories-physiological, metabolic, molecular, and cellular. We have found that, from a physiological perspective, decreasing caloric intake causes body temperature in rodents to be decreased by 0.5 to 1.8 degrees C and water consumption to be increased by 80%, as is running activity, However, metabolic output per gram of lean body mass is not altered. Reproductive capacity declines, whereas the ECG waveform is preserved as caloric intake decreases. Alterations in these and other physiological functions suggests that energy intake serves as a signal to up-regulate or down-regulate functions related to the flight-or-fight response observed in placental mammals. A number of key metabolic pathways are altered as a function of lowered caloric intake, even though the rate of food consumption per gram of lean body mass remains steady during body weight decreases caused by decreasing caloric intake. Pharmacological compartmentalization, however, is altered, As caloric intake declines, changes occur in the expression of a number of drug-metabolizing enzymes, with the most striking effect seen in sex-specific growth hormones and liver-dependent phase I and phase II enzymes, Additionally, oxidative stress (free-radical and mediated damage to macromolecules) appears to decrease as a function of reduced caloric intake. A number of molecular processes also change with changes in energy consumption. Our studies have shown that, regardless of the source and nature of DNA damage, DNA repair is better preserved and/or enhanced when caloric consumption decreases. In addition, the fidelity of DNA replication increases and oncogene expression is stabilized, P53 gene expression is increased, and apoptosis is elevated by up to 500% with decreased caloric intake. At the cellular level, cell proliferation is decreased in direct proportion to lower energy intake in some but not all tissues. Studies have also shown an enhancement in immune capacity, changes:in IGF,, and accelerated rates of wound healing proportionate to declines in energy consumption. Our most recent findings,;however, have shown that the benefits associated with decreases in caloric intake only occur in the presence of sufficient nutrient quality and density. In the absence of proper nutrition, however, sensitivity to carcinogens and toxic substances appears to be enhanced. These findings are supported by independent studies. These observations have led us to conclude that, in certain organisms, when caloric intake is decreased, there is an up-regulation:of those processes that modulate the responses to a wide range of environmental stressors, This response allows for a better survival rate and a down-regulation of reproductive activity. It is our belief that, during periods of environmental stress, these systems may be essential to perpetuation of the species and the gene pool of the individual. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Merck Res Labs, Dept Safety Assessment, W Point, PA USA. Univ Tennessee, Ctr Hlth Sci, Coll Med, Dept Surg, Memphis, TN 38163 USA. RP Hart, RW (reprint author), Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 56 TC 30 Z9 33 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 1999 VL 52 IS 2 SU S BP 3 EP 12 PG 10 WC Toxicology SC Toxicology GA 268VX UT WOS:000084438400002 PM 10630584 ER PT J AU Aidoo, A Desai, VG Lyn-Cook, LE Chen, JJ Feuers, RJ Casciano, DA AF Aidoo, A Desai, VG Lyn-Cook, LE Chen, JJ Feuers, RJ Casciano, DA TI Attenuation of bleomycin-induced Hprt mutant frequency in female and male rats by calorie restriction SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE reduction of bleomycin mutagenicity; calorie restriction; Hprt; reactive oxygen species ID POLYMERASE CHAIN-REACTION; OXIDATIVE DNA-DAMAGE; DIETARY RESTRICTION; FISCHER-344 RATS; 6-THIOGUANINE-RESISTANT MUTANTS; SUPEROXIDE-DISMUTASE; METABOLIC-ACTIVATION; ANTIOXIDANT ENZYMES; CELL-PROLIFERATION; GENETIC TOXICOLOGY AB Calorie restriction modulates spontaneous and chemically induced tumors and increases maximal life span in experimental animals, however, the mechanism by which calorie restriction exerts its ameliorating effects is not fully elucidated, although reduced levels of reactive oxygen species (ROS) by calorie restriction has generated much interest. In the present study, we have determined whether or not calorie restriction would affect the mutagenic response in rats treated with bleomycin (BLM) a radiomimetic drug that is associated with DNA damage by a free radical mechanism. Fourteen weeks after weaning, the rats were divided into two groups; ad libitum (AL)-fed and 40% calorie restriction. Both AL and calorie-restricted animals were injected with 2.5, 5.0 and 10.0 mg BLM/kg, or with phosphate-buffered saline (PBS), and they were killed 4 weeks post drug treatment. Lymphocytes from the spleens were seeded in 96-well microtiter plates to determine mutant frequency in the hypoxantine guanine phosphoribosyl transferase (Hprt) gene. The mutant frequency in the BLM-treated rats was higher in AL males (P = 0.001), and AL females (P = 0.0174) than in their calorie-restricted counterparts. The difference in mutagenic response relative to AL males and AL females appeared unrelated to a low percent cloning efficiency seen in the males, since the mean absolute number of Hprt mutant clones was higher in the AL males compared to the females. A reduction in animal weight by calorie restriction was significant in both sexes (P < 0.001), but the dose effect appeared non-significant. The results indicate that calorie intake of 60% reduced the mutagenic response of BLM, a compound known to induce oxidative DNA damage, and suggest a possible decrease in ROS as a function of calorie restriction. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Aidoo, A (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 51 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD NOV 29 PY 1999 VL 430 IS 1 BP 155 EP 163 DI 10.1016/S0027-5107(99)00197-9 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 267BM UT WOS:000084334800014 PM 10592326 ER PT J AU Kulkarni, SG Harris, AJ Casciano, DA Mehendale, HM AF Kulkarni, SG Harris, AJ Casciano, DA Mehendale, HM TI Differential protooncogene expression in Sprague Dawley and Fischer 344 rats during 1,2-dichlorobenzene-induced hepatocellular regeneration SO TOXICOLOGY LA English DT Article DE differential protooncogene expression; liver regeneration; strain differences; tissue repair ID LIVER-REGENERATION; GROWTH-FACTOR; TISSUE-REPAIR; HA-RAS; C-FOS; TOXICITY; GENE; MYC; DICHLOROBENZENE; HEPATOTOXICITY AB Significant differences in hepatotoxic injury of 1,2-dichlorobenzene (o-DCB) have been reported (Gunawardhana, L., Sipes, I.G., 1991. Dichlorobenzene hepatotoxicity strain differences and structure activity relationships. Adv. Exp. Med. Biol. 283, 731-734; Stine, E.R., Gunawardhana, L., Sipes, I.G., 1991. The acute hepatotoxicity of the isomers of dichlorobenzene in Fischer 344 and Sprague-Dawley rats: isomer specific and strain-specific differential toxicity. Toxicol. Appl. Pharmacol. 109, 472-481; Valentovic, M.A., Ball, J. G., Anestis, D., Madan E., 1993a. Acute hepatic and renal toxicity of dichlorobenzene isomers in Fischer 344 rats. J. Appl. Toxicol. 13, 1-7; Kulkarni, S.G., Duong, H., Gomila, R., Mehendale, H.M., 1996. Strain differences in tissue repair response to 1,2-dichlorobenzene. Arch. Toxicol. 70, 714-723. Kulkami, S.G., Warbritton, A., Bucci, T., Mehendale, H.M., 1997. Antimitotic intervention with colchicine alters the outcome of o-DCB-induced hepatotoxicity in Fischer 344 rats. Toxicology. 120, 79-88). Although, hepatotoxic injury of o-DCB is greater in Fischer 344 (F344) when compared with Sprague Dawley (S-D) rats, this interstrain difference does not transcend into any difference in lethal effects of o-DCB. Interstrain difference in compensatory tissue repair has been suggested as the underlying mechanism for the lack of strain differences in lethality (Kulkami et al., 1996; Kulkami et al., 1997, see these refs. above). However, the mechanism(s) for this interstrain difference in tissue repair is tare) not currently understood. The objectives of the present study were (1) to investigate if the differences in compensatory tissue repair are reflected in differential protooncogene expression in S-D versus F344 rat livers and (2) to investigate if changes in protooncogene expression could explain the decrease and delay in tissue repair response beyond a threshold of 0.6 mi o-DCB/kg. Male S-D and F344 rats (8/9 weeks old) were administered either 0.6 or 1.2 mi o-DCB/kg and changes in expression of protooncogenes c-myc (immediate early) and Ha-ras (delayed early) were examined over a time course. Findings of this study indicate that the timing and extent of c-myc and Ha-ras expression varies in the two strains following administration of o-DCB. Thus, the timing and extent of compensatory liver regeneration that ensues following o-DCB administration in S-D and F344 rats is temporally concordant with the protooncogene expression in the two strains. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Louisiana Monroe, Div Toxicol, Monroe, LA 71209 USA. Univ Louisiana Monroe, Coll Pharm & Hlth Sci, Louisiana Inst Toxicol, Monroe, LA 71209 USA. Natl Ctr Toxicol Res, Div Genet Toxicol, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), Univ Louisiana Monroe, Div Toxicol, Monroe, LA 71209 USA. NR 38 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD NOV 29 PY 1999 VL 139 IS 1-2 BP 119 EP 127 DI 10.1016/S0300-483X(99)00110-9 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 262DK UT WOS:000084050200010 PM 10614693 ER PT J AU Kumar, A Dhawan, S Mukhopadhyay, A Aggarwal, BB AF Kumar, A Dhawan, S Mukhopadhyay, A Aggarwal, BB TI Human immunodeficiency virus-1-tat induces matrix metalloproteinase-9 in monocytes through protein tyrosine phosphatase-mediated activation of nuclear transcription factor NF-kappa B SO FEBS LETTERS LA English DT Article DE human immunodeficiency virus-tat; monocyte; nuclear factor-kappa B; metalloproteinase; protein tyrosine phosphatase ID TUMOR-NECROSIS-FACTOR; ENDOTHELIAL-CELLS; IV COLLAGENASE; VIRUS TYPE-1; TAT PROTEIN; T-CELLS; HIV; EXPRESSION; INFECTION; ALPHA AB We have previously shown that human immunodeficiency virus (HIV)-1-tat induces the production of matrix metalloproteinase-9 (MMP-9) in human monocytes by a mechanism that is not understood. In the present report, we demonstrate that HIV-tat-induced expression of MMP-9 is blocked by inhibitors of protein tyrosine phosphatases (PTPases), PTPase inhibitors also blocked HIV-tat-induced nuclear transcription factor NF-kappa B activation and I kappa B alpha degradation required for MMP-9 induction. These results suggest that HIV-tat induces MMP-9 in human monocytes through activation of PTPase and NF-kappa B. (C) 1999 Federation of European Biochemical Societies. C1 Univ Texas, MD Anderson Canc Ctr, Cytokine Res Sect, Dept Mol Oncol, Houston, TX 77030 USA. US FDA, Ctr Biol Evaluat & Res, Lab Immunochem, Div Transfus Transmitted Dis, Bethesda, MD 20892 USA. RP Aggarwal, BB (reprint author), Univ Texas, MD Anderson Canc Ctr, Cytokine Res Sect, Dept Mol Oncol, 1515 Holcombe St,Box 143, Houston, TX 77030 USA. RI Aggarwal, Bharat/G-3388-2013 NR 31 TC 51 Z9 52 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 26 PY 1999 VL 462 IS 1-2 BP 140 EP 144 DI 10.1016/S0014-5793(99)01487-8 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 260HK UT WOS:000083943300027 PM 10580107 ER PT J CA CDC TI Safer and healthier foods - 1900-1999 (Reprinted from MMWR, vol 48, pg 905, 1999) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint ID UNITED-STATES; INFECTIONS; OUTBREAK; PELLAGRA; EPIDEMIC; OBESITY C1 US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. USDA, Washington, DC USA. US EPA, Washington, DC 20460 USA. NIH, Div Nutr Res Coordinat, Bethesda, MD USA. CDC, Natl Ctr Hlth Stat, Atlanta, GA 30333 USA. CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. CDC, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. CDC, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. RP US EPA, Washington, DC 20460 USA. NR 34 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 24 PY 1999 VL 282 IS 20 BP 1909 EP 1912 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 257BZ UT WOS:000083763400010 ER PT J AU Gershon, SK Chang, AC Purvis, WV Salive, M AF Gershon, SK Chang, AC Purvis, WV Salive, M TI Misadministration of topical bovine thrombin SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Gershon, SK (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 13 Z9 13 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 24 PY 1999 VL 282 IS 20 BP 1919 EP 1919 DI 10.1001/jama.282.20.1919 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 257BZ UT WOS:000083763400025 PM 10580456 ER PT J AU Andrzejewski, D Weisz, A AF Andrzejewski, D Weisz, A TI Rapid quantification of hexachlorobenzene in the color additives D&C Red Nos. 27 and 28 (phloxine B) using solid-phase microextraction and gas chromatography-mass spectrometry SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE D&C Red No. 27; D&C Red No. 28; phloxines; hexachlorobenzenes; color additives ID PERFORMANCE LIQUID-CHROMATOGRAPHY; POLYCHLORINATED-BIPHENYLS; FOLLOW-UP; WATER; HYDROCARBONS; EXTRACTION; PORPHYRIA; FIBERS AB The present paper describes the development of a method for the quantification of hexachlorobenzene (HCB) in the color additives D&C Red Nos. 27 and 28 (phloxine B) using solid-phase microextraction followed by gas chromatography-mass spectrometry (GC-MS) analysis. The method is simple and fast (1 h for each analysis), generates little solvent waste, and does not involve a solid matrix, thus permitting a more efficient extraction than does a previously developed Soxhlet extraction-GC-MS method. Test portions from 30 batches of US-certified color additives D&C Red Nos. 27 and 28 were analyzed for HCB using the new method. Those batches represent domestic (five) and foreign tone) manufacturers that requested certification for the colors during the past four years. All the samples contained HCB, ranging from 0.2 ppm to 244.3 ppm. The analyses revealed significant differences in the levels of HCB across batches from the same manufacturer as well as among different manufacturers. The range of HCB levels found in the analyzed batches (0.2-244.3 ppm) suggest that the contamination with HCB may be decreased by avoiding use of starting material (tetrachlorophthalic anhydride) heavily contaminated with HCB. (C) 1999 Elsevier Science B.V. All rights reserved. C1 US FDA, Off Cosmet & Colors, Washington, DC 20204 USA. US FDA, Off Sci Anal & Support, Washington, DC 20204 USA. RP Weisz, A (reprint author), US FDA, Off Cosmet & Colors, Washington, DC 20204 USA. NR 25 TC 7 Z9 7 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD NOV 19 PY 1999 VL 863 IS 1 BP 37 EP 46 DI 10.1016/S0021-9673(99)00961-9 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 258MA UT WOS:000083841900004 PM 10591462 ER PT J AU Struble, K Piscitelli, SC AF Struble, K Piscitelli, SC TI Syndromes of abnormal fat redistribution and metabolic complications in HIV-infected patients SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article C1 NIH, Ctr Clin, Dept Pharm, Clin Pharmacokinet Res Lab, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Piscitelli, SC (reprint author), NIH, Ctr Clin, Dept Pharm, Clin Pharmacokinet Res Lab, Bldg 10,Room 1N257, Bethesda, MD 20892 USA. NR 36 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD NOV 15 PY 1999 VL 56 IS 22 BP 2343 EP 2348 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 259LM UT WOS:000083895400023 PM 10582831 ER PT J AU Chang, AC Magner, WJ Coligan, JE AF Chang, AC Magner, WJ Coligan, JE TI Aberrant development of thymocytes in mice lacking laminin-2. SO BLOOD LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. NIAID, Mol Struct Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 164 BP 40A EP 40A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300213 ER PT J AU Oshima, Y Joshi, BH Puri, RK AF Oshima, Y Joshi, BH Puri, RK TI Conversion of interleukin-13 into a high affinity agonist by a single amino acid substitution. SO BLOOD LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3940 BP 171B EP 171B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700784 ER PT J AU Holada, K Vostal, JG Theisen, PW MacAuley, C Rohwer, RG AF Holada, K Vostal, JG Theisen, PW MacAuley, C Rohwer, RG TI Scrapie infectivity in hamster blood cells does not concentrate in platelets but is enriched in peripheral leukocytes. SO BLOOD LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD USA. VAMC, Mol Neurovirol Lab, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1091 BP 246A EP 246A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301140 ER PT J AU Sakai, A Marti, GE Caporaso, N Pittaluga, S Touchman, JW Fend, F Raffeld, M AF Sakai, A Marti, GE Caporaso, N Pittaluga, S Touchman, JW Fend, F Raffeld, M TI Analysis of expressed immunoglobulin heavy chain genes in familial B-CLL. SO BLOOD LA English DT Meeting Abstract C1 NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Flow & Image Cytometry Sect, Lab Med & Mol Genet, Div Cell & Gene Therapies, Bethesda, MD 20014 USA. NCI, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, NIH, Intramural Sequencing Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4586 BP 304B EP 304B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701430 ER PT J AU Aoki, Y Yarchoan, R Chang, Y Iwamoto, A Okamoto, S Tosato, G AF Aoki, Y Yarchoan, R Chang, Y Iwamoto, A Okamoto, S Tosato, G TI Detection of viral interleukin-6 in Kaposi's sarcoma-associated herpesvirus-linked diseases. SO BLOOD LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NCI, NIH, Bethesda, MD 20892 USA. Columbia Univ, New York, NY USA. Univ Tokyo, Tokyo, Japan. Keio Univ, Tokyo, Japan. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1915 BP 431A EP 431A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301964 ER PT J AU Jain, N Carter, P Washington, GC Abassi, F Caporaso, N Marti, GE Rick, M AF Jain, N Carter, P Washington, GC Abassi, F Caporaso, N Marti, GE Rick, M TI B cell monoclonal lymphocytosis (BCML): A marker for early detection of BCLL. SO BLOOD LA English DT Meeting Abstract C1 NCI, POB, NIH, Bethesda, MD 20892 USA. US FDA, LMMG, CBER, Bethesda, MD 20014 USA. NCI, GEB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2401 BP 537A EP 537A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302450 ER PT J AU Chan, WC Alizadeh, A Eisen, M Davis, RE Ma, C Sabet, H Tran, T Powell, JI Yang, L Greiner, TC Weisenburger, DD Armitage, JO Marti, GE Moores, T Hudson, J Lossos, I Warnke, R Levy, R Botstein, D Brown, PO Staudt, LM AF Chan, WC Alizadeh, A Eisen, M Davis, RE Ma, C Sabet, H Tran, T Powell, JI Yang, L Greiner, TC Weisenburger, DD Armitage, JO Marti, GE Moores, T Hudson, J Lossos, I Warnke, R Levy, R Botstein, D Brown, PO Staudt, LM TI Gene expression in large B-cell lymphoma using cDNA microarray technology. SO BLOOD LA English DT Meeting Abstract C1 Univ Nebraska, Med Ctr, Dept Microbiol, Omaha, NE 68105 USA. Univ Nebraska, Med Ctr, Dept Med, Omaha, NE 68105 USA. Natl Canc Inst, Metab Branch, Div Clin Sci, NIH, Bethesda, MD USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. Stanford Univ, Sch Med, Stanford, CA USA. NIH, CIT, CBEL, Bioinformat & Mol Anal Sect, Bethesda, MD USA. US FDA, CBER, Bethesda, MD USA. Res Genet, Huntsville, AL USA. Univ Nebraska, Med Ctr, Dept Pathol, Omaha, NE 68105 USA. RI Alizadeh, Arash Ash/C-5594-2009 OI Alizadeh, Arash Ash/0000-0002-5153-5625 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3087 BP 698A EP 698A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303136 ER PT J AU McCardell, BA Kothary, MH Madden, JM AF McCardell, BA Kothary, MH Madden, JM TI Two-step purification and partial characterization of a variant of the Vibrio cholerae non-O1 hemolysin SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE cytolysin; hemolysin; Vibrio cholerae ID BIOTYPE-EL-TOR; ENTERO-TOXIN; ESCHERICHIA-COLI; O1; SEQUENCE; GENE AB A two-step purification method using ammonium sulfate precipitation and gel Filtration was developed for the purification of a variant of the El Tor hemolysin/cytolysin from supernatant fluids of a Vibrio cholerae non-Ol human isolate (strain 2194c). The toxin displayed delayed elution from a Sephacryl gel filtration column, eluting at between two and three column volumes. The molecular mass and isoelectric point of the purified 2194c toxin were 60 kDa and 5.3, respectively. The N-terminal amino acid sequence was ASPAPANSETNTLPHVAFYI. Purified toxin was cytolytic for Chinese hamster ovary cells and erythrocytes from several animal species. (C) 1999 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Virulence Assessment, Washington, DC 20204 USA. RP McCardell, BA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Virulence Assessment, Washington, DC 20204 USA. NR 21 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD NOV 15 PY 1999 VL 180 IS 2 BP 177 EP 182 PG 6 WC Microbiology SC Microbiology GA 255FN UT WOS:000083659000008 PM 10556709 ER PT J AU Ishii, KJ Weiss, WR Klinman, DM AF Ishii, KJ Weiss, WR Klinman, DM TI Prevention of neonatal tolerance by a plasmid encoding granulocyte-macrophage colony stimulating factor SO VACCINE LA English DT Article DE DNA vaccine; tolerance; GM-CSF ID HEPATITIS-B VIRUS; LIGAND-TREATED MICE; MALARIA DNA VACCINE; IMMUNE-RESPONSES; DENDRITIC CELLS; CIRCUMSPOROZOITE PROTEIN; ANTIBODY-RESPONSE; COSTIMULATORY MOLECULES; GENETIC IMMUNIZATION; IN-VIVO AB A plasmid DNA vaccine encoding the circumsporozoite protein of malaria (pCSP) induces protective immunity in adult mice but persistent tolerance when administered to neonates. In an effort to improve antigen presenting cell (APC) function in newborns, we co-administered pCSP with a plasmid encoding granulocyte-macrophage colony stimulating factor (pGMCSF). This combination of plasmids prevented the development of neonatal tolerance, instead eliciting a primary IgG anti-CSP immune response. Mice primed as neonates and boosted as adults mounted anamnestic responses characterized by high serum antibody titers, cytotoxic T-cell activity and antigen-specific interferon gamma (IFN gamma) production. Neonatal administration of pGMCSF accelerated the maturation of local dendritic cells, suggesting that APC function plays a key role in determining whether tolerance or immunity results from neonatal exposure to antigen. Published by Elsevier Science Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Retroviral Immunol Sect, Div Viral Prod, Bethesda, MD 20892 USA. USN, Med Res Ctr, Malaria Program, Bethesda, MD 20889 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Retroviral Immunol Sect, Div Viral Prod, Bldg 29A Room 3 D 10, Bethesda, MD 20892 USA. RI Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 45 TC 20 Z9 21 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 NOV 12 PY 1999 VL 18 IS 7-8 BP 703 EP 710 DI 10.1016/S0264-410X(99)00267-4 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 256NP UT WOS:000083731800018 PM 10547430 ER PT J AU Desta, AB Owen, RD Cress, LW AF Desta, AB Owen, RD Cress, LW TI Ornithine decarboxylase activity in developing chick embryos after exposure to 60-Hertz magnetic fields SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RAT AB Fertilized white leghorn eggs were exposed to a 4 micro-Tesla (mu T) 60 Hz horizontal magnetic field for 15, 18, 23 and 28 h, After exposure to the magnetic field, the embryos were isolated and assayed for ornithine decarboxylase (ODC) activity, ODC activity in magnetic field-exposed embryos was compared to ODC activity in sham-exposed embryos, ODC activity in magnetic field-exposed embryos was not statistically elevated above sham-exposed embryos. (C) 1999 Academic Press. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Cress, LW (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ 114,9200 Corp Blvd, Rockville, MD 20850 USA. FU NIEHS NIH HHS [Y1ES0006] NR 9 TC 2 Z9 4 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 NOV 11 PY 1999 VL 265 IS 1 BP 211 EP 213 DI 10.1006/bbrc.1999.1653 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 256JB UT WOS:000083721200036 PM 10548516 ER PT J AU Ma, L Gauville, C Berthois, Y Millot, G Johnson, GR Calvo, F AF Ma, L Gauville, C Berthois, Y Millot, G Johnson, GR Calvo, F TI Antisense expression for amphiregulin suppresses tumorigenicity of a transformed human breast epithelial cell line SO ONCOGENE LA English DT Article DE epidermal growth factor receptor; amphiregulin; antisense RNA expression constructs; transformed phenotype ID EPIDERMAL-GROWTH-FACTOR; MOUSE MAMMARY-GLAND; FACTOR RECEPTOR; FACTOR-ALPHA; CANCER CELLS; HUMAN COLON; CARCINOMA; EGF; INDUCTION; SURFACE AB The epidermal growth factor (EGF) family of receptors and their respective ligands play a major role in breast cancer progression and are the targets of new therapeutic approaches. Following immortalization with SV40 T antigen of normal human breast epithelial cells, a transformed variant cell line (NS2T2A1) was selected for its increased tumorigenicity in nude mice. This cell line was shown to have a higher expression of EGF receptors (EGFR) and amphiregulin (AR) when compared to their normal counterparts or less aggressive transformed cells. Dual staining of EGFR and AR was observed in 50-60% of NS2T2A1 cells, while 30-40% cells expressed AR only, To explore the potential tumorigenic role of AR, a 1.1 kb AR cDNA in an antisense orientation was transfected in NS2T2A1 cells. Three clones, selected by hygromycin B, expressed AR antisense RNA (AR AS1, AR AS2 and AR AS3 cell lines) in which AR protein expression was reduced (ranging from about 50 to <5%), The anchorage-independent growth of AR AS cell lines was reduced to levels ranging from 32.4-6.8% relative to the control cell line transfected with the vector alone. The clones expressing AR antisense RNA showed a reversion of the malignant phenotype when injected in nude mice, since a significant reduction of tumor intake was observed coincident with a significant tumor mass reduction (>96%), Moreover, intra-tumoral vascularization decreased significantly in tumors derived from AR AS cells (26.7, 70.7 and 50.4% of control). These in vitro and in vivo data reveal the oncogenic nature of AR in transformed breast epithelial cells and imply a role for AR in tumor angiogenesis. C1 Inst Genet Mol, Lab Pharmacol Expt & Clin, INSERM, EP 9932, F-75010 Paris, France. Fac Med Nord, F-13916 Marseille, France. US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. RP Ma, L (reprint author), Inst Genet Mol, Lab Pharmacol Expt & Clin, INSERM, EP 9932, 27 Rue Juliette Dodu, F-75010 Paris, France. NR 45 TC 39 Z9 43 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 11 PY 1999 VL 18 IS 47 BP 6513 EP 6520 DI 10.1038/sj.onc.1203042 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 256CW UT WOS:000083709200014 PM 10597254 ER PT J AU Wolff, GL Roberts, DW Mountjoy, KG AF Wolff, GL Roberts, DW Mountjoy, KG TI Physiological consequences of ectopic agouti gene expression: the yellow obese mouse syndrome SO PHYSIOLOGICAL GENOMICS LA English DT Review DE background genome; melanocortin; pseudoagouti mice; response to environmental stimuli; tumorigenesis ID MELANOCYTE-STIMULATING HORMONE; MELANOCORTIN RECEPTORS; GROWTH-HORMONE; A(VY)/ MICE; AVY/A MICE; IN-VITRO; PROTEIN; WEIGHT; LEPTIN; LOCUS AB This review summarizes primary and downstream phenotypic manifestations, with emphasis on altered responsiveness to environmental stimuli, of dominant yellow mutations at the mouse agouti locus. Obvious effects include hyperinsulinemia, obesity, stimulation of somatic growth and tumorigenesis, and coat color. Downstream influences of hyperinsulinemia and obesity on the individual's physiology determine important components of the obese yellow agouti mouse syndrome. Collectively, the phenotypic aberrations described support the concept that identical genomes are expressed in a spectrum of physiological phenotypes that reflect the complex interdependence of gene-regulated physiological pathways and processes in the organism throughout extended, but temporally ordered, periods of fetal and neonatal development and aging. This summary identifies important areas for additional research and provides integrated information required for a systematic approach to the development of interventions for common adult human health problems. C1 US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Biochem Mol Biol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pharmacol Interdisciplinary Toxicol, Little Rock, AR 72205 USA. Univ Auckland, Res Ctr Dev Med & Biol, Auckland 1, New Zealand. Univ Auckland, Dept Mol Med, Auckland 1, New Zealand. RP Wolff, GL (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM gwolff@nctr.fda.gov NR 49 TC 91 Z9 96 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD NOV 11 PY 1999 VL 1 IS 3 BP 151 EP 163 PG 13 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 317PD UT WOS:000087234100006 PM 11015573 ER PT J AU Whitcup, SM Fortin, E Lindblad, AS Griffiths, P Metcalf, JA Robinson, MR Manischewitz, J Baird, B Perry, C Kidd, IM Vrabec, T Davey, RT Falloon, J Walker, RE Kovacs, JA Lane, HC Nussenblatt, RB Smith, J Masur, H Polis, MA AF Whitcup, SM Fortin, E Lindblad, AS Griffiths, P Metcalf, JA Robinson, MR Manischewitz, J Baird, B Perry, C Kidd, IM Vrabec, T Davey, RT Falloon, J Walker, RE Kovacs, JA Lane, HC Nussenblatt, RB Smith, J Masur, H Polis, MA TI Discontinuation of anticytomegalovirus therapy in patients with HIV infection and cytomegalovirus retinitis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID COMBINATION ANTIRETROVIRAL THERAPY; IMMUNE-DEFICIENCY-SYNDROME; RELEASE GANCICLOVIR IMPLANT; POLYMERASE CHAIN-REACTION; MAINTENANCE THERAPY; AIDS; DISEASE; VIRUS; TRIAL AB Context Persons with cytomegalovirus (CMV) retinitis and acquired immunodeficiency syndrome (AIDS) have required lifelong anti-CMV therapy to prevent the progression of retinal disease and subsequent loss of vision. Objective To determine whether patients who were taking highly active antiretroviral therapy (HAART) and who had stable CMV retinitis could safely discontinue anti-CMV therapy without reactivation of their retinitis or increase in human immunodeficiency virus (HIV) viral load. Design Prospective nonrandomized interventional trial performed from July 1997 to August 1999. Setting Clinical Center of the National Institutes of Health, Bethesda, Md. Patients Fourteen patients with stable CMV retinitis and HIV infection and CD4(+) cell counts higher than 0.15 x 10(9)/L and being treated with systemic anti-CMV medications and HAART. Interventions Discontinuation of specific anti-CMV therapy. Main Outcome Measures Reactivation of CMV retinitis, development of extraocular CMV infection, detection of CMV in blood and urine, HIV burden, immunologic function; quality of life, morbidity, and mortality. Results Twelve (89.7%) of 14 patients had evidence of immune recovery uveitis before anti-CMV drugs were discontinued. No patient had reactivation of CMV retinitis or development of extraocular CMV disease during mean follow-up of 16.4 months (range, 8.3-22.0 months) without anti-CMV therapy. Human immunodeficiency viral load remained stable following cessation of anti-CMV medications, Blood and urine assays for CMV were briefly positive in 9 patients but did not predict reactivation of CMV disease. Worsening immune recovery uveitis was associated with a substantial (>3 lines) vision loss in 3 patients. Conclusions Maintenance anti-CMV medications were safely stopped in those patients who had stable CMV retinitis and elevated CD4(+) cell counts and who were taking HAART, The study demonstrates that immune recovery following potent antiretroviral therapy is effective in controlling a major opportunistic infection, even in patients with a history of severe immunosuppression. C1 NEI, Clin Branch, NIH, Bethesda, MD 20892 USA. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD USA. NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. EMMES Corp, Potomac, MD USA. US FDA, CBER, Lab Virol Retrovirol, Rockville, MD 20857 USA. Royal Free Hosp, Sch Med, Dept Virol, London, England. Wills Eye Hosp, Dept Ophthalmol, Philadelphia, PA USA. RP Whitcup, SM (reprint author), NEI, Clin Branch, NIH, 10 10S221,10 Ctr Dr,MSC 1863, Bethesda, MD 20892 USA. OI Polis, Michael/0000-0002-9151-2268 FU NIAID NIH HHS [1R01AI41687] NR 28 TC 107 Z9 114 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 3 PY 1999 VL 282 IS 17 BP 1633 EP 1637 DI 10.1001/jama.282.17.1633 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 250BD UT WOS:000083368400028 PM 10553789 ER PT J AU Orloff, DG Blazing, MA O'Connor, CM AF Orloff, DG Blazing, MA O'Connor, CM TI Atherosclerotic disease in non-insulin-dependent diabetes mellitus: Role of abnormal lipids and the place for lipid-altering therapies SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT Symposium on Diabetes and Cardiovascular Disease - Current opinions and Future Directions CY NOV 20-23, 1997 CL PINEHURST, NORTH CAROLINA ID CORONARY HEART-DISEASE; DENSITY-LIPOPROTEIN PARTICLES; AVERAGE CHOLESTEROL LEVELS; MYOCARDIAL-INFARCTION; PRIMARY-PREVENTION; ARTERY DISEASE; MEN; RISK; DYSLIPIDEMIA; TRIGLYCERIDE C1 Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. US FDA, Div Metab & Endocrine Drug Prod, Rockville, MD 20857 USA. RP Blazing, MA (reprint author), Duke Univ, Med Ctr, Dept Med, Div Cardiol, Box 3126, Durham, NC 27710 USA. NR 29 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 1999 VL 138 IS 5 BP S406 EP S412 PN 1 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 251WD UT WOS:000083468600047 PM 10539805 ER PT J AU Shieh, YSC Calci, KR Baric, RS AF Shieh, YSC Calci, KR Baric, RS TI A method to detect low levels of enteric viruses in contaminated oysters SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ROUND-STRUCTURED VIRUSES; HEPATITIS-A VIRUS; REVERSE TRANSCRIPTION PCR; MOLLUSCAN SHELLFISH; EXTRACTION; SEWAGE; ENTEROVIRUSES; CONSUMPTION; POLIOVIRUS; OUTBREAK AB Direct isolation and identification of pathogenic viruses from oysters implicated in gastroenteritis outbreaks are hampered by inefficient methods for recovering viruses, naturally occurring PCR inhibitors, and low levels of virus contamination, In this study we focused on developing rapid and efficient oyster-processing procedures that can be used for sensitive PCR detection of viruses in-raw oysters, Poliovirus type 3 (PV3) Sabin strain was used to evaluate the efficacy of virus recovery and the removal of PCR inhibitors during oyster-processing procedures. These procedures included elution, polyethylene glycol precipitation, solvent extraction, and RNA extraction. Acid adsorption-elution in which glycine buffer (pH 7.5) was used was found to retain fewer inhibitors than direct elution in which glycine buffer (pH 9.5) was used. RNA extraction in which a silica gel membrane was used was more effective than single-step RNA precipitation for removing additional nonspecific PCR inhibitors. The final 10-mu l volume of RNA concentrates obtained from 2 g of oyster tissue (concentration factor, 200-fold) was satisfactory for efficient reverse transcription-PCR detection of virus. The overall detection sensitivity of our method was 1 PFU/g of oyster tissue initially seeded with PV3, The method was utilized to investigate a 1998 gastroenteritis outbreak in California in which contaminated oysters were the suspected disease transmission vehicle. A genogroup II Norwalk-like virus was found in two of three recalled oyster samples linked by tags to the harvest dates and areas associated with the majority of cases. The method described here improves the response to outbreaks and can be used for rapid and sensitive detection of viral agents in outbreak-implicated oysters. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. Univ N Carolina, Dept Epidemiol, Program Infect Dis, Chapel Hill, NC 27599 USA. RP Shieh, YSC (reprint author), US FDA, Gulf Coast Seafood Lab, POB 158, Dauphin Island, AL 36528 USA. NR 26 TC 57 Z9 62 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD NOV PY 1999 VL 65 IS 11 BP 4709 EP 4714 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 252AQ UT WOS:000083478900001 PM 10543775 ER PT J AU Lo, M Bloom, ML Imada, K Berg, M Bollenbacher, JM Bloom, ET Kelsall, BL Leonard, WJ AF Lo, M Bloom, ML Imada, K Berg, M Bollenbacher, JM Bloom, ET Kelsall, BL Leonard, WJ TI Restoration of lymphoid populations in a murine model of X-linked severe combined immunodeficiency by a gene-therapy approach SO BLOOD LA English DT Article ID RECEPTOR-GAMMA-CHAIN; HEMATOPOIETIC PROGENITOR CELLS; BONE-MARROW TRANSPLANTATION; IL-2 RECEPTOR; BETA-CHAIN; IMMUNE RECONSTITUTION; FUNCTIONAL COMPONENT; MICE LACKING; EXPRESSION; JAK3 AB X-linked severe combined immunodeficiency (XSCID) is a life-threatening syndrome in which both cellular and humoral immunity are profoundly compromised. This disease results from mutations in the IL2RG gene, which encodes the common cytokine receptor gamma chain, gamma(c). Previously, we generated gamma(c)-deficient mice as a murine model of XSCID. We have now used lethally irradiated gamma(c)-deficient mice to evaluate a gene therapeutic approach for treatment of this disease. Transfer of the human gamma(c) gene to repopulating hematopoietic stem cells using an ecotropic retrovirus resulted in an increase in T cells, B cells, natural killer (NK) cells, and intestinal intraepithelial lymphocytes, as well as normalization of the CD4:CD8 T-cell ratio and of serum Ig levels. In addition, the restored cells could proliferate in response to interleukin-2 (IL-2). Thus, our results provide added support that gene therapy is a feasible therapeutic strategy for XSCID. Moreover, because we used a vector directing expression of human gamma(c) to correct a defect in gamma(c)-deficient mice, these data also indicate that human gamma(c) can cooperate with the distinctive cytokine receptor chains such as IL-2R beta and IL-7R alpha to mediate responses to murine cytokines in vivo. This is a US government work. There are no restrictions on its use. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NIAID, Clin Invest Lab, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Room 7N252, Bethesda, MD 20892 USA. NR 40 TC 62 Z9 63 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1999 VL 94 IS 9 BP 3027 EP 3036 PG 10 WC Hematology SC Hematology GA 249UG UT WOS:000083351200012 PM 10556186 ER PT J AU Rumsey, JM Horwitz, B Donohue, BC Nace, KL Maisog, JM Andreason, P AF Rumsey, JM Horwitz, B Donohue, BC Nace, KL Maisog, JM Andreason, P TI A functional lesion in developmental dyslexia: Left angular gyral blood flow predicts severity SO BRAIN AND LANGUAGE LA English DT Article DE dyslexia; angular gyrus; reading; regional cerebral blood flow; positron emission tomography ID READING-DISABILITY; WORD RECOGNITION; BRAIN ACTIVITY; CORTEX; CONNECTIVITY; SUBTYPES; MRI; MEN AB Functional imaging studies have shown reduced regional cerebral blood flow (rCBF) in temporal and inferior parietal regions in dyslexia. To relate such abnormalities to the severity of dyslexia, correlations between reading skill and rCBF during a series of reading tasks and visual fixation were mapped for 17 right-handed dyslexic men, ages 18-40, and 14 matched controls. These correlations uniquely identified the left angular gyrus as the most probable site of a functional lesion in dyslexia: Here, higher rCBF was associated with better reading skill in controls (p < .01), but with worse reading skill in dyslexia (p < .01). This suggests that greater reliance on this region normally facilitates reading, but impairs reading in dyslexia. Thus, developmental dyslexia may share a common localization with alexia. (C) 1999 Academic Press. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Psychol & Psychopathol Lab, Bethesda, MD 20892 USA. US FDA, Div Neuropharmacol Drug Prod, Rockville, MD 20857 USA. RP Rumsey, JM (reprint author), NIMH, Clin Neurosci Branch, Ctr Neurosci, 6001 Execut Blvd,MSC 9639, Bethesda, MD 20892 USA. EM jrumsey@box-j.nih.gov NR 49 TC 68 Z9 69 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD NOV PY 1999 VL 70 IS 2 BP 187 EP 204 DI 10.1006/brln.1999.2158 PG 18 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 257ER UT WOS:000083770000002 PM 10550226 ER PT J AU Li, AP Hartman, NR Lu, C Collins, JM Strong, JM AF Li, AP Hartman, NR Lu, C Collins, JM Strong, JM TI Effects of cytochrome P450 inducers on 17 alpha-ethinyloestradiol (EE2) conjugation by primary human hepatocytes SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE conjugation; drug-drug interactions; ethinyloestradiol; glucuronidation; hepatocytes; human; induction; metabolism; sulphation ID HUMAN-LIVER-MICROSOMES; ORAL-CONTRACEPTIVE STEROIDS; DRUG-INTERACTIONS; CLINICAL PHARMACOKINETICS; RIFAMPICIN TREATMENT; METABOLISM; ETHYNYLESTRADIOL; ETHINYLESTRADIOL; SULFATION; WOMEN AB Aims Our objective was to elucidate further the underlying mechanism responsible for therapeutic failures observed with concomitant administration of the oral contraceptive 17 alpha-ethinyloestradiol (EE2) and rifampicin. Methods We investigated both oxidative and direct conjugative [H-3]-EE2 metabolism by human Liver S9 fraction and the effect of known enzyme-inducing drugs using a human hepatocyte induction model in vitro. Results Cofactor dependent [H-3]-EE2 metabolism by human liver S9 fraction produced 2-hydroxy-[H-3]-EE2, 2-methoxy-[H-3]-EE2, and direct [H-3]-EE2 sulphate and glucuronide conjugates. Only two detectable metabolites of [H-3]-EE2 were produced by the S9 fraction in the presence of all cofactors: [H-3]-EE2-3-sulphate (75.7+/-7.6% s.d.) and 2-methoxy-H-3-EE2 (2.6% +/- 0.5% s.d.). Human hepatocytes extensively metabolized [H-3]-EE2 to its glucuronide and sulphate conjugates. Small amounts of a 2-methoxy-[H-3]-EE2 3-conjugate, less than or equal to 10%, was observed but no. 2-hydroxy-[H-3]-EE2 was detected. An unexpected finding in our study was increased [H-3]-EE2-3-sulphate production (1.5-3.3 fold, n = 3 donor livers) by hepatocytes pretreated with rifampicin compared to control hepatocytes. No statistically significant increase in [H-3]-EE2-3-sulphation was observed in hepatocytes pretreated with 3-methylcholanthrene, phenobarbitone, dexamethasone, or omeprazole over nontreated hepatocytes. To our knowledge, this is the first observation of sulphotransferase induction by rifampicin in human hepatocytes in vitro resulting in increased [H-3]-EE2 sulphation. Conclusions Our data indicate that the major EE2 metabolic products formed by human hepatocytes in vitro are direct EE2 conjugates with EE2 oxidation representing minor pathways. Further studies are required to establish the mechanism of sulphotransferase induction and the clinical relevance of our findings. C1 USFDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, Laurel, MD 20708 USA. In Vitro Technol Inc, Baltimore, MD USA. RP Strong, JM (reprint author), USFDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, MOD-1 Rm 2017,8301 Muirkirk Rd, Laurel, MD 20708 USA. OI Li, Albert/0000-0001-5772-6265 NR 53 TC 41 Z9 41 U1 0 U2 7 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0306-5251 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD NOV PY 1999 VL 48 IS 5 BP 733 EP 742 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 255NT UT WOS:000083676600013 PM 10594476 ER PT J AU Mazzola, EP Bell, SJ Turujman, SA Barrows, JN Bailey, JE McMahon, JB Germann, TK Reynolds, WF AF Mazzola, EP Bell, SJ Turujman, SA Barrows, JN Bailey, JE McMahon, JB Germann, TK Reynolds, WF TI Nuclear magnetic resonance investigations of azo-hydrazone, acid-base equilibria of FD&C Yellow No. 5 (tartrazine) SO CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE LA English DT Article DE H-1; C-13; and N-15 NMR; azo-hydrazone/acid-base equilibria; FD&C Yellow No. 5 ID N-15 AB Azo-hydrazone, acid-base equilibria were examined for the water-soluble, food color additive FD&C Yellow No. 5 (Y5), with the observation of dynamic NMR effects near, and at, pH 10, where the food colorant converts from a predominantly hydrazone tautomer (acidic to moderately basic pH) to a prevailing azo-anion resonance hybrid (high pH). Potentiometric titrations further indicate that the pK(a) of Y5 is ca. 10. These data suggest that observed NMR line broadening is due to slow proton transfer between a hydrazone-NH and water. C1 Univ Maryland, Dept Chem, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, Washington, DC 20204 USA. Univ Toronto, Dept Chem, Toronto, ON M5S 3H6, Canada. RP Mazzola, EP (reprint author), Univ Maryland, Dept Chem, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. NR 21 TC 6 Z9 6 U1 0 U2 5 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA, ONTARIO K1A 0R6, CANADA SN 0008-4042 J9 CAN J CHEM JI Can. J. Chem.-Rev. Can. Chim. PD NOV PY 1999 VL 77 IS 11 BP 1941 EP 1945 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 253FE UT WOS:000083545300027 ER PT J AU Soignet, SL Tong, WP Hirschfeld, S Warrell, RP AF Soignet, SL Tong, WP Hirschfeld, S Warrell, RP TI Clinical study of an organic arsenical, melarsoprol, in patients with advanced leukemia SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the American-Society-of-Hematology CY DEC 05-09, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol DE organic arsenical; melarsoprol; advanced leukemia; As2O3.; inorganic arsenic trioxide ID ACUTE PROMYELOCYTIC LEUKEMIA; GAMBIENSE SLEEPING SICKNESS; TRIOXIDE AS2O3; ENCEPHALOPATHY; SEPARATION; TRIAL; ACID AB Inorganic arsenic trioxide (As2O3) induces a high proportion of complete remissions in relapsed patients with acute promyelocytic leukemia (APL). Previously, we have shown that both As2O3 and melarsoprol, an organic arsenical used for the treatment of trypanosomiasis, exhibit broad antileukemic activity against both chronic and acute myeloid and lymphoid leukemia cell lines. Given the breadth of this activity, we initiated a clinical study to evaluate the pharmacokinetics, safety, and potential efficacy of melarsoprol in patients with refractory or resistant leukemia. Using the antitrypanosomal dose and schedule, patients received escalating intravenous doses daily for 3 days, repeated weekly for 3 weeks. Doses were 1 mg/kg on day 1, 2 mg/kg on day 2, and 3.6 mg/kg on day 3 and on all days thereafter, up to a maximum daily dose of 200 mg. Eight patients [6 AML (2 morphologic APL), 1 CML, 1 CLL] were treated. Mean peak plasma concentrations of the parent drug were obtained immediately after injection, ranged from 1.2 mu g/ml on day 1 to 2.4 mu g/ml on day 3, were dose proportional, and decayed with a t(1/2 beta) congruent to 15 min. A minor clinical response (regression of splenomegaly and lymphadenopathy) was observed in a patient with chronic lymphocytic leukemia. Central nervous system (CNS) toxicity proved limiting on this dose and schedule. Three patients experienced generalized grand mal seizures during the second week of therapy. We concluded that this dose and schedule of melarsoprol is associated with excessive CNS toxicity and that verification of the striking preclinical activity in patients with leukemia will require developing an alternative dose and schedule. C1 Cornell Univ, Coll Med, Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Cornell Univ, Coll Med, Mem Sloan Kettering Canc Ctr, Dept Med,Leukemia Serv, New York, NY USA. US FDA, Ctr Drug Evaluat & Res, Dept Hlth & Human Serv, Rockville, MD 20857 USA. RP Soignet, SL (reprint author), Cornell Univ, Coll Med, Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 23 TC 41 Z9 43 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD NOV PY 1999 VL 44 IS 5 BP 417 EP 421 DI 10.1007/s002800050998 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 241WG UT WOS:000082906400010 PM 10501916 ER PT J AU Von Tungeln, LS Xia, QS Herreno-Saenz, D Bucci, TJ Heflich, RH Fu, PP AF Von Tungeln, LS Xia, QS Herreno-Saenz, D Bucci, TJ Heflich, RH Fu, PP TI Tumorigenicity of nitropolycyclic aromatic hydrocarbons in the neonatal B6C3F(1) mouse bioassay and characterization of ras mutations in liver tumors from treated mice SO CANCER LETTERS LA English DT Article DE nitropolycyclic aromatic hydrocarbons; neonatal B6C3F(1) mouse; liver tumors; K-ras oncogene ID DNA ADDUCT FORMATION; HAMSTER OVARY CELLS; SALMONELLA-TYPHIMURIUM; METABOLISM; 3-NITROBENZOPYRENE; PROTOONCOGENE; 1-NITROSOBENZOPYRENE; 3-NITROSOBENZOPYRENE; 1-NITROBENZOPYRENE; 2-NITROFLUORANTHENE AB The nitropolycyclic aromatic hydrocarbons (nitro-PAHs) 1-, 2-, and 3-nitrobenzo[a]pyrene, 1- and 3-nitrobenzo[e]pyrene, 2-and 3-nitrofluoranthene, 9-nitrodibenz[a,c]anthracene, and two of the parent PAHs fluoranthene and dibenz[a, c]anthracene were tested for tumorigenicity in the neonatal male B6C3F(1) mouse. 6-Nitrochrysene was used as a positive control. Mice were administered three intraperitoneal injections of test agent (400 nmol total) on 1, 8, and 15 days after birth and evaluated for liver and lung tumors at 12 months of age. 2-Nitrobenzo[a]pyrene and 6-nitrochrysene induced a high incidence of liver tumors (91-100%), while the remaining test compounds did not induce tumors at a rate significantly higher than the solvent control. 6-Nitrochrysene was the only test agent to produce a significant increase in the frequency of lung tumors. K- and H-ras mutations were analyzed in liver tumors of treated mice and mainly occurred at the first base of K-ras codon 13, resulting in GGC --> CGC transversion. Since most of the tested nitro-PAHs are mutagens in vitro, the results of this study indicate that the in vitro mutagenicity of these compounds does not correlate with their tumorigenicity in the neonatal B6C3F(1) mouse bioassay, Also, the results indicate that liver tumors from mice treated with nitro-PAHs possess ms mutations typical of PAHs and their derivatives. (C) 1999 Published by Elsevier Science Ireland Ltd. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Puerto Rico, Dept Pharmacol, San Juan, PR 00936 USA. Natl Ctr Toxicol Res, Pathol Associates Int, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 28 TC 6 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 0304-3835 J9 CANCER LETT JI Cancer Lett. PD NOV 1 PY 1999 VL 146 IS 1 BP 1 EP 7 DI 10.1016/S0304-3835(99)00206-2 PG 7 WC Oncology SC Oncology GA 249UN UT WOS:000083351800001 PM 10656603 ER PT J AU Melnyk, S Pogribna, M Miller, BJ Basnakian, AG Pogribny, IP James, SJ AF Melnyk, S Pogribna, M Miller, BJ Basnakian, AG Pogribny, IP James, SJ TI Uracil misincorporation, DNA strand breaks, and gene amplification are associated with tumorigenic cell transformation in folate deficient/repleted Chinese hamster ovary cells SO CANCER LETTERS LA English DT Article DE folate deficiency; deoxynucleotides; uracil; DNA methylation; mutation; cell transformation; gene amplification ID DEOXYNUCLEOTIDE POOL IMBALANCE; FOLIC-ACID; MEGALOBLASTIC-ANEMIA; ALKYLATING-AGENTS; ESCHERICHIA-COLI; FRAGILE SITES; IN-VITRO; P53 GENE; DEFICIENCY; CANCER AB Clinical and experimental evidence has linked nutritional folic acid status to both anti- and procarcinogenic activity. Folate supplementation of normal cells appears to have a protective effect; however, folate supplementation of initiated cells may promote neoplastic progression. Given these considerations, the present series of experiments examines alterations in DNA metabolism and cumulative DNA lesions using an in vitro model of folate deprivation and repletion. DNA repair-deficient CHO-UV5 cells were cultured in Ham's F-12 medium or in custom-prepared Ham's F-12 medium lacking in folic acid, thymidine and hypoxanthine for a period of 18 days without cell passage. The results indicated that progressive folate and nucleotide depletion leads to a significant increase in the ratio of dUTP/dTTP and to the misincorporation of uracil into DNA, These alterations were accompanied by growth inhibition, DNA strand breaks, abasic sites and phenotypic abnormalities. After 14 days in culture, there was significant increase in gene amplification potential in the chronically folate-deficient cells, but no significant increase in anchorage-independent growth or in neoplastic transformation. Acute folate repletion of the deficient cells was used as a proliferative stimulus under conditions of dNTP pool imbalance and multiple lesions in DNA. A further increase in gene amplification was accompanied by anchorage-independent growth and neoplastic cell transformation as evidenced by aggressive tumor growth in Balb/c nu/nu mice. Using a sensitive in vitro model system, these results emphasize the essentiality of folic acid for de novo nucleotide synthesis and the integrity of the DNA. However, the in vivo relevance, especially in terms of tumorigenic potential, is not clear. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. RP James, SJ (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 49 TC 79 Z9 84 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD NOV 1 PY 1999 VL 146 IS 1 BP 35 EP 44 DI 10.1016/S0304-3835(99)00213-X PG 10 WC Oncology SC Oncology GA 249UN UT WOS:000083351800005 PM 10656607 ER PT J AU Culp, SJ Blankenship, LR Kusewitt, DF Doerge, DR Mulligan, LT Beland, FA AF Culp, SJ Blankenship, LR Kusewitt, DF Doerge, DR Mulligan, LT Beland, FA TI Toxicity and metabolism of malachite green and leucomalachite green during short-term feeding to Fischer 344 rats and B6C3F(1) mice SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE malachite green; leucomalachite green; DNA adducts; P-32-postlabeling; apoptosis ID LIQUID-CHROMATOGRAPHY AB Malachite green, an N-methylated diaminotriphenylmethane dye, has been widely used as an antifungal agent in commercial fish hatcheries. Malachite green is reduced to and persists as leucomalachite green in the tissues of fish. Female and male B6C3F(1) mice and Fischer 344 rats were fed up to 1200 ppm malachite green or 1160 ppm leucomalachite green for 28 days to determine the toxicity and metabolism of the dyes. Apoptosis in the transitional epithelium of the urinary bladder occurred in all mice fed the highest dose of leucomalachite green. This was not observed with malachite green. Hepatocyte vacuolization was present in rats administered malachite green or leucomalachite green. Rats given leucomalachite green also had apoptotic thyroid follicular epithelial cells. Decreased T4 and increased TSH levels were observed in male rats given leucomalachite green. A comparison of adverse effects suggests that exposure of rats or mice to leucomalachite green causes a greater number of and more severe changes than exposure to malachite green. N-demethylated and N-oxidized malachite green and leucomalachite green metabolites, including primary arylamines, were detected by high performance liquid chromatography/mass spectrometry in the livers of treated rats. P-32-PostlabeIing analyses indicated a single adduct or co-eluting adducts in the liver DNA. These data suggest that malachite green and leucomalachite green are metabolized to primary and secondary arylamines in the tissues of rodents and that these derivatives, following subsequent activation, may be responsible for the adverse effects associated with exposure to malachite green. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Culp, SJ (reprint author), Natl Ctr Toxicol Res, HFT-110,3900 NCTR Rd, Jefferson, AR 72079 USA. RI Kusewitt, Donna/E-8107-2011 NR 16 TC 85 Z9 107 U1 1 U2 15 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD NOV 1 PY 1999 VL 122 IS 3 BP 153 EP 170 DI 10.1016/S0009-2797(99)00119-2 PG 18 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 239UY UT WOS:000082789100002 PM 10682936 ER PT J AU Husain, SR Puri, RK AF Husain, SR Puri, RK TI Interleukin-13 receptor as a specific molecular target for cytotoxin therapy of human renal cell carcinoma in a xenograft model. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD USA. NR 0 TC 1 Z9 1 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 NOV PY 1999 VL 5 SU S MA 180 BP 3766S EP 3766S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700180 ER PT J AU Joshi, BH Puri, RK AF Joshi, BH Puri, RK TI Identification and characterization of IL-13 and IL-4 receptor complex in Pancreatic carcinoma cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 NOV PY 1999 VL 5 SU S MA 375 BP 3804S EP 3804S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700374 ER PT J AU Kawakami, K Leland, P Puri, RK AF Kawakami, K Leland, P Puri, RK TI Interleukin-4 targets therapeutic toxins to human head and neck cancer cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 5 SU S MA 374 BP 3804S EP 3804S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700373 ER PT J AU Wiegand, RA Doyle, TD Grieshaber, CK LoRusso, PM Kassab, J Jasti, BR Parchment, RE AF Wiegand, RA Doyle, TD Grieshaber, CK LoRusso, PM Kassab, J Jasti, BR Parchment, RE TI Normal-phase separation of XK469 enantiomers (R : NSC-698215,S : NSC-698216) applied to preclinical pharmacology. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 US FDA, CDER, Prod Qual Res, Rockville, MD 20857 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48201 USA. NR 0 TC 0 Z9 0 U1 1 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 NOV PY 1999 VL 5 SU S MA 542 BP 3838S EP 3839S PG 2 WC Oncology SC Oncology GA 260JL UT WOS:000083945700539 ER PT J AU Bai, R Ewell, J Nguyen, N Brossi, A Hamel, E AF Bai, R Ewell, J Nguyen, N Brossi, A Hamel, E TI Mapping the binding site of the A ring of colchicine on beta-tubulin: the covalent reactions of 2-chloroacetyl-2-demethylthiocolchicine (2CTC) and 3-chloroacetyl-3-demethylthiocolchicine (3CTC) with cysteine residues 239 and 354. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NIDDK, Struct Biol Lab, Bethesda, MD USA. US FDA, Fac Biotechnol Resources, Bethesda, MD 20014 USA. NCI, Sci Applicat Int Corp, Frederick, MD 21701 USA. NCI, Lab Drug Discovery Res & Dev, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 5 SU S MA 630 BP 3856S EP 3856S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700625 ER PT J AU de Lacerda, L Carvalho, JAR Stannard, B Werner, H Boguszewski, MCS Sandrini, R Malozowski, SN LeRoith, D Underwood, LE AF de Lacerda, L Carvalho, JAR Stannard, B Werner, H Boguszewski, MCS Sandrini, R Malozowski, SN LeRoith, D Underwood, LE TI In vitro and in vivo responses to short-term recombinant human insulin-like growth factor-1 (IGF-1) in a severely growth-retarded girl with ring chromosome 15 and deletion of a single allele for the type 1 IGF receptor gene SO CLINICAL ENDOCRINOLOGY LA English DT Article ID FACTOR-BINDING PROTEIN-2; HORMONE INSENSITIVITY SYNDROME; DISTAL LONG ARM; FACTOR-I; POSTNATAL-GROWTH; LARON SYNDROME; SECRETION; IDENTIFICATION; FIBROBLASTS; EXPRESSION AB OBJECTIVES Patients with single allele defects in the gene encoding the type 1 IGF receptor have been reported to have growth failure, but fibroblasts from affected patients have not exhibited insensitivity to the effects of IGF-I in vitro. The in vitro and in vivo responses to short-term recombinant human IGF-I (rhIGF-I) in a severely growth-retarded girl with ring chromosome 15 and deletion of a single allele for the type 1 IGF receptor gene have been investigated. DESIGN AND PATIENT The child exhibited prenatal and severe post-natal growth failure, and delayed psychomotor development. Southern blotting revealed a 50% reduction in IGF-I receptor DNA, and in an RNase protection assay (RPA), a quantitatively similar reduction in steady-state mRNA for type 1 IGF receptor. rhIGF-I was administered in graded doses of 40, 60 and 80 mu g/kg twice daily by subcutaneous injection for periods of 2-2.5 days each. RESULTS During rhIGF-I treatment, mean urinary nitrogen excretion was unchanged and urinary calcium rose to 60% greater than in the pre-treatment period, rhIGF-I injections produced only a modest decrease in indices of GH secretion, assessed by frequent (every 20 min) sampling over periods of 12 h. There was no significant difference between the mean GH concentrations during rhIGF-I treatment (5.32+/-6.2mU/I) compared with that before rhIGF-I treatment (8.46+/-10.2 mU/I). Mean IGFBP-3-values were increased (4.5 mg/l before vs. 5.4 mg/l during rhIGF-I). TSH values after injection of TRH were not significantly reduced by IGF-I (mean of all values, 18.6 mU/I vs. 15.5 mU/I during rhIGF-I treatment). In vitro binding of radiolabelled IGF-I to the patient's fibroblasts was less than that bound by control fibroblasts (patient, 0.69% binding by 248000 cells, vs. 1 41% binding by 260000 fibroblasts from an age-matched control). However, the patient's fibroblasts exhibited a growth response in vitro to the addition of IGF-I in a fashion similar to that of control fibroblasts. CONCLUSIONS These studies show evidence in each of the indices examined of in vivo resistance to IGF-I and suggest that the growth retardation observed in such patients may be the direct result of the absence of one of the alleles encoding the type 1 IGF receptor. C1 Univ Fed Parana, Dept Paediat, BR-80060000 Curitiba, Parana, Brazil. NIDDK, Diabet Branch, NIH, Bethesda, MD USA. US FDA, Rockville, MD 20857 USA. Univ N Carolina, Dept Paediat, Chapel Hill, NC 27515 USA. RP de Lacerda, L (reprint author), Univ Fed Parana, Hosp Clin, Paediat Endocrine Unit, Rua Padre Camargo 250, BR-80060900 Curitiba, Parana, Brazil. EM lacerda@hc.ufpr.br RI Carvalho, Julienne/G-5043-2013 OI Carvalho, Julienne/0000-0002-6263-344X NR 40 TC 26 Z9 27 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 EI 1365-2265 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD NOV PY 1999 VL 51 IS 5 BP 541 EP 550 DI 10.1046/j.1365-2265.1999.00799.x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 257JB UT WOS:000083777800003 PM 10594514 ER PT J AU Myers, MJ Farrell, DE Baker, JD Cope, CV Evock-Clover, CM Steele, NC AF Myers, MJ Farrell, DE Baker, JD Cope, CV Evock-Clover, CM Steele, NC TI Challenge differentially affects cytokine production and metabolic status of growing and finishing swine SO DOMESTIC ANIMAL ENDOCRINOLOGY LA English DT Article DE endotoxin; INF alpha; IL-6; metabolism; swine ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; ENDOTOXIN CHALLENGE; CHROMIUM PICOLINATE; GROWTH-PERFORMANCE; LIPASE ACTIVITY; LIPOPOLYSACCHARIDE; INJURY; LIVER; PIGS AB Growing (35 kg body weight) and finishing (85 kg body weight) swine challenged with endotoxin (Escherichia coli O55:B5) at a dose of either 2 or 20 mu g/kg produced tumor necrosis factor (TNF)alpha in a dose-response relationship as measured by bioassay. Peak TNF alpha plasma levels were observed 1-2 hr post-challenge, returning to basal values 4 hr post-challenge. However, both an enzyme-linked immunosorbent assay specific for swine TNF alpha and total human TNF alpha demonstrated no dose-response relationship; peak plasma levels of immunoreactive TNF alpha were also observed 1-2 hr post-challenge. Maximal plasma interleukin-6 levels occurred 1-2 hr post-challenge and remained elevated through 8 hr post-challenge; there was no effect of lipopolysaccharide dose or metabolic status. Although the metabolic status of the animals also affected glucose levels, with growing animals exhibiting greater sensitivity compared with finishing animals, endotoxin-induced decreases in blood glucose levels were primarily dose-dependent. In contrast, changes in plasma urea nitrogen and free fatty acid (FFA) levels were strictly related to the metabolic status. Urea nitrogen levels were unchanged in growing swine, whereas they were increased in finishing swine and remained elevated 24 hr post-challenge. FFA levels in growing and finishing swine increased 3-6 hr post-challenge. FFA levels returned to basal values for finishing swine 24 hr post challenge, but in growing swine remained elevated 24 hr post-challenge. Plasma aspartate transaminase levels were increased through 24 hr post-challenge; animals given a dose of 20 mu g/kg exhibited the greatest increase. Similarly, swine challenged with a dose of 20 mu g/kg also exhibited the greatest increase in levels of conjugated bilirubin; there was no effect on unconjugated (free) bilirubin. These results demonstrate that endotoxin challenge of swine result in a pattern of changes that are dependent on both the dose of endotoxin used and the metabolic status of the animal examined. (C) 1999 Elsevier Science Inc. All rights reserved. C1 US FDA, Div Anim Res, Ctr Vet Med, Laurel, MD 20708 USA. US FDA, Div Therapeut Drugs Nonfood Anim, Ctr Vet Med, Rockville, MD 20855 USA. ARS, Growth Biol Lab, USDA, BARC E, Beltsville, MD 20705 USA. RP Myers, MJ (reprint author), US FDA, Div Anim Res, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 35 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0739-7240 J9 DOMEST ANIM ENDOCRIN JI Domest. Anim. Endocrinol. PD NOV PY 1999 VL 17 IS 4 BP 345 EP 360 DI 10.1016/S0739-7240(99)00057-0 PG 16 WC Agriculture, Dairy & Animal Science; Endocrinology & Metabolism SC Agriculture; Endocrinology & Metabolism GA 267KU UT WOS:000084357800002 PM 10628426 ER PT J AU Tao, SSH Bolger, PM AF Tao, SSH Bolger, PM TI Dietary arsenic intakes in the United States: FDA total diet study, September 1991-December 1996 SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE arsenic; dietary intakes; total diet study; USA ID CANADIAN ADULTS; TRACE-ELEMENTS; FOOD; PESTICIDES; CHEMICALS; CADMIUM; MANGANESE; REVISION; MERCURY; SAMPLES AB The FDA has conducted the Total Dietary Study (TDS), a yearly market basket programme, since 1961. It is designed to monitor the levels of toxic chemical contaminants (pesticide residues, industrial and elemental contaminants) and essential nutrients in the US food supply. It also provides information on trends in dietary concentrations and exposures for the general population. Foods are collected from retail stores once a year from each of four geographic areas of the US and are analysed either after preparation/cooking or as ready-to-eat. The latest TDS (1991-1997) data show that arsenic (inorganic and organic, greater than or equal to 0.03 ppm) was found in 63 (24%) of the 261-264 foods/mixed dishes analysed The highest concentration was found in seafood, followed by rice/rice cereal, mushrooms, and poultry. Based on the United States Department of Agriculture's 1987-1988 Nationwide Food Consumption Survey, the estimated daily total arsenic average intakes, in mu g/day, are: 2 for infants, 23 for toddlers, 20 for 6-year-old children, 13 for 10-year-old children, 15 for 14-16-year-old boys, 21 for 14-16-year-old girls, 57 for 25-30-year-old men, 28 for 25-30-year-old women, 47 for 40-45-year-old men, 37 for 40-45-year-old women, 92 for 60-65-year-old men, 72 for 60-65-year-old women, 69 for 70-year-old men, and 42 for 70-year-old women. Of the estimated total arsenic intakes for infants, 42% arise from seafood and 31% from rice/rice cereals. Of the estimated total arsenic intakes, seafood contributes 76-90% for children (2-10-year olds), 79-85% for 14-16-year olds, and 89-96% for adults (greater than or equal to 25-30-year olds); rice/rice cereals contributes 4-8% for children, 8% for 14-16-year olds, and 1-4% for adults (greater than or equal to 25-30-year olds). C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Tao, SSH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 29 TC 110 Z9 111 U1 4 U2 34 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD NOV PY 1999 VL 16 IS 11 BP 465 EP 472 DI 10.1080/026520399283759 PG 8 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 249PC UT WOS:000083340600003 PM 10755138 ER PT J AU Sprando, RL Pestka, J Collins, TFX Rorie, J O'Donnell, M Hinton, D Chirtel, S AF Sprando, RL Pestka, J Collins, TFX Rorie, J O'Donnell, M Hinton, D Chirtel, S TI The effect of vomitoxin (deoxnivalenol) on testicular morphology, testicular spermatid counts and epididymal sperm counts in IL-6KO [B6129-IL6 (TmlKopf) (IL-6 gene deficient)] and WT [B6129F2 (wild type to B6129-IL6 with an intact IL-6 gene)] mice SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE mouse; spermatogenesis; testes; vomitoxin; deoxynivalenol ID SPRAGUE-DAWLEY RATS; DEOXYNIVALENOL VOMITOXIN; SERTOLI CELLS; SPLENIC LYMPHOCYTES; IGA NEPHROPATHY; LEYDIG-CELLS; WINTER-WHEAT; PEYERS PATCH; INTERLEUKIN-6; MYCOTOXINS AB The potential of vomitoxin (VT) to affect testicular morphology and testicular and epididymal sperm counts was assessed in three strains of mice: IL-6KO [B6129-IL6 (tmlKopf) (IL-6 gene deficient)], WT [B6129F2 (wild type to B6129-IL6 with an intact IL-6 gene)] and B6C3F(1) mice in a 90-day feeding study. The treated mice received VT at a concentration of 10 ppm in their diet. The body weight of VT-treated animals was significantly reduced compared with control animals. Slight changes, not statistically significant, were observed in relative testis weight and testicular spermatid counts. Histological changes were not apparent in the testes of VT-treated animals. The diameter of the seminiferous tubules, the height of the seminiferous epithelium and the number of Sertoli cell nucleoli per cross-sectioned seminiferous tubule in the VT-treated groups were not significantly different from their respective untreated controls. The IL-6KO and B6C3F(1) VT-treated mice had significantly reduced cauda epididymal weights compared with their respective controls. These changes were not attributed to decreased sperm counts and this finding suggests that VT may exert an adverse affect on the epididymis. Published by Elsevier Science Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Toxicol Res, Laurel, MD 20708 USA. Michigan State Univ, Dept Food Sci & Human Nutr, E Lansing, MI 48824 USA. Michigan State Univ, Natl Food Safety & Toxicol Ctr, E Lansing, MI 48824 USA. RP Sprando, RL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Toxicol Res, 8301 Muirkirk Rd, Laurel, MD 20708 USA. FU NIEHS NIH HHS [ES-03358] NR 43 TC 1 Z9 1 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD NOV PY 1999 VL 37 IS 11 BP 1073 EP 1079 DI 10.1016/S0278-6915(99)00103-9 PG 7 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 254FB UT WOS:000083600300004 PM 10566878 ER PT J AU Hood, HL Kraeling, MEK Robl, MG Bronaugh, RL AF Hood, HL Kraeling, MEK Robl, MG Bronaugh, RL TI The effects of an alpha hydroxy acid (glycolic acid) on hairless guinea pig skin permeability SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE glycolic acid; skin permeability; hairless guinea pig ID INVITRO PERCUTANEOUS-ABSORPTION; HUMAN STRATUM-CORNEUM; BARRIER AB The barrier integrity of hairless guinea pig skin after treatment with an alpha hydroxy acid was assessed through in vivo topical application of an oil-in-water emulsion containing 5 or 10% glycolic acid at pH 3.0. The control was a commercial moisturizing lotion, pH 7.8. A dosing regimen for the glycolic acid formulations that was tolerated by the hairless guinea pigs and significantly decreased stratum corneum turnover time was determined using the dansyl chloride staining technique. Once-daily dosing of hairless guinea pig skin for 3 weeks with the glycolic acid formulations resulted in approximately a 36-39% decrease in stratum corneum turnover time compared with the control lotion. After this treatment, hairless guinea pigs were sacrificed for the in vitro measurement of the percutaneous absorption of [C-14]hydroquinone and [C-14]musk xylol. No significant differences in the 24-hour absorption of either test compound were found for skin treated with the control lotion or the glycolic acid formulations. There were also no significant differences found in the absorption of [H-3]water through skin from the different treatment groups. Although no increase in skin penetration occurred after treatment with the glycolic acid formulations, histology revealed approximately a twofold increase in epidermal thickness. Also the number of nucleated cell layers nearly doubled in skin treated with 5% and 10% glycolic acid compared with the control lotion and untreated skin. These studies demonstrate that substantial changes in the structure of hairless guinea pig epidermis can occur without significant effect on skin permeability of two model compounds. Published by Elsevier Science Ltd. All lights reserved. C1 US FDA, Off Cosmet & Colors, Laurel, MD 20708 USA. US FDA, Off Beltsville Tech Operat, Laurel, MD 20708 USA. RP Bronaugh, RL (reprint author), US FDA, Off Cosmet & Colors, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 16 TC 18 Z9 18 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD NOV PY 1999 VL 37 IS 11 BP 1105 EP 1111 DI 10.1016/S0278-6915(99)00100-3 PG 7 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 254FB UT WOS:000083600300008 PM 10566882 ER PT J AU Herman, BA Harris, GR AF Herman, BA Harris, GR TI Theoretical study of steady-state temperature rise within the eye due to ultrasound insonation SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article AB The soft tissue thermal index (TIS), as defined in the AIUM/NEMA Output Display Standard, may not be relevant with respect to eye exposure, primarily because of differences in actual vs. assumed acoustic and thermal properties. Therefore, a theoretical study of temperature rise within the eye due to ultrasound insonation was undertaken to compare the TIS with more exact calculations. At each plane in the direction of propagation, the focused ultrasound beam was modeled as a disc of uniform intensity. Each disc becomes a heat source, and integration over all discs provides the total temperature rise at any axial position. Calculations were done assuming the ultrasound beam intersects the lens of the eye as well as for the case in which the beam does not intersect the lens. Results were found for frequencies of 7.0 MHZ to 40 MHZ, transducer diameters of 0.2 cm to 1.0 cm, and focal lengths ranging from 0.2 cm to 3.0 cm. Perfusion was assumed negligible and thermal and acoustic parameters were taken from reported studies. For every case, the ratio of maximum temperature rise to the TIS (assuming constant output power) was calculated. For the lens case, the ratio varied from 7.35 to 0.8. For the no-lens case, the ratio varied from 4.1 to 0.4. These results indicate that the TIS is not adequate to represent the temperature rise occurring within the eye upon insonation. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Herman, BA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NR 14 TC 13 Z9 14 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD NOV PY 1999 VL 46 IS 6 BP 1566 EP 1574 DI 10.1109/58.808882 PG 9 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 261VE UT WOS:000084029700028 PM 18244355 ER PT J AU Klinman, DM Conover, J Coban, C AF Klinman, DM Conover, J Coban, C TI Repeated administration of synthetic oligodeoxynucleotides expressing CpG motifs provides long-term protection against bacterial infection SO INFECTION AND IMMUNITY LA English DT Article ID IMMUNOSTIMULATORY DNA-SEQUENCES; NECROSIS-FACTOR-ALPHA; INTERFERON-GAMMA; CUTTING EDGE; IN-VIVO; CELLS; IMMUNIZATION; INDUCTION; MURINE; INTERLEUKIN-12 AB Synthetic oligodeoxynucleotides (ODN) expressing unmethylated CPS motifs stimulate an innate immune response characterized by the production of polyreactive immunoglobulin M antibodies and immunomodulatory cytokines. This immune response has been shown to protect mice from challenge by Listeria monocytogenes and Francisella tularensis for up to 2 weeks. By repeatedly administering CpG ODN two to four times/month, we found that this protection could be maintained indefinitely. Protection was associated with a significant increase in the number of spleen cells that could be triggered by subsequent pathogen exposure to secrete gamma interferon and interleukin-6 in vivo (P < 0.01). ODN-treated animals remained healthy and developed neither macroscopic nor microscopic evidence of tissue damage or inflammation. Thus, repeated administration of CpG ODN may provide a safe means of conferring long-term protection against infectious pathogens. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bldg 29A Rm 3 D 10, Bethesda, MD 20892 USA. RI Coban, Cevayir/B-2129-2012 NR 30 TC 117 Z9 129 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1999 VL 67 IS 11 BP 5658 EP 5663 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 249QD UT WOS:000083343000016 PM 10531213 ER PT J AU Lee, LH Burg, E Baqar, S Bourgeois, AL Burr, DH Ewing, CP Trust, TJ Guerry, P AF Lee, LH Burg, E Baqar, S Bourgeois, AL Burr, DH Ewing, CP Trust, TJ Guerry, P TI Evaluation of a truncated recombinant flagellin subunit vaccine against Campylobacter jejuni SO INFECTION AND IMMUNITY LA English DT Article ID COLI VC167 FLAGELLIN; POSTTRANSLATIONAL MODIFICATION; INTESTINAL COLONIZATION; TRAVELERS DIARRHEA; ANTIGENS; MOTILITY; IDENTIFICATION; PATHOGENESIS; INFECTION; PROTEINS AB A recombinant protein comprising the maltose-binding protein (MBP) of Escherichia coli fused to amino acids 5 to 337 of the FlaA flagellin of Campylobacter coli VC167 was evaluated for immunogenicity and protective efficacy against challenge by a heterologous strain of campylobacter, Campylobacter jejuni 81-176, in two murine models. The sequence of the flaA gene of strain 81-176 revealed a predicted protein which was 98.1% similar to that of VC167 FlaA over the region expressed in the fusion protein. Mice were immunized intranasally with two doses of 3 to 50 mu g of MBP-FlaA, given 8 days apart, with or without 5 mu g of the mutant E. coli heat-labile enterotoxin (LTR192G) as a mucosal adjuvant, The full range of MBP-FlaA doses were effective in eliciting antigen-specific serum immunoglobulin G (IgG) responses, and these responses were enhanced by adjuvant use, except in the highest dosing group. Stimulation of FlaA-specific intestinal secretory IgA (sIgA) responses required immunization with higher doses of MBP-FlaA (greater than or equal to 25 mu g) or coadministration of lower doses with the adjuvant, When vaccinated mice were challenged intranasally 26 days after immunization, the best protection was seen in animals given 50 mu g of MBP-FlaA plus LTR192G. The protective efficacies of this dose against disease symptoms and intestinal colonization were 81.1 and 84%, respectively. When mice which had been immunized with 50 mu g of MBP-FlaA plus LTR192G intranasally were challenged orally with 8 x 10(10), 8 x 10(9), or 8 x 10(8) cells of strain 81-176, the protective efficacies against intestinal colonization at 7 days postinfection were 71.4, 71.4, and 100%, respectively. C1 Natl Naval Med Ctr, Naval Med Res Ctr, Enter Dis Program, Gaithersburg, MD 20889 USA. US FDA, Beltsville, MD 20708 USA. Univ Victoria, Dept Biochem & Microbiol, Victoria, BC V8W 3P6, Canada. RP Guerry, P (reprint author), Natl Naval Med Ctr, Naval Med Res Ctr, Enter Dis Program, 8901 Wisconsin Ave, Gaithersburg, MD 20889 USA. RI Guerry, Patricia/A-8024-2011 NR 45 TC 59 Z9 64 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 NOV PY 1999 VL 67 IS 11 BP 5799 EP 5805 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 249QD UT WOS:000083343000034 PM 10531231 ER PT J AU Elkins, KL Bosio, CM Rhinehart-Jones, TR AF Elkins, KL Bosio, CM Rhinehart-Jones, TR TI Importance of B cells, but not specific antibodies, in primary and secondary protective immunity to the intracellular bacterium Francisella tularensis live vaccine strain SO INFECTION AND IMMUNITY LA English DT Article ID CD4(+) T-CELLS; INFLUENZA-VIRUS INFECTION; LYMPHOCYTE-DEFICIENT MICE; NUDE MICE; RESISTANCE; MEMORY; GENE; LVS; GENERATION; INTERFERON AB Although there appears to be little if any role for specific antibodies in protection against intracellular bacteria, such as the model pathogen F. tularensis live vaccine strain (LVS), the role of B cells themselves in primary and secondary infection with such bacteria has not been examined directly. We show here that mice deficient in mature B cells and antibodies (B-cell knockout mice) are marginally compromised in controlling primary sublethal infection but are 100-fold less well protected against secondary lethal challenge than are their normal counterparts. This defect in optimal specific protective immunity uas readily reconstituted by the transfer of primed, and to a lesser degree, unprimed B cells, but not by the transfer of specific antibodies. The results indicate a previously unappreciated role for B cells in secondary immunity to intracellular pathogens through a function other than antibody production. C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Lab Mycobacteria, Rockville, MD 20852 USA. RP Elkins, KL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Lab Mycobacteria, 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA. RI Bosio, Catharine/D-7456-2015 NR 50 TC 77 Z9 79 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 NOV PY 1999 VL 67 IS 11 BP 6002 EP 6007 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 249QD UT WOS:000083343000063 PM 10531260 ER PT J AU Kenyon, TA Kenyon, AS Kgarebe, BV Mothibedi, D Binkin, NJ Layloff, TP AF Kenyon, TA Kenyon, AS Kgarebe, BV Mothibedi, D Binkin, NJ Layloff, TP TI Detection of substandard fixed-dose combination tuberculosis drugs using thin-layer chromatography SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE tuberculosis; treatment; drug quality; thin-layer chromatography; pharmaceutical management; counterfeit; drugs; drug-resistant TB; fixed-dose combinations ID RESISTANCE AB SETTING: A convenience sample of 13 fixed-dose combination (FDC) tuberculosis (TB) drugs from 'The Fixed Dose Combination Project' was analysed in laboratories at the University of Botswana and the US Food and Drug Administration (FDA). OBJECTIVE: TO determine actual versus stated content of drugs in these FDCs. DESIGN: Chemical analysis was performed using thin-layer chromatography (TLC) as a screening method, and ultraviolet (UV) spectrophotometry or liquid chromatography (LC) as confirmation. FDCs with content outside of 85-115% of stated concentration were defined as substandard. RESULTS: All 13 FDCs contained the stated drugs. However, four (31%) were substandard, including two (15%) with low rifampicin content, one (8%) with excessive rifampicin, and one (8%) with excessive pyrazinamide. Both FDCs with low rifampicin contained four drugs and failed TLC screening. The FDC with excessive rifampicin was not detected by TLC screening. Using UV as the gold standard, the sensitivity of TLC for low rifampicin was 2/2 (100%), and the specificity was 9/10 (90%). CONCLUSION: This Study found that 31% of the FDCs in 'The Fixed Dose Combination Project' had substandard content, irrespective of bioavailability. Low rifampicin content, which can be reliably detected by TLC screening, was identified in both four-drug FDC products and is particularly worrisome. TB drugs should be screened for quality using TLC to optimise treatment outcomes and to prevent increases in acquired drug resistance. C1 BOTUSA Project, Gaborone, Botswana. US Ctr Dis Control & Prevent, Natl Ctr HIV STD TB Prevent, Atlanta, GA USA. US FDA, Div Testing & Appl Analyt Dev, St Louis, MO USA. Univ Botswana, Dept Chem, Gaborone, Botswana. RP Kenyon, TA (reprint author), Amer Embassy Gaborone State Dept, BOTUSA Project, Washington, DC 20521 USA. NR 15 TC 11 Z9 11 U1 0 U2 5 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD NOV PY 1999 VL 3 IS 11 SU 3 BP S347 EP S350 PG 4 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 256FQ UT WOS:000083715600015 PM 10593716 ER PT J AU Hinkley, SF Fettinger, JC Dudley, K Jarvis, BB AF Hinkley, SF Fettinger, JC Dudley, K Jarvis, BB TI Memnobotrins and memnoconols: Novel metabolites from Memnoniella echinata SO JOURNAL OF ANTIBIOTICS LA English DT Article ID BIOLOGICAL PROPERTIES; HERICENONE-A; MONOPHOSPHATASE; INHIBITORS AB Four novel metabolites have been isolated from a rice culture of Memnoniella echinata (JS6308) by solvent extraction and radial silica chromatography. The structures were elucidated by spectroscopic techniques, and the absolute stereochemistry of memnobotrin A determined by X-ray crystallography. C1 Univ Maryland, Dept Chem & Biochem, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Jarvis, BB (reprint author), Univ Maryland, Dept Chem & Biochem, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. OI Hinkley, Simon F.R./0000-0002-1831-8389 NR 30 TC 22 Z9 22 U1 0 U2 3 PU JAPAN ANTIBIOT RES ASSN PI TOKYO PA 2 20 8 KAMIOSAKI SHINAGAWA KU, TOKYO, 141, JAPAN SN 0021-8820 J9 J ANTIBIOT JI J. Antibiot. PD NOV PY 1999 VL 52 IS 11 BP 988 EP 997 PG 10 WC Biotechnology & Applied Microbiology; Immunology; Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Immunology; Microbiology; Pharmacology & Pharmacy GA 259ZH UT WOS:000083923500006 PM 10656571 ER PT J AU Kijak, PJ Cope, CV Pedersoli, WM AF Kijak, PJ Cope, CV Pedersoli, WM TI Determination of oxytetracycline in bovine kidney and medicated milk replacer by liquid chromatography SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TETRACYCLINE AB Improvements and optimization of AOAC INTERNATIONAL Official Method 995.09 for the detection of oxytetracycline in bovine kidney at the new U.S. tolerance of 12 ppm are reported, Recoveries from kidney fortified at 4 concentrations over the range of 3-40 ppm averaged 84-98%. Results from the kidney of a calf fed medicated milk replacer containing oxytetracycline are also reported. Additionally, adaptation of this method to the detection of oxytetracycline in medicated milk replacer is discussed. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Kijak, PJ (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 4 TC 4 Z9 4 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 1999 VL 82 IS 6 BP 1329 EP 1333 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 258UT UT WOS:000083858100011 PM 10589484 ER PT J AU Pensabene, JW Fiddler, W Donoghue, DJ AF Pensabene, JW Fiddler, W Donoghue, DJ TI Isolation of chloramphenicol from whole eggs by supercritical fluid extraction with in-line collection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ELECTRON-CAPTURE DETECTION; GAS-CHROMATOGRAPHY; RESIDUES; CONFIRMATION; SULFONAMIDES; ANIMALS; MILK; MEAT AB Egg consumption, at more than 65 billion per year in the United States, represents a potentially significant source of exposure to drug residues, particularly if the laying hens are treated with antimicrobial compounds or fed a diet containing medicated feed. Residues resulting from the use of chloramphenicol (CAP) is especially problematic if this compound is not used in accordance with national registration, e.g., for the control of Salmonella microorganisms in poultry. The mast commonly used methods for the determination of CAP in biological samples require the use of large amounts of organic solvent. As a result, a less solvent intensive supercritical fluid extraction (SFE) method was developed for CAP in whole chicken eggs, and the results were compared with those for a solvent extraction procedure. In the SFE method, the egg sample is extracted with supercritical CO2 (without a modifier) at 10 000 psi (680 bar), 80 degrees C, and an expanded gas flow rate of 3.0 L/min to a total volume of 150 L. The CAP is trapped in-line on a Florisil sorbent bed. The CAP is eluted post-SFE by using the liquid chromatographic mobile phase solvent (water-methanol), and determined on a Cs column with ultraviolet detection at 280 nm. Recovery from eggs fortified at the 10 ppb level (n = 6) was 81.2 +/- 4.3%. To obtain eggs containing incurred CAP, hens were given a single daily dose of 75 mg CAP (orally by gelatin capsule) for 2 consecutive days, and the eggs were collected over a 12-day period. The mean value for "normally incurred" CAP in the eggs (n = 17) analyzed by SFE ranged from none detected to 174.5 ppb, with an overall mean of 60.5 ppb, compared with a mean of 60.4 ppb for the solvent extraction method. No significant difference in resuits was found between methods. However, the SFE method is more rapid, uses less solvent, and gives recoveries similar to those for the solvent extraction method, making it ideal for regulatory monitoring. C1 ARS, USDA, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. US FDA, Ctr Vet Med, Div Anim Res, Laurel, MD 20708 USA. RP Pensabene, JW (reprint author), ARS, USDA, Eastern Reg Res Ctr, 600 E Mermaid Ln, Wyndmoor, PA 19038 USA. NR 22 TC 13 Z9 17 U1 1 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 1999 VL 82 IS 6 BP 1334 EP 1339 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 258UT UT WOS:000083858100012 PM 10589485 ER PT J AU Schenck, FJ Lagman, LH AF Schenck, FJ Lagman, LH TI Multiresidue determination of abamectin, doramectin, ivermectin, and moxidectin in milk using liquid chromatography and fluorescence detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID BOVINE-MILK; PLASMA; AVERMECTINS; CATTLE; DERIVATIZATION; ANTHELMINTICS; MILBEMYCINS; RESIDUES AB Abamectin, doramectin, ivermectin, and moxidectin are macrocyclic lactones derived from soil dwelling actinomycetes, and are very effective against nematode, insect, and arthropod infestations. These compounds, known as endectocides, have been approved for use in beef cattle in the United States; however, they are currently not approved for use in dairy cattle. Abamectin, doramectin, ivermectin, and moxidectin residues were isolated from milk by a series of liquid-liquid extraction steps, derivatized with trifluoroacetic anhydride, and determined by liquid chromatography with fluorescence detection. Recovery studies were performed in 2 laboratories. Recoveries of >80% (1-30 ng/mL) were achieved for all 4 compounds. C1 US FDA, Baltimore Dist Lab, Baltimore, MD 21201 USA. Agr Mkt Serv, USDA, Eastern Lab, Gastonia, NC 28054 USA. RP Schenck, FJ (reprint author), US FDA, 60 8th St NE, Atlanta, GA 30309 USA. NR 26 TC 29 Z9 34 U1 0 U2 4 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 1999 VL 82 IS 6 BP 1340 EP 1344 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 258UT UT WOS:000083858100013 PM 10589486 ER PT J AU Yuan, R Flockhart, DA Balian, JD AF Yuan, R Flockhart, DA Balian, JD TI Pharmacokinetic and pharmacodynamic consequences of metabolism-based drug interactions with alprazolam, midazolam, and triazolam SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Review ID HUMAN LIVER-MICROSOMES; SYSTEMIC ANTIMYCOTICS KETOCONAZOLE; ORAL DOSE PHARMACOKINETICS; HEALTHY-VOLUNTEERS; IN-VITRO; CLINICAL PHARMACOKINETICS; PLASMA-CONCENTRATIONS; DYNAMIC CONSEQUENCES; CYTOCHROME-P450 3A; HUMAN-PERFORMANCE AB This review was conducted to identify the current data on drug interactions with alprazolam, midazolam, and triazolam to guide practitioners in the use of these drugs. The Medline electronic database from 1966 through 1998 was used to identify clinical studies of the pharmacokinetic effect of drugs on these three benzodiazepines. Of a total of 491 literature reports identified, 59 prospective studies met our selection criteria. The pharmacokinetic parameters of AUC, C-max, t(1/2), and t(max) were evaluated for changes following an interaction. To allow comparison between studies, changes in the parameters were normalized relative to the control values. Pharmacodynamic effects and measures, when reported in the original studies as statistically significant, were classified as a strong interaction, and when the interaction was present but not statistically significant, they were classified as mild in this review. As a result, clinically significant drug interactions were noted for all three benzodiazepines, although it is clear that statistically significant pharmacokinetic changes do not always translate into clinically significant pharmacodynamic consequences. All three benzodiazepines were susceptible to drug interactions, but oral dosing of midazolam and triazolam resulted in greater alterations in the pharamcokinetic parameters than alprazolam due to their larger presystemic extraction. Ketoconazole and itraconazole were found to be the most potent metabolic inhibitors that prolonged the duration of or intensified the magnitude of the dynamic response produced by the three benzodiazepines. Rifampin, carbamazepine, and phenytoin were noted to be potent metabolic inducers, and their treatments result in loss of benzodiazepine therapeutic efficacy In conclusion, potent metabolic inhibitors and inducers can either significantly prolong or diminish the dynamic effects of benzodiazepines via their influence on the pharmacokinetics of benzodiazepines. (C)1999 the American College of Clinical Pharmacology. C1 US FDA, CDER, OPS, OCPB,DPE 1, Rockville, MD 20857 USA. Georgetown Univ, Med Ctr, Dept Med, Div Clin Pharmacol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Pharmacol, Div Clin Pharmacol, Washington, DC 20007 USA. RP Yuan, R (reprint author), US FDA, CDER, OPS, OCPB,DPE 1, HFD-860,5600 Fishers Lane,Woodmont 2 Bldg,Room 40, Rockville, MD 20857 USA. FU NIGMS NIH HHS [T-32-GM08386] NR 91 TC 60 Z9 61 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD NOV PY 1999 VL 39 IS 11 BP 1109 EP 1125 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 248DZ UT WOS:000083261200002 PM 10579141 ER PT J AU Goldman, SA AF Goldman, SA TI Use of a mail-out continuing education article to teach health professionals about drug-induced disease SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID CLINICAL-PHARMACOLOGY; HOSPITALIZED-PATIENTS; ADVERSE; PROGRAM; EVENTS; SURVEILLANCE; ADMISSIONS; DISCOVERY; MEDWATCH; COSTS AB A U.S. Food and Drug Administration [FDA]/Georgetown University Medical Center conference was the basis for "Clinical Therapeutics and the Recognition of Drug-induced Disease, " the first MEDWATCH continuing education (CE) mail-out article. Developed as a major component of FDA MEDWATCH post-marketing surveillance outreach, the article used a clinical therapeutic approach to discuss topics including adverse drug events (ADEs) pharmacology and ADE reporting. Distributed nationwide through the A MEDWATCH Partners, health professionals applied far CE credit by completing a self-assessment examination. With the overall response rate slightly more than 2%, 15, 260 health professionals (55% physicians and 37% pharmacists) received CE credit. Evaluation of the initial approximate two-thirds (N = 10,021) of successfully completed exams found 99% agreement that stated learning objectives were met, and the article relevant to their clinical practice; spontaneous comments/letters were also very positive. The highest percentage responding specialists were internists (28%) and psychiatrists (17%), with notable differences found among specialties for response rate versus relative article distribution (such as relatively low response rates among surgeons and radiology/radiation physics specialists). The number of health professionals receiving CE credit, coupled with examination performance and overall response, indicates that "Clinical Therapeutics and the Recognition of Drug-induced Disease" was well received and fulfilled learning objectives. The results provide encouragement for this continuing educational approach. C1 US FDA, Rockville, MD 20857 USA. RP Goldman, SA (reprint author), Knoll Pharmaceut Co, MEDWATCH, 3000 Continental Dr N, Mt Olive, NJ 07828 USA. NR 25 TC 2 Z9 2 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD NOV PY 1999 VL 39 IS 11 BP 1126 EP 1135 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 248DZ UT WOS:000083261200003 PM 10579142 ER PT J AU Hesselman, DM Motes, ML Lewis, JP AF Hesselman, DM Motes, ML Lewis, JP TI Effects of a commercial heat-shock process on Vibrio vulnificus in the American oyster, Crassostrea virginica, harvested from the Gulf Coast SO JOURNAL OF FOOD PROTECTION LA English DT Article ID STORAGE; REDUCE AB Oysters (Crassostrea virginica) harvested from the Gulf Coast, containing 10(2) to 10(4) most probable number (MPN) per gram of Vibrio vulnificus, were subjected to a commercial heat-shock process. After 1 to 4 min at internal oyster meat temperatures exceeding 50 degrees C, shellstock oysters were shucked, chilled, washed, and packed. V. vulnificus and total bacterial levels in Gulf Coast oysters were significantly reduced from 1 to 4 logs in the finished product. Similar reductions were not observed in shellstock oysters that were subject to conventional processing. Under the National Shellfish Sanitation Program, heat shocking is an acceptable process to use to assist in the shucking of shellstock. This research revealed that the heat-shock process may also serve to significantly reduce V. vulnificus in summer Gulf Coast oysters. C1 US FDA, Mobile Resident Post, Mobile, AL 36693 USA. US FDA, Charleston Resident Post, Charleston, SC 29413 USA. N Carolina Dept Environm & Nat Resources, Morehead City, NC 28557 USA. RP Motes, ML (reprint author), US FDA, Mobile Resident Post, Mobile, AL 36693 USA. NR 21 TC 14 Z9 16 U1 0 U2 4 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD NOV PY 1999 VL 62 IS 11 BP 1266 EP 1269 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 253MA UT WOS:000083559300005 PM 10571315 ER PT J AU Sechler, JMG Hansal, SA Morris, DI McFarland, HI Rosenberg, AS AF Sechler, JMG Hansal, SA Morris, DI McFarland, HI Rosenberg, AS TI Antigen presentation determines the fate of the T memory response in vivo after sublethal gamma-irradiation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DEXAMETHASONE-INDUCED APOPTOSIS; RESTING B-CELLS; TOLERANCE INDUCTION; GENE-EXPRESSION; PLASMA-CELLS; NAIVE; SUPPRESSION; COSTIMULATION; LYMPHOCYTES; REJECTION AB The survival of memory T cells is critical to vaccination strategies for infectious diseases and cancer, whereas their elimination may be crucial for treatment of autoimmune states. We examined the consequences of gamma-irradiation, which induces apoptosis of memory T cells in vitro, on the memory response to MHC class I alloantigen in vivo. Sublethal gamma-irradiation of primed mice eliminated accelerated rejection of skin allografts but failed to induce tolerance. Accelerated rejection: was restored in irradiated mice by infusion of bone marrow cells expressing the priming alloantigen on immunostimulatory APCs (dendritic cells),: whereas the memory response was not restored by infusion of bone marrow cells expressing the priming alloantigen on nonstimulatory APCs (B cells). Strikingly, irradiated mice infused with nonstimulatory; bone marrow APCs exhibited long-term survival or tolerance to skin grafts expressing the priming MHC class I alloantigen. The mechanism of tolerance in this setting is explored. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. RP Rosenberg, AS (reprint author), Bldg 29A,Room 2B-12,8800 Rockville Pike, Bethesda, MD 20892 USA. RI McFarland, Hugh/K-1503-2016 OI McFarland, Hugh/0000-0002-3322-038X NR 37 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1999 VL 163 IS 9 BP 4701 EP 4706 PG 6 WC Immunology SC Immunology GA 248BT UT WOS:000083256000011 PM 10528167 ER PT J AU Malozowski, S Koller, E AF Malozowski, S Koller, E TI Safety and regulatory issues in anabolic agents' use and development SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article; Proceedings Paper CT 23rd Clinical Congress of the American-Society-for-Parenteral-and-Enteral-Nutrition CY JAN 31-FEB 03, 1999 CL SAN DIEGO, CALIFORNIA SP Amer Soc Parenteral & Enteral Nutrit C1 US FDA, CDER, Div Endocrine & Metab Drug Prod, Rockville, MD 20857 USA. RP Malozowski, S (reprint author), US FDA, CDER, Div Endocrine & Metab Drug Prod, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC PARENTERAL & ENTERAL NUTRITION PI SILVER SPRING PA 8630 FENTON STREET SUITE 412, SILVER SPRING, MD 20910 USA SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD NOV-DEC PY 1999 VL 23 IS 6 SU S BP S214 EP S215 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 255VW UT WOS:000083691700008 PM 10571458 ER PT J AU Mahmood, I AF Mahmood, I TI Allometric issues in drug development SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Review ID IN-VITRO DATA; PHARMACOKINETIC PARAMETERS; METABOLIC-CLEARANCE; SCALE-UP; HUMANS; PREDICTION; ANIMALS; INTEGRATION; BINDING; DOG AB The concept of correlating pharmacokinetic parameters with body weight from different animal species has become a useful tool in drug development. The allometric approach is based on the power function, where the body weight of the species is plotted against the pharmacokinetic parameter(s) of interest. Clearance, volume of distribution, and elimination half-life are the three most frequently extrapolated pharmacokinetic parameters. Over the years, many approaches have been suggested to improve the prediction of these pharmacokinetic parameters in humans from animal data. A literature review indicates that there are different degrees of success with different methods for different drugs. Overall, though interspecies scaling requires refinement and better understanding, the approach has lot of potential during the drug development process. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1 HFC860, Woodmont Off Ctr 2, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1 HFC860, Woodmont Off Ctr 2, Room 4079,1451 Rockville Pike, Rockville, MD 20852 USA. NR 40 TC 54 Z9 54 U1 1 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD NOV PY 1999 VL 88 IS 11 BP 1101 EP 1106 DI 10.1021/js9902163 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 252TC UT WOS:000083517500001 PM 10564055 ER PT J AU Walsh, DL Chwirut, DJ Kotz, RM AF Walsh, DL Chwirut, DJ Kotz, RM TI Environmental degradation of natural rubber latex gloves: The effects of elevated temperature on tensile strength SO JOURNAL OF TESTING AND EVALUATION LA English DT Article DE gloves; natural rubber latex; tensile strength; chlorination; environmental degradation AB Various styles of latex gloves were oven-aged for 7, 14. and 21 days at 70 degrees C and then subjected to tension testing per ASTM D 412. Rye of seven powder-free glove styles exhibited dramatic decreases in tensile strength after 7 to 14 days at 70 degrees C, with total decreases in tensile strength ranging from 70 to over 90% after 21 days of aping. These five styles were examination gloves that were later confirmed to be chlorinated. In contrast, a chlorinated surgical glove, a non-chlorinated examination glove, and all of the powdered gloves (examination and surgical) subjected to the same conditions exhibited total decreases in tensile strength ranging from 0 to 25% after 21 days. These results suggest that chlorination, a process commonly used in the manufacture of powder-free gloves, may have detrimental effects an the ability of natural rubber latex to retain its barrier integrity after exposure to severely elevated temperatures. C1 US FDA, Off Sci & Technol, Rockville, MD 20852 USA. US FDA, Off Surveillance & Biometr, Rockville, MD 20852 USA. RP Walsh, DL (reprint author), US FDA, Off Sci & Technol, HFZ-150,9200 Corporate Blvd, Rockville, MD 20852 USA. NR 5 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0090-3973 J9 J TEST EVAL JI J. Test. Eval. PD NOV PY 1999 VL 27 IS 6 BP 396 EP 401 PG 6 WC Materials Science, Characterization & Testing SC Materials Science GA 287YT UT WOS:000085535600006 ER PT J AU Gammell, PM Harris, GR AF Gammell, PM Harris, GR TI Time delay spectrometry for hydrophone calibrations below 1 MHz SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article AB Knowing the response of miniature ultrasonic hydrophones at frequencies below 1 MHz is important for assessing the accuracy of acoustic pressure pulse measurements in medical ultrasound applications. Therefore, a time delay spectrometry (TDS) system was developed as an efficient means to measure hydrophone sensitivity in this frequency range. In TDS a swept-frequency signal is transmitted. A tracking receiver distinguishes arrivals with different propagation delays by their frequency offset relative to the signal being transmitted, thus eliminating spurious signals such as those reflected from the water surface or tank walls. Two piezoelectric ceramic source transducers were used: a standard planar disk and a disk with varying thickness to broaden the thickness-resonance. This latter design was preferred for its more uniform response without significant sensitivity loss. TDS is not an absolute method, but it was demonstrated to provide efficient, accurate calibrations via comparison with a reference hydrophone using a substitution technique. (C) 1999 Acoustical Society of America. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Gammell, PM (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NR 8 TC 6 Z9 6 U1 0 U2 1 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD NOV PY 1999 VL 106 IS 5 BP L41 EP L46 DI 10.1121/1.427181 PG 6 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 257MN UT WOS:000083785800070 PM 10573913 ER PT J AU Turturro, A Witt, WW Lewis, S Hass, BS Lipman, RD Hart, RW AF Turturro, A Witt, WW Lewis, S Hass, BS Lipman, RD Hart, RW TI Growth curves and survival characteristics of the animals used in the biomarkers of aging program SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID CALORIC RESTRICTION; BODY-WEIGHT; MECHANISMS; LONGEVITY; NEOPLASIA; BIOASSAYS; MICE AB The collaborative Interagency Agreement between the National Center for Toxicological Research (NCTR) and the National Institute on Aging (NIA) was aimed at identifying and validating a panel of biomarkers of aging bl rodents ill order to rapidly test the efficacy and safety of interventions designed to slow aging. Another aim was to provide a basis for developing biomarkers of aging in humans, using the assumption that biomarkers that were useful across different genotypes and species were sensitive to fundamental processes that would extrapolate to humans. Caloric restriction (CR), the only intervention that consistently extends both mean and maximal life span in a variety of species, was used to provide a model with extended life span. C57B1/6NNia, DBA/2JNia, B6D2F1, and B6C3F1 mice and Brown Norway (BN/RijNia), Fischer (F344/NNia) and Fischer x Brown Norway hybrid (F344 x BN F1) rats were bred and maintained on study. NCTR generated data from over 60,000 individually housed animals of the seven different genotypes and both sexes, approximately half ad libitum (AL) fed, the remainder CR. Approximately half the animals half shipped to offsite NIA investigators internationally with the majority of the remainder maintained at NCTR until they died. The collaboration supplied a choice of healthy, long-lived rodent models to investigators, while allowing for the development of some of the most definitive information on life spall, food consumption, and growth characteristics in these genotypes under diverse feeding paradigms. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Vet Serv, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Bionet Corp, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Off Director, Jefferson, AR 72079 USA. Tufts Univ, USDA, Human Nutr Res Ctr, Boston, MA 02111 USA. RP Turturro, A (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 27 TC 319 Z9 324 U1 1 U2 9 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 NOV PY 1999 VL 54 IS 11 BP B492 EP B501 DI 10.1093/gerona/54.11.B492 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 331XL UT WOS:000088043900005 PM 10619312 ER PT J AU Zheng, Q AF Zheng, Q TI Progress of a half century in the study of the Luria-Delbruck distribution SO MATHEMATICAL BIOSCIENCES LA English DT Review DE Luria-Delbruck model; Luria-Delbruck distribution; estimation of mutation rate; Poisson-stopped-sum distribution; filtered Poisson process ID FLUCTUATION ANALYSIS; GENE AMPLIFICATION; MUTATION-RATES; MUTANTS; NUMBER; POPULATIONS; MODELS AB The Luria-Delbruck mutation model has been mathematically formulated in a number of ways. This review article examines four most important formulations, focusing on important practical issues closely linked with the distribution of the number of mutants. These issues include the probability generating functions, moments (cumulants), computational methods and asymptotics. This review emphasizes basic principles which not only help to unify existing results but also allow for a few useful extensions. In addition, the review offers a historical perspective and some new explanations of divergent moments. (C) 1999 Published by Elsevier Science Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Zheng, Q (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, HFT-20,3900 NCTR Dr, Jefferson, AR 72079 USA. NR 36 TC 69 Z9 69 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD NOV-DEC PY 1999 VL 162 IS 1-2 BP 1 EP 32 DI 10.1016/S0025-5564(99)00045-0 PG 32 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 262HK UT WOS:000084061000001 PM 10616278 ER PT J AU DeBell, KE Stoica, BA Veri, MC Di Baldassarre, A Miscia, S Graham, LJ Rellahan, BL Ishiai, M Kurosaki, T Bonvini, E AF DeBell, KE Stoica, BA Veri, MC Di Baldassarre, A Miscia, S Graham, LJ Rellahan, BL Ishiai, M Kurosaki, T Bonvini, E TI Functional independence and interdependence of the Src homology domains of phospholipase C-gamma 1 in B-cell receptor signal transduction SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; INDUCED TYROSINE PHOSPHORYLATION; T-CELL; ANTIGEN RECEPTOR; C-GAMMA; SH2 DOMAIN; CATALYTIC ACTIVITY; MOLECULAR-CLONING; GENETIC-EVIDENCE; LYMPHOCYTES-B AB B-cell receptor (BCR)-induced activation of phospholipase C-gamma 1 (PLC gamma 1) and PLC gamma 2 is crucial for B-cell function, While several signaling molecules have been implicated in PLC gamma activation, the mechanism coupling PLC gamma to the BCR remains undefined. The role of PLC gamma 1 SH2 and SH3 domains at different steps of BCR-induced PLC gamma 1 activation was examined by reconstitution in a PLC gamma-negative B-cell line. PLC gamma 1 membrane translocation required a functional SH2 N-terminal [SH2(N)] domain, was decreased by mutation of the SH3 domain, but was unaffected by mutation of the SH2(C) domain. Tyrosine phosphorylation did not require the SH2(C) or SH3 domains but depended exclusively on a functional SH2(N) domain, which mediated the association of PLC gamma 1 with the adapter protein, BLNK. Forcing PLC gamma 1 to the membrane via a myristoylation signal did not bypass the SH2(N) domain requirement for phosphorylation, indicating that the phosphorylation mediated by this domain is not due to membrane anchoring alone. Mutation of the SH2(N) or the SH2(C) domain abrogated BCR-stimulated phosphoinositide hydrolysis and signaling events, while mutation of the SH3 domain partially decreased signaling. PLC gamma 1 SH domains, therefore, have interrelated but distinct roles in BCR-induced PLC gamma 1 activation. C1 US FDA, Ctr Biol Evaluat & Res, Div Monocolonal Antibodies, Immunobiol Lab, Bethesda, MD 20014 USA. RP US FDA, Ctr Biol Evaluat & Res, Div Monocolonal Antibodies, Immunobiol Lab, 29B 3NN10,8800 Rockville Pike, Bethesda, MD 20014 USA. EM bonvini@box-b.nih.gov RI STOICA, BOGDAN/H-9782-2013 OI STOICA, BOGDAN/0000-0002-2501-6434 NR 75 TC 31 Z9 31 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1999 VL 19 IS 11 BP 7388 EP 7398 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 247CM UT WOS:000083203100010 PM 10523627 ER PT J AU Ghedin, E Debrabant, A Engel, J Dwyer, D AF Ghedin, E Debrabant, A Engel, J Dwyer, D TI Trafficking of a GFP chimera in Leishmania is differentially regulated by a GPI-anchored carbohydrate SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. US FDA, CBER, Rockville, MD 20857 USA. UCSF, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 517 BP 90A EP 90A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500518 ER PT J AU Debrabant, A Lee, N Dwyer, D Nakhasi, H AF Debrabant, A Lee, N Dwyer, D Nakhasi, H TI Overexpression of the endoplasmic reticulum chaperone calreticulin in Leishmania donovani results in altered release of secretory proteins. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 US FDA, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 2392 BP 413A EP 413A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502393 ER PT J AU Yui, K Goto, K Ikemoto, S Ishiguro, T Angrist, B Duncan, GE Sheitman, BB Lieberman, JA Bracha, SH Ali, SF AF Yui, K Goto, K Ikemoto, S Ishiguro, T Angrist, B Duncan, GE Sheitman, BB Lieberman, JA Bracha, SH Ali, SF TI Neurobiological basis of relapse prediction in stimulant-induced psychosis and schizophrenia: the role of sensitization SO MOLECULAR PSYCHIATRY LA English DT Article; Proceedings Paper CT XXth Congress of the Collegium-Internationale-Neuro-Psychopharmacologicum CY JUN 23-27, 1996 CL MELBOURNE, AUSTRALIA SP Collegium Int Neuro Psychopharm DE sensitization; stimulant; methamphetamine psychosis; spontaneous recurrence; stress; cocaine psychosis; noradrenaline; dopamine; schizophrenia; phencyclidine; rotational behavior ID PHENCYCLIDINE-INDUCED BEHAVIORS; MEDIAL PREFRONTAL CORTEX; COCAINE-INDUCED PARANOIA; DOPAMINE RELEASE; INDUCED ROTATION; METHAMPHETAMINE PSYCHOSIS; SPONTANEOUS RECURRENCE; AMPHETAMINE PSYCHOSIS; STRESS; RATS AB A number of consistent clinical observations provide direction for the hypothesis that pathological sensitization of neuronal systems may be an important factor for relapse or the onset of stimulant-induced psychosis leg, methamphetamine or amphetamine psychosis, cocaine psychosis and phencyclidine psychosis and schizophrenia. First, psychotic symptoms can be produced in normal subjects by stimulants. Secondly, a targe portion of schizophrenic patients exhibit exacerbation of psychotic symptoms in response to stimulants at doses which would not be psychotogenic in normal subjects. Lastly, the ability of stress to precipitate the onset and relapse of schizophrenia is well documented. In this regard, acute responses to stimulants provide useful information for relapse prediction of schizophrenia and substance abuse. This paper addresses the nature and role of pathological sensitization in relapse of stimulant- and phencyclidine-induced psychosis and schizophrenia, and its relation to pathophysiology of schizophrenia. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Jichi Med Sch, Dept Psychiat, Minami Kawachi, Tochigi 3290498, Japan. Jichi Med Sch, Dept Legal Med & Human Genet, Minami Kawachi, Tochigi 3290498, Japan. NYU, Sch Med, Psychiat Serv, Vet Adm Med Ctr, New York, NY 10010 USA. Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA. PTSD, VA Pacific Ctr, Honolulu, HI USA. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. EM sali@nctr.fda.gov NR 112 TC 68 Z9 70 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 1999 VL 4 IS 6 BP 512 EP 523 DI 10.1038/sj.mp.4000575 PG 12 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 258KN UT WOS:000083838500003 PM 10578232 ER PT J AU Ellwood, KC Bhathena, SJ Johannessen, JN Bryant, MA O'Donnell, MW AF Ellwood, KC Bhathena, SJ Johannessen, JN Bryant, MA O'Donnell, MW TI Biomarkers used to assess the effect of dietary xylitol or sorbitol in the rat SO NUTRITION RESEARCH LA English DT Article DE enzymes; xylitol; sorbitol; glucose; hormones; rats ID INSULIN-RECEPTORS; GLUCAGON; TOXICITY; POLYOLS; SERUM AB Because sugar alcohols can be used as bulk sweeteners and their possible lower energy values, interest has increased. Sorbitol and xylitol are hydrogenated monosaccharides that have widespread application. Male Fisher-344 rats were fed semipurified diets containing glucose without or with either 10% or 20% sorbitol or xylitol for 8 weeks following a 4-week adaptation period. The addition of sugar alcohols decreased food efficiency and total body weight gain regardless of the type fed. The addition of sugar alcohols to the diets decreased liver glucose-6-phosphate dehydrogenase (G6PD) and malic enzyme (ME). However, rats fed either 10% xylitol or sorbitol or 20% sorbitol had higher levels of epididymal fat tissue G6PD and ME. Plasma glucagon levels were decreased with the addition of sugar alcohols; whereas, in plasma insulin and glucose there was little effect. Diets containing sugar alcohols decreased levels of plasma triglyceride and cholesterol. The addition of sugar alcohols to the diets increased plasma alkaline phosphatase levels. Dietary treatments had no effect on urine or adrenal norephinephrine and epinephrine, and urine dihydroxyphenylacetic acid and dopamine. The addition of sugar alcohols to the diets had more of a metabolic effect than the type of sugar alcohol fed. Published by Elsevier Science Inc. C1 USDA ARS, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. USDA, Cooperat State Res Educ & Extens Serv, Washington, DC 20250 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Ellwood, KC (reprint author), USDA ARS, Beltsville Human Nutr Res Ctr, 5601 Sunnyside Ave, Beltsville, MD 20705 USA. NR 36 TC 8 Z9 8 U1 2 U2 3 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 NOV PY 1999 VL 19 IS 11 BP 1637 EP 1648 DI 10.1016/S0271-5317(99)00119-0 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 249XP UT WOS:000083358700005 ER PT J AU Grigonis, GJ Baldwin, S Campbell, W Campos, J Cuppucci, W Cardarelli, J Clark, P Corbin, V Crosson, E Greenawalt, H Halvorsen, J Allen-Bradley, JJ Motise, P Prasad, B Riloff, J Takonis, P Thome, R Turocy, M Wyrick, M AF Grigonis, GJ Baldwin, S Campbell, W Campos, J Cuppucci, W Cardarelli, J Clark, P Corbin, V Crosson, E Greenawalt, H Halvorsen, J Allen-Bradley, JJ Motise, P Prasad, B Riloff, J Takonis, P Thome, R Turocy, M Wyrick, M CA PDA Supplier Auditing & Qualificat TI PDA Technical Report No. 32: Auditing of suppliers providing computer products and services for regulated pharmaceutical operations SO PDA JOURNAL OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY LA English DT Editorial Material C1 Merck & Co Inc, Rahway, NJ 07065 USA. Alcon Labs Inc, Ft Worth, TX USA. Agouron Pharmaceut, La Jolla, CA 92037 USA. Berlex Labs Inc, Wayne, NJ 07470 USA. Waters Corp, Milford, MA 01757 USA. US FDA, Rockville, MD 20857 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Grigonis, GJ (reprint author), Merck & Co Inc, Rahway, NJ 07065 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PARENTERAL DRUG ASSOC INC PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 620, BETHESDA, MD 20814 USA SN 1076-397X J9 PDA J PHARM SCI TECH JI PDA J. Pharm. Sci. Technol. PD NOV-DEC PY 1999 VL 53 IS 6 BP 360 EP 360 PG 1 WC Engineering, Biomedical; Pharmacology & Pharmacy SC Engineering; Pharmacology & Pharmacy GA 283WL UT WOS:000085299000010 ER PT J AU Baker, SS Flores, CA Georgieff, MK Jacobson, MS Jaksic, T Krebs, NF AF Baker, SS Flores, CA Georgieff, MK Jacobson, MS Jaksic, T Krebs, NF CA Comm Nutr TI Calcium requirements of infants, children, and adolescents SO PEDIATRICS LA English DT Article ID BONE-MINERAL DENSITY; DIETARY CALCIUM; SKELETAL MASS; SUPPLEMENTATION; GIRLS; RATES; ABSORPTION; RICKETS; GROWTH; OSTEOPOROSIS AB This statement is intended to provide pediatric caregivers with advice about the nutritional needs of calcium of infants, children, and adolescents. It will review the physiology of calcium metabolism and provide a review of the data about the relationship between calcium intake and bone growth and metabolism. In particular, it will focus on the large number of recent studies that have identified a relationship between childhood calcium intake and bone mineralization and the potential relationship of these data to fractures in adolescents and the development of osteoporosis in adulthood. The specific needs of children and adolescents with eating disorders are not considered. C1 USDA, Washington, DC 20250 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. NICHHD, Bethesda, MD 20205 USA. NIDDKD, Bethesda, MD 20205 USA. US FDA, Rockville, MD 20857 USA. NR 43 TC 89 Z9 95 U1 1 U2 4 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 NOV PY 1999 VL 104 IS 5 BP 1152 EP 1157 PG 6 WC Pediatrics SC Pediatrics GA 251LW UT WOS:000083448000021 PM 10545566 ER PT J AU Tabor, E AF Tabor, E TI The epidemiology of virus transmission by plasma derivatives: clinical studies verifying the lack of transmission of hepatitis B and C viruses and HIV type 1 SO TRANSFUSION LA English DT Article ID ANTI-D IMMUNOGLOBULIN; POLYMERASE CHAIN-REACTION; INTRAVENOUS IMMUNOGLOBULIN; IMMUNE GLOBULIN; LYMPHOTROPIC VIRUS; BLOOD PRODUCTS; NON-A; INFECTION; INACTIVATION; FRACTIONATION C1 US FDA, Off Blood Res & Review, Bethesda, MD 20014 USA. RP Tabor, E (reprint author), US FDA, CBER, HFM 300 1401 Rockville Pike,Suite 400N, Rockville, MD 20852 USA. NR 56 TC 80 Z9 83 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 NOV-DEC PY 1999 VL 39 IS 11-12 BP 1160 EP 1168 DI 10.1046/j.1537-2995.1999.39111160.x PG 9 WC Hematology SC Hematology GA 263KR UT WOS:000084124300002 PM 10604241 ER PT J AU Stoughton, DM Zapata, G Picone, R Vann, WF AF Stoughton, DM Zapata, G Picone, R Vann, WF TI Identification of Arg-12 in the active site of Escherichia coli K1CMP-sialic acid synthetase SO BIOCHEMICAL JOURNAL LA English DT Article DE N-acetylneuraminic acid; enzyme mutagenesis; sugar activation ID GROUP-B; CMP; PURIFICATION; SYNTHASE; SEQUENCE; CLONING; ENZYME; GENES; LIVER AB Escherichia coli K1 CMP-sialic acid synthetase catalyses the synthesis of CMP-sialic acid from CTP and sialic acid. The active site of the 418 amino acid E, coli enzyme was localized to its N-terminal half. The bacterial CMP-sialic acid synthetase enzymes have a conserved motif, IAIIPARXXSKGLXXKN, at their N-termini. Several basic residues have been identified at or near the active site of the E. coli enzyme by chemical modification and site-directed mutagenesis. Only one of the lysines in the N-terminal motif, Lys-21, appears to be essential for activity. Mutation of Lys-21 in the N-terminal motif results in an inactive enzyme. Furthermore, Arg-12 of the N-terminal motif appears to be an active-site residue, based on the following evidence. Substituting Arg-12 with glycine or alanine resulted in inactive enzymes, indicating that this residue is required for enzymic activity. The Arg-12 --> Lys mutant was partially active, demonstrating that a positive charge is required at this site. Steady-state kinetic analysis reveals changes in K-cat, K-m and K-s for CTP, which implicates Arg-12 in catalysis and substrate binding. C1 US FDA, Lab Bacteriol Toxins, Div Bacterial Prod, OVRR,CBER, Bethesda, MD 20892 USA. RP Vann, WF (reprint author), US FDA, Lab Bacteriol Toxins, Div Bacterial Prod, OVRR,CBER, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 25 TC 9 Z9 9 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD OCT 15 PY 1999 VL 343 BP 397 EP 402 DI 10.1042/0264-6021:3430397 PN 2 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 250LX UT WOS:000083390800016 PM 10510306 ER PT J AU Jones, KD Aoki, Y Chang, Y Moore, PS Yarchoan, R Tosato, G AF Jones, KD Aoki, Y Chang, Y Moore, PS Yarchoan, R Tosato, G TI Involvement of interleukin-10 (IL-10) and viral IL-6 in the spontaneous growth of Kaposi's sarcoma herpesvirus-associated infected primary effusion lymphoma cells SO BLOOD LA English DT Article ID EPSTEIN-BARR-VIRUS; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE; HUMAN B-CELLS; DNA-SEQUENCES; MEMBRANE-PROTEIN; LYMPHOCYTES-B; AIDS; TRANSFORMATION; EXPRESSION; CYTOKINE AB Primary effusion lymphoma (PEL) is a distinct type of lymphoma associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. To determine the factors responsible for the unrestrained proliferation of PEL, we have studied the growth factor requirements of the PEL-derived BCBL-1 and BC-1 cell lines. Both cell lines were found to be autocrine growth factor dependent and to release human interleukin-6 (IL-6), viral IL-6 (vIL-6), and human IL-10 in the culture supernatant. To establish whether these cytokines contribute to autocrine growth, neutralizing antibodies against human IL-6, vIL-6, human IL-10, and soluble IL-10 receptor were used. These experiments showed that human IL-10 and, to a lesser degree, vIL-6 serve as autocrine growth factors for BCBL-1 and BC-1 cells. Thus, human IL-10 and vIL-6 are growth factors released and used by PEL cells for autonomous proliferation and may be critical to the development and progression of PEL. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. Columbia Univ, Sch Publ Hlth, Dept Pathol, New York, NY USA. NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. RP Tosato, G (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Room 2D16,Bldg 29A,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Chang, Yuan/F-4146-2011; Moore, Patrick/F-3960-2011 OI Moore, Patrick/0000-0002-8132-858X NR 45 TC 168 Z9 171 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 1999 VL 94 IS 8 BP 2871 EP 2879 PG 9 WC Hematology SC Hematology GA 244PM UT WOS:000083060000037 PM 10515891 ER PT J AU Kenney, RT Sacks, DL Sypek, JP Vilela, L Gam, AA Evans-Davis, K AF Kenney, RT Sacks, DL Sypek, JP Vilela, L Gam, AA Evans-Davis, K TI Protective immunity using recombinant human IL-12 and alum as adjuvants in a primate model of cutaneous leishmaniasis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AMERICAN TEGUMENTARY LEISHMANIASIS; MAJOR PLUS BCG; PROPHYLACTIC IMMUNIZATION; SUBCUTANEOUS IMMUNIZATION; NONHUMAN-PRIMATES; VERVET MONKEYS; MURINE MODEL; VACCINE; INFECTION; INTERLEUKIN-12 AB Protection from cutaneous leishmaniasis, a chronic ulcerating skin lesion affecting millions, has been achieved historically using live virulent preparations of the parasite. Killed or recombinant Ags that could be safer as vaccines generally require an adjuvant for induction of a strong Th1 response in murine models. Murine rIL-12 as an adjuvant with soluble Leishmania Ag has been shown to protect susceptible mice. We used 48 rhesus macaques to assess the safety, immunogenicity, and efficacy of a vaccine combining heat-killed Leishmania amazonensis with human rIL-12 (rhIL-12) and alum (aluminum hydroxide gel) as adjuvants. The single s.c. vaccination was found to be safe and immunogenic, although a small transient s.c. nodule developed at the site. Groups receiving rhIL-12 had an augmented in vitro Ag-specific IFN-gamma response after vaccination, as well as increased production of IgG. No increase in IL-4 or IL-10 was found in cell culture supernatants from either control or experimental groups. Delayed hypersensitivity reactions were not predictive of protection. Intradermal forehead challenge infection with 10(7) metacyclic L. amazonensis promastigotes at 4 wk demonstrated protective immunity in all 12 monkeys receiving 2 mu g rhIL-12 with alum and Ag. Partial efficacy was seen with lower doses of rhIL-12 and in groups lacking either adjuvant. Thus, a single dose vaccine with killed Ag using rhIL-12 and alum as adjuvants was safe and fully effective in this primate model of cutaneous leishmaniasis. This study extends the murine data to primates, and provides a basis for further human trials. C1 US FDA, Ctr Biol Evaluat & Res, Lab Parasit Biol & Biochem, Bethesda, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Div Vet Med, Bethesda, MD 20852 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Genet Inst, Andover, MA 01810 USA. Biotechnol Unit, Biobras, Montes Claros, Brazil. RP Kenney, RT (reprint author), 1401 Rockville Pike,HFM-416, Rockville, MD 20852 USA. NR 50 TC 97 Z9 101 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1999 VL 163 IS 8 BP 4481 EP 4488 PG 8 WC Immunology SC Immunology GA 243AK UT WOS:000082974800051 PM 10510390 ER PT J AU Chew, GL Higgins, KM Gold, DR Muilenberg, ML Burge, HA AF Chew, GL Higgins, KM Gold, DR Muilenberg, ML Burge, HA TI Monthly measurements of indoor allergens and the influence of housing type in a northeastern US city SO ALLERGY LA English DT Article DE allergens; cat; cockroach; dust mite; seasonal variation ID DUST MITE ALLERGEN; FEL-D-I; DERMATOPHAGOIDES-FARINAE; SEASONAL-VARIATION; HOUSEHOLD DUST; P-I; EXPOSURE; ASTHMA; PTERONYSSINUS; SENSITIZATION AB Background: We examined seasonal variation of dust-mile (Der f 1 and Der p 1), cat (Fel d 1), and cockroach (Bla g 1) allergens in Boston, while adjusting for other covariates. Limited data are available on seasonal patterns of indoor allergen concentrations for different geographic regions in the USA. Understanding within-home seasonal variation of allergens is important epidemiologically and clinically. Methods: From June 1995 to June 1996, dust samples were vacuumed monthly from the bed, bedroom floor; and kitchen of 20 homes. Indoor temperatures were measured monthly and used in calculating relative and absolute humidity. Monthly home characteristics questionnaires were completed by an adult resident of each home. Dust samples were assayed by enzyme-linked immunosorbent assays. Results: Der f I and Der p 1 in beds and floors peaked in the autumn months, Fel d 1 peaked in winter and spring, and Bla g 1 was highest in summer. Dust-mite allergen concentrations were 1.9-2.4 times higher in autumn than spring, but the levels in beds were 19-31 times higher in houses than those in apartments. Although Fel d 1 levels in beds were 2.4 times higher in spring than summer, homes with cats had levels 224 times higher than those without cats. Similarly, Bla g 1 levels in kitchens were 2.1 times higher in summer than winter, but apartments had, levels five times higher than those of houses. Conclusions: Sampling season is a source of within-home dust-mite, fat, and cockroach allergen variation in-the northeastern USA. However, the influence of housing type and owning a cat far outweighed the seasonal Variation of these indoor allergens. C1 Columbia Univ, Sch Publ Hlth, Div Environm Hlth Sci, New York, NY 10032 USA. US FDA, Rockville, MD 20857 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Chew, GL (reprint author), Columbia Univ, Sch Publ Hlth, Div Environm Hlth Sci, 60 Haven Ave B-1, New York, NY 10032 USA. NR 25 TC 77 Z9 82 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-4538 J9 ALLERGY JI Allergy PD OCT PY 1999 VL 54 IS 10 BP 1058 EP 1066 DI 10.1034/j.1398-9995.1999.00003.x PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 245JV UT WOS:000083105400005 PM 10536884 ER PT J AU James, SJ Pogribna, M Pogribny, IP Melnyk, S Hine, RJ Gibson, JB Yi, P Tafoya, DL Swenson, DH Wilson, VL Gaylor, DW AF James, SJ Pogribna, M Pogribny, IP Melnyk, S Hine, RJ Gibson, JB Yi, P Tafoya, DL Swenson, DH Wilson, VL Gaylor, DW TI Abnormal folate metabolism and mutation in the methylenetetrahydrofolate reductase gene may be maternal risk factors for Down syndrome SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE methylenetetrahydrofolate reductase; Down syndrome; folate; homocysteine; mutation; DNA methylation; MTHFR 677C -> T mutation; trisomy 21 ID CLASSICAL SATELLITE DNA; ADENOSYL-L-HOMOCYSTEINE; NEURAL-TUBE DEFECTS; COLORECTAL-CANCER; VASCULAR-DISEASE; SPINA-BIFIDA; P53 GENE; METHYLATION; DEFICIENCY; HYPOMETHYLATION AB Background: Down syndrome, or trisomy 21, is a complex genetic disease resulting from the presence of 3 copies of chromosome 21. The origin of the extra chromosome is maternal in 95% of cases and is due to the failure of normal chromosomal segregation during meiosis. Although advanced maternal age is a major risk factor for trisomy 21, most children with Down syndrome are born to mothers <30 y of age. Objective: On the basis of evidence that abnormal folate and methyl metabolism can lead to DNA hypomethylation and abnormal chromosomal segregation, we hypothesized that the C-to-T substitution at nucleotide 677 (677C --> T) mutation of the methylenetetrahydrofolate reductase (MTHFR) gene may be a risk factor for maternal meiotic nondisjunction and Down syndrome in young mothers. Design: The frequency of the MTHFR 677C --> T mutation was evaluated in 57 mothers of children with Down syndrome and in 50 age-matched control mothers. Ratios of plasma homocysteine to methionine and lymphocyte methotrexate cytotoxicity were measured as indicators of functional folate status. Results: A significant increase in plasma homocysteine concentrations and lymphocyte methotrexate cytotoxicity was observed in the mothers of children with Down syndrome, consistent with abnormal folate and methyl metabolism Mothers with the 677C --> T mutation had a 2.6-fold higher risk of having a child with Down syndrome than did mothers without the T substitution (odds ratio: 2.6; 95% CI: 1.2, 5.8; P < 0.03). Conclusion: The results of this initial study indicate that folate metabolism is abnormal in mothers of children with Down syndrome and that this may be explained, in part, by a mutation in the MTHFR gene. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72029 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Nutr & Dietet, Little Rock, AR 72205 USA. Arkansas Childrens Hosp, Div Pediat Genet, Little Rock, AR 72202 USA. Trisomy 21 Res Inc, San Jose, CA 95192 USA. Saginaw Valley State Univ, University Ctr, MI 48710 USA. Louisiana State Univ, Inst Environm Studies, Baton Rouge, LA 70803 USA. Louisiana State Univ, Inst Mutagenesis, Baton Rouge, LA 70803 USA. RP James, SJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT 140,3900 NCTR Rd, Jefferson, AR 72029 USA. NR 40 TC 275 Z9 294 U1 0 U2 10 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 1999 VL 70 IS 4 BP 495 EP 501 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 239PR UT WOS:000082779100012 PM 10500018 ER PT J AU Smith, ME Eller, NL McFarland, HF Racke, MK Raine, CS AF Smith, ME Eller, NL McFarland, HF Racke, MK Raine, CS TI Age dependence of clinical and pathological manifestations of autoimmune demyelination - Implications for multiple sclerosis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; VASCULAR ENDOTHELIAL-CELLS; NECROSIS-FACTOR-ALPHA; BRITISH-ISLES SURVEY; INBRED GUINEA-PIGS; T-LYMPHOCYTES; ANTIGEN EXPRESSION; OPTIC NEURITIS AB A prominent feature of the clinical spectrum of multiple sclerosis (MS) is its high incidence of onset in the third decade of life and the relative rarity of clinical manifestations during childhood and adolescence, features suggestive of age-related restriction of clinical expression. Experimental allergic encephalomyelitis (EAE), a model of central nervous system (CNS) autoimmune demyelination with many similarities to MS, has a uniform rapid onset and a high incidence of clinical and pathological disease in adult (mature) animals. Like MS, EAE is most commonly seen and studied in female adults. In this study, age-related resistance to clinical EAE has been examined with the adoptive transfer model of EAE in SJL mice that received myelin basic protein-sensitized cells from animals 10 days (sucklings) to 12 weeks (young adults) of age. A variable delay before expression of clinical EAE was observed between the different age groups, The preclinical period was longest in the younger (<14 days of age) animals, and shortest in animals 6 to 8 weeks old at time of transfer. Young animals initially resistant to EAE eventually expressed well-developed clinical signs by 6 to 7 weeks of age. This was followed by a remitting, relapsing clinical course. For each age at time of sensitization, increased susceptibility of females compared to males was observed. Examination of the CNS of younger animal groups during the preclinical period showed lesions of acute EAE. Older age groups developed onset of signs coincident with acute CNS lesions. This age-related resistance to clinical EAE in developing mice is reminiscent of an age-related characteristic of MS previously difficult to study in vivo. The associated subclinical CNS pathology and age-related immune functions found in young animals may be relevant to the increasing clinical expression of MS with maturation, and may allow study of factors associated with the known occasional poor correlation of CNS inflammation and demyelination and clinical changes in this disease. C1 NIAID, Div Acquired Immunodeficiency Syndrome, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO USA. Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10467 USA. RP Smith, ME (reprint author), NIAID, Div Acquired Immunodeficiency Syndrome, Bldg 6700B,Room 5105,Rockledge Dr, Bethesda, MD 20892 USA. FU NINDS NIH HHS [R01 NS008952, NS 11920, NS 07098, P50 NS011920, NS 08952, T32 NS007098] NR 71 TC 43 Z9 44 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 1999 VL 155 IS 4 BP 1147 EP 1161 DI 10.1016/S0002-9440(10)65218-2 PG 15 WC Pathology SC Pathology GA 246UU UT WOS:000083183600019 PM 10514398 ER PT J AU Parshikov, IA Freeman, JP Williams, AJ Moody, JD Sutherland, JB AF Parshikov, IA Freeman, JP Williams, AJ Moody, JD Sutherland, JB TI Biotransformation of N-acetylphenothiazine by fungi SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID MORICIZINE AB Cultures of the fungi Aspergillus niger, Cunninghamella verticillata, and Penicillium simplicissimum, grown in a sucrose/peptone medium, transformed N-acetylphenothiazine to N-acetylphenothiazine sulfoxide (from 13% to 28% of the total) and phenothiazine sulfoxide (from 5% to 27%). Phenothiazin-3-one (4%) and phenothiazine N-glucoside (4%) were also produced by C. verticillata, The probable intermediate, phenothiazine, was detected only in cultures of P, simplicissimum (6%). C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. OI Parshikov, Igor/0000-0003-1466-1128 NR 12 TC 11 Z9 11 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD OCT PY 1999 VL 52 IS 4 BP 553 EP 557 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 252YM UT WOS:000083529900014 PM 10570803 ER PT J AU Stern, RS Beer, JZ Mills, DK AF Stern, RS Beer, JZ Mills, DK TI Lack of consensus among experts on the choice of UV therapy for psoriasis SO ARCHIVES OF DERMATOLOGY LA English DT Article ID REVASCULARIZATION PROCEDURES; PUVA; RADIATION; PSORALEN; CANCER; RISK AB Context: Each lear tens of thousands of patients in the United States are treated with UV-B radiation or psoralen plus UV-A radiation (PUVA) for a variety of skin disorders. Although PUVA is generally considered more effective, it is also more toxic and more expensive. The degree of consensus among experts in prescribing these alternative treatments has not been quantified. Objectives: To quantify variation among specialty clinics in the type of ultraviolet therapy used to treat specific skin conditions and assess factors associated with the use of specific treatments. Design: Survey conducted during two 2-week periods in the late fall of 1994 and early spring of 1995. Setting: Thirty-nine specialty clinics in 17 US geographic areas in 14 states and Washington, DC. Participants: A total of 3401 patients treated with UV radiation one or more times. Outcome Measures: Type of UV therapy used and indications for treatment, age, sex, number of patients treated, and geographic location of each clinic. Results: The proportion of patients at each center treated with PUVA ranged from 0% to 93% (mean, 41%). Clinic size and geographic location, demographic characteristics of the patients, and diagnosis did not explain these large intercenter differences. Conclusions: Among specialized clinics, there is little consistency in the use of alternative therapies, which differ substantially in safety and cost, but whose relative efficacy is not well quantified. There is a lack of consensus among experts about the circumstances in which the greater risks and costs of PUVA are outweighed by its possibly greater efficacy, especially in the treatment of psoriasis. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Stern, RS (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. RI Mills, DeEtta/G-8532-2015 OI Mills, DeEtta/0000-0002-9977-7834 NR 10 TC 10 Z9 10 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD OCT PY 1999 VL 135 IS 10 BP 1187 EP 1192 DI 10.1001/archderm.135.10.1187 PG 6 WC Dermatology SC Dermatology GA 244DK UT WOS:000083036400004 PM 10522665 ER PT J AU Kasuga, F Igimi, S Nakayama, M Iwanaga, T Hungerford, JM Machii, K Kumagai, S Jun, L Yanaihara, N AF Kasuga, F Igimi, S Nakayama, M Iwanaga, T Hungerford, JM Machii, K Kumagai, S Jun, L Yanaihara, N TI Characterization of rat sodium channels in neuroendocrine cells using region-specific antibodies SO BIOMEDICAL RESEARCH-TOKYO LA English DT Article ID ADRENAL-MEDULLARY CELLS; CHROMAFFIN CELLS; ALPHA-SUBUNIT; MESSENGER-RNA; BRAIN; SITE; BREVETOXIN; SUBTYPES; LOCALIZATION; EXPRESSION AB Using two anti-peptide antibodies, which recognized a conserved region within subtypes of alpha-subunit of rat sodium channel and a relatively divergent sequence specific to subtype II (R-II), rat sodium channels in neuroendocrine cells were examined. Rat adrenal medulla was stained by both antisera; RY 137, which was raised against peptide corresponding to well-conserved region of alpha-subunit between domain 4 segment 5 (D4S5) and D4S6, stained the nucleus of medulla cells, while RY 143, which was raised against R-II-specific region between D1S6 and D2S1, stained the cellular membrane. Antisera inhibited the cell burst response of mouse neuroblastoma cell line, Neuro-2a, against the combination treatment with ouabain, veratridine and brevetoxin PbTx-1. These results indicate clearly the region-specific antibodies produced in the present study were useful for detection and characterization of sodium channels in rats. C1 Natl Inst Infect Dis, Dept Biomed Food Res, Shinjuku Ku, Tokyo 1628640, Japan. Hokkaido Univ, Grad Sch Vet Med, Lab Anat, Sapporo, Hokkaido 0600810, Japan. US FDA, Seafood Prod Res Ctr, Bothell, WA 98041 USA. Natl Inst Publ Hlth, Dept Vet Publ Hlth, Minato Ku, Tokyo 1088638, Japan. Yanaihara Inst Inc Awakura, Fujinomiya 4180011, Japan. RP Kasuga, F (reprint author), Natl Inst Infect Dis, Dept Biomed Food Res, Shinjuku Ku, Toyama 1-23-1, Tokyo 1628640, Japan. NR 33 TC 0 Z9 0 U1 0 U2 1 PU BIOMEDICAL RESEARCH PRESS LTD PI TOKYO PA 5F KYOWA BLDG, 2-1-3 KYOBASHI, CHUO-KU, TOKYO, 104-0031, JAPAN SN 0388-6107 J9 BIOMED RES-TOKYO JI Biomed. Res. PD OCT PY 1999 VL 20 IS 5 BP 295 EP 300 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 287JE UT WOS:000085502100006 ER PT J AU Thompson, CD Frazier-Jessen, MR Rawat, R Nordan, RP Brown, RT AF Thompson, CD Frazier-Jessen, MR Rawat, R Nordan, RP Brown, RT TI Evaluation of methods for transient transfection of a murine macrophage cell line, RAW 264.7 SO BIOTECHNIQUES LA English DT Article ID LIPOPOLYSACCHARIDE; GENE AB Monocyte/macrophage cell lines are fastidious cells commonly used in transient transfection experiments. In the course (of a study of gene regulation by lipopolysaccharide (LPS), lye have compared several methods for DNA-mediated cell transfection to determine which would be optimally applicable to the macrophage line, RAW 264.7. Both the response level (LPS inducibility) and the degree of inter-assay variation were evaluated for each transfection technique The following methods were compared: LIPOFECTIN(R), LIPOFECTAMINE(TM), LIPOFECTAMINE PLUS(TM), SyperFect(TM), Ca-3(PO4)(2) DNA co-precipitation, DEAE dextran-mediated transfection and electroporation. The transfected plasmid DNA included a luciferase reporter construct containing the junB minimal promoter under the control of an LPS-inducible 1300-bp regulatory fragment downstream of junB 5'-flanking sequence, as well as a beta-galactosidase reporter construct under the adenovirus promoter and enhancer used as an internal control. Electroporation, followed by a resting period of 16-24 h before stimulation with LPS, had the highest inducibility of all methods. DEAE dextran and Ca-3(PO4)(2) precipitation showed the least and the greatest inter-assay variation, respectively. For all other methods, inter-assay variability fell within this range. The results presented may serve as both a general reference and a guide for reporter gene studies in this or other macrophage cell lines. C1 US FDA, CBER, OTRR, Rockville, MD 20852 USA. Univ Maryland, College Pk, MD 20742 USA. RP Thompson, CD (reprint author), US FDA, CBER, OTRR, HFM-564,1401 Rockville Pike, Rockville, MD 20852 USA. NR 5 TC 19 Z9 20 U1 1 U2 4 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD OCT PY 1999 VL 27 IS 4 BP 824 EP + PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 253LE UT WOS:000083557400030 PM 10524325 ER PT J AU Pike, SE Yao, L Setsuda, J Jones, KD Cherney, B Appella, E Sakaguchi, K Nakhasi, H Atreya, CD Teruya-Feldstein, J Wirth, P Gupta, G Tosato, G AF Pike, SE Yao, L Setsuda, J Jones, KD Cherney, B Appella, E Sakaguchi, K Nakhasi, H Atreya, CD Teruya-Feldstein, J Wirth, P Gupta, G Tosato, G TI Calreticulin and calreticulin fragments are endothelial cell inhibitors that suppress tumor growth SO BLOOD LA English DT Article ID INTERFERON-INDUCIBLE PROTEIN-10; ANGIOGENESIS IN-VIVO; NITRIC-OXIDE; POTENT INHIBITOR; BINDING PROTEIN; RECEPTOR; THERAPY; CANCER; THROMBOSPONDIN-1; IDENTIFICATION AB Several angiogenesis inhibitors are fragments of larger proteins that are themselves not active as angiogenesis inhibitors. Vasostatin, the N-terminal domain of calreticulin inclusive of amino acids 1-180, is an angiogenesis inhibitor that exerts antitumor effects in vivo. In the present study, we examined whether the full-length calreticulin molecule shares the antiangiogenic and antitumor activities of vasostatin. Similar to vasostatin, calreticulin selectively inhibited endothelial cell proliferation in vitro, but not cells of other lineages, and suppressed angiogenesis in vivo. When inoculated into athymic mice, calreticulin inhibited Burkitt tumor growth comparably with vasostatin. Calreticulin lacking the N-terminal 1-120 amino acids inhibited endothelial cell proliferation in vitro and Burkitt tumor growth in vivo comparably with vasostatin. An internal calreticulin fragment encompassing amino acids 120-180 also inhibited endothelial cell proliferation in vitro and angiogenesis in vivo comparably with calreticulin and vasostatin. These results suggest that the antiangiogenic activities of vasostatin reside in a domain that is accessible from the full-length calreticulin molecule and localize to calreticulin N-terminal amino acids 120-180, Thus, calreticulin and calreticulin fragments are inhibitors of angiogenesis that directly target endothelial cells, inhibit angiogenesis, and suppress tumor growth. This information may be critical in designing targeted inhibitors of pathological angiogenesis that underlies cancer and other diseases. This is a US government work. There are no restrictions on its use. C1 Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NCI, DBS, Cell Biol Lab, Bethesda, MD USA. NCI, DCS, Pathol Lab, Bethesda, MD USA. NCI, DBS, Expt Carcinogenesis Lab, Bethesda, MD USA. RP Tosato, G (reprint author), Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 41 TC 131 Z9 146 U1 0 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 1999 VL 94 IS 7 BP 2461 EP 2468 PG 8 WC Hematology SC Hematology GA 242HT UT WOS:000082935000035 PM 10498619 ER PT J AU Freudenheim, JL Ambrosone, CB Moysich, KB Vena, JE Graham, S Marshall Jr Muti, P Laughlin, R Nemoto, T Harty, LC Crits, GA Chan, AWK Shields, PG AF Freudenheim, JL Ambrosone, CB Moysich, KB Vena, JE Graham, S Marshall, JR Muti, P Laughlin, R Nemoto, T Harty, LC Crits, GA Chan, AWK Shields, PG TI Alcohol dehydrogenase 3 genotype modification of the association of alcohol consumption with breast cancer risk SO CANCER CAUSES & CONTROL LA English DT Article DE alcohol; alcohol dehydrogenase; breast neoplasms; epidemiology; genetic polymorphisms ID HUMAN-LIVER ALCOHOL; ALDEHYDE DEHYDROGENASES; POSTMENOPAUSAL WOMEN; GENETIC-POLYMORPHISM; PREMENOPAUSAL WOMEN; HUMAN STOMACH; ACETALDEHYDE; ESTROGENS; ETHANOL; PLASMA AB Objectives: Because alcohol dehydrogenase 3 (ADH(3)) is rate-limiting in alcohol oxidation and is polymorphic, we examined ADH(3) genotype in relation to alcohol intake and breast cancer risk. Methods: We conducted a case-control study among Caucasian women aged 40-85 with incident, pathologically confirmed breast cancer and controls, frequency-matched on age and county. Queries included alcohol intake in the past 20 years. Genomic DNA was genotyped for the exon VIII ADH polymorphism by PCR followed by restriction enzyme digestion. Computation of odds ratios (OR) and 95% confidence intervals (CI) was by unconditional logistic regression. Results: We found increased risk among pre- (OR 2.3, 95%, CI 1.2-4.3) but not postmenopausal women (OR 1.1, 95% CI 0.7-1.7) associated with ADH(3)(1-1) compared to ADH(3)(1-2) and ADH(3)(2-2) genotypes. Risk was increased for premenopausal women with the ADH(3)(1-1) genotype and alcohol intake above the median (OR 3.6, 95% CI 1.5-8.8) compared to lighter drinkers with the ADH(3)(2-2) or ADH(3)(1-2) genotypes. ORs were close to null for premenopausal women in other drinking and genotype groups and for postmenopausal women categorized by genotype and alcohol consumption. Conclusion: Among premenopausal women there may be a group more genetically susceptible to an alcohol consumption effect on breast cancer risk. C1 SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Roswell Pk Canc Inst, Buffalo, NY USA. Arizona Canc Ctr, Tucson, AZ USA. SUNY Buffalo, Dept Surg, Buffalo, NY 14260 USA. NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Res Inst Addict, Buffalo, NY USA. RP Freudenheim, JL (reprint author), SUNY Buffalo, Dept Social & Prevent Med, 270 Farber Hall, Buffalo, NY 14214 USA. RI Shields, Peter/I-1644-2012 FU NCI NIH HHS [CA/ES 62995, CA11535] NR 56 TC 63 Z9 64 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD OCT PY 1999 VL 10 IS 5 BP 369 EP 377 DI 10.1023/A:1008950717205 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 237VE UT WOS:000082676100007 PM 10530606 ER PT J AU Guengerich, FP Mundkowski, RG Voehler, M Kadlubar, FF AF Guengerich, FP Mundkowski, RG Voehler, M Kadlubar, FF TI Formation and reactions of N-7-Aminoguanosine and derivatives SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID CARCINOGEN 4-NITROQUINOLINE 1-OXIDE; NUCLEIC-ACIDS; CHEMICAL ALTERATIONS; ELECTROPHILIC AMINATION; ADDUCT FORMATION; AQUEOUS-SOLUTION; CELLULAR DNA; GUANINE; 8-HYDROXY-2'-DEOXYGUANOSINE; MECHANISM AB Arylamines are mutagens and carcinogens and are thought to initiate tumors by forming adducts with DNA. The major adducts are C-8-guanyl, and we have previously suggested a role for guanyl-N-7 intermediates in the formation process. N-7-Aminoguanosine (Guo) was synthesized and characterized, with the position of the NH2 at N7 established by two-dimensional rotating frame Overhauser enhancement NMR spectroscopy. In DMF, N-7-NH(2)Guo formed C-8-NH(2)Guo and the cyclic product C-8:5'-O-cycloGuo. In aqueous media, these products were formed along with 8-oxo-7,8-dihydroGuo, N-7-NH(2)guanine, and a product characterized as a purine 8,9-ring-opened derivative (N-aminoformamidopyrimidine). The rate of aqueous decomposition of N-7-NH(2)Guo increased with pH, with a t(1/2) of 10 h at pH 7 and a t(1/2) of 2 h at pH 9. The rate of migration of NH2 from N7 to C8 is fast enough to explain the formation of C-8-NH(2)Guo from the reaction of 2,4-dinitrophenoxyamine with Guo but not the formation of C-8-(arylamino)Guo in the reaction of Guo with aryl hydroxylamine esters; however, the fluorenyl moiety may facilitate the proposed rearrangement by stabilizing an incipient negative charge in the transfer. In the reaction of Guo with N-hydroxy-2-aminofluorene and acetylsalicylic acid, a peak with the mass spectrum expected for N-7-(2-aminofluorenyl)Guo was detected early in the reaction and was distinguished from C-8-(2-aminofluorenyl)Guo. NMR experiments with [8-C-13]Guo also provided some additional support for transient formation of N-7-(2-aminofluorenyl)Guo. We conclude that a guanyl-N-7 intermediate is reasonable in the reaction of activated arylamines with nucleic acids, although an exact rate of transfer of an N-7-arylamine group to the C8 position has not yet been quantified. The results provide an explanation for the numerous products associated with modification of DNA by activate arylamines. However, the contribution of "direct" reaction at the guanine C8 atom cannot be excluded. C1 Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Ctr Mol Toxicol, Nashville, TN 37232 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Guengerich, FP (reprint author), Vanderbilt Univ, Sch Med, Dept Biochem, 221 Kirkland Hall, Nashville, TN 37232 USA. FU NCI NIH HHS [R35CA44353]; NIEHS NIH HHS [P30ES00267] NR 48 TC 30 Z9 30 U1 1 U2 3 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 OCT PY 1999 VL 12 IS 10 BP 906 EP 916 DI 10.1021/tx990094u PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 248DF UT WOS:000083259500006 PM 10525265 ER PT J AU Singh, GJP Adams, WP Lesko, LJ Shah, VP Molzon, JA Williams, RL Pershing, LK AF Singh, GJP Adams, WP Lesko, LJ Shah, VP Molzon, JA Williams, RL Pershing, LK TI Development of in vivo bioequivalence methodology for dermatologic corticosteroids based on pharmacodynamic modeling SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT 96th Annual Meeting of the American-Society-of-Clinical-Pharmacology-and-Therapeutics CY MAR 15-17, 1995 CL SAN DIEGO, CALIFORNIA SP Amer Soc Clin Pharm & Therapeut ID COMPARATIVE BIO-AVAILABILITY; SKIN BLANCHING ASSAY; BETAMETHASONE DIPROPIONATE; VASOCONSTRICTOR ASSAYS; TOPICAL STEROIDS; P-PHARM; BIOAVAILABILITY AB Background: Dermatologic corticosteroid products produce skin blanching that is related to clinical potency and dose. (For application of the vasoconstrictor assay to bioavailability and bioequivalence assessment, dose is defined in terms of duration of treatment exposure [dose duration], so the terms dose and dose duration have been used interchangeably). The vasoconstrictor assay is the method of choice to assess dermatologic corticosteroid products bioequivalence if dose-response is validated, This article examines dose-response validation to meet objectives of US Food and Drug Administration (PDA) bioequivalence guidance for dermatologic corticosteroid products, Methods: An exploratory dose-response study was conducted to determine applicability of the empirical maximum effect (E-max) model to the individual subject and population dose-response relationships of six dermatologic corticosteroid product creams that varied from the most to the least potent classes. Products were applied to the skin of 10 healthy subjects in each of two dosing periods for dose durations of 0.5, 1, 2, and 6 hours. Skin blanching was measured by reflectance colorimeter through 24 hours after application. Area under the effect curve (AUEC) was determined for each dose duration, An E-max model was fitted to the AUEC versus dose duration data. A similar analysis was conducted for a bioequivalence study on two formulations of a dermatologic corticosteroid product in 40 healthy subjects. Results: In the exploratory study, the number of individual subject data sets for which the E-max model provided an acceptable fit generally increased with the potency of the dermatologic corticosteroid product. On the basis of population modeling, dose-response data of all products, except the lowest potency cream, were adequately described by the E-max model. Values for population ED50 (the dose duration required to achieve 50% of the fitted AUEC(max) value) decreased with increase in dermatologic corticosteroid product potency. Conclusions: Acceptable model fits to all individual subject dose-response data were not achieved for any dermatologic corticosteroid product. However, population dose-responses were adequately described by the E-max model. On the basis of these data, the optimal dose duration used for comparison of multisource dermatologic corticosteroid products is recommended to be equal to the ED50 based on population modeling of pilot dose-response study data. C1 Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA. US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Singh, GJP (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Off Gener Drugs,Div Bioequivalence, 7500 Standish Pl, Rockville, MD 20855 USA. NR 28 TC 20 Z9 22 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD OCT PY 1999 VL 66 IS 4 BP 346 EP 357 DI 10.1053/cp.1999.v66.a101209 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 251XC UT WOS:000083470800005 PM 10546918 ER PT J AU Vela, M Heredia, NL Feng, P Garcia-Alvarado, JS AF Vela, M Heredia, NL Feng, P Garcia-Alvarado, JS TI DNA probe analysis for the carriage of enterotoxigenic Clostridium perfringens in feces of a Mexican subpopulation SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article ID SPORULATION; DIARRHEA; STRAINS; GROWTH AB Clostridium perfringens has been implicated as a causative agent of foodborne poisoning, infectious diarrhea (not associated with foods), gas gangrene, and several veterinary diseases. Fecal carriage of enterotoxigenic strains of this bacterium appears to be important in the development of infections diarrhea and as a source of C. perfringens contamination of foods. In this work, carriage of this bacterium in feces of a Mexican population was analyzed. C. perfringens was found in 126 of the 200 fecal samples obtained from healthy individuals from northern Mexico. The samples had an average of 7.4 x 10(3) spores per gram, with the elderly population showing the highest levels. Dot blot analyses using a dig-labeled probe specific for the enterotoxin gene showed that 7% of the samples had isolates with toxigenic potential. (C) 1999 Elsevier Science Inc. C1 Univ A Nuevo Leon, Fac C Biol, Dept Microbiol & Inmunol, San Nicolas, Mexico. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Garcia-Alvarado, JS (reprint author), Apdo Postal 124-F, San Nicolas 66451, NL, Mexico. RI Garcia, Santos/F-5193-2010 NR 22 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD OCT PY 1999 VL 35 IS 2 BP 101 EP 104 DI 10.1016/S0732-8893(99)00058-9 PG 4 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 248GT UT WOS:000083267300002 PM 10579088 ER PT J AU Calvert, WS Holihan, V AF Calvert, WS Holihan, V TI Pharmaceutical Research and Manufacturers of America Food and Drug Administration cooperation in building capabilities for electronic submission of postmarketing safety data SO DRUG INFORMATION JOURNAL LA English DT Article DE postmarketing; ICH; electronic submission; adverse drug reactions; E2b AB The cooperative efforts of the Food and Drug Administration (FDA) and the pharmaceutical industry in implementing International Council on Harmonization (ICH) guidelines to establish a practical protocol for electronic transfer of individual case safety reports are described. Nonexpedited safety reports were selected as rest material and a multidisciplinary task force guided progress. The issues and problems that were confronted are indicated, along with a summary of how they were overcome. The accomplishments and the unique working style of this task force are highlighted and suggestions are made for future work to consolidate and build upon the success that has been realized. C1 US FDA, Ctr Drug Evaluat & Res, Informat Technol Staff, OPDRA,ITS, Rockville, MD 20857 USA. Schering Plough Corp, PHRMA Task Force, Kenilworth, NJ 07033 USA. RP Calvert, WS (reprint author), US FDA, Ctr Drug Evaluat & Res, Informat Technol Staff, OPDRA,ITS, 5600 Fishers Lane HFD-734,Room 15B23, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU DRUG INFORMATION ASSOCIATION PI FORT WASHINGTON PA 501 OFFICE CENTER DR, STE 450, FORT WASHINGTON, PA 19034-3212 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD OCT-DEC PY 1999 VL 33 IS 4 BP 1093 EP 1099 PG 7 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 256LG UT WOS:000083726300013 ER PT J AU Moody, JD Freeman, JP Cerniglia, CE AF Moody, JD Freeman, JP Cerniglia, CE TI Biotransformation of doxepin by Cunninghamella elegans SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID DEPRESSED-PATIENTS; METABOLITES; IDENTIFICATION; MANAGEMENT AB A filamentous fungus, Cunninghamella elegans ATCC 9245, was used as a microbial model of mammalian metabolism to biotransform doxepin, a tricyclic antidepressant drug. Doxepin is produced as an 85: 15% mixture of the trans- (E) and cis- (Z) forms. After 96 h of incubation in Sabouraud dextrose broth, 28% of the drug was metabolized to 16 metabolites. No change in the trans-(E) and cis-(Z) ratio of doxepin was observed. Metabolites were isolated by reversed phase HPLC and identified by H-1 NMR and mass spectroscopic analysis. The major metabolites were (E)-2-hydroxydoxepin, (E)-3-hydroxydoxepin, (Z)-8-hydroxydoxepin, (E)-2-hydroxy-N-desmethyldoxepin, (E)-3- hydroxy-N-desmethyldoxepin, (E)-4-hydroxy-N-desmethyldoxepin, (Z)- and (E)-8-hydroxy-N-desmethyldoxepin, (E)-N-acetyl- N-desmethyldoxepin, (E)-N-desmethyl-N-formyldoxepin, (E)-N-acetyldidesmethyldoxepin, (E)- and (Z)-doxepin-N-oxide, and (E)- and (Z)-N-desmethyldoxepin. Six of the metabolites produced by C. elegans were essentially similar to those obtained in human metabolism studies, although nine novel metabolites were identified. C1 Natl Ctr Toxicol Res, Div Microbiol, US FDA, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Chem, US FDA, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), Natl Ctr Toxicol Res, Div Microbiol, US FDA, Jefferson, AR 72079 USA. NR 16 TC 23 Z9 26 U1 1 U2 3 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 OCT PY 1999 VL 27 IS 10 BP 1157 EP 1164 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 241BG UT WOS:000082861700009 PM 10497142 ER PT J AU Flurer, CL AF Flurer, CL TI Analysis of antibiotics by capillary electrophoresis SO ELECTROPHORESIS LA English DT Review DE capillary electrophoresis; antibiotics; review ID MICELLAR ELECTROKINETIC CHROMATOGRAPHY; PERFORMANCE LIQUID-CHROMATOGRAPHY; LASER-INDUCED FLUORESCENCE; ZONE-ELECTROPHORESIS; MIGRATION BEHAVIOR; HUMAN PLASMA; SEPARATION; SULFONAMIDES; OXYTETRACYCLINE; SUBSTANCES AB The broad category of antibiotics encompasses some of the most widely prescribed pharmaceuticals in the world. As is the case with any pharmaceutical, an antibiotic must be characterized in terms of its potency and the presence and quantity of impurities. Additionally, any residue or metabolite that may be present as a result of its use must be monitored. Many capillary electrophoretic techniques have been utilized in the analysis of antibiotics, addressing the various aspects of quantifying, profiling, and monitoring. Some of the more recent applications are summarized in this review article. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Flurer, CL (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. NR 37 TC 19 Z9 20 U1 0 U2 6 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD OCT PY 1999 VL 20 IS 15-16 BP 3269 EP 3279 DI 10.1002/(SICI)1522-2683(19991001)20:15/16<3269::AID-ELPS3269>3.0.CO;2-3 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 279LC UT WOS:000085044400019 PM 10596829 ER PT J AU Cooper, GS Miller, FW Pandey, JP AF Cooper, GS Miller, FW Pandey, JP TI The role of genetic factors in autoimmune disease: Implications for environmental research SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Workshop on Linking Environmental Agents to Autoimmune Diseases CY SEP 01-03, 1998 CL RES TRIANGLE PK, NORTH CAROLINA SP NIH, Off Rare Dis, NIH, Off Res Womens Hlth, NIH, NIEHS, NIH, NIAID, NIH, NIDDK, NIH, NIAMS, US EPA, Amer Autoimmune Related Dis Assoc Inc, Juvenile Diaabetes Fdn Int DE autoimmune diseases; gene-environment interactions; genetics; major histocompatibility complex; multiple sclerosis; rheumatoid arthritis; systemic lupus erythematosus; type I diabetes mellitus ID SYSTEMIC LUPUS-ERYTHEMATOSUS; DEPENDENT DIABETES-MELLITUS; EOSINOPHILIA-MYALGIA-SYNDROME; MAJOR HISTOCOMPATIBILITY COMPLEX; PRIMARY SJOGRENS-SYNDROME; DRUG-INDUCED LUPUS; 3 ETHNIC-GROUPS; HLA CLASS-II; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS AB Studies in both humans and in animal models of specific disorders suggest that polymorphisms of multiple genes are involved in conferring either a predisposition to or protection from autoimmune diseases. Genes encoding polymorphic proteins that regulate immune responses or the rates and extent of metabolism of certain chemical structures have been the focus of much of the research regarding genetic susceptibility. We examine the type and strength of evidence concerning genetic factors and disease etiology, drawing examples from a number of autoimmune diseases. Twin studies of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type I diabetes, and multiple sclerosis (MS) indicate that disease concordance in monozygotic twins is 4 or more times higher than in dizygotic twins. Strong familial associations (odds ratio ranging from 5-10) are seen in studies of MS, type I diabetes, Graves disease, discoid lupus, and SLE. Familial association studies have also reported an increased risk of several systemic autoimmune diseases among relatives of patients with a systemic autoimmune disease. This association may reflect a common etiologic pathway with shared genetic or environmental influences among these diseases. Recent genomewide searches in RA, SLE, and MS provide evidence for multiple susceptibility genes involving major histocompatibility complex (MHC) and non-MHC loci; there is also evidence that many autoimmune diseases share a common set of susceptibility genes. The multifactorial nature of the genetic risk factors and the low penetrance of disease underscore the potential influence of environmental factors and gene-environment interactions on the etiology of autoimmune diseases. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. US FDA, Lab Mol & Dev Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch, A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. OI Miller, Frederick/0000-0003-2831-9593 NR 117 TC 69 Z9 71 U1 0 U2 4 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1999 VL 107 SU 5 BP 693 EP 700 DI 10.2307/3434329 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 246XP UT WOS:000083190400008 PM 10502533 ER PT J AU Schwetz, BA AF Schwetz, BA TI Responding to environmental issues: Lessons learned SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material ID BREAST-CANCER; CHEMICALS C1 US FDA, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Rockville, MD 20857 USA. EM bschwetz@oc.fda.gov NR 18 TC 0 Z9 0 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1999 VL 107 IS 10 BP A488 EP A489 DI 10.2307/3454554 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 246BR UT WOS:000083143700001 PM 10504155 ER PT J AU Hayward, DG Nortrup, D Gardner, A Clower, M AF Hayward, DG Nortrup, D Gardner, A Clower, M TI Elevated TCDD in chicken eggs and farm-raised catfish fed a diet with ball clay from a southern United States mine SO ENVIRONMENTAL RESEARCH LA English DT Article ID DIBENZO-P-DIOXIN; POLYCHLORINATED DIBENZOFURANS; HUMAN EXPOSURE; SAMPLES; PCDDS; PCDFS; CONTAMINATION; FOOD; INCINERATION; PATTERNS AB The U.S. Food and Drug Administration (FDA) terminated the use of ball clay from a mine in Mississippi as an additive in animal feed after discovering nanogram per gram concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). The FDA collected chicken eggs and farm-raised catfish in affected areas and throughout the remaining continental United States to assess levels of 2,3,7,8-TCDD. A new method using quadrupole ion storage tandem-in-time mass spectrometry (QISTMS) measured the 2,3,7,8-TCDD levels in 42 catfish fillet composites, 3 Tilapia fillet composites, 46 chicken egg samples, and 6 chicken feeds. Six catfish composites and 20 egg samples had 2,3,7,8-TCDD concentrations significantly above 1.0 pg/g wet weight of fillet or whole egg. Farm-raised catfish not exposed to feed containing ball clay had a mean 2,3,7,8-TCDD concentration of 0.12 pg/g. The TCDD isomer pattern in ball clay differed from the TCDD isomer pattern in a fly ash sample and from the "chick edema factor" TCDD pattern in a sample of reference toxic fat used as a feed ingredient in the 1950s. C1 US FDA, Washington, DC 20204 USA. RP Hayward, DG (reprint author), US FDA, 200 C St SW, Washington, DC 20204 USA. NR 39 TC 56 Z9 57 U1 2 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD OCT PY 1999 VL 81 IS 3 BP 248 EP 256 DI 10.1006/enrs.1999.3976 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 246BF UT WOS:000083142700009 PM 10585021 ER PT J AU Cook, KK Mitchell, GV Grundel, E Rader, JI AF Cook, KK Mitchell, GV Grundel, E Rader, JI TI HPLC analysis for trans-vitamin K-1 and dihydro-vitamin K-1 in margarines and margarine-like products using the C-30 stationary phase SO FOOD CHEMISTRY LA English DT Article DE trans-vitamin K-1; dihydro-vitamin K-1; margarines; margarine-like products; C30 stationary phase ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CAROTENOID ISOMERS; DIETARY-INTAKE; PHYLLOQUINONE; OILS; DIHYDRO-VITAMIN-K-1; MENAQUINONE-4; SEPARATION AB A C-30 column successfully separated the cis and trans isomers of vitamin K-1 in margarines, reduced-fat margarine-like products and in their ingredient oils. We also measured the compound 2'3'-dihydro-vitamin K-1, a derivative formed during hydrogenation of oils containing vitamin K-1. We compared an enzymatic procedure, currently under AOAC collaborative study for milk and infant formulas, with a more direct extraction method in analyzing margarines and margarine-like products. Both methods have good precision and were applicable to the majority of products examined. Margarines or margarine-like products identifying liquid soybean oil, hydrogenated soybean oil or liquid canola oil as their primary ingredients contained about 50-160 mu g vitamin K-1/100 g. Blends of sunflower and soybean oils contained < 50 mu g vitamin K-1/100 g. Hardened or "stick" margarines contained more 2'3'-dihydro-vitamin K-1 than "soft" or "tub" products (122-285 mu g/100 g vs 38-131 mu g/100 g, respectively). Eight of 18 products (44%) contained 10% or more of the Reference Daily Intake for vitamin K-1 per serving. Higher-fat margarines contained more vitamin K-1 than their lower-fat counterparts. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Food Labeling, Washington, DC 20204 USA. RP Rader, JI (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Labeling, 200 C St SW, Washington, DC 20204 USA. NR 24 TC 24 Z9 24 U1 2 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0308-8146 J9 FOOD CHEM JI Food Chem. PD OCT PY 1999 VL 67 IS 1 BP 79 EP 88 DI 10.1016/S0308-8146(99)00090-4 PG 10 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 220NY UT WOS:000081673100013 ER PT J AU Buchanan, RL Bagi, LK AF Buchanan, RL Bagi, LK TI Microbial competition: effect of Pseudomonas fluorescens on the growth of Listeria monocytogenes SO FOOD MICROBIOLOGY LA English DT Article ID CARNOBACTERIUM-PISCICOLA LK5; SODIUM-CHLORIDE; MODIFIED ATMOSPHERES; SPOILAGE BACTERIA; PRECOOKED CHICKEN; SCOTT-A; TEMPERATURE; MILK; PH; 13-DEGREES-C AB Listeria monocytogenes Scott A was cultured alone and in coculture with Pseudomonas fluorescens ATCC 33231 to characterize quantitatively the effects of microbial competition on the growth of this psychrotrophic pathogen. The bacteria were cultured in brain-heart infusion broth (BHI), using a 3 x 3 x 3 x 2 complete factorial design to assess the impact of temperature (4, 12, 19 degrees C) initial pH (5.0, 6.0,7.0) and sodium chloride content (5, 25, 45 gl(-1)) on the interaction between the two microorganisms. Samples were periodically plated on BHI agar and Vogel Johnson agar to obtain total counts and L. monocytogenes counts, respectively. Growth curves were generated by fitting the data to the Gompertz equation and the derived growth kinetics were compared. When P. fluorescens did influence the growth of L. monocytogenes, the primary effect was a suppression of the maximum population density (MPD) reached by the pathogen. Suppression of L. monocytogenes was generally associated with low incubation temperatures (4 degrees C) and sodium chloride levels (5 and 25 gl(-1)) Slight increases (< 1.0 log cfu ml(-1) in the MPD attained by L. monocytogenes were observed when grown in the presence of P. fluorescens at higher temperatures (12 and 19 degrees C) and sodium chloride levels (25 and 45 gl(-1) when the pH was 5.0. The current study supports earlier work that indicates that reliance on microbial competition as a barrier to control L. monocytogenes in refrigerated foods will require detailed knowledge of how the interaction between the pathogen and the microflora is affected by environmental and food characteristics such as storage temperature, pH, and water activity. (C) 1999 Academic Press. C1 USDA ARS, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. RP Buchanan, RL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 22 TC 48 Z9 49 U1 3 U2 14 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD OCT PY 1999 VL 16 IS 5 BP 523 EP 529 DI 10.1006/fmic.1998.0264 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 250NU UT WOS:000083395100011 ER PT J AU Windsor, RA Li, CQ Boyd, NR Hartmann, KE AF Windsor, RA Li, CQ Boyd, NR Hartmann, KE TI The use of significant reduction rates to evaluate health education methods for pregnant smokers: A new harm reduction behavioral indicator? SO HEALTH EDUCATION & BEHAVIOR LA English DT Article; Proceedings Paper CT 1995 National Conference on Smoking Cessation - Alternative Strategies CY 1995 CL JOHNS HOPKINS UNIV, BALTIMORE, MARYLAND HO JOHNS HOPKINS UNIV ID SMOKING CESSATION METHODS; BIRTH-WEIGHT; MATERNAL SMOKING; 2000 OBJECTIVES; COST-BENEFIT; WOMEN; COTININE; IMPACT; TRIAL; DISSEMINATION AB This article evaluates the evidence to support the use of biochemical measurement of significant reduction (SR) rates among pregnant smokers as a new behavioral indicator of "harm reduction" (HR). The results of four studies-three randomized patient education clinical trials of pregnant smokers (Trials I, II. and III) and an epidemiological study (Study IV)-are presented. Among Trial I, II, and III cohorts of pregnant smokers, control group SR rates of 7% (I), 9% (II), and 20% (III) were increased among experimental groups to 17% (I), 18% (II), and 32% (III) by the same patient education methods. Analyses of infant birthweight data in Study IV found that a patient SR rate representing a 50% or more decrease between a baseline and follow-up test was associated with an increase in adjusted birthweight of 92 grams. C1 Univ Alabama, Smoke Free Families Natl Program Off, Dept Obstet Gynecol, Sch Med,Robert Wood Johnson Fdn, Birmingham, AL 35233 USA. Univ Alabama, Dept Human Studies, Birmingham, AL USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Personal Improvement Comp Syst Inc, Reston, VA USA. Univ N Carolina, Chapel Hill, NC USA. RP Windsor, RA (reprint author), Univ Alabama, Smoke Free Families Natl Program Off, Dept Obstet Gynecol, Sch Med,Robert Wood Johnson Fdn, OHB 560, Birmingham, AL 35233 USA. NR 40 TC 32 Z9 32 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD OCT PY 1999 VL 26 IS 5 BP 648 EP 662 DI 10.1177/109019819902600506 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 236UD UT WOS:000082616800005 PM 10533170 ER PT J AU Kawai, HF Furuke, K Gagneten, S Kaneko, S Harris, C Feinstone, SM AF Kawai, HF Furuke, K Gagneten, S Kaneko, S Harris, C Feinstone, SM TI Hepatitis C virus core protein confers growth advantage and specific protection from TNF-alpha mediated cell death on immortalizednormal human hepatocyte cell line but does not change cell cycle profile nor NF-kappa B activation status. SO HEPATOLOGY LA English DT Meeting Abstract C1 Kanazawa Univ, Sch Med, Kanazawa, Ishikawa 920, Japan. US FDA, Bethesda, MD 20014 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 SU S MA 619 BP 315A EP 315A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700616 ER PT J AU Arichi, T Saito, T Major, ME Shirai, M Engelhard, VH Feinstone, SM Berzofsky, JA AF Arichi, T Saito, T Major, ME Shirai, M Engelhard, VH Feinstone, SM Berzofsky, JA TI A DNA vaccine as a prophylaxis for hepatitis C virus (HCV) infection. HCV specific CTL induction and protection from HCV-recombinant vaccinia infection in an HLA-A2.1 transgenic mouse model. SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20014 USA. Univ Virginia, Charlottesville, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 SU S MA 994 BP 409A EP 409A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700994 ER PT J AU Hsia, CC Scudamore, CH Di Bisceglie, AM Momosaki, S Tabor, E AF Hsia, CC Scudamore, CH Di Bisceglie, AM Momosaki, S Tabor, E TI Silent hepatitis B virus in HBsAg-seronegative hepatocellular carcinoma patients. SO HEPATOLOGY LA English DT Meeting Abstract C1 Vancouver Gen Hosp, Vancouver, BC, Canada. St Louis Univ, St Louis, MO 63103 USA. US FDA, CBER, OBRR, DTTD, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 SU S MA 1121 BP 441A EP 441A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794701119 ER PT J AU Arichi, T Major, M Wedemeyer, H Nascimbeni, M Gagneten, S Kolykhalov, AA Berzofsky, JA Rice, CM Feinstone, SM Rehermann, B AF Arichi, T Major, M Wedemeyer, H Nascimbeni, M Gagneten, S Kolykhalov, AA Berzofsky, JA Rice, CM Feinstone, SM Rehermann, B TI A vigorous HCV-helicase specific T helper response dominates in the liver of a chimpanzee during acute, self-limited hepatitis C SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NIDDK, LDS, NIH, Bethesda, MD USA. Washington Univ, St Louis, MO 63130 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 SU S MA 1171 BP 453A EP 453A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794701168 ER PT J AU An, S Kawai, H Berry, C Feinstone, SM He, XS Brown, PO Greenberg, HB AF An, S Kawai, H Berry, C Feinstone, SM He, XS Brown, PO Greenberg, HB TI Analysis of differential gene expression at the response of human liver cells to hepatitis C virus core protein expression SO HEPATOLOGY LA English DT Meeting Abstract C1 Stanford Univ, Sch Med, Stanford, CA 94305 USA. US FDA, Bethesda, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 SU S MA 1405 BP 512A EP 512A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794701403 ER PT J AU Gao, G Buskell-Bales, Z Seeff, LB Tabor, E AF Gao, G Buskell-Bales, Z Seeff, LB Tabor, E TI Changes in the hypervariable region in isolates of the hepatitis C virus from one patient over a two-year interval. SO HEPATOLOGY LA English DT Meeting Abstract C1 US FDA, CBER, DTTD, OBRR, Rockville, MD 20857 USA. Vet Adm Med Ctr, Washington, DC 20422 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 SU S MA 1726 BP 592A EP 592A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794701722 ER PT J AU Choi, JY Park, JM Kim, BS Tabor, E AF Choi, JY Park, JM Kim, BS Tabor, E TI Detection of CpG methylation in portions of the hepatitis B virus genome in patients with chronic hepatitis B infection. SO HEPATOLOGY LA English DT Meeting Abstract C1 Catholic Univ, Coll Med, Dept Internal Med, Seoul, South Korea. US FDA, Bethesda, MD 20014 USA. US FDA, CBER, OBRR, DTTD, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 SU S MA 1908 BP 637A EP 637A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794701903 ER PT J AU Momosaki, S Hsia, C Nakashima, Y Kojiro, M Tabor, E AF Momosaki, S Hsia, C Nakashima, Y Kojiro, M Tabor, E TI Silent hepatitis B virus infection in hepatitis C virus-associated hepatocellular carcinoma in Japan. SO HEPATOLOGY LA English DT Meeting Abstract C1 US FDA, Bethesda, MD 20014 USA. Kurume Univ, Dept Pathol, Kurume, Fukuoka 830, Japan. US FDA, CBER, OBRR, DTTD, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 SU S MA 1907 BP 637A EP 637A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794701901 ER PT J AU Park, YM Tabor, E Kim, BS AF Park, YM Tabor, E Kim, BS TI Mutations of precore and proximal core regions of hepatitis B virus genome in serum of hepatocellular carcinoma patients SO HEPATOLOGY RESEARCH LA English DT Article DE HBV; mutant HBV; precore gene mutation; core gene mutation; HCC ID NUCLEOTIDE-SEQUENCE ANALYSIS; CHRONIC ACTIVE HEPATITIS; FULMINANT-HEPATITIS; E-ANTIGEN; LIVER-TRANSPLANTATION; ACUTE EXACERBATION; RECURRENT DISEASE; CHRONIC INFECTION; HBV VARIANTS; MUTANT AB In the present study, genetic alterations of the precore and proximal core regions (codons 1-50) were determined in HBV isolated from the serum of 58 patients with HCC and hepatitis B surface antigen (HBsAg) in their serum to identify any role of such genetic changes in HBV genome for hepatocarcinogenesis. DNA extracted from the serum of 16 patients with chronic hepatitis B but no HCC were used as controls. In HCC patients, mutations of T-1846, C-1858, A(1896), and A(1899) were identified in 48, 5, 86 and 36%, respectively. A(1896) mutation is associated with T-1846 and A(1899) mutations more frequently in HCC patients than in chronic hepatitis B patients. Fourteen mutations of the proximal core region in HBV genomes from HCC patients were observed in codons 5, 13, 21, 22, 26, 27, 31, 35 and 41. The median number of mutations in the proximal core gene was 7 from HBeAg-negative HCCs, 5 in HBeAg-positive HCCs, and 4 in patients with chronic hepatitis B without HCC. These results suggest that mutations of the precore and proximal core gene sequences may preferentially occur in specific nucleotides and the continuous replication of such mutant HBV might play a role in HBV-related hepatocarcinogenesis. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 NCI, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Transfus Transmitted Dis, Bethesda, MD USA. Kangnam St Marys Hosp, Dept Internal Med, Seoul 137040, South Korea. Catholic Univ Korea, Coll Med, WHO,Seocho Ku, Collaborating Ctr Reference & Res Viral Hepatitis, Seoul 137040, South Korea. RP Park, YM (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 38 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1386-6346 J9 HEPATOL RES JI Hepatol. Res. PD OCT PY 1999 VL 16 IS 1 BP 49 EP 58 DI 10.1016/S1386-6346(99)00038-8 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 247BF UT WOS:000083200200006 ER PT J AU Tiffany, LJ Garcia-Ojeda, PA Stein, KE AF Tiffany, LJ Garcia-Ojeda, PA Stein, KE TI Determination of the IgG2a allotype of CXB recombinant inbred mouse strains by a PCR-based method SO IMMUNOGENETICS LA English DT Article DE immunoglobulin; allotype; recombinant inbred strains; IgG2a; mouse ID GENES; ALLELES; FAMILY; LOCUS C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. RP Stein, KE (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, 29 Lincoln Dr, Bethesda, MD 20892 USA. NR 11 TC 3 Z9 3 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 OCT PY 1999 VL 50 IS 1-2 BP 71 EP 73 DI 10.1007/s002510050688 PG 3 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 249GP UT WOS:000083325200010 PM 10541809 ER PT J AU Goeckeritz, BE Flora, M Witherspoon, K Vos, Q Lees, A Dennis, GJ Pisetsky, DS Klinman, DM Snapper, CM Mond, JJ AF Goeckeritz, BE Flora, M Witherspoon, K Vos, Q Lees, A Dennis, GJ Pisetsky, DS Klinman, DM Snapper, CM Mond, JJ TI Multivalent cross-linking of membrane Ig sensitizes murine B cells to a broader spectrum of CpG-containing oligodeoxynucleotide motifs, including their methylated counterparts, for stimulation of proliferation and Ig secretion SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE antibodies; B lymphocytes; cellular activation; CpG; oligodeoxynucleotides; rodent; spleen ID BACTERIAL-DNA; SYNTHETIC OLIGONUCLEOTIDES; MONOCLONAL-ANTIBODIES; INDEPENDENT ANTIGENS; AUTOIMMUNE-DISEASE; INTERFERON-GAMMA; ACTIVATION; INDUCTION; INTERLEUKIN-12; IMMUNOGLOBULIN AB We have previously reported that a cells that are activated by multivalent but not bivalent membrane Ig cross-linking ligands synergize with various B cell activators culminating in enhanced B cell proliferation, In this study we asked whether a cells that are activated by a multivalent mig cross-linking agonist could respond to oligodeoxynucleotides (ODN) containing non-stimulatory motifs, Earlier reports have shown that ODN containing a CpG motif in which the cytosine is unmethylated and is flanked by two 5' purines and two 3' pyrimidines induce high levels of B cell activation, while ODN whose CpG are methylated or flanked by sequences other than the optimal two 5' purines and two 3' pyrimidines were non-stimulatory. In this manuscript we show that when B cells are stimulated in vitro with dextran-conjugated anti-IgD antibodies (anti-IgD-dex), as the multivalent mig ligand, their proliferation is enhanced and they can be induced to secrete Ig in response to ODN containing various non-optimal motifs, both methylated and non-methylated, Furthermore we could induce synergistic levels of proliferation with concentrations of anti-IgD-dex that were in the picomolar concentration range and with concentrations of ODN that were 10- to 100-fold less than previously reported to be necessary for mitogenic activity, These data provided a model to explain how low concentrations of a multi-epitope-expressing microorganism in the context of mammalian (methylated) or microorganism (non-methylated) DNA can lead to dysregulated B cell proliferation and Ig secretion. C1 Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Biomed Instrumentat Ctr, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Dept Med, Rheumatol Serv, Washington, DC 20307 USA. Duke Univ, Med Ctr, Durham Vet Adm Hosp, Med Res Serv,Div Immunol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Durham Vet Adm Hosp, Med Res Serv,Div Rheumatol & Immunol, Durham, NC 27710 USA. US FDA, Ctr Biol Evaluat, Retroviral Immunol Sect, Bethesda, MD 20892 USA. RP Goeckeritz, BE (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, Room A3060, Bethesda, MD 20814 USA. FU NIAID NIH HHS [AI36588] NR 27 TC 43 Z9 45 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD OCT PY 1999 VL 11 IS 10 BP 1693 EP 1700 DI 10.1093/intimm/11.10.1693 PG 8 WC Immunology SC Immunology GA 246KE UT WOS:000083162300012 PM 10508187 ER PT J AU Low, NH McLaughlin, M Hofsommer, HJ Hammond, DA AF Low, NH McLaughlin, M Hofsommer, HJ Hammond, DA TI Capillary gas chromatographic detection of invert sugar in heated, adulterated, and adulterated and heated apple juice concentrates employing the equilibrium method SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE authenticity; apple juice; invert sugar ID ORANGE JUICE AB The equilibrium method is introduced for the detection of invert sugar addition to apple juice. The method consists of a pre-equilibration of the sample with dry pyridine at 50 degrees C for 20 min followed by the addition of trimethylsilylimidazole and heating at 75 degrees C for 40 min. The resulting derivatized carbohydrates are then analyzed by capillary gas chromatography. This method was successfully used by independent laboratories to distinguish heated pure, intentionally adulterated (with invert sugar), and intentionally adulterated and then heated apple juice concentrates. The equilibrium method was shown to give significantly lower coefficients of variation for this sample set when compared to the original capillary gas chromatographic method. In addition, these results indicate that it may also be an effective method for the detection of medium invert sugar, depending on the level of the fingerprint oligosaccharides in this sweetener. C1 Univ Saskatchewan, Dept Appl Microbiol & Food Sci, Saskatoon, SK S7N 5A8, Canada. US FDA, Washington, DC USA. GfL, Berlin, Germany. Reading Sci Serv Ltd, Reading, Berks, England. RP Low, NH (reprint author), Univ Saskatchewan, Dept Appl Microbiol & Food Sci, Saskatoon, SK S7N 5A8, Canada. NR 11 TC 14 Z9 15 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD OCT PY 1999 VL 47 IS 10 BP 4261 EP 4266 DI 10.1021/jf990457w PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 247VR UT WOS:000083242100052 PM 10552799 ER PT J AU Huang, SM Lesko, LJ Williams, RL AF Huang, SM Lesko, LJ Williams, RL TI Assessment of the quality and quantity of drug-drug interaction studies in recent NDA submissions: Study design and data analysis issues SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT 99th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 30-APR 01, 1998 CL NEW ORLEANS, LOUISIANA SP Amer Soc Clin Pharmacol & Therapeut ID IMMUNODEFICIENCY-VIRUS PROTEASE; TERFENADINE; PHARMACOKINETICS; KETOCONAZOLE; ERYTHROMYCIN; INHIBITORS; MIBEFRADIL; RITONAVIR AB This report investigates the quality and quantity of drug-drug interaction studies in recent new drug applications (NDAs). Eighty-nine studies contained in 14 NDAs submitted between December 1995 and November 1996 to the U.S. Food and Drug Administration (FDA) were reviewed. The results indicated that the median number of clinical drug-drug interaction studies per NDA was 6, almost double that of a 1994-1995 survey: In vitro metabolism data were present in 70% of the submissions. More than 50% of the submissions contained interaction studies using a battery of drugs (cimetidine, digoxin, or warfarin) without optimal use of the in vitro metabolism or in vivo mass balance data. Various study designs using a median number of 12 subjects were employed in the evaluation of drug-drug interactions. Some of the important study design factors such as dose size, dosing regimen, dosing duration, and timing of coadministration were considered, although not consistently by the sponsors in their study design. Seventy-five percent of the studies used normal, healthy male subjects, and 25% used patients for whom the new molecular entities were intended in 33% of the studies, female subjects were also recruited Although the majority (80%) of the submissions still used p-values to determine the significance of drug interactions, 30% used a more relevant equivalence approach with 90% confidence intervals for key pharmacokinetic and/or pharmacodynamic parameter ratios to assess the extent of drug interactions. Overall, 82% of the studies concluded no interaction. Although population pharmacokinetic analysis can be a useful tool in studying drug-drug interactions, only 21% of the submissions used this approach. In summary, this assessment reveals that the quantity and qualify of drug-drug interaction studies in NDAs have improved over the pears. These improvements, as wen as others that can be implemented should result in more informative labeling and better patient care. FDA guidance for industry dealing with the design, analysis, and labeling language of in vivo metabolic drug-drug interactions has been developed to assist sponsors and FDA reviewers with these issues. Journal of Clinical Pharmacology 1999;39:1006-1014 (C)1999 the American College of Clinical Pharmacology. C1 US FDA, OPS, CDER, Rockville, MD 20852 USA. US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20852 USA. RP Huang, SM (reprint author), US FDA, OPS, CDER, HFD-850,WOC-2,Rm 3016,1451 Rockville Pike, Rockville, MD 20852 USA. NR 37 TC 44 Z9 46 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD OCT PY 1999 VL 39 IS 10 BP 1006 EP 1014 DI 10.1177/00912709922011764 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 239RM UT WOS:000082783500002 PM 10516934 ER PT J AU Reddy, NR Solomon, HM Rhodehamel, EJ AF Reddy, NR Solomon, HM Rhodehamel, EJ TI Comparison of margin of safety between sensory spoilage and onset of Clostridium botulinum toxin development during storage of modified atmosphere (MA)-packaged fresh marine cod fillets with MA-packaged aquacultured fish fillets SO JOURNAL OF FOOD SAFETY LA English DT Article ID NONPROTEOLYTIC TYPE-B; SHELF-LIFE EXTENSION; SALMON FILLETS; GROWTH; VACUUM; RISK AB The margin of safety between shelf-life (onset of sensory spoilage) and potential time to toxin production by Clostridium botulinum type E in retail type packages of fresh marine cod fillets packaged in high barrier film under selected atmospheres [100% air, a modified atmosphere (MA) containing 75% CO2:25% N-2, and vacuum] and stored under refrigeration (4C) and temperature-abuse conditions (8 and 16C) was investigated. Margin of safety data of MA-packaged marine cod fillets was also compared with MA-packaged aquacultured tilapia, catfish, and salmon fillets. Sensory spoilage preceded onset of toxin presence for the marine cod fillets packaged in any of the atmospheres and storage temperatures tested. At BC, none of the marine cod fillets packaged in either atmosphere developed toxin, even 20 days after spoilage, as determined by sensory characteristics. During storage at refrigeration and mild (BC) temperature-abuse conditions MA-packaged marine cod showed a greater margin of safety compared to aquacultured tilapia, catfish, and salmon packaged under the same atmospheres and conditions. Fat content appeared to potentially influence the margin of safety in MA-packaged aquacultured fresh fish fillets during storage. C1 US FDA, Div Food Proc & Packaging, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. US FDA, Div Microbiol Studies, Washington, DC 20204 USA. Cryovac Sealed Air Corp, Duncan, SC 29334 USA. RP Reddy, NR (reprint author), US FDA, Div Food Proc & Packaging, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. NR 21 TC 13 Z9 14 U1 0 U2 1 PU FOOD NUTRITION PRESS INC PI TRUMBULL PA 6527 MAIN ST, P O BOX 374, TRUMBULL, CT 06611 USA SN 0149-6085 J9 J FOOD SAFETY JI J. Food Saf. PD OCT PY 1999 VL 19 IS 3 BP 171 EP 183 DI 10.1111/j.1745-4565.1999.tb00243.x PG 13 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 258AM UT WOS:000083815900002 ER PT J AU Trepka, MJ Archer, JR Altekruse, SF Proctor, ME Davis, JP AF Trepka, MJ Archer, JR Altekruse, SF Proctor, ME Davis, JP TI An increase in sporadic and outbreak-associated Salmonella enteritidis infections in Wisconsin: The role of eggs SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID UNITED-STATES; PHAGE TYPE-4; CONSUMPTION; RESTAURANT; EXPERIENCE; COUNTY AB In Wisconsin, reported Salmonella enterica serotype enteritidis (SE) infections during 1997 more than doubled compared with the previous 9 years. A case-control study was conducted to determine risk factors for sporadic infections, and results of outbreak investigations were reviewed. Eating raw eggs (matched odds ratio [MOR] = 14.5; 95% confidence interval [CI], 1.7-591.6), eating raw or undercooked eggs (MOR = 5.8; 95% CI, 1.3-28.0), eating any eggs (MOR = 4.2; 95% CI, 1.2-16.2), and dining at a restaurant (MOR = 4.7; 95% CI, 1.4-18.4) were associated with infection in the case-control study. For 3 of the 8 outbreaks, a probable source was identified, in each instance, foods containing eggs. Human infections decreased after eggs were diverted from implicated flocks. This epidemic demonstrates the continuing need for quality assurance on egg farms and enhanced education of consumers and commercial food preparers regarding safe handling of eggs. C1 Wisconsin Div Publ Hlth, Bur Communicable Dis, Madison, WI 53703 USA. Ctr Dis Control & Prevent, Epidem Intelligence Serv, State Branch,Div Appl Publ Hlth Training, Epidemiol Program Off,Natl Ctr Infect Dis, Atlanta, GA USA. Ctr Dis Control & Prevent, US FDA, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis,Natl Ctr Infect Dis, Atlanta, GA USA. RP Davis, JP (reprint author), Wisconsin Div Publ Hlth, Bur Communicable Dis, 1414 E Washington Ave,Room 241, Madison, WI 53703 USA. NR 18 TC 30 Z9 31 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 1999 VL 180 IS 4 BP 1214 EP 1219 DI 10.1086/314984 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 243WB UT WOS:000083019500036 PM 10479150 ER PT J AU Hart, PH Bonder, CS Balogh, J Dickensheets, HL Donnelly, RP Finlay-Jones, JJ AF Hart, PH Bonder, CS Balogh, J Dickensheets, HL Donnelly, RP Finlay-Jones, JJ TI Differential responses of human monocytes and macrophages to IL-4 and IL-13 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE alpha chain; gamma chain; inflammatory cells ID RECEPTOR GAMMA-CHAIN; SYNOVIAL-FLUID MACROPHAGES; INTERLEUKIN (IL)-13 BINDING; INFLAMMATORY BOWEL-DISEASE; FUNCTIONAL COMPONENT; BLOOD MONOCYTES; ALPHA CHAIN; SIGNAL-TRANSDUCTION; IFN-GAMMA; EXPRESSION AB The primary interleukin-4 (IL-4) receptor complex on monocytes (type I IL-4 receptor) includes the 140-kDa alpha chain (IL-4 R alpha) and the IL-2 receptor gamma chain, gamma(c), which heterodimerize for intracellular signaling, resulting in suppression of lipopolysaccharide (LPS)-inducible inflammatory mediator production, The activity of IL-13 on human monocytes is very similar to that of IL-4 because the predominant signaling chain (IL-4R alpha) is common to both receptors, In fact, IL-4R alpha. with IL-13R alpha 1 is designated both as an IL-13 receptor and the type II IL-4 receptor. When the antiinflammatory activities of IL-4 and IL-13 were investigated on synovial fluid macrophages and compared with the responses by monocytes isolated from the patients at the same time as joint drainage, the response profiles differed with some responses similar in the two cell populations, others reduced on the inflammatory cells. Similar differences were recorded in the response profiles to IL-P and IL-13 by monocytes and monocytes cultured for 7 days in macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage CSF (GM-CSF) (monocyte-derived macrophages, MDMac), MDMac have reduced gamma(c) mRNA levels and reduced expression of the functional 64-kDa gamma(c), There was a similar loss of IL-13R alpha 1 mRNA on monocyte differentiation. In turn, there was a significant reduction in the ability of IL-4 and IL-13 to activate STAT6, These findings suggest that different functional responses to IL-4 and IL-13 by human monocytes and macrophages may result from reduced expression of gamma(c) and IL-13R alpha 1. C1 Flinders Univ S Australia, Sch Med, Dept Microbiol & Infect Dis, Adelaide, SA 5001, Australia. US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. RP Hart, PH (reprint author), Flinders Univ S Australia, Sch Med, Dept Microbiol & Infect Dis, GPO Box 2I00, Adelaide, SA 5001, Australia. RI Finlay-Jones, John/C-2421-2013 NR 39 TC 63 Z9 70 U1 0 U2 6 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 OCT PY 1999 VL 66 IS 4 BP 575 EP 578 PG 4 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 245ZM UT WOS:000083138700007 PM 10534111 ER PT J AU Kennelly, EJ Flynn, TJ Mazzola, EP Roach, JA McCloud, TG Danford, DE Betz, JM AF Kennelly, EJ Flynn, TJ Mazzola, EP Roach, JA McCloud, TG Danford, DE Betz, JM TI Detecting potential teratogenic alkaloids from blue cohosh rhizomes using an in vitro rat embryo culture SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID QUINOLIZIDINE ALKALOIDS; CAULOPHYLLUM THALICTROIDES; C-13-NMR; SYSTEM AB The novel alkaloid thalictroidine (1), as well as the known alkaloids taspine (2), magnoflorine (3), anagyrine (4), baptifoline (5), 5,6-dehydro-alpha-isolupanine (6), alpha-isolupanine (7), lupanine (8), N-methylcytisine (9), and sparteine (10), were identified from an extract of Caulophyllum thalictroides rhizomes. N-Methylcytisine exhibited teratogenic activity in the rat embryo culture (REC), an in vitro method to detect potential teratogens. The structure of 1 was elucidated using various spectroscopic methods, primarily by NMR techniques. Thalictroidine, anagyrine, and a-isolupanine were not teratogenic in the REC at tested concentrations. Taspine (2) showed high embryotoxicity, but no teratogenic activity, in the REC. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Kennelly, EJ (reprint author), CUNY Herbert H Lehman Coll, Dept Biol Sci, 250 Bedford Pk Blvd W, Bronx, NY 10468 USA. OI Flynn, Thomas/0000-0002-7248-0643 NR 24 TC 36 Z9 39 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD OCT PY 1999 VL 62 IS 10 BP 1385 EP 1389 DI 10.1021/np9901581 PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 250CL UT WOS:000083371400008 PM 10543898 ER PT J AU Rabbani, PI Sheikh, NM Chirtel, SJ Jackson, R Ruffin, G AF Rabbani, PI Sheikh, NM Chirtel, SJ Jackson, R Ruffin, G TI Effects of long-term consumption of high doses of fish oil concentrates on clinical parameters in male and female rats SO JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY LA English DT Article DE fish oil; n-3 fatty acids; toxicity; clinical parameters ID POLYUNSATURATED FATTY-ACIDS; CORONARY HEART-DISEASE; DOCOSAHEXAENOIC ACID; LIPID-PEROXIDATION; CORN-OIL; PLASMA-LIPIDS; MENHADEN OIL; VITAMIN-E; OMEGA-3; METABOLISM AB Many studies suggest that a diet supplemented with fish oil concentrates (FOCs) may provide protection against cardiovascular and other diseases. The possible harmful effects of long-term consumption of high doses of FOCs, however, have not been adequately investigated. Corn oil, fish oil (MaxEPA) and various mixtures of the oils were administered by gavage to 120 male and 120 female rats, 5 d/wk for 13 wk at the rate of 5 mL/kg/d. Although MaxEPA had no effect on prothrombin time or activated partial thromboplastin time, it caused a statistically significant diminution of the total serum cholesterol level. Correlations between relative liver and spleen weights and dose levels were positive but a negative correlation was found between dose levels and serum vitamin E concentration. In female rats, the negative correlations between dose levels and serum iron and triglyceride levels were highly significant. The pathology data showed no remarkable lesions in any of the tissues examined. Results of this study suggest that long-term consumption of high levels of FOCs in rats may reduce serum cholesterol and triglycerides and adversely affect serum iron level and relative liver weight in female rats and relative spleen weights in both sexes. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Rabbani, PI (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 46 TC 12 Z9 12 U1 0 U2 1 PU CENTER ACADEMIC PUBL JAPAN PI TOKYO PA 4-16 YAYOI 2-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0301-4800 J9 J NUTR SCI VITAMINOL JI J. Nutr. Sci. Vitaminol. PD OCT PY 1999 VL 45 IS 5 BP 553 EP 565 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 259CK UT WOS:000083876200005 PM 10683808 ER PT J AU Wilk, A Grajkowski, A Phillips, LR Beaucage, SL AF Wilk, A Grajkowski, A Phillips, LR Beaucage, SL TI The 4-[N-methyl-N-(2,2,2-trifluoroacetyl)amino]butyl group as an alternative to the 2-cyanoethyl group for phosphate protection in the synthesis of oligodeoxyribonucleotides SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID SULFUR-TRANSFER REAGENT; 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE; OLIGONUCLEOTIDE SYNTHESIS; PHOSPHORAMIDITE; DEPROTECTION; DERIVATIVES; ACTIVATION; SUPPORTS; CLEAVAGE; MONOMERS AB The 4-[N-methyl-N-(2,2,2-trifluoroacetyl)amino]butyl group for phosphate protection in the synthesis of oligodeoxyribonucleotides has been developed to completely prevent nucleobase alkylation by acrylonitrile that could potentially occur upon deprotection of the traditional 2-cyanoethyl phosphate protecting group. The properties of this new phosphate protecting group were evaluated using the model phosphotriester 9. The mechanism of phosphate deprotection was studied by treating 9 with concentrated NH4OH. NMR analysis,of the deprotection reaction demonstrated that cleavage of the N-trifluoroacetyl group is rate-limiting. The resulting phosphotriester intermediate 13 was also shown to undergo rapid cyclodeesterification to produce O,O-diethyl phosphate 15 and N-methylpyrrolidine -16 (Scheme 2). Given the facile removal of the 4-[N-methyl-N-(2,2,2-trifluoroacetyl)amino]butyl phosphate protecting group under mild basic conditions, its utilization in oligonucleotide synthesis began with the preparation of the deoxyribonucleoside phosphoramidites 4a-d (Scheme 3). The coupling efficiency of 4a-d and conventional a-cyanoethyl deoxyribonucleoside phosphoramidites 24a-d was then compared in the solid-phase synthesis of the 20-mer d(ATCCGTAGCTAAGGTCATGC). As previously observed in the deprotection of 9, the 4-[N-methyl,N-(2,2,2-trifluoroacetyl)amino]butyl phosphate protecting groups were easily and completely removed from the oligonucleotide by using either concentrated NH4OH or pressurized ammonia gas. Analysis of the deprotected oligomer by polyacrylamide gel electrophoresis (Figure 3) indicated that the phosphoramidites 4a-d are as efficient as the 2-cyanoethyl phosphoramidites 24a-d in the synthesis of the 20-mer. Furthermore, following digestion of the crude 20-mer by snake venom phosphodiesterase and bacterial alkaline phosphatase, HPLC analysis showed complete hydrolysis to individual nucleosides and no detectable nucleobase modification. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Frederick, MD 21701 USA. RP Beaucage, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 34 TC 34 Z9 34 U1 3 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD OCT 1 PY 1999 VL 64 IS 20 BP 7515 EP 7522 DI 10.1021/jo990835w PG 8 WC Chemistry, Organic SC Chemistry GA 244DP UT WOS:000083036800033 ER PT J AU Sullivan, KE Kim, NA Goldman, D Petri, MA Petri, A AF Sullivan, KE Kim, NA Goldman, D Petri, MA Petri, A TI C4A deficiency due to a 2 bp insertion is increased in patients with systemic lupus erythematosus SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE complement; systemic lupus erythematosus; C4A; immune complex; MHC ID MAJOR HISTOCOMPATIBILITY COMPLEX; BLACK-AMERICANS; GENE DELETION; CLASS-II; SUSCEPTIBILITY; SLE; POLYMORPHISM; ASSOCIATION; MULTICENTER; HAPLOTYPES AB Objective. The association of C4A deficiency with systemic lupus erythematosus (SLE) is well documented. In Caucasian populations, the most common cause of C4A deficiency is a large gene deletion in linkage disequilibrium with a conserved MHC haplotype. Because of this linkage disequilibrium, it has been difficult to determine which of the genes constitutes the disease susceptibility allele. Evidence from non-caucasoid populations has supported a role for C4A deficiency in SLE. We investigated whether a specific genetic cause of C4A deficiency, not associated with A1, B8, DR3, is found with increased frequency in SLE compared to controls. Methods. Polymerase chain reaction was used to identify carriers of a 2 base pair (bp) insertion in exon 29. In total, 188 patients with SLE from the Johns Hopkins lupus cohort and 222 controls were genotyped. Results. The 2 bp insertion was found more frequently in patients with SLE compared to controls and was more common in Caucasian than in African American SLE patients. There were no clinical differences between patients that carried the mutation and those that did not. Conclusion. The association of this C4A null allele with SLE supports a role fur C4A deficiency independent of other MHC associations in the etiopathogenesis of SLE. C1 Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. US FDA, Off Testing & Res, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Johns Hopkins Univ, Sch Med, Div Rheumatol, Baltimore, MD USA. RP Sullivan, KE (reprint author), Childrens Hosp Philadelphia, Div Infect Dis & Immunol, 34th St & Civic Ctr Blvd, Philadelphia, PA 19104 USA. OI Sullivan, Kathleen/0000-0003-4018-1646 FU NCRR NIH HHS [CRC RR00722]; NIAMS NIH HHS [R01 AR43727, R29 AR043172] NR 29 TC 27 Z9 30 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 OCT PY 1999 VL 26 IS 10 BP 2144 EP 2147 PG 4 WC Rheumatology SC Rheumatology GA 243TY UT WOS:000083014300015 PM 10529130 ER PT J AU Fein, SB Falci, CD AF Fein, SB Falci, CD TI Infant formula preparation, handling, and related practices in the United States SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID FEEDING PRACTICES; PRESCHOOL-CHILDREN; WATER-INTOXICATION; LEAD-EXPOSURE; BOTULISM; CEREAL; GROWTH; TRIAL; FOOD; LIFE AB Objective To describe practices related to infant formula feeding: diluting and concentrating formula, mixing formula with warm tap water, sterilizing, storing prepared formula, heating in a microwave oven, putting the baby to bed with a bottle, and adding cereal and sweeteners to formula; to analyze characteristics related to compliance with recommended practices; and to examine the relation between formula handling and infant diarrhea. Subjects/design Subjects were mothers who fed their infants formula (more than 1,000 subjects at each infant age). Data are from the US Food and Drug Administration's Infant Feeding Practices Study (IFPS), a national longitudinal survey with a nonprobability sample. Data were collected by mail, and formula practices were included at infant ages 2, 5, and 7 months. Statistical analyses performed Logistic regression was conducted and percentages and odds ratios were calculated, adjusting for instruction in preparing formula from a health care professional, education, income, age, parity, work status, and breast-feeding practices. Results Failure to comply with recommendations was high for several practices with clear health implications; 33% of mothers mixed formula with warm tap water and up to 48% heated bottles in a microwave oven. Mothers of 2-month-old infants who received instruction from a health care professional and who breast-fed showed increased compliance, but few demographic characteristics, such as education, were related. Diarrhea increased with ambient holding of formula for older infants. Application Advice from a health care professional can improve formula-handling behaviors. Dietitians and other health care professionals should provide information on proper preparation and handling of infant formula to all infant caregivers. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Univ Minnesota, Minneapolis, MN USA. RP Fein, SB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW,HSF 727, Washington, DC 20204 USA. OI Falci, Christina/0000-0001-6314-0316 NR 59 TC 23 Z9 23 U1 0 U2 8 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 OCT PY 1999 VL 99 IS 10 BP 1234 EP 1240 DI 10.1016/S0002-8223(99)00304-1 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 243UB UT WOS:000083014700022 PM 10524388 ER PT J AU Yin, JJ Mossoba, MM Kramer, JKG Yurawecz, MP Eulitz, K Morehouse, KM Ku, YO AF Yin, JJ Mossoba, MM Kramer, JKG Yurawecz, MP Eulitz, K Morehouse, KM Ku, YO TI Effects of conjugated linoleic acid on oxygen diffusion-concentration product and depletion in membranes by using electron spin resonance spin-label oximetry SO LIPIDS LA English DT Article ID LIPID-PEROXIDATION; FUMONISIN B-1; FATTY-ACIDS; PARAMAGNETIC-RESONANCE; OXIDATIVE STRESS; FREE-RADICALS; IN-VIVO; ANTIOXIDANT; BILAYERS; ATHEROSCLEROSIS AB The effect of conjugated linoleic acid (CLA) on the relation between structure and function of membranes is described in this paper. Electron spin resonance (ESR) spin-label oximetry was used in the present study to evaluate if oxygen transport and oxygen depletion were affected by incorporation of CLA instead of linoleic acid into membrane phospholipids. Specifically, 1-stearoyl-2-(9cis,11trans-octadecadienoyl)-phosphorylcholine (SCLAPC) was incorporated into soy plant phosphatidylcholine (soy PC) or egg yolk PC (EYPC) bilayers. The use of spin labels attached to different carbons along the fatty acid chain makes it possible to carry out structural and oximetric determinations with the same test sample. For example, the incorporation of 5 mol% SCLAPC increased the oxygen diffusion-concentration product in soy PC or EYPC liposomes at 37 degrees C, slightly decreased the ordering of the hydrocarbon chains at the C10 and C12 positions (in the region of the conjugated double bonds), and increased the rate of oxygen depletion from the aqueous medium. Similar results were not obtained by incorporating 5 mol% of 1-stearoyl-2-linoleoyl-PC (SLPC). In our model system, free-radical generation was initiated by extended incubation of the liposomes, by induction by 2,2'-azobis(2-amidinopropane)hydrochloride, or by ultraviolet irradiation of H2O2 The rate of consumption of molecular oxygen was studied by monitoring the oxygen concentration in the aqueous phases of the liposomes. The effect of 5 mol% SCLAPC in soy PC was significantly larger than 5 mol% SLPC in soy PC; the response patterns with soy PC and EYPC were similar. Furthermore, 5 mol% SCLAPC in 1-palmitoyl-2-linoleoyl-PC showed similar oxygen consumption to that observed with 5 mol% SCLAPC in EYPC. On the other hand, 5 mol% SCLAPC in synthetic PC membranes containing saturated or monounsaturated fatty acids showed low oxygen depletion rates. The perturbation of membrane structure and the increase of the relative oxy; gen diffusion-concentration products provided a potential mechanism by which CLA incorporated into membrane lipids could affect oxidative stress. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Food Res Ctr, So Crop Protect, Guelph, ON N1G 2W1, Canada. RP Yin, JJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS 717,200 C St SW, Washington, DC 20204 USA. RI Yin, Jun Jie /E-5619-2014 NR 45 TC 10 Z9 10 U1 0 U2 1 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PD OCT PY 1999 VL 34 IS 10 BP 1017 EP 1023 DI 10.1007/s11745-999-0452-y PG 7 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 253KZ UT WOS:000083556900002 PM 10580328 ER PT J AU Danam, RP Lu, MH Lewis, SM Djuric, Z Tang, N Hart, RW AF Danam, RP Lu, MH Lewis, SM Djuric, Z Tang, N Hart, RW TI The effect of dietary fat on malondialdehyde concentrations in Fischer 344 rats SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE dietary fat; malondialdehyde; lipid peroxidation; cerebellum; kidney; liver; age ID THIOBARBITURIC ACID TEST; LIPID-PEROXIDATION; OXIDATIVE STRESS; DEGENERATIVE DISEASES; PROTEIN OXIDATION; TISSUE-INJURY; DNA DAMAGE; BRAIN; LIVER; MALONALDEHYDE AB The effects of dietary fat and age on the level of malondialdehyde (MDA), a product of lipid peroxidation, were investigated in cerebellum, kidney, and liver tissues of female Fischer 344 rats. Groups of rats were fed diets containing various levels of corn oil (3, 5, 10, 15, or 20%), starting at 57 days of age, for a duration of 2, 10, or 20 weeks. High fat diets are thought to promote tumor formation, diabetes, and cardiovascular diseases via induction of oxidation stress, and this can begin early in the lifespan. However, it was observed that rats chronically consuming 3 and 5% corn oil diets yielded significantly higher levels of MDA, as analyzed by high-performance liquid chromatography, compared with those fed higher fat diets. After 20 weeks of feeding, the concentration of MDA in each of the three organs studied showed no significant differences among rats consuming diets containing 10, 15, or 20% corn oil. The levels of MDA were highest in the cerebellum, followed by kidney, and lowest in liver. Over the 20-week feeding period, a decrease in MDA level in both cerebellum and liver was observed. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Coll Med, Dept Pediat, Little Rock, AR 72205 USA. Bionet Corp, Jefferson, AR 72079 USA. Wayne State Univ, Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA. RP Lu, MH (reprint author), US FDA, Natl Ctr Toxicol Res, HFT-130,3900 NCTR Rd, Jefferson, AR 72079 USA. EM mlu@nctr.fda.gov RI Djuric, Zora/H-5147-2013 OI Djuric, Zora/0000-0002-8886-8853 NR 52 TC 4 Z9 6 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD OCT 1 PY 1999 VL 110 IS 1-2 BP 87 EP 99 DI 10.1016/S0047-6374(99)00057-3 PG 13 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 249DW UT WOS:000083318400008 PM 10580694 ER PT J AU Khan, SA Nawaz, MS Khan, AA Cerniglia, CE AF Khan, SA Nawaz, MS Khan, AA Cerniglia, CE TI Simultaneous detection of erythromycin-resistant methylase genes ermA and ermC from Staphylococcus spp. by multiplex-PCR SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE multiplex-PCR; erythromycin-resistant methylase gene; ermA; ermC ID ENTEROBACTERIACEAE HIGHLY RESISTANT; COAGULASE-NEGATIVE STAPHYLOCOCCI; POLYMERASE CHAIN-REACTION; STREPTOGRAMIN ANTIBIOTICS; AUREUS; FAMILY; EPIDEMIOLOGY; LINCOSAMIDES; MACROLIDES; MEMBERS AB A comparative analysis of the two most dominant erythromycin-resistance determinant genes in Staphylococcus spp., namely, the ermA and ermC genes, was carried out. Sixty erythromycin-resistant strains of Staphylococcus spp. were tested, of which 24 were avian and 36 were clinical isolates. Our results indicated the prevalence of ermA over the ermC gene as opposed to the widely held opinion of the ermC gene being the most dominant resistance determinant gene. A multiplex-PCR assay was developed to detect the presence of ermA and ermC genes. Two pairs of primers, specific for the detection of ermA and ermC genes, were used in a multiplex-polymerase chain reaction (PCR) assay to yield amplified DNA products of 610 and 520 bp, respectively. Their digestion with restriction enzyme FokI that yielded a 477 bp and a 132 bp digestion product for ermA and a 333 bp and a 187 bp digestion product for ermC confirmed the authenticity of PCR products. The method could be used to amplify the ermA and ermC genes with as little as 5 pg of template DNA. The use of excess primers or the template DNA resulted in gene-specific amplification and no non-specific amplification was observed by changing the primer to primer or template to primer ratios. Furthermore, no amplification from erythromycin-sensitive S. aureus strain was observed. Using this assay, the poultry strains were found to contain either ermA alone (50%) or a combination of ermA (100%) and ermC (50%) both. The clinical strains contained either ermA (94.5%) or ermC (5.5%) but never both. The gene-specific internal probes were also used to verify the above findings and a high degree of correlation between the multiplex PCR and Southern hybridization data was observed. (C) 1999 Academic Press. C1 US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Nawaz, MS (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 20 TC 25 Z9 30 U1 1 U2 6 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD OCT PY 1999 VL 13 IS 5 BP 381 EP 387 DI 10.1006/mcpr.1999.0265 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 245PN UT WOS:000083117500007 PM 10508560 ER PT J AU Cogswell, ME Scanlon, KS Fein, SB Schieve, LA AF Cogswell, ME Scanlon, KS Fein, SB Schieve, LA TI Medically advised, mother's personal target, and actual weight gain during pregnancy SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID WHITE WOMEN; INSTITUTE; GUIDELINES; RETENTION; ADVICE AB Objective: To evaluate whether advice on pregnancy weight gain from health care professionals, women's target weight gain (how much weight women thought they should gain), and actual weight gain corresponded with the 1990 Institute of Medicine recommendations. Methods: predominantly white, middle-class women participating in a mail panel reported their prepregnancy weights, heights, and advised and target weight gains on a prenatal questionnaire (n = 2237), and their actual weight gains on a neonatal questionnaire (n = 1661). Recommended weight gains were categorized for women with low body mass index (BMI) (less than 19.8 kg/m(2)) as 25-39 lb; for women with average BMI (19.8-26.0 kg/m(2)) as 25-34 lb; and for women with high BMI (more than 26.0-29.0 kg/m(2)) and very high BMI (more than 29.0 kg/m(2)) as 15-24 lb. Results: Twenty-seven percent of the women reported that they had received no medical advice about pregnancy weight gain. Among those who received advice, 14% (95% confidence interval [CI] 12%, 16%) had been advised to gain less than the recommended range and 22% (95% CI 20%, 24%) had been advised to gain more than recommended. The odds of being advised to gain more than recommended were higher among women with high BMIs and with very high BMIs compared with women with average BMIs. Black women were more likely than white women to report advice to gain less than recommended. Advised and target weight gains were associated strongly with actual weight gain. Receiving no advice was associated with weight gain outside the recommendations. Conclusion: Greater efforts are required to improve medical advice about weight gain during pregnancy. (Obstet Gynecol 1999;94:616-22.). C1 Ctr Dis Control & Prevent, Div Nutr & Phys Activ, Natl Ctr Chron Dis Prevent & Hlth Promot, Epidem Intelligence Serv,Epidemiol Program Off, Atlanta, GA 30341 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Anal & Support, Washington, DC 20204 USA. RP Cogswell, ME (reprint author), Ctr Dis Control & Prevent, Div Nutr & Phys Activ, Natl Ctr Chron Dis Prevent & Hlth Promot, Epidem Intelligence Serv,Epidemiol Program Off, Mail Stop K-25,4770 Buford Highway, Atlanta, GA 30341 USA. NR 18 TC 133 Z9 134 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 1999 VL 94 IS 4 BP 616 EP 622 DI 10.1016/S0029-7844(99)00375-0 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 239QN UT WOS:000082781300024 PM 10511369 ER PT J AU Beitz, J AF Beitz, J TI Quality-of-life end points in oncology drug trials SO ONCOLOGY-NEW YORK LA English DT Article ID RESISTANT PROSTATE-CANCER; MITOXANTRONE; PREDNISONE; PAIN AB Health-related quality of life (HRQL) is a multidimensional construct that represents the patient's perspective oil valued aspects of health and functioning. Over the last several years, the pharmaceutical industry, as well as health care providers and the patient advocacy community, have shown increasing interest in HRQL as an outcome measure. Pharmaceutical companies and other sponsors of cancer clinical trials are seeking novel approaches with which to establish the benefits of treatment and to differentiate their products from other marketed products. Health care providers hope to provide cancer patients with therapies that positively affect their quality of life. To date, however, most oncology drug approvals have been based on traditional end points, such as survival and tumor response rate. This article will focus on some of the lessons learned from recent reviews of HRQL data and will describe some of the many challenges that lie ahead. C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Beitz, J (reprint author), US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, HFD-15,5600 Fishers Lane, Rockville, MD 20857 USA. NR 14 TC 9 Z9 9 U1 1 U2 1 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD OCT PY 1999 VL 13 IS 10 BP 1439 EP 1442 PG 4 WC Oncology SC Oncology GA 392WF UT WOS:000166435000024 PM 10549568 ER PT J AU Ilev, IK Waynant, RW AF Ilev, IK Waynant, RW TI Uncoated hollow taper as a simple optical funnel for laser delivery SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article ID WAVE-GUIDES; YAG LASER; FIBER; TRANSMISSION AB We propose a simple uncoated hollow taper as a novel technique for laser radiation delivery and laser-to-optical waveguide coupling over a wide spectral range. The principle of operation of the hollow taper is based on the effect of light at grazing incidence. An uncoated Pyrex-glass hollow taper is used for direct launching, without any intermediate focusing elements, of laser radiation including from powerful lasers into the taper. Because of the high reflectance coefficients close to 100% at the light grazing incidence, we obtain high laser-to-taper coupling efficiency exceeding 90% for a He-Ne laser (lambda=632.8 nm) and 80% for a Er:YAG laser (lambda=2.94 mu m). (C) 1999 American Institute of Physics. [S0034-6748(99)02310-2]. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-134, Rockville, MD 20857 USA. NR 15 TC 11 Z9 11 U1 1 U2 2 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0034-6748 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD OCT PY 1999 VL 70 IS 10 BP 3840 EP 3843 DI 10.1063/1.1150042 PG 4 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 240TY UT WOS:000082842300005 ER PT J AU Poindexter, BJ Shafer, BC Mondoro, TH Vostal, JG AF Poindexter, BJ Shafer, BC Mondoro, TH Vostal, JG TI Increase in the pH and mean platelet volume of platelets, pheresis products submitted to the FDA for quality control testing SO TRANSFUSION LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1999 VL 39 IS 10 SU S BP 21S EP 21S PG 1 WC Hematology SC Hematology GA 247EK UT WOS:000083207500099 ER PT J AU Pomper, GJ Rick, ME Epstein, JS Read, EJ AF Pomper, GJ Rick, ME Epstein, JS Read, EJ TI Management of severe von Willebrand's disease with cryoprecipitate collected by repeated apheresis of a single dedicated donor SO TRANSFUSION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1999 VL 39 IS 10 SU S BP 112S EP 113S PG 2 WC Hematology SC Hematology GA 247EK UT WOS:000083207500535 ER PT J AU Poindexter, BJ Shafer, BC Mondoro, TH Vostal, JG AF Poindexter, BJ Shafer, BC Mondoro, TH Vostal, JG TI An evaluation of platelets, pheresis products submitted to the FDA for quality control testing SO TRANSFUSION LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1999 VL 39 IS 10 SU S BP 122S EP 122S PG 1 WC Hematology SC Hematology GA 247EK UT WOS:000083207500579 ER PT J AU Stewart, SFC AF Stewart, SFC TI A rotating torus phantom for assessing color Doppler accuracy SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE color Doppler accuracy; Doppler ultrasound phantom; color Doppler ultrasound ID BLOOD-FLOW; ULTRASOUND; INSTRUMENTS; QUANTIFICATION; JETS AB A rotating torus phantom was designed to assess the accuracy of color Doppler ultrasound. A thin rubber tube was filled with blood analog fluid and joined at the ends to form a torus, then mounted on a disk submerged in water and rotated at constant speeds by a motor. Flow visualization experiments and finite element analyses demonstrated that the fluid accelerates quickly to the speed of the torus and spins as a solid body. The actual fluid velocity was found to be dependent only on the motor speed and location of the sample volume. The phantom was used to assess the accuracy of Doppler-derived velocities during two-dimensional (2-D) color imaging using a commercial ultrasound system. The Doppler-derived velocities averaged 0.81 +/- 0.11 of the imposed velocity, with the variations significantly dependent on velocity, pulse-repetition frequency and wall filter frequency (p < 0.001). The torus phantom was found to have certain advantages over currently available Doppler accuracy phantoms: 1. It has a high maximum velocity; 2. it has low velocity gradients, simplifying the calibration of 2-D color Doppler; and 3. it uses a real moving fluid that gives a realistic backscatter signal, (C) 1999 World Federation for Ultrasound in Medicine & Biology. C1 US FDA, Hydrodynam & Acoust Branch, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Stewart, SFC (reprint author), US FDA, Hydrodynam & Acoust Branch, Ctr Devices & Radiol Hlth, 9200 Corp Blvd, HFZ-132, Rockville, MD 20850 USA. NR 25 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 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD OCT PY 1999 VL 25 IS 8 BP 1251 EP 1264 DI 10.1016/S0301-5629(99)00084-8 PG 14 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 244RB UT WOS:000083063600010 PM 10576268 ER PT J AU Anello, C AF Anello, C TI Emerging and recurrent issues in drug development SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 2nd International Conference on Medical Statistics CY JUL 22-25, 1997 CL DE MONTFORT UNIV, DE MONTFORT, ENGLAND SP Montfort Univ HO DE MONTFORT UNIV ID CLINICAL-TRIALS AB This paper reviews several emerging and recurrent issues relating to the drug development process. These emerging issues include changes to the FDA regulatory environment, internationalization of drug development, advances in computer technology and visualization tools, and efforts to incorporate meta-analysis methodology. Recurrent issues include: renewed interest in statistical methods for handling subgroups in the design and analysis of clinical trials; renewed interest in alternatives to the 'intention-to-treat' analysis in the presence of non-compliance in randomized clinical trials; renewed interest in methodology to address the multiplicities resulting from a variety of sources inherent in the drug development process, and renewed interest in methods to assure data integrity. These emerging and recurrent issues provide a continuing challenge to the international community of statisticians involved in drug development. Moreover, the involvement of statisticians with different perspectives continues to enrich the held and contributes to improvement in the public health. Published in 1999 by John Wiley & Sons, Ltd. This article is a US Government work and is in the public domain in the United States. C1 US FDA, Off Epidemiol & Biostat, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Anello, C (reprint author), US FDA, Off Epidemiol & Biostat, Ctr Drug Evaluat & Res, 5600 Fishers Lane,Parklawn Bldg,Room 15B33,HFD 70, Rockville, MD 20857 USA. NR 23 TC 5 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 30 PY 1999 VL 18 IS 17-18 BP 2301 EP 2309 DI 10.1002/(SICI)1097-0258(19990915/30)18:17/18<2301::AID-SIM256>3.0.CO;2-X PG 9 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 234WR UT WOS:000082507800009 PM 10474140 ER PT J AU Fenichel, RR AF Fenichel, RR TI Mibefradil was not rushed to market in United States SO BRITISH MEDICAL JOURNAL LA English DT Letter C1 US FDA, Div Cardiorenal Drug Prod, Rockville, MD 20857 USA. RP Fenichel, RR (reprint author), US FDA, Div Cardiorenal Drug Prod, HFD-110,5600 Fishers Lane, Rockville, MD 20857 USA. NR 1 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 0959-8138 J9 BRIT MED J JI Br. Med. J. PD SEP 25 PY 1999 VL 319 IS 7213 BP 852 EP 852 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 241CR UT WOS:000082865200045 PM 10496843 ER PT J AU Shapiro, MA Fitzsimmons, SP Clark, KJ AF Shapiro, MA Fitzsimmons, SP Clark, KJ TI Characterization of a B cell surface antigen with homology to the S100 protein MRP8 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CALCIUM-BINDING PROTEINS; MONOCLONAL-ANTIBODY; CHEMOTACTIC PROTEIN; HUMAN NEUTROPHILS; HUMAN-MONOCYTES; S-100 PROTEINS; BRAIN; CP-10; TRANSLOCATION; ABUNDANT AB The S100 proteins comprise a large sub-family of the EF-hand calcium-binding proteins. Here we describe a novel monoclonal antibody recognizing a B cell surface antigen. This monoclonal antibody immunoprecipitates three proteins in the 12-18 kDa range and the smallest of these proteins has a striking homology at its amino-terminus to human MRP8, a myeloid specific member of the S100 family. Similarly to MRP8 in myeloid cells, this antigen is expressed in the cytoplasm of B cells and is secreted by LPS-induced activated B cells. This surface antigen is not B cell specific. Since MRP8 is not expressed by lymphoid cells, however, this antibody appears to recognize a new member of the S100 family. (C) 1999 Academic Press. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Shapiro, MA (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Bethesda, MD 20892 USA. NR 52 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 16 PY 1999 VL 263 IS 1 BP 17 EP 22 DI 10.1006/bbrc.1999.1205 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 238LT UT WOS:000082712300004 PM 10486246 ER PT J AU Britt, JS Carson, MC von Bredow, JD von Bredow, JD Condon, RJ AF Britt, JS Carson, MC von Bredow, JD von Bredow, JD Condon, RJ TI Antibiotic residues in milk samples obtained from cows after treatment for papillomatous digital dermatitis SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article ID DAIRY-CATTLE AB Objective-To determine whether there would be detectable antibiotic residues in milk obtained from dairy cattle with papillomatous digital dermatitis (PDD) after topical treatment with oxytetracycline. Design-Randomized controlled clinical trial. Animals-28 lactating Holstein cows with PDD. Procedure-Cows were assigned to 2 treatment groups. Treatment 1 (n = 16) consisted of spraying of PDD lesions with 15 ml of a solution containing 100 mg of oxytetracycline/ml; lesions were sprayed twice daily for 7 days, using a garden sprayer. Treatment 2 (n = 12) consisted of a one-time application of a bandage that consisted of cotton soaked with 20 ml of a solution containing 100 mg of oxytetracycline/ml. Milk samples were obtained before and after treatment and assayed for tetracycline content by use of high-performance liquid chromatography and a commercially available tetracycline screening test. Results-None of the cows in either treatment group had violative residues of oxytetracycline in milk samples. Conclusions and Clinical Relevance-Producers treating lactating cows that have PDD, via topical application of oxytetracycline solution at the concentrations reported in this study, have a low risk of causing violative antibiotic residues in milk. C1 Univ Wisconsin, Sch Vet Med, Dept Med Sci, Madison, WI 53706 USA. US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Britt, JS (reprint author), Western Kentucky Univ, Dept Agr, Bowling Green, KY 42101 USA. NR 23 TC 17 Z9 18 U1 3 U2 8 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 SEP 15 PY 1999 VL 215 IS 6 BP 833 EP 836 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 234EK UT WOS:000082471400021 PM 10496140 ER PT J AU Ishima, R Freedberg, DI Wang, YX Louis, JM Torchia, DA AF Ishima, R Freedberg, DI Wang, YX Louis, JM Torchia, DA TI Flap opening and dimer-interface flexibility in the free and inhibitor-bound HIV protease, and their implications for function SO STRUCTURE LA English DT Article DE chemical exchange; dynamics; NMR; protein; relaxation ID VIRUS TYPE-1 PROTEASE; HUMAN-IMMUNODEFICIENCY; MOLECULAR-DYNAMICS; HUMAN-IMMUNODEFICIENCY-VIRUS-1 PROTEASE; RETROVIRAL PROTEASES; CRYSTAL-STRUCTURES; NMR-SPECTROSCOPY; CHEMICAL-SHIFT; TIME SCALES; RELAXATION AB Background: H-1 and N-15 transverse relaxation measurements on perdeuterated proteins are ideally suited for detecting backbone conformational fluctuations on the millisecond-microsecond timescale. The identification of conformational exchange on this timescale by measuring the relaxation of both H-1 and N-15 holds great promise for the elucidation of functionally relevant conformational changes in proteins. Results: We measured the transverse H-1 and N-15 relaxation rates of backbone amides of HIV-1 protease in its free and inhibitor-bound forms. An analysis of these rates, obtained as a function of the effective rotating frame field, provided information about the timescale of structural fluctuations in several regions of the protein. The flaps that cover the active site of the inhibitor-bound protein undergo significant changes of backbone (phi, psi) angles, on the 100 mu s timescale, in the free protein. In addition, the intermonomer beta-sheet interface of the bound form, which from protease structure studies appears to be rigid, was found to fluctuate on the millisecond timescale. Conclusions: We present a working model of the flap-opening mechanism in free HIV-1 protease which involves a transition from a semi-open to an open conformation that is facilitated by interaction of the Phe53 ring with the substrate. We also identify a surprising fluctuation of the beta-sheet intermonomer interface that suggests a structural requirement for maturation of the protease. Thus, slow conformational fluctuations identified by H-1 and N-15 transverse relaxation measurements can be related to the biological functions of proteins. C1 Natl Inst Dent & Cranofacial Res, Struct Mol Biol Unit, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Bethesda, MD 20892 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Torchia, DA (reprint author), Natl Inst Dent & Cranofacial Res, Struct Mol Biol Unit, Bethesda, MD 20892 USA. EM torchia@yoda.nidr.nih.gov NR 53 TC 193 Z9 193 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 EI 1878-4186 J9 STRUCTURE JI Structure PD SEP 15 PY 1999 VL 7 IS 9 BP 1047 EP 1055 DI 10.1016/S0969-2126(99)80172-5 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 238BL UT WOS:000082691000007 PM 10508781 ER PT J AU Korvick, JA Elashoff, MR Cavaille-Coll, M AF Korvick, JA Elashoff, MR Cavaille-Coll, M TI A commentary on a randomized active-controlled trial of mycophenolate mofetil in heart transplant recipients SO TRANSPLANTATION LA English DT Letter C1 US FDA, CDER, Rockville, MD 20857 USA. RP Korvick, JA (reprint author), US FDA, CDER, 5600 Fishers Lane,HFD-590, Rockville, MD 20857 USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD SEP 15 PY 1999 VL 68 IS 5 BP 708 EP 709 DI 10.1097/00007890-199909150-00020 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 242KE UT WOS:000082939200020 PM 10507494 ER PT J AU Dickensheets, HL Venkataraman, C Schindler, U Donnelly, RP AF Dickensheets, HL Venkataraman, C Schindler, U Donnelly, RP TI Interferons inhibit activation of STAT6 by interleukin 4 in human monocytes by inducing SOCS-1 gene expression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE; IFN-GAMMA; TYROSINE PHOSPHORYLATION; TRANSCRIPTION FACTOR; JANUS KINASE; IL-4-INDUCED EXPRESSION; SIGNAL TRANSDUCERS; HUMAN-LYMPHOCYTES; JAK1 EXPRESSION; MESSENGER-RNA AB Interferons (IFNs) inhibit induction by IL-4 defined. IL-4 activates gene expression by inducing tryosine of multiple genes in human monocytes. However, the mechanism by which IFNs mediate this inhibition has not been phosphorylation, homodimerization, and nuclear translocation of the latent transcription factor, STAT6 (signal transducer and activator of transcription-6). STAT6-responsive elements are characteristically present in the promoters of IL-4-inducible genes. Because STAT6 activation is essential for IL-4-induced gene expression, we examined the ability of type I and type II IFNs to regulate activation of STAT6 by IL-4 in primary human monocytes. Pretreatment of monocytes with IFN-beta or IFN-gamma, but not IL-1, IL-2, macrophage colony-stimulating factor, granulocyte/macrophage colony-stimulating factor, IL-6, or transforming growth factor beta suppressed activation of STAT6 by IL-4. This inhibition was associated with decreased tyrosine phosphorylation and nuclear translocation of STAT6 and was not evident unless the cells were preincubated with IFN for at least 1 hr before IL-4 stimulation. Furthermore, inhibition by IFN could be blocked by cotreatment with actinomycin D and correlated temporally with induction of the JAK/STAT inhibitory gene, SOCS-1, Forced expression of SOCS-1 in a macrophage cell line, RAW264, markedly suppressed trans-activation of an IL-4-inducible reporter as well as IL-6- and IFN-gamma-induced reporter gene activity. These findings demonstrate that IFNs inhibit IL-4-induced activation of STAT6 and STAT6-dependent gene expression, at least in part, by inducing expression of SOCS-1. C1 US FDA, Div Cytokine Biol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Tularik Inc, S San Francisco, CA 94080 USA. RP Donnelly, RP (reprint author), US FDA, Div Cytokine Biol, Ctr Biol Evaluat & Res, HFM-505,1401 Rockville Pike, Rockville, MD 20852 USA. NR 54 TC 132 Z9 136 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 14 PY 1999 VL 96 IS 19 BP 10800 EP 10805 DI 10.1073/pnas.96.19.10800 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 235ZQ UT WOS:000082574100052 PM 10485906 ER PT J AU Temple, R AF Temple, R TI Higher standards for epidemiologic studies-replication prior to publication? Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Temple, R (reprint author), US FDA, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 8 PY 1999 VL 282 IS 10 BP 937 EP 938 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 231XD UT WOS:000082335900015 ER PT J AU Pogribny, I Yi, P James, SJ AF Pogribny, I Yi, P James, SJ TI A sensitive new method for rapid detection of abnormal methylation patterns in global DNA and within CpG islands SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CYTOSINE METHYLATION; EARLY EVENT; P53 GENE; METHYLTRANSFERASE; CANCER; HEPATOCARCINOGENESIS; HYPOMETHYLATION; DEFICIENCY; EXPRESSION; LIVERS AB To assess alterations in DNA methylation density in both global DNA and within CpG islands, we have developed a simple method based on the use of methylation-sensitive restriction endonucleases that leave a 5' guanine overhang after DNA cleavage, with subsequent single nucleotide extension with radiolabeled [H-3]dCTP. The methylation-sensitive restriction enzymes HpaII and AciI have relatively frequent recognition sequences at CpG sites that occur randomly throughout the genome, BssHII is a methylation sensitive enzyme that similarly leaves a guanine overhang, but the recognition sequence is nonrandom and occurs predominantly at unmethylated CpG sites within CpG islands. The selective use of these enzymes can be used to screen for alterations in genome-wide methylation and CpG island methylation status, respectively. The extent of [H-3]dCTP incorporation opposite the exposed guanine after restriction enzyme treatment is directly proportional to the number of unmethylated (cleaved) CpG; sites. The "cytosine-extension assay" has several advantages over existing methods because (a) radiolabel incorporation is independent of the integrity of the DNA, (b) methylation detection does not require PCR amplification or DNA methylase reactions, and (c) it is applicable to ng quantities of DNA. Using DNA extracted from normal human liver and from human hepatocellular carcinoma, the applicability of the assay is demonstrated by the detection of an increase in genome-wide hypomethylation and CpG island hypermethylation in the tumor DNA. (C) 1999 Academic Press. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci Hosp, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. RP James, SJ (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 21 TC 163 Z9 166 U1 0 U2 6 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 7 PY 1999 VL 262 IS 3 BP 624 EP 628 DI 10.1006/bbrc.1999.1187 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 235AH UT WOS:000082516200011 PM 10471374 ER PT J AU Hitchins, VM Merritt, K AF Hitchins, VM Merritt, K TI Decontaminating particles exposed to bacterial endotoxin (LPS) SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article DE endotoxin; ethanol; murine macrophages; nitric oxide; particles ID CELL-LINE; LIPOPOLYSACCHARIDE AB Lipopolysaccharide (LPS),which comes from the cell wall of gram-negative bacteria., can stimulate murine macrophage cells to produce nitric oxide (NO), cytokines, such as tumor necrosis factor-alpha, and interleukins,such as IL-6. When examining the biological effects of particles on macrophages,it is important to have no contaminating LPS associated with the particles and none with any cell culture media or supplies since even very low levels of LPS are stimulatory. The presence or absence of LPS was observed in two ways: (1) the amount of NO produced by RAW 264.7 murine macrophage cells, and (2) the Limulus amebocyte lysate (LAL) test. Treating;particles with 70% ethanol at room temperature for 48 h, followed by washing the polymethylmethacrylate (PMMA) particles with endotoxin-free phosphate-buffered saline three times, decontaminated LPS and LPS-treated PMMA particles. When given LPS that had been treated with 70% ethanol for 48 h at room temperature or at 37 degrees C, cells did not produce NO above control levels. Negative LAL, tests indicated the presence of extremely low levels or the complete absence of LPS in 70% ethanol-treated LPS. (C) 1999 John Wiley & Sons, Inc. J Biomed Mater Res, 46, 434-437, 1999. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Hitchins, VM (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-112,5600 Fishers Lane, Rockville, MD 20857 USA. NR 7 TC 46 Z9 48 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD SEP 5 PY 1999 VL 46 IS 3 BP 434 EP 437 PG 4 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 209QY UT WOS:000081061000017 PM 10398002 ER PT J AU Abu-Lafi, S Turujman, SA AF Abu-Lafi, S Turujman, SA TI Reproducibility of the separation of astaxanthin stereoisomers on Pirkle covalent L-leucine and D-phenylglycine columns SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE stereoisomer separation; astaxanthin ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MESO-ASTAXANTHIN; MOBILE-PHASE; WILD SALMON; PREDICTION; RETENTION; PACKING; CONSOLIDATION; CAROTENOIDS; ENANTIOMERS AB The reproducibility of the separation of astaxanthin stereoisomers on columns packed with Pirkle covalent L-leucine chiral stationary phase (CSP) was examined by comparing six columns purchased from the same manufacturer. Differences were found even for columns packed with CSP from the same lot. The reproducibility of columns packed with Pirkle covalent D-phenylglycine CSP was also examined by comparing columns purchased from the same manufacturer as well as from different manufacturers. Significant differences were found for columns packed by different manufacturers. Chiral column-to-column reproducibility for complex stereoisomeric separations should therefore not be taken for granted. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Turujman, SA (reprint author), US FDA, Off New Drug Chem HFD 540 830, Ctr Drug Evaluat & Res, 9201 Corp Blvd, Rockville, MD 20850 USA. NR 33 TC 12 Z9 13 U1 3 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD SEP 3 PY 1999 VL 855 IS 1 BP 157 EP 170 DI 10.1016/S0021-9673(99)00700-1 PG 14 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 236MU UT WOS:000082604000010 PM 10514981 ER PT J AU Stewart, CW Slikker, W AF Stewart, CW Slikker, W TI Hyperthermia-enhanced serotonin (5-HT) depletion resulting from D-fenfluramine exposure is preventable. SO LIFE SCIENCES LA English DT Article DE fenfluramine; ambient temperature; hyperthermia; 5-HT ID BRAIN-SEROTONIN; RELEASE; RATS; DEXFENFLURAMINE; NEUROTOXICITY; TEMPERATURES; MECHANISMS; INHIBITION; TOLERANCE AB Recent findings intricate that elevations in body temperature during acute d-fenfluramine (Fen) exposure enhance long-term 5-HT depletion. Therefore, we hypothesized that when repeated exposure to d-Fen produced repeated elevations in body temperature, 5-HT reductions would be greater in comparison to a single d-Fen exposure. Groups of animals were exposed to d-Fen for 1 or 4 days in a 28 degrees C environment. Exposure to d-Fen in the 28 degrees C environment induced an increase in body temperature and resulted in a long-term decrease in brain 5-HT. However, brain 5-HT was not different between the two groups. An additional experiment revealed that if the initial exposure to d-Fen does not induce elevations in body temperature, then long-term 5-HT depletion can be prevented. We conclude that the central nervous system rapidly adapts to the 5-HT depleting action of d-Fen thereby preventing further decreases in 5-HT concentrations from d-Fen exposure. In addition, this rapid adaptation circumvented the hyperthermia-enhanced 5-HT depletion that results from d-Fen exposure in a warm environment. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. RP Slikker, W (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 18 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD SEP 3 PY 1999 VL 65 IS 15 BP 1531 EP 1536 DI 10.1016/S0024-3205(99)00397-5 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 233XU UT WOS:000082453100002 PM 10574218 ER PT J AU Sagripanti, JL Bonifacino, A AF Sagripanti, JL Bonifacino, A TI Bacterial spores survive treatment with commercial sterilants and disinfectants SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID MEDICAL DEVICES; AGENTS AB This study compared the activity of commercial liquid sterilants and disinfectants on Bacillus subtilis spores deposited on three types of devices made of noncorrodible, corrodible, or polymeric material. Products like Renalin, Exspor, Wavicide-01, Cidexplus, and cupric ascorbate were tested under conditions specified for liquid sterilization. These products, at the shorter times indicated for disinfection, and popular disinfectants, like Clorox, Cavicide, and Lysol were also studied. Data obtained with a sensitive and quantitative test suggest that commercial liquid sterilants and disinfectants are less effective on contaminated surfaces than generally acknowledged. C1 US FDA, Mol Biol Branch HFZ113, Div Life Sci, Off Sci & Technol,Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Sagripanti, JL (reprint author), US FDA, Mol Biol Branch HFZ113, Div Life Sci, Off Sci & Technol,Ctr Devices & Radiol Hlth, 5600 Fishers Ln, Rockville, MD 20857 USA. NR 25 TC 28 Z9 29 U1 1 U2 16 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD SEP PY 1999 VL 65 IS 9 BP 4255 EP 4260 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 233HL UT WOS:000082421400077 PM 10473448 ER PT J AU Tall, BD La Peyre, JF Bier, JW Miliotis, MD Hanes, DE Kothary, MH Shah, DB Faisal, M AF Tall, BD La Peyre, JF Bier, JW Miliotis, MD Hanes, DE Kothary, MH Shah, DB Faisal, M TI Perkinsus marinus extracellular protease modulates survival of Vibrio vulnificus in eastern oyster (Crassostrea virginica) hemocytes SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID IN-VITRO; PROPAGATION; PRODUCTS AB The in vitro effects of the Perkinsus marinus serine protease on the intracellular survival of Vibrio vulnificus in oyster hemocytes were examined by using a time-course gentamicin internalization assay. Results showed that protease-treated hemocytes were initially slower to internalize V. vulnificus than untreated hemocytes. After 1 h, the elimination of V. vulnificus by treated hemocytes was significantly suppressed compared with hemocytes infected with invasive and noninvasive controls. Our data suggest that the serine protease produced by P. marinas suppresses the vibriocidal activity of oyster hemocytes to effectively eliminate V. vulnificus, potentially leading to conditions favoring higher numbers of vibrios in oyster tissues. C1 US FDA, Div Microbiol Studies HFS517, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. US FDA, Div Sci & Appl Technol, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. US FDA, Div Virulence Assessment, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Coll William & Mary, Sch Marine Sci, Virginia Inst Marine Sci, Gloucester Point, VA 23062 USA. RP Tall, BD (reprint author), US FDA, Div Microbiol Studies HFS517, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. OI Tall, Ben/0000-0003-0399-3629 NR 19 TC 36 Z9 37 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD SEP PY 1999 VL 65 IS 9 BP 4261 EP 4263 PG 3 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 233HL UT WOS:000082421400078 PM 10473449 ER PT J AU Kassarov, L AF Kassarov, L TI Are birds able to taste and reject butterflies based on 'beak mark tasting'? A different point of view SO BEHAVIOUR LA English DT Article ID CARDENOLIDES; PREDATION; LARVAE; RAT AB It is widely accepted that birds are able to taste toxic chemical substances in the wings of a butterfly by grabbing or pecking a small piece of the wing without disrupting the integrity of the integument ('beak mark tasting'). If found toxic, the bird will release the insect unharmed. This supposition has been used to explain some aspects of the interrelationship between birds as predators and butterflies as prey, especially the role of birds in the evolution of butterfly color patterns. It also is used to support the theory of aposematise coloration, especially in butterflies. On the basis of the anatomy of the avian gustatory apparatus, the distribution of the taste buds in the beak cavity, and the physiology of taste, this author considers this supposition a misconception. The frequent beak marks seen on the wings of aposematic butterflies are not considered to be a proof of taste rejection by birds after contact with the chemical compound(s) supposed to provide the insect with a chemical defense, but a sign of active escape of the butterfly from its captor. Some aspects of the interrelationship between birds and butterflies, considered to be well explained on the basis of taste rejection of butterflies via 'beak mark tasting' by the birds, are critically discussed in this paper. C1 FDACS, DPI, Florida State Collect Anthropods, Gainesville, FL 32614 USA. RP Kassarov, L (reprint author), 130 Spruce St 28B, Philadelphia, PA 19106 USA. NR 63 TC 10 Z9 11 U1 2 U2 14 PU BRILL ACADEMIC PUBLISHERS PI LEIDEN PA PLANTIJNSTRAAT 2, P O BOX 9000, 2300 PA LEIDEN, NETHERLANDS SN 0005-7959 J9 BEHAVIOUR JI Behaviour PD SEP PY 1999 VL 136 BP 965 EP 981 DI 10.1163/156853999501676 PN 8 PG 17 WC Behavioral Sciences; Zoology SC Behavioral Sciences; Zoology GA 259NK UT WOS:000083899800003 ER PT J AU Pipkin, JL Hinson, WG Young, JF Rowland, KL Shaddock, JG Tolleson, WH Duffy, PH Casciano, DA AF Pipkin, JL Hinson, WG Young, JF Rowland, KL Shaddock, JG Tolleson, WH Duffy, PH Casciano, DA TI Induction of stress proteins by electromagnetic fields in cultured HL-60 cells SO BIOELECTROMAGNETICS LA English DT Article DE magnetic fields; cell culture; electrophoresis; "heat shock" proteins ID CALORIC RESTRICTED RATS; SALIVARY-GLAND CELLS; HEAT-SHOCK PROTEIN; MAGNETIC-FIELDS; RETINOIC ACID; CELLULAR TRANSCRIPTION; POLYACRYLAMIDE GELS; CHILDHOOD-CANCER; ELECTRIC-FIELDS; NUCLEAR-PROTEIN AB HL-60 cells in culture were exposed for 2 h to a sinusoidal 0.1 or 1 mT (1 or 10 Gauss) magnetic field at 60 Hz and pulse labeled after exposure with radioactive isotopes by incubation by using either [S-35]methionine, [H-3]leucine, or [P-33]phosphate. The radioactive labels were incorporated into cellular proteins through synthesis or phosphorylation. Proteins were extracted from electrostatically sorted nuclei, and the heat shock/stress proteins (sp) were analyzed for synthesis and phosphorylation by two-dimensional polyacrylamide gel electrophoresis. In the control cultures (no exposure to the magnetic field), sp 72c (cognate form) was faintly observed. A 0.1 mT exposure did not show sp metabolism to be different from that of the controls; however, after a 1 mT exposure of the HL-60 cells, sp 70i (inducible form) was synthesized ([35S]methionine incorporation). Sp 90 was not synthesized at either field level, but was phosphorylated ([P-33]phosphate incorporation) in the 1 mT exposure. Sp 27 (isoforms a and b) was induced after a 1 mT exposure as reflected by labeling with [H-3]leucine. These sps were not detected after a 0.1 mT exposure. After a 1 mT exposure and labeling with [P-33], Sp 27 isoforms b and c were phosphorylated whereas isoform 'a' was not observed. Sps 70i, 72c, and 90 were identified by commercial sp antibodies. Likewise, polypeptides a, b, and c were verified as sp 27 isoforms by Western blotting. Statistical evaluation of sp areas and densities, determined from fluorographs by Western-blot analysis, revealed a significant increase in spa 90 and 27a after a 1 mT magnetic field exposure. The 1 mT magnetic field interacts at the cellular level to induce a variety of sp species. Bioelectromagnetics 20:347-357, 1999. Published 1999 Wiley-Liss,Inc.dagger C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Hinson, WG (reprint author), Natl Ctr Toxicol Res, HFT-300,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 78 TC 54 Z9 57 U1 3 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0197-8462 J9 BIOELECTROMAGNETICS JI Bioelectromagnetics PD SEP PY 1999 VL 20 IS 6 BP 347 EP 357 DI 10.1002/(SICI)1521-186X(199909)20:6<347::AID-BEM3>3.0.CO;2-I PG 11 WC Biology; Biophysics SC Life Sciences & Biomedicine - Other Topics; Biophysics GA 228XG UT WOS:000082162200003 PM 10453062 ER PT J AU Cui, L Hung, HMJ Wang, SJ AF Cui, L Hung, HMJ Wang, SJ TI Modification of sample size in group sequential clinical trials SO BIOMETRICS LA English DT Article DE interim analysis; power; sample size; type I error ID INTERIM ANALYSES AB In group sequential clinical trials, sample size reestimation can be a complicated issue when it allows for change of sample size to be influenced by an observed sample path. Our simulation studies show that increasing sample size based on an interim estimate of the treatment difference can substantially inflate the probability of type I error in most practical situations. A new group sequential test procedure is developed by modifying the weights used in the traditional repeated significance two-sample mean test. The new test has the type I error probability preserved at the target level and can provide a substantial gain in power with the increase of sample size. Generalization of the new procedure is discussed. C1 US FDA, OB CDER, Div Biometr 1, Rockville, MD 20852 USA. US FDA, OB CDER, Div Biometr 2, Rockville, MD 20857 USA. RP Cui, L (reprint author), US FDA, OB CDER, Div Biometr 1, 1451 Rockville Pike, Rockville, MD 20852 USA. FU DRS NIH HHS [RSR-096-010A] NR 13 TC 211 Z9 212 U1 0 U2 10 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1999 VL 55 IS 3 BP 853 EP 857 PG 5 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 237XZ UT WOS:000082683000026 PM 11315017 ER PT J AU Weerahandi, S Berger, VW AF Weerahandi, S Berger, VW TI Exact inference for growth curves with intraclass correlation structure SO BIOMETRICS LA English DT Article DE compound symmetry; generalized inference; longitudinal data; repeated measures ID GENERALIZED P-VALUES; TESTS AB We consider repeated observations taken over time for each of several subjects. For example, one might consider the growth curve of a cohort of babies over time. We assume a simple linear growth curve model. Exact results based on sufficient statistics (exact tests of the null hypothesis that a coefficient is zero, or exact confidence intervals for coefficients) are not available to make inference on regression coefficients when an intraclass correlation structure is assumed. This paper will demonstrate that such exact inference is possible using generalized inference. C1 BELLCORE, Morristown, NJ 07960 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Weerahandi, S (reprint author), BELLCORE, MCC 1C217B,445 South St, Morristown, NJ 07960 USA. NR 13 TC 39 Z9 45 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1999 VL 55 IS 3 BP 921 EP 924 DI 10.1111/j.0006-341X.1999.00921.x PG 4 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 237XZ UT WOS:000082683000038 PM 11315029 ER PT J AU Schenck, FJ Howard-King, V AF Schenck, FJ Howard-King, V TI Rapid solid phase extraction cleanup for pesticide residues in fresh fruits and vegetables SO BULLETIN OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY LA English DT Article ID LIQUID-CHROMATOGRAPHY C1 US FDA, Baltimore Dist Lab, Baltimore, MD 21201 USA. RP Schenck, FJ (reprint author), US FDA, 60 8th St NE, Atlanta, GA 30309 USA. NR 8 TC 30 Z9 35 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0007-4861 J9 B ENVIRON CONTAM TOX JI Bull. Environ. Contam. Toxicol. PD SEP PY 1999 VL 63 IS 3 BP 277 EP 281 PG 5 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 231PZ UT WOS:000082320100001 PM 10475903 ER PT J AU King, RS Teitel, CH Shaddock, JG Casciano, DA Kadlubar, FF AF King, RS Teitel, CH Shaddock, JG Casciano, DA Kadlubar, FF TI Detoxification of carcinogenic aromatic and heterocyclic amines by enzymatic reduction of the N-hydroxy derivative SO CANCER LETTERS LA English DT Article; Proceedings Paper CT 7th International Conference on Carcinogenic and Mutagenic N-Substituted Aryl Compounds CY NOV 04-06, 1998 CL NAGOYA, JAPAN DE heterocyclic amine; aromatic amine; detoxification; N-hydroxy; PhIP; A alpha C; IQ; MeIQx ID HEPATIC MICROSOMES; LIVER-MICROSOMES; CYTOCHROME-P450; RAT AB The metabolic activation pathways associated with carcinogenic aromatic and heterocyclic amines have long been known to involve N-oxidation, catalyzed primarily by cytochrome P4501A2, and subsequent O-esterification, often catalyzed by acetyltransferases (NATs) and sulfotransferases (SULTs). We have found a new enzymatic mechanism of carcinogen detoxification: a microsomal NADH-dependent reductase that rapidly converts the N-hydroxy arylamine back to the parent amine. The following N-OH-arylamines and N-OH-heterocyclic amines were rapidly reduced by both human and rat liver microsomes: N-OH-4-aminoazobenzene, N-OH-4-aminobiphenyl (N-OH-ABP), N-OH-aniline, N-OH-2-naphthylamine, N-OH-2-aminofluorene, N-OH-4,4'-methylenebis(2-chloroaniline) (N-OH-MOCA), N-OH-1-naphthyamine, N-OH-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP), N-OH-2-amino-alpha-carboline (N-OH-A alpha C), N-OH-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (N-OH-MeIQx), and N-OH-2-amino-3-methylimidazo[4,5-f]quinoline (N-OH-IQ). In addition, primary rat hepatocytes and human HepG2 cells efficiently reduced N-OH-PhIP to PhIP. This previously unrecognized detoxification pathway may limit the bioavailability of carcinogenic N-OH heterocyclic and aromatic amines for further activation, DNA adduct formation, and carcinogenesis. (C) 1999 Published by Elsevier Science Ireland Ltd. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet Toxicol, Jefferson, AR 72079 USA. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RI King, Roberta/A-1749-2010 OI King, Roberta/0000-0002-3550-4255 NR 7 TC 50 Z9 51 U1 2 U2 7 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD SEP 1 PY 1999 VL 143 IS 2 BP 167 EP 171 DI 10.1016/S0304-3835(99)00119-6 PG 5 WC Oncology SC Oncology GA 234QH UT WOS:000082495500014 PM 10503898 ER PT J AU Beland, FA Fullerton, NF Smith, BA Mittelstaedt, RA Heflich, RH AF Beland, FA Fullerton, NF Smith, BA Mittelstaedt, RA Heflich, RH TI Hprt lymphocyte mutant frequency in relation to DNA adduct formation in rats fed the hepatocarcinogen 2-acetylaminofluorene SO CANCER LETTERS LA English DT Article; Proceedings Paper CT 7th International Conference on Carcinogenic and Mutagenic N-Substituted Aryl Compounds CY NOV 04-06, 1998 CL NAGOYA, JAPAN DE 2-acetylaminofluorene; hypoxanthine-guanine phosphoribosyltransferase; DNA adducts; mutations ID ETHYL-N-NITROSOUREA; IN-VIVO MUTATION; FISCHER-344 RATS; T-LYMPHOCYTES; INDUCTION; REMOVAL; GENE; 7,12-DIMETHYLBENZANTHRACENE; 1,6-DINITROPYRENE; SEQUENCE AB The lymphocyte hypoxanthine-guanine phosphoribosyltransferase (Hprt) assay is frequently used as a biomarker for the exposure of both humans and laboratory animals to potentially carcinogenic agents. To obtain information concerning the sensitivity of the rat Hprt lymphocyte assay toward aromatic amine carcinogens, male F344 rats were fed 0.02% 2-acetylaminofluorene (2-AAF) for 1 month and then returned to control diet for 2 months. At 4, 27, 48, 62, and 90 days after the initiation of 2-AAF-feeding, the frequency of mutants in the Hprt gene was determined. In addition, DNA was isolated from liver nuclei, spleen lymphocytes, bone marrow, and thymus, and DNA adducts were analyzed by P-32-postlabeling. 2-AAF feeding resulted in a significant induction of 6-thioguanine-resistant T-lymphocytes and the mutant frequency continued to increase after the 2-AAF feeding was stopped. The same major DNA adduct, N-(deoxyguanosin-8-yl)-2-aminofluorene, was detected in liver, spleen lymphocytes, bone marrow, and thymus. DNA adduct levels were greatest in the tumor target tissue (liver) but occurred in all T-lymphocyte compartments, being highest in spleen lymphocytes. The DNA adduct levels were highest at the end of the 1-month 2-AAF feeding period and decreased rapidly in all tissues. The data indicate that the Hprt lymphocyte mutagenesis assay detects arylamine carcinogens, but with relatively low sensitivity. (C) 1999 Published by Elsevier Science Ireland Ltd. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 27 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD SEP 1 PY 1999 VL 143 IS 2 BP 249 EP 255 DI 10.1016/S0304-3835(99)00134-2 PG 7 WC Oncology SC Oncology GA 234QH UT WOS:000082495500029 PM 10503913 ER PT J AU Kimura, S Kawabe, M Ward, JM Morishima, H Kadlubar, FF Hammons, GJ Fernandez-Salguero, P Gonzalez, FJ AF Kimura, S Kawabe, M Ward, JM Morishima, H Kadlubar, FF Hammons, GJ Fernandez-Salguero, P Gonzalez, FJ TI CYP1A2 is not the primary enzyme responsible for 4-aminobiphenyl-induced hepatocarcinogenesis in mice SO CARCINOGENESIS LA English DT Article ID METABOLIC-ACTIVATION; CYTOCHROME P4501A2; AROMATIC-AMINES; N-OXIDATION; LIVER; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; CARCINOGENESIS; CAFFEINE; ADDUCTS; BIOTRANSFORMATION AB 4-Aminobiphenyl (4-ABP), a potent carcinogen in rodents (liver cancer) and human (bladder cancer), is found as an environmental contaminant and in tobacco smoke. Hemoglobin adducts and lung DNA adducts of 3-ABP are found in tobacco smokers. In vitro metabolism studies with human and rat liver microsomes have shown that CYP1A2 is primarily responsible for catalyzing N-hydroxylation, the initial step in the metabolic activation of 4-ABP, To determine whether this P450 is a rate limiting pathway for hepatocarcinogenesis, CYP1A2-null mice were analyzed at 16 months of age and were compared with wild-type mice in their response to 4-ABP using the neonatal mouse bioassay and two different doses of the carcinogen. Overall differences in incidences of hepatocellular adenoma, carcinoma and preneoplastic foci were not significant between either genotypes or 4-ABP doses used, whereas small, but significant, differences were found for specific types of foci, These results suggest that while CYP1A2 levels may not be rate limiting for 4-ABP metabolism to produce tumors and foci, it may modulate the induction process of some types of liver foci in either a positive or negative manner. In vitro studies using CYP1A2-null and wild-type mouse liver microsomes revealed that CYP1A2 is not the sole P450 required for 4-ABP N-hydroxylation and that another, yet to be identified, P450 is likely to be involved. C1 NCI, Met Lab, NIH, Bethesda, MD 20892 USA. NCI, Vet & Tumor Pathol Sect, Anim Sci Branch, Frederick, MD 21702 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Kimura, S (reprint author), NCI, Met Lab, NIH, Bldg 37,Room 3E-24, Bethesda, MD 20892 USA. EM shioko@helix.nih.gov OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 27 TC 53 Z9 54 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 SEP PY 1999 VL 20 IS 9 BP 1825 EP 1830 DI 10.1093/carcin/20.9.1825 PG 6 WC Oncology SC Oncology GA 232RA UT WOS:000082382700023 PM 10469630 ER PT J AU Darsey, JA Lay, JO Holland, RD AF Darsey, JA Lay, JO Holland, RD TI Deconvolution of composite mass spectra by artificial neural networks SO CHIMICA OGGI-CHEMISTRY TODAY LA English DT Article AB In this paper we present the performance of an artificial neural network based model for deconvolution of composite mass spectra representing sixteen mixtures containing from, two to five components. Twenty-five electron impact mass spectra were used to train the neural network prior to examination of the mixtures. More than half of these compounds were either isomeric or isobaric with another compound present in the training set. The artificial neural network based model correctly identified individual components from these composite mass spectra even though all of the network training involved spectra from individual compounds. For mixtures of three or less compounds no false positive or false negative identifications were observed. When mixtures included up to five compounds a false positive identification of the same compound was observed in two of the mixtures. However, this false positive correlated with the presence of a chlorine isotope pattern rather than the presence of an isomeric or isobaric component. C1 Univ Arkansas, Dept Chem, Little Rock, AR 72204 USA. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RI Lay, Jackson/G-1007-2011 OI Lay, Jackson/0000-0003-3789-2527 NR 12 TC 1 Z9 1 U1 0 U2 0 PU TEKNOSCIENZE PUBL PI MILAN PA VIA AURELIO SAFFI 23, 20123 MILAN, ITALY SN 0392-839X J9 CHIM OGGI JI Chim. Oggi-Chem. Today PD SEP PY 1999 VL 17 IS 9 BP 41 EP 44 PG 4 WC Biotechnology & Applied Microbiology; Chemistry, Multidisciplinary SC Biotechnology & Applied Microbiology; Chemistry GA 247CN UT WOS:000083203200006 ER PT J AU Yamaguchi, K Sawada, T Naraki, T Igata-Yi, R Shiraki, H Horii, Y Ishii, T Ikeda, K Asou, N Okabe, H Mochizuki, M Takahashi, K Yamada, S Kubo, K Yashiki, S Waltrip, RW Carbone, KM AF Yamaguchi, K Sawada, T Naraki, T Igata-Yi, R Shiraki, H Horii, Y Ishii, T Ikeda, K Asou, N Okabe, H Mochizuki, M Takahashi, K Yamada, S Kubo, K Yashiki, S Waltrip, RW Carbone, KM TI Detection of Borna disease virus-reactive antibodies from patients with psychiatric disorders and from horses by electrochemiluminescence immunoassay SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID PERIPHERAL-BLOOD MONONUCLEAR; RNA; CELLS; SCHIZOPHRENIA; INFECTION; BDV AB The prevalence of Borna disease virus (BDV)-specific antibodies among patients with psychiatric disorders and healthy individuals has varied in several reports using several different serological assay methods. A reliable and specific method for anti-BDV antibodies needs to be developed to clarify the pathological significance of BDV infections in humans. We developed a new electrochemiluminescence immunoassay (ECLIA) for the antibody to BDV that uses two recombinant proteins of BDV, p40 and p24 (full length). Using this ECLIA, we examined 3,476 serum samples from humans with various diseases and 917 sera from blood donors in Japan for the presence of anti-BDV antibodies. By ECLIA, 26 (3.08%) of 845 schizophrenia patients and 9 (3.59%) of 251 patients with mood disorders were seropositive for BDV. Among 323 patients with other psychiatric diseases, 114 with neurological diseases, 75 with chronic fatigue syndrome, 85 human immunodeficiency virus-infected patients, 50 with autoimmune diseases including rheumatoid arthritis and systemic lupus erythematosis and 17 with leprosy, there was no positive case except one case each with alcohol addiction, AIDS, and dementia. Although 19 (1.36%) of 1,393 patients with various ocular diseases, 10 (1.09%) of 917 blood donors, and 3 (4.55%) of 66 multitransfused patients were seropositive for BDV-specific antigen, high levels of seroprevalence in schizophrenia patients and young patients (16 to 59 years old) with mood disorders were statistically significant. The immunoreactivity of seropositive sera could be verified for specificity by blocking with soluble p40 and/or p24 recombinant protein. Anti-p24 antibody was more frequent than p40 antibody in most cases, and in some psychotic patients antibody profiles showed only p40 antibody. Although serum positive for both p40 and p24 antibodies was not found in this study, the p40 ECLIA count in schizophrenia patients was higher than that of blood donors. Furthermore, we examined 90 sera from Japanese feral horses. Antibody profiles of control human samples are similar to that of naturally BDV-infected feral horses. We concluded that BDV infection was associated in some way with psychiatric disorders. C1 Kumamoto Univ, Sch Med, Blood Transfus Serv, Ikeda, Kumamoto 860, Japan. Eisai Tsukuba Res Labs, Div Diagnost, Tsukuba, Ibaraki, Japan. Kumamoto City Publ Hlth Off, Kumamoto, Japan. Fukuoaka Red Cross Blood Ctr, Fukuoka, Japan. Miyazaki Univ, Fac Agr, Dept Vet Internal Med, Miyazaki 88921, Japan. Tokyo Inst Psychiat, Dept Ultrastruct & Histochem, Tokyo, Japan. Kurume Univ, Sch Med, Dept Ophthalmol, Kurume, Fukuoka 830, Japan. Fukushima Med Coll, Dept Microbiol, Fukushima, Japan. Kyushu Univ, Sch Med, Dept Psychiat Med, Fukuoka 812, Japan. Kagoshima Univ, Sch Med, Dept Neuropsychiat & Virol, Kagoshima 890, Japan. Univ Mississippi, Med Ctr, Dept Psychiat, Jackson, MS 39216 USA. US FDA, Div Viral Prod, Washington, DC 20204 USA. RP Yamaguchi, K (reprint author), Kumamoto Univ, Sch Med, Blood Transfus Serv, Honjo 1-1-1, Ikeda, Kumamoto 860, Japan. NR 26 TC 37 Z9 40 U1 1 U2 3 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 SEP PY 1999 VL 6 IS 5 BP 696 EP 700 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 235LE UT WOS:000082542500012 PM 10473520 ER PT J AU Sacchi, CT Brandt, ME Whitney, AM Mayer, LW Lemos, APS Melles, CEA Solari, CA Frasch, CE AF Sacchi, CT Brandt, ME Whitney, AM Mayer, LW Lemos, APS Melles, CEA Solari, CA Frasch, CE TI Neisseria meningitidis subtype nomenclature - Reply SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Letter C1 Ctr Dis Control & Prevent, Meningitis & Special Pathogens Branch, Atlanta, GA 30333 USA. Adolfo Lutz Inst, Dept Bacteriol, Sao Paulo, Brazil. Fdn Oswaldo Cruz, Dept Bacteriol, Rio De Janeiro, Brazil. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Sacchi, CT (reprint author), Ctr Dis Control & Prevent, Meningitis & Special Pathogens Branch, Mailstop D-11,1600 Clifton Rd, Atlanta, GA 30333 USA. NR 4 TC 0 Z9 0 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 SEP PY 1999 VL 6 IS 5 BP 771 EP 772 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 235LE UT WOS:000082542500028 ER PT J AU Fritsch, C Brown, JL Kassis, JA Muller, J AF Fritsch, C Brown, JL Kassis, JA Muller, J TI The DNA-binding Polycomb group protein Pleiohomeotic mediates silencing of a Drosophila homeotic gene SO DEVELOPMENT LA English DT Article DE Drosophila; PcG genes; PRE; pho; YY1 ID BITHORAX COMPLEX; REGULATORY ELEMENTS; UBX GENE; ULTRABITHORAX EXPRESSION; SPATIAL EXPRESSION; RESPONSE ELEMENTS; MELANOGASTER; REPRESSION; HUNCHBACK; BOUNDARIES AB Polycomb group (PcG) proteins repress homeotic genes in cells where these genes must remain inactive during development. This repression requires cia-acting silencers, also called PcG response elements. Currently, these silencers are ill-defined sequences and it is not known how PcG proteins associate with DNA. Here, we show that the Drosophila PcG protein Pleiohomeotic binds to specific sites in a silencer of the homeotic gene Ultrabithorax. In an Ultrabithorax reporter gene, point mutations in these Pleiohomeotic binding sites abolish PcG repression in vivo. Hence, DNA-bound Pleiohomeotic protein may function in the recruitment of other non-DNA-binding PcG proteins to homeotic gene silencers. C1 Max Planck Inst Entwicklungsbiol, D-72076 Tubingen, Germany. US FDA, Dev Biol Lab, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Muller, J (reprint author), Max Planck Inst Entwicklungsbiol, Spemannstr 35-3, D-72076 Tubingen, Germany. OI Kassis, Judith/0000-0001-9268-3213 NR 51 TC 129 Z9 133 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD SEP PY 1999 VL 126 IS 17 BP 3905 EP 3913 PG 9 WC Developmental Biology SC Developmental Biology GA 239WP UT WOS:000082793200017 PM 10433918 ER PT J AU Nduaka, CI Taylor, RE Green, S Flynn, T Sathyamoorthy, V Sprando, RL Johannessen, JN AF Nduaka, CI Taylor, RE Green, S Flynn, T Sathyamoorthy, V Sprando, RL Johannessen, JN TI Glutamate release from chick retina explants in response to domoic acid SO IN VITRO & MOLECULAR TOXICOLOGY-A JOURNAL OF BASIC AND APPLIED RESEARCH LA English DT Article ID RAT-BRAIN SYNAPTOSOMES; ENDOGENOUS AMINO-ACIDS; KAINIC ACID; GANGLION-CELLS; NEUROTOXICITY; RECEPTORS; ASPARTATE; INVITRO; KAINATE; MECHANISMS AB Release of endogenous glutamate (GLU) evoked by an exogenous excitotoxin such as kainate can contribute to central nervous system (CNS) excitotoxicity. In this study, the possibility that this mechanism accounts for reported domoic acid (DOM) toxicity was investigated using the isolated chick retina. Exposing retinas to 0-100 mu M DOM for 40 min caused an increased efflux of lactate dehydrogenase (LDH) and a dose-related release of GLU into the incubation medium. Neuronal damage following exposure to DOM was confirmed by histologic examination of the retina, DOM-induced GLU release occurred at 27 and 37 degrees C and was more pronounced in medium containing a low calcium concentration (0.1 mM). In contrast, K+ evoked GLU release occurred only at 37 degrees C in 2 mM calcium, but not at 27 degrees C. DOM-induced GLU release was reduced in hyperosmolar medium (medium + 100 mM sucrose). Similar to GLU release, the LDH release occurred at both 27 and 37 degrees C and was reduced in hyperosmolar medium. These results suggest that an increase in membrane permeability secondary to osmotic swelling and lysis rather than a calcium-dependent vesicular exocytosis mechanism is responsible for GLU and LDH release. GYKI 52466, a selective noncompetitive antagonist of the non-NMDA receptor, prevented neuronal degeneration and GLU/LDH release. MK-801, a highly potent noncompetitive NMDA receptor blocker, reduced neuronal injury (33% decrease in LDH release), but did not reduce DOM-evoked GLU release significantly. Typical excitotoxic lesions were produced at all concentrations tested, with amacrine cells hi the inner nuclear layer being the most severely affected, Released GLU contributed to further excitotoxic injury, exacerbating the neurotoxic action of DOM in isolated embryonic chick retina. C1 US FDA, CFSAN, Div Toxicol Res, Laurel, MD 20708 USA. Howard Univ, Coll Med, Dept Pharmacol, Washington, DC 20059 USA. RP Johannessen, JN (reprint author), US FDA, CFSAN, Div Toxicol Res, 8301 Muirkirk Rd, Laurel, MD 20708 USA. OI Flynn, Thomas/0000-0002-7248-0643 NR 43 TC 3 Z9 4 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1097-9336 J9 IN VITRO MOL TOXICOL JI In Vitro Mol. Toxicol.-J. Basic Appl. Res. PD FAL PY 1999 VL 12 IS 3 BP 173 EP 182 PG 10 WC Toxicology SC Toxicology GA 321KB UT WOS:000087453700006 ER PT J AU Agranovich, I Scott, DE Terle, D Lee, K Golding, B AF Agranovich, I Scott, DE Terle, D Lee, K Golding, B TI Down-regulation of Th2 responses by Brucella abortus, a strong Th1 stimulus, correlates with alterations in the B7.2-CD28 pathway SO INFECTION AND IMMUNITY LA English DT Article ID T-CELL ACTIVATION; AUTOIMMUNE-DISEASE; IMMUNE-RESPONSE; IL-4 PRODUCTION; DISTINCT ROLES; IFN-GAMMA; B-ABORTUS; V3 LOOP; CD28; CTLA-4 AB Down-regulation of the Th2-like response induced by ovalbumin-alum (OVA/alum) immunization by heat-killed Brucella abortus was not reversed by anti-IL-12 antibody treatment or in gamma interferon (IFN-gamma) knockout mice, suggesting that induction of Th1 cytokines was not the only mechanism involved in the B. abortus-mediated inhibition of the Th2 response to OVA/alum. The focus of this study was to determine whether an alternative pathway involves alteration in expression of costimulatory molecules, First we show that the Th2-like response to OVA/alum is dependent on B7.2 interaction with ligand since it can be abrogated by anti-B7.2 treatment. Expression of costimulatory molecules was then studied in mice immunized with OVA/alum in the absence or presence of B. abortus. B7.2, but not B7.1, was up-regulated on mouse non-T and T cells following immunization,vith B. abortus. Surprisingly, B. abortus induced down-regulation of CD28 and upregulation of B7.2 on murine CD4(+) and CD8(+) T cells. These effects on T cells were maximal for CD28 and B7.2 at 40 to 48 h and were not dependent on interleukin-12 (IL-12) or IFN-gamma. On the basis of these results, we propose that the IL-12/IFN-gamma-independent inhibition of Th2 responses to OVA/alum is secondary to the effects of B. abortus on expression of costimulatory molecules on T cells. We suggest that down-regulation of CD28 following activation inhibits subsequent differentiation of Th0 into Th2 cells. In addition, decreased expression of CD28 and increased expression of B7.2 on T cells would favor B7.2 interaction with CTLA-4 on T cells, and this could provide a negative signal to developing Th2 cells. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Plasma Derivat, Bethesda, MD 20852 USA. RP Golding, B (reprint author), Bldg 29,Rm 232,1401 Woodmont,Rockville Pike, Rockville, MD 20852 USA. NR 52 TC 17 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1999 VL 67 IS 9 BP 4418 EP 4426 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 228LU UT WOS:000082138600016 PM 10456882 ER PT J AU Li, ZM Howard, A Kelley, C Delogu, G Collins, F Morris, S AF Li, ZM Howard, A Kelley, C Delogu, G Collins, F Morris, S TI Immunogenicity of DNA vaccines expressing tuberculosis proteins fused to tissue plasminogen activator signal sequences SO INFECTION AND IMMUNITY LA English DT Article ID T-LYMPHOCYTE INDUCTION; MYCOBACTERIUM-TUBERCULOSIS; INTERFERON-GAMMA; IMMUNE-RESPONSE; MICE; IMMUNIZATION; VACCINATION; PROTECTION; INFECTION; EFFICACY AB Novel tuberculosis DNA vaccines encoding native ESAT-6, MPT-64, KatG, or HBHA mycobacterial proteins or the same proteins fused to tissue plasminogen activator (TPA) signal sequences were evaluated for their capacity to elicit humoral, cell-mediated, and protective immune responses in vaccinated mice. While all eight plasmids induced specific humoral responses, the constructs expressing the TPA fusions generally evoked higher antibody responses in vaccinated hosts. Although most of the DNA vaccines tested induced a substantial gamma interferon response in the spleen, the antigen-specific lung responses were 2- to 10-fold lower than the splenic responses at the time of challenge. DNA vaccines encoding the ESAT-6, MPT-64, and KatG antigens fused to TPA signal sequences evoked significant protective responses in mice aerogenically challenged with low doses of Mycobacterium tuberculosis Erdman 17 to 21 days after the final immunization. However, the protective response induced by live Mycobacterium bovis BCG vaccine was greater than the response induced by any of the DNA vaccines tested. These results suggest that the tuberculosis DNA vaccines were able to elicit substantial immune responses in suitably vaccinated mice, but further refinements to the constructs or the use of alternative immunization strategies will be needed to improve the efficacy of these vaccine candidates. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mycobacteria, OVRR, Bethesda, MD 20892 USA. RP Morris, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mycobacteria, OVRR, HFM 431,Bldg 29,Room 502,29 Lincoln Dr, Bethesda, MD 20892 USA. RI Delogu, Giovanni/I-3701-2012 OI Delogu, Giovanni/0000-0003-0182-8267 NR 43 TC 130 Z9 153 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1999 VL 67 IS 9 BP 4780 EP 4786 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 228LU UT WOS:000082138600065 PM 10456931 ER PT J AU Lee, CJ AF Lee, CJ TI Advances in pneumococcal vaccines SO INFECTIONS IN MEDICINE LA English DT Article DE pneumococcal vaccine; immunity; immune response; Streptococcus pneumoniae; preventive medicine ID RESISTANT STREPTOCOCCUS-PNEUMONIAE; CAPSULAR POLYSACCHARIDE VACCINE; UNITED-STATES; CONJUGATE VACCINE; ANTIBODY-RESPONSE; CHILDREN; BACTEREMIA; INFECTIONS; DISEASE; MICE AB Streptococcus pneumoniae is a leading cause of serious infection in young children, immunodeficient persons, and the elderly. However, the efficacy of the current 23-valent pneumococcal polysaccharide (PS) vaccine has ranged from 56% to 81% against invasive disease and is not recommended for young children. Therefore, more immunogenic pneumococcal vaccines are needed that can also be used in children younger than 2 years. Clinical trials of conjugate vaccines with capsular PS linked to protein carriers showed improved immunogenicity. Animal studies have been conducted to express pneumococcal cell-surface protein genes in mammalian cells for use in new types of conjugate vaccines. These experimental vaccines have rapidly cleared bacteria from the blood of mice following challenge with certain capsular types of pneumococci. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Lee, CJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 77 TC 6 Z9 6 U1 0 U2 1 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0749-6524 J9 INFECT MED JI Infect. Med. PD SEP PY 1999 VL 16 IS 9 BP 596 EP + PG 12 WC Infectious Diseases SC Infectious Diseases GA 241KX UT WOS:000082883200009 ER PT J AU Mahmood, I Miller, R AF Mahmood, I Miller, R TI Comparison of the Bayesian approach and a limited sampling model for the estimation of AUC and C-max: a computer simulation analysis SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE Bayesian approach; limited sampling model; AUC and C-max estimation; computer simulation analysis ID MAXIMUM PLASMA-CONCENTRATION; UNDER-THE-CURVE; AREA; PHARMACOKINETICS; CARBAMAZEPINE AB Objectives: To compare two limited sampling methods (Bayesian and the limited sampling model) for the estimation of AUC and C-max following a single oral dose of a hypothetical drug. Methods: The plasma concentration vs time data sets for 50 subjects using a linear one- or two-compartment pharmacokinetic model were generated by simulation. The limited sampling model (LSM) was developed using samples from 10 subjects using one or two time points. The simulated plasma concentrations were also used for Bayesian evaluation. Bayesian analysis was performed on Non-Mem and mean pharmacokinetic parameters used for simulation were assumed as population pharmacokinetic parameters. In addition a test drug was also used to compare the predicted AUC and C-max for the two approaches. Results: Both methods were validated in 40 subjects for the hypothetical drug and in 12 subjects for the test drug. Both methods provided good estimates of AUC and C-max. Conclusion: The results indicate that the LSM is similar to the Bayesian method and may be used in lieu of the Bayesian approach in estimating AUC and C-max, using one or two samples in clinical settings without detailed pharmacokinetic studies. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1, Woodmont Off,Ctr 2, Rockville, MD 20892 USA. RP Mahmood, I (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1, Woodmont Off,Ctr 2, 1451 Rockville Pike, Rockville, MD 20892 USA. NR 18 TC 15 Z9 15 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI MUNCHEN-DEISENHOFEN PA BAHNHOFSTRABE 9 POSTFACH 49, W-8024 MUNCHEN-DEISENHOFEN, GERMANY SN 0946-1965 J9 INT J CLIN PHARM TH JI Int. J. Clin. Pharmacol. Ther. PD SEP PY 1999 VL 37 IS 9 BP 439 EP 445 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 235DL UT WOS:000082524700003 PM 10507242 ER PT J AU Li, R Serdula, MK Williamson, DF Bowman, BA Graham, DJ Green, L AF Li, R Serdula, MK Williamson, DF Bowman, BA Graham, DJ Green, L TI Dose-effect of fenfluramine use on the severity of valvular heart disease among fen-phen patients with valvulopathy SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE dose-effect; fenfluramine-phentermine; severity of valvulopathy ID APPETITE-SUPPRESSANT DRUGS; OBESE PATIENTS AB OBJECTIVE: To determine whether the severity of valvulopathy was associated with the dosage of fenfluramine taken by fenfluramine-phentermine users with valvulopathy, DESIGN: Out of 105 suspected valvulopathy case reports received by the US Food and Drug Administration (FDA) among fenfluramine-phentermine users, 74 patients meeting FDA case definition for valvulopathy were included in this study. Patients with severe valvulopathy were classified as those either undergoing valve replacement surgery or having severe aortic or mitral regurgitation; all other patients were considered to have less severe valvulopathy. RESULTS: The proportion with severe valvulopathy increased from 20-66% with increasing fenfluramine dosage from less than or equal to 40 mg/d to greater than or equal to 60 mg/d, Compared with patients taking <40 mg/d fenfluramine, patients taking greater than or equal to 60 mg/d had an adjusted odds ratio of 9.2 (95% confidence interval = 2.1-40.8) for severe valvulopathy, CONCLUSION: Compared to patients with less severe valvulopathy, those with severe valvulopathy were substantially more likely to have taken greater than or equal to 60 mg/d fenfluramine. C1 Ctr Dis Control & Prevent, Epidem Intelligence Serv, Epidemiol Program Off, Atlanta, GA 30341 USA. Ctr Dis Control & Prevent, Div Nutr & Phys Act, Atlanta, GA 30341 USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Diabet Translat, Atlanta, GA 30341 USA. US FDA, Div Pharmacovigilance & Epidemiol, Reports Evaluat Branch, Rockville, MD 20857 USA. RP Li, R (reprint author), Ctr Dis Control & Prevent, Div Nutr & Phys Act, Mailstop K26,4770 Buford Hwy NE, Atlanta, GA 30341 USA. NR 12 TC 20 Z9 20 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD SEP PY 1999 VL 23 IS 9 BP 926 EP 928 DI 10.1038/sj.ijo.0801020 PG 3 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 233WB UT WOS:000082449200003 PM 10490797 ER PT J AU Minemura, M Tanimura, H Tabor, E AF Minemura, M Tanimura, H Tabor, E TI Overexpression of multidrug resistance genes MDR1 and cMOAT in human hepatocellular carcinoma and hepatoblastoma cell lines SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE multidrug resistance; hepatocellular carcinoma; hepatoblastoma ID DRUG-RESISTANCE; EXPRESSION; CANCER; DOXORUBICIN; REVERSAL AB Overexpression of either of the multidrug resistance genes MDR1 and MRP is associated with resistance of tumors to multiple chemotherapeutic agents. Overexpression of MDR1 has been reported in some cell lines derived from human hepatocellular carcinomas (HCC) and hepatoblastomas (HB). The human gene for cMOAT ('canalicular multispecific organic anion transporter'), a homologue of MRP, is thought to mediate hepatobiliary excretion of organic anions and to be associated with cisplatin resistance. In this study, expression levels of MDR1 and cMOAT were examined in 9 human HCC and HE cell lines and 10 other human cancer cell lines. Overexpression of the cMOAT gene was observed in all 9 HCC and HE cell lines and 3 of 10 other cancer cell lines. Co-overexpression of the cMOAT and MDR1 genes was observed in 7 of 9 HCC and HE cell lines, but in none of the 10 other cancer cell lines. Seven of the HCC and HE cell lines that had overexpression of the cMOAT gene were shown to be highly resistant to cisplatin compared to 2 HCC cell lines with low levels of cMOAT expression. These findings suggest that overexpression of cMOAT could contribute to cisplatin resistance in HCC and HB. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Oita Med Sch, Dept Surg 2, Oita, Japan. RP Tabor, E (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-300,1401 Rockville Pike, Rockville, MD 20852 USA. NR 17 TC 59 Z9 61 U1 0 U2 1 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 SEP PY 1999 VL 15 IS 3 BP 559 EP 563 PG 5 WC Oncology SC Oncology GA 224DH UT WOS:000081881400022 PM 10427140 ER PT J AU Rao, PS Lyn-Cook, BD Littlefield, NA Mehendale, HM AF Rao, PS Lyn-Cook, BD Littlefield, NA Mehendale, HM TI High glucose concentration alters cell proliferation dynamics in human hepatoma cells SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE cell cycle; cell division; glucose; HuH7 cells; thioacetamide; tissue repair ID CARBON-TETRACHLORIDE HEPATOTOXICITY; LIVER-REGENERATION; HEPATOCELLULAR REGENERATION; TISSUE-REPAIR; C-MYC; DNA-SYNTHESIS; INJURY; GROWTH; THIOACETAMIDE; EXPRESSION AB The aim of this study was to develop an in vitro model to investigate the molecular mechanisms of glucose-induced inhibition of cell proliferation. HuH7 cells were grown in the presence or absence of glucose for 7 days and cell proliferation was stimulated by exposure to thioacetamide, Lactate dehydrogenase leakage and H-3-thymidine incorporation were used as indices of toxicity and DNA synthesis, respectively. Cell cycle progression and protooncogene expression was monitored by flow cytometry and slot-blot analyses. Toxicity caused by thioacetamide regressed with time in the presence of 11 mM glucose (control). However, in the presence of 28 mM glucose, sustained toxicity was evident as mirrored by lactate dehydrogenase leakage. Peak DNA synthesis noted at 48 hours in the thioacetamide-treated group (11 mM glucose) was significantly diminished in the presence of 28 mM glucose. Increased c-myc expression was observed as early as 30 minutes in the thioacetamide-treated group. When cells were exposed to 28 mM glucose, c-myc expression was delayed and diminished. Methylation profile studies revealed no appreciable changes, but c-myc was significantly amplified in the control, thioacetamide-, and in the presence of 28 mM of glucose-treated groups which correlated with mRNA changes in these groups. In the glucose-pretreated group (28 mM) significant amplification of the c-myc gene was observed at later time points but there was no change in the mRNA expression, indicating that the expression was delayed. This study shows that high glucose concentrations diminish DNA synthesis and cell cycle progression normally stimulated by thioacetamide. It is concluded that high glucose concentration causes cell cycle arrest via perturbation in protooncogene expression and hence the use of high glucose concentrations in therapy should be carefully examined in situations where postsurgical healing and healing after xenobiotic-induced injury are encountered. C1 NE Louisiana Univ, Coll Pharm & Hlth Sci, Div Toxicol, Monroe, LA 71209 USA. Natl Ctr Toxicol Res, Div Nutr Toxicol, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), NE Louisiana Univ, Coll Pharm & Hlth Sci, Div Toxicol, 700 Univ Ave, Monroe, LA 71209 USA. NR 42 TC 7 Z9 7 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD SEP-OCT PY 1999 VL 18 IS 5 BP 297 EP 306 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 252HF UT WOS:000083495500002 ER PT J AU Nguyen, GT Carrington, M Beeler, JA Dean, M Aledort, LM Blatt, PM Cohen, AR DiMichele, D Eyster, ME Kessler, CM Konkle, B Leissinger, C Luban, N O'Brien, SJ Goedert, JJ O'Brien, TR AF Nguyen, GT Carrington, M Beeler, JA Dean, M Aledort, LM Blatt, PM Cohen, AR DiMichele, D Eyster, ME Kessler, CM Konkle, B Leissinger, C Luban, N O'Brien, SJ Goedert, JJ O'Brien, TR TI Phenotypic expressions of CCR5-Delta 32/Delta 32 homozygosity SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE AIDS; CCR5; chemokine; chemokine; receptors; epidemiology; genetics; HIV-1; hemophilia; hepatitis C virus; hypertension; lymphocytes; therapy ID HUMAN IMMUNODEFICIENCY VIRUS; HIV-1 INFECTION; CHEMOKINE RECEPTORS; DISEASE PROGRESSION; DELETION ALLELE; CCR5; RESISTANCE; AIDS; GENE; CORECEPTOR AB Objective: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-Delta 32/Delta 32 homozygous genotype has phenotypic expressions other than those related to HIV-1. Design: Study subjects were white homosexual men or men with hemophilia who were not infected with HIV-1. In this study, 15 CCR5-Delta 32/Delta 32 homozygotes were compared with 201 CCR5 wild-type (+/+) subjects for a wide range of clinical conditions and laboratory assay results ascertained during prospective cohort studies and routine clinical care. CCR5-Delta 32 genotype was determined by polymerase chain reaction, followed by single-stranded conformational polymorphism analysis. Results: Hypertension and conditions attributable to hemophilia were the only diagnoses frequently found in clinical records of CCR5-Delta 32/Delta 32 study subjects. Based on blood pressure measurement and treatment history, CCR5-Delta 32/Delta 32 homozygotes had a 2.8-fold higher prevalence of hypertension than age-matched CCR5-+/+ study subjects (95% confidence interval [CI], 1.2-6.4; p = .01); none of the homozygotes had severe hypertension. Hematologic measures were generally similar across the genotypes, but total lymphocyte counts were similar to 20% higher in CCR5-Delta 32/Delta 32 study subjects than in CCR5-+/+ study subjects (p < .05). Among patients with hemophilia who were infected with hepatitis C virus (HCV), mean alanine aminotransferase levels were 117% higher among CCR5-Delta 32/Delta 32 homozygotes (p < .05), but serum HCV levels did not differ by CCR5-Delta 32 genotype. CCR5-Delta 32/Delta 32 homozygous study subjects had a lower prevalence of antibodies to measles virus than those with other genotypes, but this association was not confirmed in a group of blood donors. The prevalence of antibodies to nine other common viruses, HBV, and HCV was not related to CCR5 genotype. Conclusions: CCR5-Delta 32/Delta 32 homozygotes are generally similar to wild-type persons. Confirmatory investigations are required to determine whether hypertension, increased lymphocyte counts, and higher hepatic enzyme levels in the presence of HCV infection represent true phenotypic expressions of this genotype. CCR5-Delta 32/Delta 32 homozygosity does not provide broad protection against viral infections. C1 US Dept HHS, Viral Epidemiol Branch, NCI, Rockville, MD 20852 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD USA. US FDA, Div Viral Prod, Bethesda, MD 20014 USA. NCI, Lab Genomic Divers, Frederick, MD 21701 USA. Mt Sinai Med Ctr, Hemophilia Ctr, New York, NY 10029 USA. Christiana Hosp, Delaware Clin & Lab Phys, Newark, DE USA. Childrens Hosp Philadelphia, Hemophilia Ctr, Dept Hematol, Philadelphia, PA 19104 USA. Cornell Univ, Med Ctr, New York Hosp, Dept Pediat Hematol Oncol, New York, NY 10021 USA. Penn State Univ, Milton S Hershey Med Ctr, Sch Med, Div Hematol Oncol, Hershey, PA 17033 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Thomas Jefferson Univ Hosp, Cardeza Fdn Hemophilia Ctr, Philadelphia, PA 19107 USA. Tulane Univ, Sch Med, Hematol Oncol Sect, New Orleans, LA 70112 USA. Childrens Hosp, Natl Med Ctr, Dept Hematol Oncol, Hemophilia Ctr, Washington, DC 20010 USA. RP O'Brien, TR (reprint author), US Dept HHS, Viral Epidemiol Branch, NCI, 6120 Execut Blvd 8016, Rockville, MD 20852 USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [N01-CP-33002, N01-CP-40521] NR 39 TC 46 Z9 47 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD SEP 1 PY 1999 VL 22 IS 1 BP 75 EP 82 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 245TV UT WOS:000083125000010 PM 10534150 ER PT J AU Ciolino, LA McCauley, HA Fraser, DB Barnett, DY Yi, TY Turner, JA AF Ciolino, LA McCauley, HA Fraser, DB Barnett, DY Yi, TY Turner, JA TI Reversed phase ion-pair liquid chromatographic determination of nicotine in commercial tobacco products. 1. Moist snuff SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE nicotine; moist snuff; tobacco; alkaloids; reversed phase ion-pair liquid chromatography ID ALKALOIDS AB The official methods for the determination of nicotine in commercial tobacco products (AOAC, CORESTA) are based on approaches that are not selective for nicotine (colorimetric measurement, steam distillation, perchloric acid titration), and the availability of published methods based on state-of-the-art chromatographic methods is limited. Reversed phase ion-pair liquid chromatography has been established as a viable alternative for the analysis of basic analytes. A reversed phase ion-pair liquid chromatographic method for the determination of nicotine in commercial tobacco products was developed and optimized in separate experiments (Ciolino, L. A.; Turner, J. A.; McCauley, H. A; Smallwood, A. W.; Yi, T. Y. J. Chromatogr. 1999a, 852 (2), 451-463). An extensive within-laboratory performance study of the optimized method was subsequently conducted, and results are presented here for the determination of nicotine in commercial moist snuff. Results for the determination of nicotine in commercial cigarettes are presented in a subsequent paper (Ciolino, L. A.; Fraser, D. B.; Yi, T. Y.; Turner, J. A.; Barnett, D. Y.; McCauley, H. A. J. Agric. Food Chem. 1999b, 47, 3713-3717). C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45202 USA. RP Ciolino, LA (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. NR 32 TC 7 Z9 8 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD SEP PY 1999 VL 47 IS 9 BP 3706 EP 3712 DI 10.1021/jf990049s PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 238GM UT WOS:000082702600039 PM 10552709 ER PT J AU Ciolino, LA Fraser, DB Yi, TY Turner, JA Barnett, DY McCauley, HA AF Ciolino, LA Fraser, DB Yi, TY Turner, JA Barnett, DY McCauley, HA TI Reversed phase ion-pair liquid chromatographic determination of nicotine in commercial tobacco products. 2. Cigarettes SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE nicotine; cigarettes; tobacco; alkaloids; reversed phase ion-pair liquid chromatography AB A reversed phase ion-pair liquid chromatographic method for the determination of nicotine in commercial tobacco products was previously developed and optimized (Ciolino, L. A.; Turner, J. A.; McCauley, H. A.; Smallwood, A. W.;Yi, T. Y. J. Chromatogr. 1999a, 852 (2), 451-463) and provided reliable results for the determination of nicotine in commercial moist snuff(Ciolino, L. A.; McCauley, H. A.; Fraser, D. B.; Barnett, D. Y.; Yi, T. Y.; Turner, J. A. J. Agric. Food Chem. 1999b, 47, 3706-3712). The method uses an aqueous-based sample extraction and provides rapid separation of nicotine from the minor tobacco alkaloids and other commercial tobacco components. In the present work, the method is evaluated for the determination of nicotine in commercial cigarettes and compared to both an official AOAC method for total alkaloids in tobacco (AOAC, AOAC Official Methods of Analysis of AOAC International, 16th ed.; AOAC International: Gaithersburg, MD, 1995; pp 30-31), and a published GC method (Lyerly, L. A.; Greene, G. H. Beitr. Tabakforsch. 1976, 8 (6), 359-361). Good agreement was obtained between the ion-pair LC method and the GC method with relative differences in determined nicotine contents of 0.6 to 5% for a series of commercial and reference cigarettes. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45202 USA. RP Ciolino, LA (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. NR 8 TC 8 Z9 9 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD SEP PY 1999 VL 47 IS 9 BP 3713 EP 3717 DI 10.1021/jf990050r PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 238GM UT WOS:000082702600040 PM 10552710 ER PT J AU Holder, CL Churchwell, MI Doerge, DR AF Holder, CL Churchwell, MI Doerge, DR TI Quantification of soy isoflavones, genistein and daidzein, and conjugates in rat blood using LC/ES-MS SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE genistein; soy; isoflavone; electrospray mass spectrometry ID MASS-SPECTROMETRY; EXCRETION; PLASMA AB Genistein is the principal soy isoflavone to which the putative beneficial effects of soy consumption have been attributed; however, the possibility of adverse biological effects (e.g., estrogenic, antithyroid) has also been raised. This paper describes development and validation of a simple and sensitive analytical method for the determination of genistein in the blood of rats receiving dietary genistein (<0.5-1250 mu g of genistein aglycone/g of chow). The method uses serum/plasma deproteination, liquid-liquid extraction, deuterated genistein and daidzein internal standards, isocratic LC separation, and electrospray mass spectrometric quantification using selected ion monitoring. Extraction efficiency is approximately 85%, the detection limits for genistein and daidzein from 50 mu L of rat blood are approximately 5 nM, and the limit of quantification is approximately 15 nM. Interassay precision (relative standard deviation 4.5-4.6%) and intraassay precision (3.3-6.7%) were determined from replicate analysis of a spiked control and an incurred serum sample. The distribution of conjugated and unconjugated forms of genistein in the blood of rats was determined using selective enzyme hydrolysis. The glucuronide was the predominant metabolite (>90%), and only small amounts of the sulfate conjugate and the aglycone were observed at all dose levels. No evidence for additional metabolites was obtained. The 7- and 4'-glucuronide conjugates of genistein were identified using electrospray mass spectrometry and H-1 NMR. Total blood genistein ranged from <15 nM in animals fed soy-free control diet to as high as 8.9 mu M in male rats fed 1250 mu g of genistein/g of chow and encompasses blood isoflavone levels observed in humans consuming a typical Asian diet and nutritional supplements (0.1-1 mu M) and infants consuming soy formulas (2-7 mu M). C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 15 TC 115 Z9 126 U1 1 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD SEP PY 1999 VL 47 IS 9 BP 3764 EP 3770 DI 10.1021/jf9902651 PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 238GM UT WOS:000082702600049 PM 10552719 ER PT J AU Hall, M Sykes, PA Fairclough, DL Lucchese, LJ Rogers, P Staruszkiewicz, W Bateman, RC AF Hall, M Sykes, PA Fairclough, DL Lucchese, LJ Rogers, P Staruszkiewicz, W Bateman, RC TI A test strip for diamines in tuna SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CANNED TUNA; HISTAMINE; FISH; CADAVERINE; PUTRESCINE; ASSAY; INHIBITION; SAMPLES; OXIDASE AB This study describes the production of a solid-phase assay (test strip/dipstick test) for putrescine and cadaverine in tuna based on the coupling of an amine oxidase to a peroxidase/dye system. The assay was linear to 75 mu M in phosphate buffer, and the minimum detectable concentration was 0.5 mu M (<0.1 ppm), corresponding to 0.01 mg% in spiked extracts. Intra- and interassay precisions were <20%. Test strips were stable at 4 degrees C for at least 12 months. Lysine, ornithine, and histidine did not react with the assay, and histamine reacted only minimally. Sixteen fish samples were tested by test strip and the standard AOAC protocol, and results were in good agreement. C1 Univ So Mississippi, Dept Chem & Biochem, Hattiesburg, MS 39406 USA. Univ So Mississippi, Dept Med Technol, Hattiesburg, MS 39406 USA. AMC Canc Res Ctr, Ctr Res Methodol & Biometry, Denver, CO 80214 USA. Serim Res Corp, Elkhart, IN 46514 USA. US FDA, Off Seafood, Washington, DC 20204 USA. RP Bateman, RC (reprint author), Univ So Mississippi, Dept Chem & Biochem, Hattiesburg, MS 39406 USA. NR 37 TC 3 Z9 3 U1 0 U2 1 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 1999 VL 82 IS 5 BP 1102 EP 1108 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 239UU UT WOS:000082788700010 PM 10513011 ER PT J AU Trucksess, MW Tang, YF AF Trucksess, MW Tang, YF TI Solid-phase extraction method for patulin in apple juice and unfiltered apple juice SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID CHROMATOGRAPHY AB Patulin, a mold metabolite, is commonly found in rotting apples. Some countries regulate patulin at levels ranging from 30 to 50 mu g/L. Most analytical methods for patulin in apple juice include liquid-liquid partitions. A solid-phase extraction method has been developed for apple juice and unfiltered apple juice in the United States. A portion of the test sample (5 mL) was passed through a macroporous copolymer cartridge and was washed with 1 mt 1% sodium bicarbonate and then with 1 mt 1% acetic acid. Patulin was eluted with 3 mt 2% acetonitrile in anhydrous ethyl ether and was determined by reversed-phase liquid chromatography with UV detection at 276 nm. Recoveries ranged from 93 to104% in test samples spiked at 20-100 mu g/L. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. WHO, Joint Inst Food Safety & Appl Nutr, Washington, DC 20204 USA. Shanghai Hlth & Quarantine, Shanghai, Peoples R China. RP Trucksess, MW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 13 TC 46 Z9 47 U1 0 U2 6 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 1999 VL 82 IS 5 BP 1109 EP 1113 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 239UU UT WOS:000082788700011 PM 10513012 ER PT J AU Cantellops, D Reid, AP Eitenmiller, RR Long, AR AF Cantellops, D Reid, AP Eitenmiller, RR Long, AR TI Determination of lipids in infant formula powder by direct extraction methylation of lipids and fatty acid methyl esters (FAME) analysis by gas chromatography SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID HYDROLYSIS AB Fatty acid methyl esters (FAMEs) of pure triglyceride standards, oils, and fat from dry matrixes were formed by transesterification using sodium methoxide in methanol-hexane. FAMEs were produced by direct addition of sodium methoxide-hexane to samples and heating to simultaneously extract and transesterify acyl lipids. FAMEs were quantitated by capillary gas chromatography (GC) over a fatty acid concentration range of 0 to 1.7 mg/mL (r greater than or equal to 0.9997). Total fat was calculated as the sum of individual fatty acids expressed as triglyceride equivalents, in accordance with nutrition labeling guidelines. Saturated, polyunsaturated, and monounsaturated fats were calculated as sums of individual free fatty acids. Absolute recoveries determined from individual fatty acids in test samples ranged from 69.7 to 106%, Recoveries (relative to the C13:0 internal standard) for individual fatty acids in test samples ranged from 95 to 106%, Reproducibility was constant at each fatty acid level in the reaction mixture (n = 5, coefficient of variation [CV] <2%). Absolute recovery determined from the sum of total fatty acids in standard reference material (SRM) 1846 (powdered infant formula) was 96.4%. Analysis of SRM 1846 gave results that agreed closely with the certified fat and fatty acid values. Analysis of commercial infant formula gave results that were comparable to those obtained with AOAC Method 996.01. The direct extraction methylation procedure is rapid, and the transesterification of acyl lipids to form FAMEs is complete within 15 min. Classical saponification and refluxing are not required. This method provides FAMEs free of interferences and easily quantitated by GC or confirmed by GC/mass spectrometry (MS). Unambiguous MS identification of individual FAMEs derived from pure standards, SRM 1846, and powdered infant formula product was obtained. C1 US FDA, SE Reg Lab, Atlanta Ctr Nutrient Anal, Atlanta, GA 30309 USA. Univ Georgia, Dept Food Sci & Technol, Athens, GA 30602 USA. RP Cantellops, D (reprint author), US FDA, SE Reg Lab, Atlanta Ctr Nutrient Anal, 60 8th St, Atlanta, GA 30309 USA. NR 15 TC 26 Z9 26 U1 1 U2 17 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 1999 VL 82 IS 5 BP 1128 EP 1139 PG 12 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 239UU UT WOS:000082788700013 PM 10513013 ER PT J AU Chase, GW Eitenmiller, RR Long, AR AF Chase, GW Eitenmiller, RR Long, AR TI Liquid chromatographic analysis of vitamin K-1 in milk-based infant formula with matrix solid-phase dispersion SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ALPHA-TOCOPHERYL ACETATE; PHYLLOQUINONE VITAMIN-K-1; ELECTROCHEMICAL DETECTION; FLUOROMETRIC DETECTION; RETINYL PALMITATE; AMERICAN DIET; FOOD SOURCES; HUMAN-PLASMA; HPLC; OILS AB A liquid chromatographic method for vitamin K-1 in milk-based infant formula is described. The vitamins are extracted from infant formula by matrix solid-phase dispersion and quantitated by reversed-phase chromatography with fluorescence detection. Vitamin K-1 is converted to the fluorescent hydroquinone with a postcolumn zinc reductive reactor. The limit of detection is 12 pg, and the limit of quantitation is 38 pg on-column. Linear responses were obtained in the range 0.55-22.1 ng/mL(r(2) = 0.9998). Recoveries of vitamin K-1 from an analyte-fortified blank material for milk-based infant formula averaged 91.7% (n = 25). The method provides a rapid, specific, and easily controlled assay for vitamin K-1 in fortified infant formula. C1 US FDA, SE Reg Lab, Atlanta, GA 30309 USA. Univ Georgia, Dept Food Sci & Technol, Athens, GA 30602 USA. RP Chase, GW (reprint author), US FDA, SE Reg Lab, 60 8th St, Atlanta, GA 30309 USA. NR 30 TC 9 Z9 9 U1 1 U2 6 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 1999 VL 82 IS 5 BP 1140 EP 1145 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 239UU UT WOS:000082788700014 PM 10513014 ER PT J AU Pfenning, AP Roybal, JE Turnipseed, SB Gonzales, SA Hurlbut, JA AF Pfenning, AP Roybal, JE Turnipseed, SB Gonzales, SA Hurlbut, JA TI Determination of residues of azamethiphos in salmon tissue by liquid chromatography with fluorescence detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A liquid chromatographic (LC) method with fluorescence detection (FLD) is described for determining residues of the pesticide azamethiphos (AZA) in salmon tissue. The sample is extracted with ethyl acetate, centrifuged, dehydrated with anhydrous sodium sulfate, evaporated, reconstituted in water, and defatted with hexane. The aqueous phase is passed through a C-18 solid-phase extraction (SPE) column. The SPE column is eluted with methanol, and the eluate is evaporated to dryness and then taken up in 10% acetonitrile (ACN) in water. The analyte is determined by LC using a C18 column, ACN-H2O (32 + 68) mobile phase, and FLD with excitation at 230 nm and emission at 345 nm. Composited salmon tissues were fortified with AZA at 5, 10, 21, 42, and 83 ng/g or ppb (target level, X = 10 ng/g). Overall recoveries were 86%, with between-day variability of 5.3%. The method detection limit was calculated as 1.2 ppb AZA based on a 5 g sample. The limit of quantitation as determined empirically by this method is the lower limit of the standard curve, approximately 5 ppb. C1 US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO 80225 USA. RP Pfenning, AP (reprint author), US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO 80225 USA. NR 4 TC 4 Z9 4 U1 1 U2 5 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 1999 VL 82 IS 5 BP 1224 EP 1228 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 239UU UT WOS:000082788700025 PM 10513020 ER PT J AU Griffin, BR Gollon, JL Hobbs, MS Kadlubar, FF Brand, CD AF Griffin, BR Gollon, JL Hobbs, MS Kadlubar, FF Brand, CD TI Effect of waterborne potassium permanganate exposure on manganese content in liver and axial muscle of channel catfish SO JOURNAL OF AQUATIC ANIMAL HEALTH LA English DT Article ID DIGESTION AB Adult channel catfish Ictalurus punctatus were exposed to waterborne potassium permanganate for 12 weeks to determine if such exposure would alter the manganese content of axial muscle or liver tissue. Continuous exposure to 0.5 mg KMnO4/L or exposlire to 1 or 2 mg KMnO4/L on alternate days did not cause a significant increase in manganese in axial muscle or liver tissue. The mean (+/-SE) concentration of manganese in axial muscle of unexposed controls was 0.262 +/- 0.018 mg/kg (wet weight). Means of manganese concentrations in axial muscle of the three exposure groups during the 12 weeks of exposure were 0.289 +/- 0.021 mg/kg, 0.269 +/- 0.018 mg/kg, and 0.239 +/- 0.013 mg/kg for 0.5 (continuous), 1, or 2 mg/L (alternate days), respectively. At specific sampling times there were differences between controls and exposure groups; however, no trend toward higher or lower manganese concentrations in muscle could be detected within groups. The mean (+/-SE) concentration of manganese in liver tissue of controls was 1.67 +/- 0.09 mg/kg (wet weight). Manganese concentrations in liver tissue of the three exposure groups were 1.57 +/- 0.07 mg/kg, 1.68 +/- 0.08 mg/kg, and 1.58 +/- 0.10 mg/kg, for 0.5 (continuous), 1, or 2 mg/L (alternate days), respectively. Manganese was thought to accumulate in liver tissue, however, there were no statistically significant differences between those groups and the controls. Results suggest that potassium permanganate used as a waterborne disease therapeutant for channel catfish does not alter manganese content of edible muscle of channel catfish and should not present any hazard to human consumers. C1 ARS, Stuttgart Natl Aquaculture Res Ctr, USDA, Stuttgart, AR 72160 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Griffin, BR (reprint author), ARS, Stuttgart Natl Aquaculture Res Ctr, USDA, POB 860, Stuttgart, AR 72160 USA. NR 16 TC 4 Z9 4 U1 0 U2 1 PU AMER FISHERIES SOC PI BETHESDA PA 5410 GROSVENOR LANE SUITE 110, BETHESDA, MD 20814-2199 USA SN 0899-7659 J9 J AQUAT ANIM HEALTH JI J. Aquat. Anim. Health PD SEP PY 1999 VL 11 IS 3 BP 305 EP 309 DI 10.1577/1548-8667(1999)011<0305:EOWPPE>2.0.CO;2 PG 5 WC Fisheries; Veterinary Sciences SC Fisheries; Veterinary Sciences GA 316TT UT WOS:000087184700014 ER PT J AU Kinnear, SM Boucher, PE Stibitz, S Carbonetti, NH AF Kinnear, SM Boucher, PE Stibitz, S Carbonetti, NH TI Analysis of BvgA activation of the pertactin gene promoter in Bordetella pertussis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID RNA-POLYMERASE; TRANSCRIPTIONAL ACTIVATION; VIRULENCE FACTORS; MAMMALIAN-CELLS; TOXIN PROMOTER; DNA-BINDING; EXPRESSION; SEQUENCES; PROTEIN; CONSTRUCTION AB Bordetella pertussis, the causative agent of whooping cough, regulates expression of its virulence factors via a two-component signal transduction system encoded by the bvg regulatory locus. It has been shown by activation kinetics that several of the virulence factors are differentially regulated. fha is transcribed at 10 min following an inducing signal, while ptx is not transcribed until 2 to 4 h after the inducing signal. We present data indicating that prn is transcribed at 1 h, an intermediate time compared to those of fha and ptx. We have identified cis-acting sequences necessary for expression of pm in B. pertussis by using prn-lac fusions containing alterations in the sequence upstream of the prn open reading frame. In vitro transcription and DNase I footprinting analyses provided evidence to support our hypothesis that BvgA binds to this sequence upstream of prn to activate transcription from the promoter. Our genetic data indicate that the region critical for prn activation extends upstream to position -84. However, these data do not support the location of the prn transcription start site as previously published. We used a number of methods, including prn-lac fusions, reverse transcriptase PCR, and 5' rapid amplification of cDNA ends, to localize and identify the bvg-dependent 5' end of the prn transcript to the cytosine at -125 with respect to the published start site. C1 Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Bethesda, MD 20892 USA. RP Carbonetti, NH (reprint author), Univ Maryland, Sch Med, Dept Microbiol & Immunol, BRB-13-009,655 W Baltimore St, Baltimore, MD 21201 USA. FU NIAID NIH HHS [AI32946] NR 31 TC 36 Z9 39 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 1999 VL 181 IS 17 BP 5234 EP 5241 PG 8 WC Microbiology SC Microbiology GA 231PB UT WOS:000082318000013 PM 10464192 ER PT J AU Schmitt, MP AF Schmitt, MP TI Identification of a two-component signal transduction system from Corynebacterium diphtheriae that activates gene expression in response to the presence of heme and hemoglobin SO JOURNAL OF BACTERIOLOGY LA English DT Article ID TOXIN REPRESSOR DTXR; ESCHERICHIA-COLI O157-H7; OUTER-MEMBRANE PROTEIN; IRON-TRANSPORT; PORPHYROMONAS-GINGIVALIS; YERSINIA-ENTEROCOLITICA; HAEMOPHILUS-INFLUENZAE; SHIGELLA-DYSENTERIAE; DEPENDENT REGULATION; BINDING AB Corynebacterium diphtheriae, the causative agent of diphtheria, utilizes various host compounds to acquire iron. The C. diphtheriae hmuO gene encodes a heme oxygenase that is involved in the utilization of heme and hemoglobin as iron sources. Transcription of the hmuO gene in C. diphtheriae is controlled under a dual regulatory mechanism in which the diphtheria toxin repressor protein (DtxR) and iron repress expression while either heme or hemoglobin is needed to activate transcription. In this study, two clones isolated from a C. diphtheriae chromosomal library were shown to activate transcription from the hmuO promoter in Escherichia coli, Sequence analysis revealed that these activator clones each carried distinct genes whose products had significant homology to response regulators of two-component signal transduction systems. Located upstream from each of these response regulator homologs are partial open reading frames that are predicted to encode the C-terminal portions of sensor kinases. The full-length sensor kinase gene for each of these systems was cloned from the C. diphtheriae chromosome, and constructs each carrying one complete sensor kinase gene and its cognate response regulator were constructed. One of these constructs, pTSB20, which carried the response regulator (chrA) and its cognate sensor kinase (chrS), mas shown to strongly activate transcription from the hmuO promoter in a heme-dependent manner in E. coli. A mutation in chrA (chrAD50N), which changed a conserved aspartic acid residue at position 50, the presumed site of phosphorylation by ChrS, to an asparagine, abolished heme-dependent activation. These findings suggest that the sensor kinase ChrS is invoiced in the detection of heme and the transduction of this signal, via a phosphotransfer mechanism, to the response regulator ChrA, which then activates transcription of the hmuO promoter. This is the first report of a bacterial two-component signal transduction system that controls gene expression through a heme-responsive mechanism. C1 US FDA, Lab Bacterial Toxins, Div Bacterial Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Schmitt, MP (reprint author), US FDA, Lab Bacterial Toxins, Div Bacterial Prod, Ctr Biol Evaluat & Res, Bldg 29,Room 108,8800 Rockville Pike, Bethesda, MD 20892 USA. EM schmitt@cber.fda.gov NR 52 TC 52 Z9 53 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 1999 VL 181 IS 17 BP 5330 EP 5340 PG 11 WC Microbiology SC Microbiology GA 231PB UT WOS:000082318000025 PM 10464204 ER PT J AU Stibitz, S Yang, MS AF Stibitz, S Yang, MS TI Genomic plasticity in natural populations of Bordetella pertussis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; CHROMOSOME; EVOLUTION; SEQUENCE AB We determined the genomic organization of 14 clinical strains of Bordetella pertussis isolated over an 18-month period in Alberta, Canada. The maps of these 14 strains, while demonstrating general similarity of gene order, display a number of examples of genomic rearrangements in the form of large chromosomal inversions. C1 US FDA, Div Bacterial Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Stibitz, S (reprint author), US FDA, Div Bacterial Prod, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 16 TC 25 Z9 26 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 1999 VL 181 IS 17 BP 5512 EP 5515 PG 4 WC Microbiology SC Microbiology GA 231PB UT WOS:000082318000050 PM 10464229 ER PT J AU Calvo, MS Barton, CN Park, YK AF Calvo, MS Barton, CN Park, YK TI Lack of association of net endogenous acid production with femoral bone mass: Findings from the third national health and nutrition examination survey, 1988-94 (NHANES III). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 US FDA, CFSAN, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA 1196 BP S181 EP S181 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100198 ER PT J AU Gorski, JP Apone, S Shaffer, KA Batchelder, A Jean, W Williams, JA Shacter, E Eyre, DR AF Gorski, JP Apone, S Shaffer, KA Batchelder, A Jean, W Williams, JA Shacter, E Eyre, DR TI Hypercalcemia induced in rat marrow ablation model coincides with a peak in bone resorption assessed by the NTx marker. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ Missouri, Kansas City, MO 64110 USA. Ostex Internat Inc, Seattle, WA USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Univ Washington, Sch Med, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SA214 BP S362 EP S362 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100915 ER PT J AU Looker, AC Dawson-Hughes, B Calvo, MS Gunter, EW Sahyoun, N AF Looker, AC Dawson-Hughes, B Calvo, MS Gunter, EW Sahyoun, N TI Low serum vitamin D levels appear common in southern US whites during winter. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 CDC, NCHS, Hyattsville, MD USA. Tufts Univ, Boston, MA 02111 USA. US FDA, Washington, DC 20204 USA. CDC, NCEH, Atlanta, GA 30333 USA. USDA, Washington, DC 20250 USA. RI Sahyoun, Nadine/G-2608-2011 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SA292 BP S381 EP S381 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100993 ER PT J AU Davit, B Reynolds, K Yuan, R Ajayi, F Conner, D Fadiran, E Gillespie, B Sahajwalla, C Huang, SM Lesko, LJ AF Davit, B Reynolds, K Yuan, R Ajayi, F Conner, D Fadiran, E Gillespie, B Sahajwalla, C Huang, SM Lesko, LJ TI FDA evaluations using in vitro metabolism to predict and interpret in vivo metabolic drug-drug interactions: Impact on labeling SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS PROTEASE; HUMAN LIVER-MICROSOMES; REUPTAKE-INHIBITOR ANTIDEPRESSANTS; HUMAN CYTOCHROMES P450; IN-VITRO; P-GLYCOPROTEIN; CLINICAL PHARMACOKINETICS; WARFARIN-FLUCONAZOLE; ALPRAZOLAM; RITONAVIR AB Recent advances in in vitro metabolism methods have led to an improved ability to predict clinically relevant metabolic drug-drug interactions. To address the relationships of in vitro metabolism data and in vivo metabolism outcomes, the Office of Clinical Pharmacology and Biopharmaceutics in the Center for Drug Evaluation and Research, Food and Drug Administration, evaluated a number of recently approved new drug applications. The goal of these evaluations was to determine the contribution of in vitro metabolism data in (1) predicting in vivo drug-drug interactions, (2) determining the need to conduct on in vivo drug-drug interaction study, and (3) incorporating findings into drug product labeling. Ten cases are presented in this article. They fall into two major groups: (1) in vitro data were predictive of in vivo results, and (2) in vitro data were not predictive of in vivo results. Discussion of these cases highlights factors limiting predictability of in vivo metabolic interactions fi om in vitro metabolism data. The integration of these findings into drug product labeling is also discussed. Journal of Clinical Pharmacology 1999;39:899-910 (C) 1999 the American College of Clinical Pharmacology. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. RP Huang, SM (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, HFD 850,WOC 2,Room 3016,1451 Rockville Pike, Rockville, MD 20852 USA. NR 63 TC 60 Z9 61 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 1999 VL 39 IS 9 BP 899 EP 910 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 229DF UT WOS:000082177700002 PM 10471980 ER PT J AU Yates, RL Havery, DC AF Yates, RL Havery, DC TI Determination of phenol, resorcinol, salicylic acid and alpha-hydroxy acids in cosmetic products and salon preparations SO JOURNAL OF COSMETIC SCIENCE LA English DT Article ID LIQUID-CHROMATOGRAPHIC DETERMINATION; TRICHLOROACETIC-ACID; CHEMICAL PEEL; GLYCOLIC ACID; SKIN-CANCER; LACTIC-ACID; PERFORMANCE; URINE; METABOLITES AB A method is described for the determination of glycolic acid, lactic acid, citric acid, phenol, resorcinol, salicyclic acid, alpha-hydroxyocranoic acid, and alpha-hydroxydecanoic acid in commercial creams and lotins. A mixture of the product and a filter aid was extracted with an appropriate solvent. The extracts were cleaned up by either solid-phase extraction chromatography or ion-exchange chromatography. The resulting extracts were analyzed by HPLC using a C-8 column. Recoveries of citric acid, lactic acid, phenol, resorcinol, and salicylic acid added to a simple emulsion ranged from 99% to 102%, while recoveries of glycolic acid averaged 93% alpha-Hydroxyoctanoic acid and alpha-hydroxydecanoic acid recoveries from a commercial lotion ranged from 90% to 101%. The results of surveys of commercial products obtained directly from manufacturers, and purchased from salons, retail stores, and through the mail, from 1992 to 1996, are presented. C1 US FDA, Off Cosmet & Colors, Washington, DC 20204 USA. RP Yates, RL (reprint author), US FDA, Off Cosmet & Colors, 200 C St SW, Washington, DC 20204 USA. NR 46 TC 8 Z9 11 U1 1 U2 5 PU SOC COSMETIC CHEMISTS PI NEW YORK PA 120 WALL STREET, SUITE 2400, NEW YORK, NY 10005-4088 USA SN 0037-9832 J9 J COSMET SCI JI J. Cosmet. Sci. PD SEP-OCT PY 1999 VL 50 IS 5 BP 315 EP 325 PG 11 WC Chemistry, Applied; Dermatology SC Chemistry; Dermatology GA 279WE UT WOS:000085067400004 ER PT J AU Miscia, S Di Baldassarre, A Sabatino, G Bonvini, E Rana, RA Vitale, M Di Valerio, V Manzoli, FA AF Miscia, S Di Baldassarre, A Sabatino, G Bonvini, E Rana, RA Vitale, M Di Valerio, V Manzoli, FA TI Inefficient phospholipase C activation and reduced Lck expression characterize the signaling defect of umbilical cord T lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL ANTIGEN RECEPTOR; NUCLEOTIDE-BINDING-PROTEINS; TYROSINE KINASES; BLOOD-LYMPHOCYTES; GENETIC-EVIDENCE; PERTUSSIS TOXIN; PHOSPHORYLATION; TRANSDUCTION; FIBROBLASTS; P59(FYN) AB Adult and neonatal immunocompetent cells exhibit important functional distinctions, including differences in cytokine production and susceptibility to tolerance induction, We have investigated the molecular features that characterize the immune response of cord blood-derived T lymphocytes compared with that of adult T lymphocytes, Our findings demonstrate that phospholipase C (PLC) isozymes, which play a pivotal role in the control of protein kinase C activation and Ca2+ mobilization, are differently expressed in cord and adult T lymphocytes. PLC beta 1 and delta 1 are expressed at higher levels in cord T cells, while PLC beta 2 and gamma 1 expression is higher in adult T lymphocytes, PLC delta 2 and gamma 2 appear to be equally expressed in both cell types, In addition, a functional defect in PLC activation via CD3 ligation or pervanadate treatment, stimuli that activate tyrosine kinases, was observed in cord blood T cells, whereas treatment with aluminum tetrafluoride (AlF4-), a G protein activator, demonstrated a similar degree of PLC activation in cord and adult T cells. The impaired PLC activation of cord blood-derived T cells was associated with a a very low expression of the Src kinase, Lck, along with a reduced level of ZAP70, No mitogenic response to CD3 ligation was observed in cord T cells, However, no signaling defect was apparent downstream of PLC activation, as demonstrated by the mitogenic response of cord T cells to the pharmacologic activation of protein kinase C and Ca2+ by treatment with PM and ionomycin. Thus, neonatal cord blood-derived T cells shown a signaling immaturity associated with inadequate PLC gamma activation and decreased Lck expression. C1 Univ G DAnnunzio, Ist Morfol Umana Normale, Cattedra Neonatol, I-66100 Chieti, Italy. Univ Bologna, Ist Anat Umana Normale, I-40126 Bologna, Italy. Univ Brescia, Sez Anat Umana, Dipartimento Sci Biomed & Biotecnol, Brescia, Italy. Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Immunobiol Lab, Rockville, MD 20852 USA. RP Miscia, S (reprint author), Univ G DAnnunzio, Ist Morfol Umana Normale, Cattedra Neonatol, Via Vestini 6, I-66100 Chieti, Italy. RI Vitale, Marco/O-8751-2015 OI Vitale, Marco/0000-0002-3261-6868 NR 38 TC 31 Z9 31 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1999 VL 163 IS 5 BP 2416 EP 2424 PG 9 WC Immunology SC Immunology GA 228FA UT WOS:000082125400012 PM 10452976 ER PT J AU Quakyi, EK Frasch, CE Buller, N Tsai, CM AF Quakyi, EK Frasch, CE Buller, N Tsai, CM TI Immunization with meningococcal outer-membrane protein vesicles containing lipooligosaccharide protects mice against lethal experimental group B Neisseria meningitidis infection and septic shock SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TUMOR-NECROSIS-FACTOR; MONOCLONAL-ANTIBODY; FACTOR-ALPHA; ENDOTOXIN; SEPSIS; ASSOCIATION; MONOCYTES; POLYSACCHARIDE; INTERLEUKIN-10; CYTOKINES AB Detergent-treated group B Neisseria meningitidis outer membrane vesicles (D-OMVs) from wild-type M986 and from nonencapsulated mutant M986-non-capsule variant (NCV) were compared as immunogens. Eight weeks after 3 consecutive immunizations with the immunogens, mice were challenged with a lethal dose of purified endotoxin or heat-killed or living N. meningitidis, plus D-galactosamine (400 mg/kg). D-OMVs from M986 induced bactericidal antibodies to both M986 (B:2a:P1.5,2:L3,7) and 6275 (B:2a:P1.2,5:L3) and protected the animals against both strains, whereas D-OMVs from M986-NCV did not protect the animals against infection with 6275 even when high serum bactericidal activity was induced. Tumor necrosis factor-alpha detected after bacterial infection was high in both protected and unprotected mice; interleukin (IL)-6 was high in mice that died but low in animals that survived. Exogenous administration of recombinant mouse IL-6 reversed the immunogens' protective effects. Protection against infection in mice does not necessarily correlate with the measured levels of serum bactericidal antibody alone, opsonic antibody alone, or cytokine profile alone. A comprehensive assessment of the preclinical. efficacy of group B outer-membrane protein vaccines should include monitoring humoral antibodies, cytokine response, and protective effects against lethal infection. C1 US FDA, Div Bacterial Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Quakyi, EK (reprint author), US FDA, Div Bacterial Prod, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 36 TC 11 Z9 11 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1999 VL 180 IS 3 BP 747 EP 754 DI 10.1086/314927 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 230HT UT WOS:000082246300023 PM 10438363 ER PT J AU Godar, DE AF Godar, DE TI Light and death: Photons and apoptosis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS LA English DT Article; Proceedings Paper CT 47th Montagna Annual Symposium on the Biology of Skin CY AUG 19-23, 1998 CL SNOWMASS, COLORADO SP Orentrich Fdn, Natl Psoriasis Fdn DE phototherapy; radiation; reactive oxygen species; ultraviolet ID RADIATION-INDUCED APOPTOSIS; PERMEABILITY TRANSITION PORE; PROGRAMMED CELL-DEATH; UV-INDUCED IMMEDIATE; PHOTODYNAMIC THERAPY; ULTRAVIOLET-LIGHT; CYTOCHROME-C; FAS-LIGAND; DELAYED APOPTOSIS; EPITHELIAL-CELLS AB Phototherapies like photodynamic therapy (PDT), UVA1, WB, and PUVA treat skin diseases. These phototherapies work because they alter cytokine profiles, change immune cytotoxicity in the skin, and directly kill diseased cells by apoptosis, Apoptosis is a term that only describes the morphologic changes a cell undergoes during this mode of cell death. The terms "immediate", "intermediate", and "delayed" apoptosis segregate the different apoptotic mechanisms into three kinetic categories, whereas the terms preprogrammed cell death (pre-PCD) and programmed cell death (PCD) describe the underlying mechanisms. Immediate apoptosis (T less than or equal to 0.5 h postexposure) is triggered by singlet-oxygen damage that opens the mitochondrial megachannel, which can be mediated by PDT or UVA1 radiation. It is a pre-PCD mechanism of apoptosis, i.e., protein synthesis is not required post-insult, because all the necessary components are constitutively synthesized and only need to be activated. Intermediate apoptosis (T less than or equal to 4 h > 0.5 h) is initiated by receptor cross-linking on the plasma membrane, which can be achieved using high doses of WB or UVC radiation, It is also a pre-PCD mechanism. Delayed apoptosis (T > 4 h) is induced by DNA damage that can be caused by X-rays, PUVA, WC, UVB, UVA, and PDT, It is a PCD mechanism of apoptosis, i.e., protein synthesis is required post-insult. These three apoptotic mechanisms each access one of two "points-of-no-return" located on the mitochondrial membrane, which activate different, but not mutually exclusive, final pathways of apoptosis, This review discusses the Latest findings on these apoptotic mechanisms and their implications in phototherapies. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Godar, DE (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12709 Twinbrook Pkwy, Rockville, MD 20857 USA. NR 80 TC 54 Z9 55 U1 0 U2 5 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1087-0024 J9 J INVEST DERM SYMP P JI J. Invest. Dermatol. Symp. Proc. PD SEP PY 1999 VL 4 IS 1 BP 17 EP 23 DI 10.1038/sj.jidsp.5640175 PG 7 WC Dermatology SC Dermatology GA 267GA UT WOS:000084348400005 PM 10537002 ER PT J AU Flexner, C Abramson, SB Snyderman, R Dieterich, DT Korn, D Temple, R Sherwood, L Goldblatt, D AF Flexner, C Abramson, SB Snyderman, R Dieterich, DT Korn, D Temple, R Sherwood, L Goldblatt, D TI Patients, physicians, and clinical trials: The other side of the coins SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Editorial Material C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. NYU, Sch Med, New York, NY USA. Hosp Joint Dis, New York, NY 10003 USA. Duke Univ, Durham, NC 27706 USA. Cabrii Med Ctr, New York, NY USA. Assoc Amer Med Coll, Washington, DC 20037 USA. US FDA, Ctr Drugs, Rockville, MD 20857 USA. US FDA, Arthrit Advisory Comm, Rockville, MD 20857 USA. RP Flexner, C (reprint author), Johns Hopkins Univ, Baltimore, MD 21218 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD SEP PY 1999 VL 47 IS 8 BP 343 EP 357 PG 15 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 237FB UT WOS:000082643700001 ER PT J AU Laskin, BL Choyke, P Keenan, GF Miller, FW Rider, LG AF Laskin, BL Choyke, P Keenan, GF Miller, FW Rider, LG TI Novel gastrointestinal tract manifestations in juvenile dermatomyositis SO JOURNAL OF PEDIATRICS LA English DT Article ID POLYMYOSITIS; ESOPHAGEAL; ABNORMALITIES; DISEASE AB We report a case of juvenile dermatomyositis in which a dilated atonic esophagus was associated with delayed gastric emptying and intestinal mucosal thickening, resulting in a radiographic "stacked coin" appearance. These findings, which can also occur in infectious, neoplastic, or other immune-mediated diseases, broaden the spectrum of gastrointestinal tract manifestations in juvenile dermatomyositis. Physicians should be alert fbr these treatable manifestations in children with myositis who present with unexplained gastrointestinal symptoms, which are reversible with immunosuppressive therapy. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Lab Mol & Dev Immunol, Bethesda, MD 20892 USA. NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NIAMSD, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Rider, LG (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Lab Mol & Dev Immunol, Bldg 29B,Room 2G11,HMF 561,8800 Rockville Pike, Bethesda, MD 20892 USA. OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 NR 16 TC 9 Z9 10 U1 0 U2 0 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 SEP PY 1999 VL 135 IS 3 BP 371 EP 374 DI 10.1016/S0022-3476(99)70137-X PG 4 WC Pediatrics SC Pediatrics GA 237NM UT WOS:000082662800023 PM 10484806 ER PT J AU Teisl, MF Levy, AS Derby, BM AF Teisl, MF Levy, AS Derby, BM TI The effects of education and information source on consumer awareness of diet-disease relationships SO JOURNAL OF PUBLIC POLICY & MARKETING LA English DT Article ID NUTRITION INFORMATION; HEALTH CLAIMS; CEREAL MARKET; FOOD LABELS; KNOWLEDGE; ATTITUDES; WAGES; SALES AB Information about diet-disease relationships provided by the news media is associated with increases in consumer awareness of these relationships. However, consumer awareness levels have declined during time periods when nutrient information increasingly was provided in food advertising. People with higher (lower) education levels were more (less) aware of diet-disease relationships. In general, the authors do not find strong evidence that media- or firm-provided information decreases the difference in awareness between more and less educated persons. C1 Univ Maine, Dept Resource Econ & Policy, Orono, ME 04469 USA. US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. RP Teisl, MF (reprint author), Univ Maine, Dept Resource Econ & Policy, Orono, ME 04469 USA. OI teisl, mario/0000-0002-2021-9208 NR 53 TC 23 Z9 23 U1 2 U2 10 PU AMER MARKETING ASSOC PI CHICAGO PA 311S WACKER DR, STE S800, CHICAGO, IL 60606-6629 USA SN 0743-9156 J9 J PUBLIC POLICY MARK JI J. Public Policy Mark. PD FAL PY 1999 VL 18 IS 2 BP 197 EP 207 PG 11 WC Business SC Business & Economics GA 263RQ UT WOS:000084139400006 ER PT J AU Madsen, EL Dong, F Frank, GR Garra, BS Wear, KA Wilson, T Zagzebski, JA Miller, HL Shung, KK Wang, SH Feleppa, EJ Liu, T O'Brien, WD Topp, KA Sanghvi, NT Zaitsev, AV Hall, TJ Fowlkes, JB Kripfgans, OD Miller, JG AF Madsen, EL Dong, F Frank, GR Garra, BS Wear, KA Wilson, T Zagzebski, JA Miller, HL Shung, KK Wang, SH Feleppa, EJ Liu, T O'Brien, WD Topp, KA Sanghvi, NT Zaitsev, AV Hall, TJ Fowlkes, JB Kripfgans, OD Miller, JG TI Interlaboratory comparison of ultrasonic backscatter, attenuation, and speed measurements SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE measurements; speed; attenuation; backscatter; interlaboratory comparison ID IN-VIVO; TISSUE; LIVER AB in a study involving 10 different sites, independent results of measurements of ultrasonic properties on equivalent tissue-mimicking samples are reported and compared. The properties measured were propagation speed, attenuation coefficients, and backscatter coefficients. Reasonably good agreement exists for attenuation coefficients, but less satisfactory results were found for propagation speeds. As anticipated, agreement was not impressive in the case of backscatter coefficients. Results for four sites agreed rather well in both absolute values and frequency dependence, and results from other sites were lower by as much as an order of magnitude. The study is valuable for laboratories doing quantitative studies. C1 Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA. Georgetown Univ, Dept Radiol, Washington, DC USA. Univ Kansas, Med Ctr, Dept Radiol, Kansas City, KS 66103 USA. CIRS Inc, Norfolk, VA USA. Penn State Univ, Bioengn Program, University Pk, PA 16802 USA. Chung Yuan Christian Univ, Chungli, Taiwan. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Riverside Res Inst, New York, NY USA. Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. Univ Illinois, Dept Elect & Comp Engn, Urbana, IL 61801 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Washington Univ, Dept Phys, St Louis, MO 63130 USA. RP Univ Wisconsin, Dept Med Phys, 1300 Univ Ave,Room 1530, Madison, WI 53706 USA. RI Hall, Timothy/K-3632-2012; OI Kripfgans, Oliver/0000-0003-2905-1496 FU NCI NIH HHS [R01CA39224]; NHLBI NIH HHS [R37HL40302]; NIGMS NIH HHS [R42GM54377] NR 27 TC 119 Z9 119 U1 1 U2 17 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 EI 1550-9613 J9 J ULTRAS MED JI J. Ultrasound Med. PD SEP PY 1999 VL 18 IS 9 BP 615 EP 631 PG 17 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 230FH UT WOS:000082240800007 PM 10478971 ER PT J AU Ye, ZP Liu, T Offringa, DP McInnis, J Levandowski, RA AF Ye, ZP Liu, T Offringa, DP McInnis, J Levandowski, RA TI Association of influenza virus matrix protein with ribonucleoproteins SO JOURNAL OF VIROLOGY LA English DT Article ID A VIRUS; M1 PROTEIN; NUCLEAR TRANSPORT; RNA; MEMBRANE; M2; HEMAGGLUTININ; LOCALIZATION; INHIBITION; PEPTIDES AB To characterize the sites and nature off binding of influenza A virus matrix protein (M1) to ribonucleoprotein (RNP), M1 of A/WSN/33 was altered by deletion or site-directed mutagenesis, expressed in vitro, and allowed to attach to RNP under a variety of conditions. Approximately 70% of the wild-type (Wt) M1 bound to RNP at pH 7.0, but less than 5% of M1 associated with RNP at pH 5.0. Increasing the concentration of NaCl reduced M1 binding, but even at a high salt concentration (0.6 M NaCl), approximately 20% of the input M1 was capable of binding to RNP. Mutations altering potential M1 RNA-binding regions (basic amino acids 101RKLKR105 and the zinc finger motif at amino acids 148 to 162) had varied effect: mutations of amino acids 101 to 105 reduced RNP binding compared to the Wt M1, but mutations of zinc finger motif did not. Treatment of RNP with RNase reduced M1 binding by approximately half, but even M1 mutants lacking RNA-binding regions had residual binding to RNase-treated RNP provided that the N-terminal 76 amino acids of M1 (containing two hydrophobic domains) were intact. Addition of detergent to the reaction mixture further reduced binding related to the N-terminal 76 amino acids and showed the greatest effect for mutations affecting the RNA-binding regions of basic amino acids. The data suggest that M1 interacts with both the RNA and protein components of RNP in assembly and disassembly of influenza A viruses. C1 US FDA, Lab Pediat & Resp Viral Dis, Div Viral Prod, Off Vaccines Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Ye, ZP (reprint author), Bldg 29A,Rm 1D22,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 35 TC 108 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 SEP PY 1999 VL 73 IS 9 BP 7467 EP 7473 PG 7 WC Virology SC Virology GA 225ME UT WOS:000081964700042 PM 10438836 ER PT J AU Haas, MJ Kramer, JKG McNeill, G Scott, K Foglia, TA Sehat, N Fritsche, J Mossoba, MM Yurawecz, MP AF Haas, MJ Kramer, JKG McNeill, G Scott, K Foglia, TA Sehat, N Fritsche, J Mossoba, MM Yurawecz, MP TI Lipase-catalyzed fractionation of conjugated linoleic acid isomers SO LIPIDS LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; GEOTRICHUM-CANDIDUM; FATTY-ACIDS; SUBSTRATE SPECIFICITIES; ATHEROSCLEROSIS; IDENTIFICATION; PURIFICATION; DERIVATIVES; SEPARATION; ENRICHMENT AB The abilities of lipases produced by the fungus Geotrichum candidum to selectively fractionate mixtures of conjugated linoleic acid (CLA) isomers during esterification of mixed CLA free fatty acids and during hydrolysis of mixed CLA methyl esters were examined. The enzymes were highly selective for cis-9,trans-11-18:2. A commercial CLA methyl ester preparation, containing at last 12 species representing four positional CLA isomers, was incubated in aqueous solution with either a commercial G. candidum lipase preparation (Amano GC-4) or lipase produced from a cloned high-selectivity G. candidum lipase B gene. In both instances selective hydrolysis of the cis-9,trans-11-18:2 methyl ester occurred, with negligible hydrolysis of other CLA isomers. The content of cis-9, trans-11-18:2 in the resulting free fatty acid fraction was between 94 (lipase B reaction) and 77% (CC-4 reaction). The commercial CLA mixture contained only trace amounts of trans-9,cis-11-18:2, and there was no evidence that this isomer was hydrolyzed by the enzyme. Analogous results were obtained with these enzymes in the esterification in organic solvent of a commercial preparation of CLA free fatty acids containing at least 12 CLA isomers. In this case, G. candidum lipase B generated a methyl ester fraction that contained >98% cis-9,trans-11-18:2. Geotrichum candidum lipases B and GC-4 also demonstrated high selectivity in the esterification of CLA with ethanol, generating ethyl ester fractions containing 96 and 80%, respectively, of the cis-9, trans-11 isomer. In a second set of experiments, CLA synthesized from pure linoleic acid, composed essentially of two isomers, cis-9,trans-11 and trans-10,cis-12, was utilized. This was subjected to esterification with octanol in an aqueous reaction system using Amano CC-4 lipase as catalyst. The resulting ester fraction contained up to 97% of the cis-9,trans-ll isomer. After adjustment of the reaction conditions, a concentration of 85% trans-10,cis-12-18:2 could be obtained in the unreacted free fatty acid fraction. These lipase-catalyzed reactions provide a means for the preparative-scale production of high-purity cis-9,trans-11-18:2, and a corresponding CLA fraction depleted of this isomer. C1 USDA ARS, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. Agr & Agri Food Canada, Food Res Ctr, So Crop Protect, Guelph, ON N1G 2W1, Canada. Loders Croklaan, Glen Ellyn, IL 60137 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Haas, MJ (reprint author), USDA ARS, Eastern Reg Res Ctr, 600 E Mermaid Lane, Wyndmoor, PA 19038 USA. NR 38 TC 40 Z9 44 U1 0 U2 8 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PD SEP PY 1999 VL 34 IS 9 BP 979 EP 987 DI 10.1007/s11745-999-0448-7 PG 9 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 245UP UT WOS:000083126800012 PM 10574663 ER PT J AU Wilson, SD Munson, AE Meade, BJ AF Wilson, SD Munson, AE Meade, BJ TI Assessment of the functional integrity of the humoral immune response: The plaque-forming cell assay and the enzyme-linked immunosorbent assay SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article ID HAZARD IDENTIFICATION PURPOSES; STANDARD TOXICOLOGY; ELISA; MICE; RATS; IMMUNOTOXICITY AB The plaque-forming cell (PFC) assay and enzyme-linked immunosorbent assay (ELISA) appear to have comparable sensitivity and reproducibility for measuring IgM antibody production in mice and rats immunized with sheep red blood cells (sRBCs). Both assays can be manipulated, with respect to the immunizing antigen (e.g., T-dependent vs T-independent antigen), to provide evidence as to which cell type(s) may be adversely affected by a given compound. However, the pro assay has more utility in dissecting out the target cell(s) involved. Since both the PFC assay and the ELISA may be readily conducted in the rat, it is feasible to incorporate either of these assays into standard acute and repeat dose toxicology studies. This may be accomplished by inclusion of satellite groups in the study. However, it has been suggested that the primary antibody response to sRBCs, as measured by an ELISA, may also be evaluated in the main group of animals in a toxicology study without compromise to the integrity of other toxicological endpoints (e.g., hematology, clinical chemistry, histopathology). Both approaches will provide a more extensive delineation of the safety profile of a drug or chemical. The latter approach will also reduce the number of animals needed and the cost of the study. C1 US FDA, Div Antiinflammatory Analges & Ophthalm Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NIOSH, Morgantown, WV USA. RP Wilson, SD (reprint author), US FDA, Div Antiinflammatory Analges & Ophthalm Drug Prod, Ctr Drug Evaluat & Res, 5600 Fishers Lane,HFD-550, Rockville, MD 20857 USA. NR 19 TC 18 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD SEP PY 1999 VL 19 IS 1 BP 3 EP 7 DI 10.1006/meth.1999.0821 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 243BW UT WOS:000082978100002 PM 10525432 ER PT J AU Garnick, MB Fair, WR Goldenberg, SL Gleave, M Grignon, D Fourcroy, J Sufrin, G Porterfield, H Hart, C AF Garnick, MB Fair, WR Goldenberg, SL Gleave, M Grignon, D Fourcroy, J Sufrin, G Porterfield, H Hart, C TI Fourth International Conference on Neoadjuvant Hormonal Therapy of Prostate Cancer - March 12-13, 1999 - Boston, Massachusetts - Overview consensus statement SO MOLECULAR UROLOGY LA English DT Editorial Material C1 Beth Israel Deaconess Med Ctr, Dept Urol, Boston, MA 02215 USA. Mem Sloan Kettering Canc Ctr, New York, NY USA. Beth Israel Hosp, Harvard Med Sch, Boston, MA USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Wayne State Univ, Harper Hosp, Detroit, MI 48202 USA. US FDA, Rockville, MD 20857 USA. UsTOO, Oakbrook, IL USA. Buffalo Gen Hosp, Buffalo, NY 14203 USA. RP Garnick, MB (reprint author), Beth Israel Deaconess Med Ctr, Dept Urol, 330 Brookline Ave, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1091-5362 J9 MOL UROL JI Mol. Urol. PD FAL PY 1999 VL 3 IS 3 BP 171 EP 174 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 249PV UT WOS:000083342200004 ER PT J AU Fair, W Howell, S Steers, W Heston, W Garnick, M Gleave, M Fourcroy, J AF Fair, W Howell, S Steers, W Heston, W Garnick, M Gleave, M Fourcroy, J TI Open discussion following Dr. Howell's presentation SO MOLECULAR UROLOGY LA English DT Editorial Material C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Univ Virginia, Charlottesville, VA USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. US FDA, Bethesda, MD 20014 USA. RP Fair, W (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1091-5362 J9 MOL UROL JI Mol. Urol. PD FAL PY 1999 VL 3 IS 3 BP 301 EP 302 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 249PV UT WOS:000083342200032 ER PT J AU Fourcroy, JL AF Fourcroy, JL TI Regulatory issues in prostate cancer studies SO MOLECULAR UROLOGY LA English DT Article ID QUALITY-OF-LIFE; KARNOFSKY PERFORMANCE STATUS; IMPORTANT DIFFERENCE; CLINICAL-TRIALS; END-POINTS; RESPONSIVENESS; CHEMOTHERAPY; HYPERPLASIA; VALIDITY; INDEXES AB Quality of life and informed consent are two of the important issues for designers of clinical trials. The former has physical, psychological, economic, and social components. Investigators must understand the features of the various measurement instruments and select one that is appropriate to the circumstances. It also is necessary to identify what changes are significant. Statistical significance is not identical to clinical significance. Ethical guidelines for the protection of human subjects is another important issue, Information on regulations is available on many Web sites, including that of the Food and Drug Administration. C1 US FDA, Off Hlth Affairs, Bethesda, MD 20014 USA. RP Fourcroy, JL (reprint author), 6310 Swords Way, Bethesda, MD 20817 USA. NR 35 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1091-5362 J9 MOL UROL JI Mol. Urol. PD FAL PY 1999 VL 3 IS 3 BP 329 EP 332 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 249PV UT WOS:000083342200039 ER PT J AU Gleave, M Porterfield Garnick, M Heston, W Fair, W Fourcroy, J AF Gleave, M Porterfield Garnick, M Heston, W Fair, W Fourcroy, J TI Open discussion following Mr. Porterfield's presentation SO MOLECULAR UROLOGY LA English DT Editorial Material C1 Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. UsToo Int Inc, Oak Brook, IL USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. US FDA, Bethesda, MD 20014 USA. RP Gleave, M (reprint author), Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1091-5362 J9 MOL UROL JI Mol. Urol. PD FAL PY 1999 VL 3 IS 3 BP 337 EP 337 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 249PV UT WOS:000083342200041 ER PT J AU Paule, MG Meck, WH McMillan, DE McClure, GYH Bateson, M Popke, EJ Chelonis, JJ Hinton, SC AF Paule, MG Meck, WH McMillan, DE McClure, GYH Bateson, M Popke, EJ Chelonis, JJ Hinton, SC TI The use of timing behaviors in animals and humans to detect drug and/or toxicant effects SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE comparative psychology; time production; time estimation; temporal discrimination ID RESPONSE-DURATION DIFFERENTIATION; OPERANT TEST BATTERY; SCALAR EXPECTANCY-THEORY; INTERNAL CLOCK; TIME PERCEPTION; TEMPORAL MEMORY; RHESUS-MONKEYS; D-AMPHETAMINE; ATTENTION; REINFORCEMENT AB Behavioral paradigms applicable for use in both human and nonhuman subjects for investigating aspects of timing behavior are presented with a view towards exploring their strengths, weaknesses, and utility in a variety of experimental situations. Tri-peak, peak interval, differential reinforcement of low rate responding, and temporal response differentiation procedures are highlighted. In addition, the application of timing tasks in preclinical and clinical settings is discussed: pharmacological manipulations are providing information on the neurotransmitters involved and species differences; normative data for children are being developed; and noninvasive imaging procedures are being employed in adult human subjects to explore the involvement of specific brain areas. Published by Elsevier Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Behav Toxicol Lab, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Arkansas Childrens Hosp, Ctr Appl Res & Evaluat, Little Rock, AR 72205 USA. Duke Univ, Dept Psychol, Expt & Brain Imaging & Anal Ctr, Durham, NC 27706 USA. RP Paule, MG (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, Behav Toxicol Lab, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. RI Bateson, Melissa/B-1874-2008 OI Bateson, Melissa/0000-0002-0861-0191 NR 80 TC 69 Z9 71 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD SEP-OCT PY 1999 VL 21 IS 5 BP 491 EP 502 PG 12 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 234TG UT WOS:000082500000003 PM 10492384 ER PT J AU Chilton, L Bodurtha, J Butterbrodt, MP Freeland-Hyde, B Gahagan, S Grossman, D Jantz, J Allen-Davis, JT Bechtold, D Bell, JT Brenneman, G Green, WF Postl, B Zind, B Goodrich, J Mandell, F AF Chilton, L Bodurtha, J Butterbrodt, MP Freeland-Hyde, B Gahagan, S Grossman, D Jantz, J Allen-Davis, JT Bechtold, D Bell, JT Brenneman, G Green, WF Postl, B Zind, B Goodrich, J Mandell, F CA Comm Native Amer Child Hlth Comm Infect Dis TI Immunizations for Native American children SO PEDIATRICS LA English DT Article ID INVASIVE PNEUMOCOCCAL DISEASE; VACCINE EFFICACY TRIAL; B CONJUGATE VACCINES; HEPATITIS-B; VIRUS-INFECTION; ALASKA NATIVES; EPIDEMIOLOGY; POPULATION; INFANTS; INDIANS C1 Amer Coll Obstetricians & Gynecologists, Washington, DC USA. Amer Acad Child & Adolescent Psychiat, Washington, DC USA. Johns Hopkins Ctr Amer Indian & Alaskan Native Hl, Baltimore, MD USA. Canadian Paediat Soc, Ottawa, ON, Canada. Comm Infect Dis, Elk Grove Village, IL USA. Natl Vaccine Program Off, Atlanta, GA USA. US FDA, Rockville, MD 20857 USA. AAP Council Pediat Practice, Elk Grove Village, DC USA. Amer Thorac Soc, Washington, DC USA. Ctr Dis Control & Prevent, Atlanta, GA USA. NIAID, Bethesda, MD USA. NR 22 TC 5 Z9 5 U1 1 U2 1 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 SEP PY 1999 VL 104 IS 3 BP 564 EP 567 PG 4 WC Pediatrics SC Pediatrics GA 240FV UT WOS:000082816000038 ER PT J AU Flynn, GL Shah, VP Tenjarla, SN Corbo, M DeMagistris, D Feldman, TG Franz, TJ Miran, DR Pearce, DM Sequeira, JA Swarbrick, J Wang, JCT Yacobi, A Zatz, JL AF Flynn, GL Shah, VP Tenjarla, SN Corbo, M DeMagistris, D Feldman, TG Franz, TJ Miran, DR Pearce, DM Sequeira, JA Swarbrick, J Wang, JCT Yacobi, A Zatz, JL TI Assessment of value and applications of in vitro testing of topical dermatological drug products SO PHARMACEUTICAL RESEARCH LA English DT Article; Proceedings Paper CT AAPS/FDA Workshop CY SEP 08-10, 1997 CL ARLINGTON, VIRGINIA DE SUPAC-SS; topical delivery systems; dermatologicals; release testing; FDA guidances ID INVITRO RELEASE; DIFFUSIONAL RELEASE; OINTMENTS; MATRIX; CREAMS; HYDROCORTISONE; SOLUTE AB The FDA recently issued a guidance covering practices of scaleup and post approval changes with semisolids (SUPAC-SS).(17) This guidance outlines the steps that must be taken by a company to maintain certification of its semisolid dermatological products after quantitative changes have been made in their compositions and/or after changes have been made in the sourcing of their key ingredients, in their processing, in their batch sizes, and/or after their site of manufacture has been relocated. A key element within the guidance is a release test to be used to determine if the diffusional release of a drug found in a formulation is the same after changes have been made to the formulation as it was prior to implementing the changes. The AAPS-FDA sponsored workshop was set up to explore this qualifying test. The stated aims of the workshop were: a) to illustrate the methodology and techniques of in vitro release testing, b) to show the sensitivity of in vitro release with respect to manufacturing variables and to variations in components and composition (of specific formulations), c) to recognize in vitro release testing as a useful procedure for SUPAC documentation, d) to highlight and evaluate other applications of in vitro release testing, e) to explore the degree to which in vitro release testing and bioavailability may be related, and f) to evaluate the role of in vitro release testing of topical dosage forms as a tool to improve product quality. C1 US FDA, CDER, OPS,Off Pharmaceut Sci, Rockville, MD 20857 USA. Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. Mercer Univ, So Sch Pharm, Atlanta, GA USA. RW Johnson Pharmaceut Res Inst, Raritan, NJ 08869 USA. Glaxo Inc, Res Triangle Pk, NC 27709 USA. Taro Pharmaceut, Brampton, ON, Canada. Kinet Corp, Palo Alto, CA USA. Miran Consulting Inc, Lutherville, MD USA. Altana Inc, Melville, NY USA. Schering Plough Res, Kenilworth, NJ USA. AAI Inc, Wilmington, NC USA. Johnson & Johnson Consumer Prod Inc, Skillman, NJ 08558 USA. Taro Pharmaceut USA Inc, Hawthorne, NY USA. Rutgers State Univ, Coll Pharm, Piscataway, NJ USA. RP Shah, VP (reprint author), US FDA, CDER, OPS,Off Pharmaceut Sci, HFD 350,5600 Fishers Lane, Rockville, MD 20857 USA. NR 32 TC 47 Z9 48 U1 0 U2 6 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD SEP PY 1999 VL 16 IS 9 BP 1325 EP 1330 DI 10.1023/A:1018997520950 PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 235HT UT WOS:000082536800001 PM 10496646 ER PT J AU Whitehurst, VE Vick, JA Alleva, FR Zhang, J Joseph, X Balazs, T AF Whitehurst, VE Vick, JA Alleva, FR Zhang, J Joseph, X Balazs, T TI Reversal of propranolol blockade of adrenergic receptors and related toxicity with drugs that increase cyclic AMP SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-ISCHEMIA; CYCLASE ACTIVITY; HEART-FAILURE; MECHANISMS AB An overdose of propranolol, a widely used nonselective p-adrenergic receptor blocking agent, can result in hypotension and bradycardia leading to irreversible shock and death, In addition, the blockade of adrenergic receptors can lead to alterations in neurotransmitter receptors resulting in the interruption of the activity of other second messengers and the ultimate cellular responses. In the present experiment, three agents, aminophylline, amrinone, and forskolin were tested in an attempt to reverse the potential lethal effects of a propranolol overdose in dogs, Twenty-two anesthetized beagle dogs were given a 10-min infusion of propranolol st a dose of 1 mg/kg/min, Six of the dogs, treated only with intravenous saline, served as controls. Within 15-30 min all six control dogs exhibited profound hypotension end severe bradycardia that led to cardiogenic shock and death. Seven dogs were treated with intravenous aminophylline 20 mg/kg 5 min after the end of the propranolol infusion, Within 10-15 min heart rate and systemic arterial blood pressure returned to near control levels, and all seven dogs survived, Intravenous amrinone (23 mg/kg) given to five dogs, and forskolin (1-2 mg/kg) given to four dogs, also increased heart rate and systemic arterial blood pressure but the recovery of these parameters was appreciably slower than that seen with aminophylline. All of these animals also survived with no apparent adverse effects, Histopathologic evaluation of the hearts of the dogs treated with aminophylline showed less damage (vacuolization, inflammation, hemorrhage) than the hearts from animals given propranolol alone. Results of this study showed that these three drugs, all of which increase cyclic AMP, are capable of reversing the otherwise lethal effects of a propranolol overdose in dogs. C1 US FDA, Div Pulm Drug Prod, Rockville, MD 20857 USA. US FDA, Div Appl Pharmacol & Res, Beltsville, MD 20705 USA. US FDA, Div Drug Biol, Washington, DC 20204 USA. US FDA, Div Cardiorenal Drug Prod, Rockville, MD 20857 USA. RP Whitehurst, VE (reprint author), US FDA, Div Pulm Drug Prod, HFD-570,Parklawn Bldg,5600 Fishers Lane, Rockville, MD 20857 USA. NR 16 TC 7 Z9 7 U1 0 U2 1 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 SEP PY 1999 VL 221 IS 4 BP 382 EP 385 DI 10.1046/j.1525-1373.1999.d01-96.x PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 225NM UT WOS:000081967700011 PM 10460701 ER PT J AU Nicholson, KL Hayes, BA Balster, RL AF Nicholson, KL Hayes, BA Balster, RL TI Evaluation of the reinforcing properties and phencyclidine-like discriminative stimulus effects of dextromethorphan and dextrorphan in rats and rhesus monkeys SO PSYCHOPHARMACOLOGY LA English DT Article DE dextromethorphan; dextrorphan; phencyclidine; self-administration; drug discrimination; monkey; rat ID METHYL-D-ASPARTATE; NMDA RECEPTOR ANTAGONISTS; BEHAVIORAL PHARMACOLOGY; N-ALLYLNORMETAZOCINE; CHANNEL; DRUG; KINETICS; OPIOIDS; MK-801; ABUSE AB Rationale: Dextromethorphan (DXM) and its metabolite, dextrorphan (DXO) have neuroprotective and anticonvulsant properties through their activity as N-methyl-D-aspartate (NMDA) receptor channel blockers. Based on this receptor activity, coupled with reports of DXM abuse, both were evaluated for abuse potential and phencyclidine (PCP)-like behavioral effects in two animal models. Objectives and methods: The discriminative stimulus properties of DXO and DXM were tested in rats (3-56 mg/kg DXM, i.p. and 2.2-40.9 mg/kg DXO, i.p.) and rhesus monkeys (0.3-10 mg/kg DXM, i.m. and 0.25-8.0 mg/kg DXO, i.m.) trained to discriminate PCP from saline using a standard two-lever drug-discrimination paradigm under a fixed-ratio (FR) schedule of food reinforcement. In a second set of experiments, i.v. self-administration of DXO (10-100 mu g/kg/infusion) and DXM (10-1000 mu g/kg/infusion) were tested under a FR schedule of reinforcement in monkeys trained to lever press for infusions of PCP during daily 1-h sessions. Results: In rats, both DXM and DXO produced a dose-dependent substitution for PCP. When tested in monkeys, DXM yielded partial (1 monkey) and full (2 monkeys) substitution for PCP, while DXO substituted fully for PCP in all four subjects tested. In the self-administration study, in five of the six subjects, at least one dose of DXM served as a positive reinforcer, maintaining infusion rates above those for saline. For DXO, at least one dose maintained infusion numbers well above mean saline infusion numbers in all subjects. Conclusions: Taken together, these data show that DXM has some PCP-like effects in rats and monkeys, but that they are more reliably produced by its metabolite, DXO. Thus, high doses of DXM may have some PCP-like abuse potential in humans but this potential may be associated with, or enhanced by, metabolism of DXM to DXO. C1 Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. US FDA, Controlled Subst Evaluat Team, Div Anesthet Crit Care & Addict Drug Prod, Rockville, MD 20857 USA. RP Balster, RL (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Box 980310, Richmond, VA 23298 USA. FU NIDA NIH HHS [DA-07027, DA-01442] NR 68 TC 30 Z9 30 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 SEP PY 1999 VL 146 IS 1 BP 49 EP 59 DI 10.1007/s002130051087 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 236WL UT WOS:000082622200007 PM 10485964 ER PT J AU Machado, SG Miller, R Hu, C AF Machado, SG Miller, R Hu, C TI A regulatory perspective on pharmacokinetic/pharmacodynamic modelling SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Review ID PHARMACODYNAMIC MODELS; DRUG DEVELOPMENT; PHARMACOKINETICS; STRATEGIES AB We present an integrated summary from statistical and pharmacological perspectives of pharmacokinetic/pharmacodynamic (PK/PD) modelling and its use in drug development and regulation for guiding appropriate dosing. An overview of the technical aspects of PK/PD modelling describes how structural models are constructed and refined using pharmacokinetic and pharmacodynamic principles and how random effects models are used to account for individual differences in desired (and undesired) responses due to patient characteristics. Lastly, we describe applications of PK/PD modelling for the purposes of drug labelling, for resolving a safety concern, and for improving therapeutic monitoring of anaesthetic depth during surgery. C1 US FDA, Off Biostat, CDER, HFD 705, Rockville, MD 20857 USA. US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. RP Machado, SG (reprint author), US FDA, Off Biostat, CDER, HFD 705, 5600 Fishers Lane,Room 15B45, Rockville, MD 20857 USA. NR 34 TC 19 Z9 20 U1 1 U2 2 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0962-2802 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PD SEP PY 1999 VL 8 IS 3 BP 217 EP 245 DI 10.1191/096228099674515377 PG 29 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 266FP UT WOS:000084290200004 PM 10636336 ER PT J AU Atreya, PL Kulkarni, S AF Atreya, PL Kulkarni, S TI Respiratory syncytial virus strain A2 is resistant to the antiviral effects of type I interferons and human MxA SO VIROLOGY LA English DT Article ID MESSENGER-RNA SYNTHESIS; INFLUENZA-VIRUS; CELLULAR PROTEINS; INHIBITION; REPLICATION; TRANSCRIPTION; INFECTIONS; CELLS; ALPHA; GENE AB Respiratory syncytial virus (RSV) belongs to Paramyxoviridae family of enveloped negative-strand RNA viruses and causes severe bronchiolitis and pneumonia in children younger than 2 years of age. As members of Paramyxoviridae family, RSV and parainfluenza type 3 (PIV3) have similar modes of infection and replication. A variety of negative-strand RNA virus infections, including that of PIV3, are inhibited by human MxA protein, a type I interferon (IFN)-inducible GTPase. We tested whether the MxA protein, induced either by type I human IFNs or by stable transfection of human MxA gene in human (U-87) or simian (Vero) cells, confers resistance to these cells against infection by RSV strain A2. RSV infection was resistant to antiviral effects induced by 0-10,000 U/ml type I IFNs (IFN-alpha or -beta) in both human lung epithelial, A549, and fibroblast, MRC-5 cells. RSV virus yield was reduced only by 10- to 20-fold, and viral protein synthesis was not significantly affected under conditions of IFN treatment where PIV3 yield was reduced by 1000- to 10,000-fold Human or simian cell lines constitutively expressing MxA were protected against infection by PIV3 but not by RSV. Our results indicate that RSV A2 is resistant to the antiviral effects of MxA, even though RSV and PIV3 have similar replication strategies. In IFN-treated coinfected cultures, IFN-resistant RSV A2 did not prevent the IFN-mediated inhibition of PIV3 multiplication. Hence the resistance of RSV A2 to type I IFNs does not appear to be due to soluble factors released into the medium or a disruption in the cellular antiviral machinery brought about by RSV A2 infection. C1 US FDA, Lab Pediat & Resp Viral Dis, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Atreya, PL (reprint author), US FDA, Lab Pediat & Resp Viral Dis, Div Viral Prod, Ctr Biol Evaluat & Res, HFM-445,Room 2B17,Bldg 29A,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 49 TC 57 Z9 59 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 1 PY 1999 VL 261 IS 2 BP 227 EP 241 DI 10.1006/viro.1999.9835 PG 15 WC Virology SC Virology GA 234KW UT WOS:000082484700008 PM 10497108 ER PT J AU Fang, GC Chang, CN Wu, YS Fu, PPC Yang, DG Chu, CC AF Fang, GC Chang, CN Wu, YS Fu, PPC Yang, DG Chu, CC TI Characterization of chemical species in PM2.5 and PM10 aerosols in suburban and rural sites of central Taiwan SO SCIENCE OF THE TOTAL ENVIRONMENT LA English DT Article DE PM2.5; PM10; anthropogenic element and anion species ID PARTICULATE AIR-POLLUTION; ELEMENTAL CONCENTRATIONS; MATTER; PARTICLES; EMISSIONS; CHILDREN; METALS AB Aerosol samples for PM,, (particulate matter with aerodynamic diameters less than 2.5 mu m), PM2.5-10 (particulate matter with aerodynamic diameters between 2.5 and 10 mu m) and TSP were collected from June to September 1998 at THU (suburban) and HKIT (rural) sites in central Taiwan. The ratios of PM2.5/PM10 averaged 0.70 for the daytime and 0.63 for the nighttime at THU, respectively. At HKIT, the PM2.5/PM10 ratios averaged 0.56 for the daytime and 0.72 in the nighttime, respectively. These results indicated that the PM10 concentrations contribute the majority of the PM10 concentration and PM10 concentrations contribute the majority of the TSP at both sites. The averaged PM10 concentrations at THU are higher than those measured at HKIT during the daytime period. However, the average PM2.5-10 concentrations in THU are lower than those measured at HKIT during nighttime. The samples collected were also analyzed by atomic absorption spectrophotometry for the elemental analysis of Ca, Fe, Pb, Zn, Cu, Mn and Cr, Meanwhile ion chromatography was used to analyze for the water-soluble ions: sulphate, nitrate and chloride in the Universal samples. The concentrations of heavy metals in PM10 during daytime were all higher than nighttime at THU. However, the averaged concentrations of metal elements in PM10 during day and night period were distributed irregularly at HKIT. The results indicated that for metal elements collected at HKIT have different emission sources. The concentrations of metal elements during daytime in PM10 at THU were generally higher than HKIT. The phenomena owing to the averaged PM10 particle concentrations at THU (suburban) were higher than those measured at HKIT (rural) and PM,, occupied the major portions of PM10 for both sites during the day period. For anion species, there are no significant differences between day and night period in PM10 concentrations at both suburban and rural sites. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Hungkuang Inst Technol, Dept Evnvironm Engn & Hlth, Taichung 433, Taiwan. Tunghai Univ, Dept Environm Sci, Tunghai, Taiwan. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Chien Yu Hosp, Kaohsiung, Taiwan. RP Fang, GC (reprint author), Hungkuang Inst Technol, Dept Evnvironm Engn & Hlth, Taichung 433, Taiwan. NR 20 TC 69 Z9 77 U1 5 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0048-9697 J9 SCI TOTAL ENVIRON JI Sci. Total Environ. PD AUG 30 PY 1999 VL 234 IS 1-3 BP 203 EP 212 DI 10.1016/S0048-9697(99)00276-4 PG 10 WC Environmental Sciences SC Environmental Sciences & Ecology GA 236BM UT WOS:000082578400020 PM 10507159 ER PT J AU Stewart, CW Slikker, W AF Stewart, CW Slikker, W TI Hyperthermia-enhanced serotonin (5-HT) depletion resulting from D-fenfluramine (D-Fen) exposure does not evoke a glial-cell response in the central nervous system of rats SO BRAIN RESEARCH LA English DT Article DE fenfluramine; serotonin; body temperature; GFAP ID SUBSTITUTED AMPHETAMINES; BRAIN-SEROTONIN; NEUROTOXICITY; TEMPERATURE; STRESS AB D-Fen-induced hyperthermia has been shown to coincide with an enhanced depletion of 5-HT and 5-hydroxyindole acetic acid (5-HIAA). Because these observations have relied on D-Fen exposure at multiple environmental temperatures, some have questioned the validity of the findings. Therefore, this experiment was designed to determine if the correlation between elevated body temperature and 5-HT depletion could be observed when D-Fen exposure occurred in one warm environment (28 degrees C) and to determine if a hyperthermia-enhanced glial-cell response could be evoked by D-Fen exposure. Hyperthermia-enhanced 5-HT and 5-HIAA depletion resulting from D-Fen exposure was dependent on body temperature during drug exposure. In the frontal cortex, 5-HT concentrations ranged from 3 to 45% of control values. Likewise, in the striatum and hippocampus, 5-HT concentrations ranged from 13 to 53% and 6 to 40%, respectively. The 5-HIAA concentrations had a wider range than the 5-HT concentrations for each brain region. In the frontal cortex, striatum and hippocampus, 5-HIAA ranged from 0 to 93%, 15 to 72% and 0 to 83% of control, respectively. In spite of the substantial reductions in 5-HT, there was no detectable glial-cell response. D-Fen-induced hyperthermia does not appear to cause generalized damage to neurons in the frontal cortex, striatum and hippocampus. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci Hosp, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. RP Slikker, W (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 14 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 28 PY 1999 VL 839 IS 2 BP 279 EP 282 DI 10.1016/S0006-8993(99)01732-1 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 233VZ UT WOS:000082449000008 PM 10519050 ER PT J AU Moon, H Ahn, H Kodell, RL Pearce, BA AF Moon, H Ahn, H Kodell, RL Pearce, BA TI A comparison of a mixture likelihood method and the EM algorithm for an estimation problem in animal carcinogenicity studies SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE complex; constrained optimization; cause of death; interval sacrifice; likelihood ID RODENT TUMORIGENICITY EXPERIMENTS; SURVIVAL SACRIFICE EXPERIMENTS; MAXIMUM-LIKELIHOOD; DEATH; MODEL AB Both a mixture likelihood method and the EM algorithm are implemented to estimate the time-to-onset-of and the time-to-death-from the tumor of interest in animal carcinogenicity studies. Both methods are implemented using Box's Complex Method for finding the maximum likelihood estimates of parameters for a nonlinear log-likelihood function subject to nonlinear inequality constraints. A comparison of the mixture likelihood method with the EM algorithm suggests that the mixture method may be more efficient for the problem of constrained nonparametric maximum likelihood estimation in carcinogenicity studies. The advantages of using the mixture likelihood method are illustrated with data from benzidine dihydrochloride and caloric restriction studies. (C) 1999 Elsevier Science B.V. All rights reserved. C1 SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD AUG 28 PY 1999 VL 31 IS 2 BP 227 EP 238 DI 10.1016/S0167-9473(99)00011-0 PG 12 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 229BL UT WOS:000082173600006 ER PT J AU Williamson, LC Bateman, KE Clifford, JCM Neale, EA AF Williamson, LC Bateman, KE Clifford, JCM Neale, EA TI Neuronal sensitivity to tetanus toxin requires gangliosides SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPINAL-CORD NEURONS; RAT-BRAIN; SPHINGOLIPID BIOSYNTHESIS; NEUROTRANSMITTER RELEASE; PC12 CELLS; BOTULINUM; BINDING; NEUROTOXINS; INHIBITION; MEMBRANES AB Tetanus toxin produces spastic paralysis in situ by blocking inhibitory neurotransmitter release in the spinal cord. Although di- and trisialogangliosides bind tetanus toxin, their role as productive toxin receptors remains unclear. We examined toxin binding and action in spinal cord cell cultures grown in the presence of fumonisin B-1, an inhibitor of ganglioside synthesis. Mouse spinal cord neurons grown for 3 weeks in culture in 20 mu M fumonisin B-1 develop dendrites, axons, and synaptic terminals similar to untreated neurons, even though thin layer chromatography shows a greater than 90% inhibition of ganglioside synthesis. Absence of tetanus and cholera toxin binding by toxin-horseradish peroxidase conjugates or immunofluorescence further indicates loss of mono- and polysialogangliosides. In contrast to control cultures, tetanus toxin added to fumonisin B-1-treated cultures does not block potassium-stimulated glycine release, inhibit activity-dependent uptake of FM1-43, or abolish immunoreactivity for vesicle-associated membrane protein, the toxin substrate. Supplementing fumonisin B-1-treated cultures with mixed brain gangliosides completely restores the ability of tetanus toxin to bind to the neuronal surface and to block neurotransmitter release. These data demonstrate that fumonisin B-1 protects against toxin-induced synaptic blockade and that gangliosides are a necessary component of the receptor mechanism for tetanus toxin. C1 NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Neale, EA (reprint author), NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NR 44 TC 38 Z9 39 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 AUG 27 PY 1999 VL 274 IS 35 BP 25173 EP 25180 DI 10.1074/jbc.274.35.25173 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 229KH UT WOS:000082193400099 PM 10455200 ER PT J AU Boase, J Lipsky, S Simani, P Smith, S Skilton, C Greenman, S Harrison, S Duchin, J Samadpour, M Gautom, R Lankford, S Harris, T Ly, K Green, D Kobyashi, J DeBess, E McGivern, T Mauvais, S Balan, V Fleming, D Sanchez, K Vertz, PD Mohle-Boetani, JC Seuring, D Goddard, JH Kludt, PE Bidol, SA Bender, J Sewell, CM Void, IN Marengo, L Archer, J AF Boase, J Lipsky, S Simani, P Smith, S Skilton, C Greenman, S Harrison, S Duchin, J Samadpour, M Gautom, R Lankford, S Harris, T Ly, K Green, D Kobyashi, J DeBess, E McGivern, T Mauvais, S Balan, V Fleming, D Sanchez, K Vertz, PD Mohle-Boetani, JC Seuring, D Goddard, JH Kludt, PE Bidol, SA Bender, J Sewell, CM Void, IN Marengo, L Archer, J TI Outbreak of Salmonella serotype Muenchen infections associated with unpasteurized orange juice - United States and Canada, June 1999 (reprinted from MMWR, 1999, vol 48, pg 582-585) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Univ Washington, Seattle, WA 98195 USA. Washington State Dept Hlth, Seattle, WA 98101 USA. Washington Cty Dept Hlth, Hillsboro, OR 97123 USA. Arizona Dept Hlth Serv, Infect Dis Epidemiol Sect, Phoenix, AZ 85007 USA. Calif Dept Hlth Serv, Div Communicable Dis Control, Dis Invest & Surveillance Branch, Sacramento, CA 95814 USA. JoDaviess Cty Hlth Dept, Golena, IL 61523 USA. Iowa Dept Publ Hlth, Des Moines, IA 50319 USA. Massachusetts Dept Publ Hlth, Div Epidemiol & Immunizat, Boston, MA 02111 USA. Michigan Dept Community Hlth, Communicable Dis Div, Lansing, MI 48909 USA. Minnesota Dept Hlth, Acute Dis Epidemiol Sect, Minneapolis, MN 55414 USA. New Mexico Dept Hlth, Off Epidemiol, Santa Fe, NM 87504 USA. Texas Dept Hlth, Infect Dis Epidemiol & Surveillance Div, Austin, TX 78756 USA. Wisconsin Div Publ Hlth, Bur Publ Hlth, Communicable Dis Sect, Madison, WI 53707 USA. Nova Scotia Dept Hlth, Alberta Hlth, British Columbia Ctr Dis Control, Edmonton, AB, Canada. Hlth Canada, Ctr Dis Control, Bur Infect Dis Lab, Ottawa, ON, Canada. US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. US FDA, Off Reg Operat, Rockville, MD 20857 USA. CDC, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. NR 10 TC 9 Z9 9 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 25 PY 1999 VL 282 IS 8 BP 726 EP 728 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 228CJ UT WOS:000082118800011 ER PT J AU Temple, R AF Temple, R TI Are surrogate markers adequate to assess cardiovascular disease drugs? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CORONARY HEART-DISEASE; MYOCARDIAL-INFARCTION; RANDOMIZED TRIALS; CLINICAL-TRIALS; BLOOD-PRESSURE; HYPERTENSION; MORTALITY; FAILURE; MORBIDITY; THERAPIES C1 US FDA, Ctr Drug Evaluat & Res Policy, Rockville, MD 20857 USA. RP Temple, R (reprint author), US FDA, Ctr Drug Evaluat & Res Policy, 5600 Fishers Ln,HFD 101, Rockville, MD 20857 USA. EM Temple@CDER.fda.gov NR 30 TC 187 Z9 191 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 25 PY 1999 VL 282 IS 8 BP 790 EP 795 DI 10.1001/jama.282.8.790 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 228CJ UT WOS:000082118800035 PM 10463719 ER PT J AU Dass, SB Bucci, TJ Heflich, RH Casciano, DA AF Dass, SB Bucci, TJ Heflich, RH Casciano, DA TI Evaluation of the transgenic p53(+/-) mouse for detecting genotoxic liver carcinogens in a short-term bioassay SO CANCER LETTERS LA English DT Article DE p53-transgenic mice; short-term carcinogenesis bioassay; mouse hepatic tumors; neonatal mice ID P53-DEFICIENT MICE; INDUCED TUMORIGENESIS; P53 MUTATIONS; CELL-LINES; TUMORS; HEPATOCARCINOGENESIS; DIMETHYLNITROSAMINE; 4-AMINOBIPHENYL; MODELS; ASSAY AB The transgenic p53-deficient heterozygous (p53(+/-)) mouse is prone to both spontaneous and induced tumors and has been proposed for use in a sensitive, short-term (6 months) assay for identifying genotoxic, multispecies carcinogens. It is not clear, however, if a short-term assay with p53(+/-) mice detects agents that target certain organs, in particular, the liver. In this study, we treated neonatal male p53(+/-) and p53(+/+) mice with the genotoxic carcinogens dimethylnitrosamine (DMN), 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP), and 6-nitrochrysene (6-NC). In keeping with the methodology of the proposed short-term assay, the p53(+/-) mice were evaluated for tumors 7 months after treatment. Wild-type neonatal mice treated with genotoxic carcinogens are known to develop tumors within 1 year; hence, the p53 (+/+) animals used as controls were subjected to pathological examination at 1 year of age. Our results showed that PhIP was not tumorigenic in either group of mice. Liver tumor incidence increased significantly in the p53(+/+) mice treated with DMN and 6-NC, indicating that the conditions of the bioassay were conducive to the promotion of liver tumorigenesis. On the other hand, these two chemicals failed to induce a significant increase in liver tumors in the p53(+/-) mice by seven months. This result suggests that a deficiency in the amount of p53 protein does not lead to accelerated liver tumorigenesis in mice, and contrasts with previous reports that show a decreased latency of tumors in non-liver targets. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Div Genet & Reproduct Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Dass, SB (reprint author), Biotech Serv Inc, 4610 W Commercial Dr, N Little Rock, AR 72116 USA. NR 22 TC 21 Z9 21 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD AUG 23 PY 1999 VL 143 IS 1 BP 81 EP 85 PG 5 WC Oncology SC Oncology GA 221NA UT WOS:000081732100012 PM 10465341 ER PT J AU Chu, PS Donoghue, DJ Shaikh, B AF Chu, PS Donoghue, DJ Shaikh, B TI Determination of total C-14-residues of sarafloxacin in eggs of laying hens. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 4-AGRO BP U64 EP U65 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033900131 ER PT J AU Donoghue, DJ AF Donoghue, DJ TI Predicting residue transfer into egg yolks. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Div Anim Res, Ctr Vet Med, Laurel, MD 20708 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 2-AGRO BP U64 EP U64 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033900129 ER PT J AU Kuznesof, PM AF Kuznesof, PM TI Food additive approvals in 20 minutes. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Off Premarket Approval, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 358-INOR BP U815 EP U815 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033902472 ER PT J AU Lucas, AD Kalson, JA Hutter, JC Wallis, RR AF Lucas, AD Kalson, JA Hutter, JC Wallis, RR TI Identifying toxic degradation products in cellulose acetate dialyzers. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, OST, CDRH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 73-POLY BP U420 EP U420 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226RA UT WOS:000082034001217 ER PT J AU McGowen, MM Vionnet, JA Scates, BA Vann, WF AF McGowen, MM Vionnet, JA Scates, BA Vann, WF TI Biosynthesis of polysialic acid as capsular polysaccharides in Escherichia coli. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 56-CARB BP U197 EP U197 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033900536 ER PT J AU Schenck, FJ Donoghue, DJ AF Schenck, FJ Donoghue, DJ TI Determination of organochlorine and organophosphorus pesticides in eggs using solid-phase extraction cleanup. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Baltimore Dist Lab, Baltimore, MD 21201 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 18-AGRO BP U69 EP U69 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033900145 ER PT J AU Shaikh, B Paulson, GD AF Shaikh, B Paulson, GD TI Distribution of total (14)c residue in egg yolk, white, and tissues following oral C-14 sulfamethazine administration to hens. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. USDA ARS, Biosci Res Lab, Washington, DC 20250 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 19-AGRO BP U69 EP U70 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033900146 ER PT J AU Shaikh, B Donoghue, D AF Shaikh, B Donoghue, D TI Approved drugs in US for meat-pipe and egg-laying chickens: Their potential cross-use. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1999 VL 218 MA 1-AGRO BP U64 EP U64 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 226QZ UT WOS:000082033900128 ER PT J AU Liao, W Paek, H Mabuni, C Angold, S Soliman, M AF Liao, W Paek, H Mabuni, C Angold, S Soliman, M TI Use of capillary electrophoresis with UV detection as a screening method to determine histamine in fish samples SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 12th International Symposium on High Performance Capillary Electrophoresis and Related Microscale Techniques CY JAN 23-28, 1999 CL PALM SPRINGS, CALIFORNIA DE fish; food analysis; histamine ID MICELLAR ELECTROKINETIC CHROMATOGRAPHY AB Histamine levels in fish, extracted with methanol, were determined by capillary electrophoresis (CE) using phosphate buffer pH 2.5 and U.V. detection at 210 nm. Histamine was well separated from the other co-extracted components under the given CE condition without any cleanup of the methanol extract. The average recovery of spiked histamine in various types of fish samples was 96%. Using the same methanol extracts from various fish samples, we then compared histamine concentration obtained by CE and fluorometric methods. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Calif State Dept Hlth Serv, Div Food Drug & Radiat Safety, Food & Drug Lab Branch, Los Angeles, CA 90015 USA. US FDA, Pacific Reg Lab SW, Los Angeles, CA 90015 USA. RP Liao, W (reprint author), Calif State Dept Hlth Serv, Div Food Drug & Radiat Safety, Food & Drug Lab Branch, 1521 W Pico Blvd, Los Angeles, CA 90015 USA. NR 7 TC 9 Z9 10 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD AUG 20 PY 1999 VL 853 IS 1-2 BP 541 EP 544 DI 10.1016/S0021-9673(99)00702-5 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 229VX UT WOS:000082217400060 PM 10486764 ER PT J AU Chen, JB Dobrovolsky, VN Heflich, RH AF Chen, JB Dobrovolsky, VN Heflich, RH TI Development of a mouse cell line containing the phi X174 am3 allele as a target for detecting mutation SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE transgenic; N-ethyl-N-nitrosourea; shuttle vector; SV40 large T-antigen ID TRANSGENIC MICE; HUMAN-FIBROBLASTS; MAMMALIAN-CELLS; SHUTTLE VECTORS; T-ANTIGEN; IMMORTALIZATION; MUTAGENESIS; GENE; EXPRESSION; SPECTRA AB Transgenic mice containing multiple copies of the Phi X174 am3 allele are being developed as a model for detecting tissue-specific in vivo mutation. In order to derive an analogous system for measuring am3 mutation in vitro, cells were cultured from 15-day-old C57B1/6J mouse embryos that were homozygous for the transgene and these cells were transfected with a plasmid expressing the SV40 large T-antigen. Two G418-resistant colonies were isolated from this culture and expanded to continuously proliferating cell lines (PX-1 and PX-2). Line PX-2 was treated with up to 1.0 mg/ml of N-ethyl-N-nitrosourea (ENU), assayed for survival by cloning efficiency after overnight culture, and assayed for am3 mutations after 5 days of culture. Survival decreased to 31% at the highest dose of ENU, while mutant frequency increased with dose from approximately 2 X 10(-7) in the untreated cells to 13 X 10(-7) in cultures treated with 0.6 mg/ml of ENU. PX-2 cells also were treated with 0 and 0.6 mg/ml of ENU and mutant frequency assays were performed after 5, 24, 48 and 72 h of growth. The mutant frequency in the treated culture increased to 20 X 10(-7) at 48 h and remained approximately the same at 72 h. These results indicate that PX-2 cells should be a useful resource for developing the in vivo am3 mutant assay and for evaluating the sensitivity of the am3 allele to various classes of mutagens. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Heflich, RH (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120, Jefferson, AR 72079 USA. NR 24 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD AUG 18 PY 1999 VL 444 IS 2 BP 347 EP 353 DI 10.1016/S1383-5718(99)00099-6 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 239ZT UT WOS:000082801400008 PM 10521674 ER PT J AU Purdie, N Province, DW Layloff, TP Nasr, MM AF Purdie, N Province, DW Layloff, TP Nasr, MM TI Algorithms for validating chiral properties of insulins SO ANALYTICAL CHEMISTRY LA English DT Article AB The combination of chiral ligand exchange on Cu(II) complexes in aqueous base with circular dichroism spectropolarimetric detection provides excellent avenues to validate the chirality properties of oligopeptides and proteins. The method is quick and simple and has the potential for development into an automated, routine procedure for quality control applications. Target analytes used for this first study of a protein system are human, porcine, and bovine insulins prepared by different procedures and obtained from different sources, production lots, and manufacturers. The analytical specificity of the test makes the method a potentially useful technique for validating the chirality properties of many peptide and protein forms. C1 Oklahoma State Univ, Dept Chem, Stillwater, OK 74078 USA. US FDA, CDER, DTAAD, St Louis, MO 63101 USA. RP Purdie, N (reprint author), Oklahoma State Univ, Dept Chem, Stillwater, OK 74078 USA. NR 7 TC 2 Z9 2 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD AUG 15 PY 1999 VL 71 IS 16 BP 3341 EP 3346 DI 10.1021/ac990071k PG 6 WC Chemistry, Analytical SC Chemistry GA 227HM UT WOS:000082075100006 PM 10464473 ER PT J AU Rasooly, L Rasooly, A AF Rasooly, L Rasooly, A TI Real time biosensor analysis of Staphylococcal enterotoxin A in food SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE biosensor; foodborne toxins; Staphylococcal enterotoxins ID SURFACE-PLASMON RESONANCE; HEAT INACTIVATION; IN-VITRO; ASSAY; RECEPTOR; AUREUS; GENE; MHC AB Currently there is no 'real-time' detection system to identify food borne toxins. In order to develop such a system, we have used a evanescent wave biosensor for real time detection of staphylococcal enterotoxin A (SEA) in foods. The approach used here is sandwich biosensor, a method utilizing two antibodies. The toxin binds initially to a capturing antibody which is bound covalently on the surface of the biosensor detector. The second antibody binds to the captured toxin. We were able to measure SEA in foods with little or no background interference, demonstrating that biosensor-based measurement of SEA was possible not only with purified SEA but also in complex food matrices such as hot dogs, potato salad, milk and mushrooms. Autoclaved samples of SEA did not evoke a positive response. With both purified SEA and SEA-spiked foods, the assay sensitivity is 10-100 ng/g depending on the material tested and the assay is rapid (<4 min) when a single antibody is used. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21218 USA. US FDA, Div Microbiol Studies, Washington, DC 20204 USA. Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Baltimore, MD USA. RP Rasooly, A (reprint author), Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21218 USA. NR 28 TC 52 Z9 56 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD AUG 15 PY 1999 VL 49 IS 3 BP 119 EP 127 DI 10.1016/S0168-1605(99)00053-7 PG 9 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 233CE UT WOS:000082407300002 PM 10490222 ER PT J AU Calarota, SA Leandersson, AC Bratt, G Hinkula, J Klinman, DM Weinhold, KJ Sandstrom, E Wahren, B AF Calarota, SA Leandersson, AC Bratt, G Hinkula, J Klinman, DM Weinhold, KJ Sandstrom, E Wahren, B TI Immune responses in asymptomatic HIV-1-infected patients after HIV-DNA immunization followed by highly active antiretroviral treatment SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CYTOTOXIC T-LYMPHOCYTES; NUCLEIC-ACID VACCINATION; REGULATORY GENES; INFECTED PATIENTS; CELL RESPONSES; REV; NEF; REPLICATION; EXPRESSION AB Intensive chemotherapy is capable of reducing the viral load in HIV-l-infected individuals while infected cells are still present. A special property of DNA immunization is to induce both new CTL and Ab responses. We evaluated the possibility of inducing new immune responses in already infected individuals by means of DNA constructs encoding the nef, rev, or tat regulatory HIV-1 genes. Significant changes in viral loads and CD4(+) counts were observed in four patients,tho started highly active antiretroviral treatment (HAART) during the immunization study. The DNA immunization induced Ag-specific T cell proliferation, which persisted up to 9 mo after the last DNA injection, and cytolytic activities but did not, by itself, reduce viral load. Increased levels of CTL precursor cells were induced in all nine DNA-immunized patients. The profile of IFN-gamma secretion observed when human PBMC were transfected with the nef, rev and tar DNA resembled that found in the CTI, activity (nef > tat > rev). Ab responses that occurred after immunizations were of a low magnitude. In accordance with the high IL-6 production induced by the nef DNA plasmid, IgG titers were highest in patients immunized with nef DNA, The initiation of HAART appears to contribute to the induction of new HIV-specific CTL responses, but by itself did not cause obvious re-induction of these activities. C1 Karolinska Inst, Microbiol & Tumorbiol Ctr, Swedish Inst Infect Dis Control, SE-17182 Solna, Sweden. South Hosp, Dept Dermatovenereol, Stockholm, Sweden. US FDA, Sect Retroviral Immunol, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. RP Wahren, B (reprint author), Karolinska Inst, Microbiol & Tumorbiol Ctr, Swedish Inst Infect Dis Control, SE-17182 Solna, Sweden. OI Hinkula, Jorma/0000-0003-1908-5609 NR 51 TC 89 Z9 89 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 AUG 15 PY 1999 VL 163 IS 4 BP 2330 EP 2338 PG 9 WC Immunology SC Immunology GA 224LH UT WOS:000081900200082 PM 10438897 ER PT J AU Kang, SH AF Kang, SH TI An optimal property of the exact multinomial test and the extended Fisher's exact test SO STATISTICS & PROBABILITY LETTERS LA English DT Article DE Stirling's formula; Bahadur efficiency; Pearson's chi-square test; conditional inference ID CONTINGENCY-TABLES; ALGORITHM; X2 AB In the goodness-of-fit test of parameters of the multinomial distribution we show that the exact multinomial test is asymptotically equivalent to the likelihood ratio test by using Stirling's formula. In an r x c contingency table, we show rat the extended Fisher's exact test conditional on row and column margins for the test of independence is also asymptotically equivalent to the likelihood ratio test. From the Bahadur asymptotic optimality of the likelihood ratio test in both unconditional and conditional cases, we prove that the two exact tests are asymptotically optimal in the sense of Bahadur efficiency. (C) 1999 Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7152 J9 STAT PROBABIL LETT JI Stat. Probab. Lett. PD AUG 15 PY 1999 VL 44 IS 2 BP 201 EP 207 DI 10.1016/S0167-7152(99)00010-3 PG 7 WC Statistics & Probability SC Mathematics GA 216PM UT WOS:000081451100013 ER PT J AU Ciolino, LA Turner, JA McCauley, HA Smallwood, AW Yi, TY AF Ciolino, LA Turner, JA McCauley, HA Smallwood, AW Yi, TY TI Optimization study for the reversed-phase ion-pair liquid chromatographic determination of nicotine in commercial tobacco products SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE tobacco; nicotine; alkaloids ID ALKALOIDS AB The availability of published methods for the determination of nicotine in commercial tobacco products based on state-of-the-art chromatographic methods is limited. Nicotine is a diprotic base with pK(a)'s of 3.12 (pyridine ring) and 8.02 (pyrrolidine ring). Other monoprotic and diprotic bases are also present in commercial tobacco including anatabine, nornicotine, anabasine, and cotinine. In this paper, the chromatography of nicotine and the minor tobacco alkaloids under reversed-phase ion-pairing conditions is thoroughly studied. The results of this study are used to understand the retention mechanisms of the tobacco alkaloids, to examine their observed elution order with respect to fundamental analyte properties (size,functionality, and acid-base strength), and to select optimum chromatographic conditions for the determination of nicotine in commercial tobacco products. Published by Elsevier Science B.V. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45202 USA. RP Ciolino, LA (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. NR 21 TC 31 Z9 34 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD AUG 13 PY 1999 VL 852 IS 2 BP 451 EP 463 DI 10.1016/S0021-9673(99)00639-1 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 230EZ UT WOS:000082240000011 PM 10481983 ER PT J AU Ehresman, K Lynfield, R Danila, R Black, S Shinefield, H Fireman, B Cordova, S AF Ehresman, K Lynfield, R Danila, R Black, S Shinefield, H Fireman, B Cordova, S TI Intussusception among recipients of rotavirus vaccine - United States, 1998-1999 (Reprinted from MMWR, vol 48, pg 577, 1999) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Minnesota Dept Hlth, Minneapolis, MN 55414 USA. Kaiser Permanente, Vaccine Study Ctr, Oakland, CA USA. US FDA, Div Biostat & Epidemiol, Rockville, MD 20857 USA. Natl Ctr Infect Dis, Viral Gastroenteritis Sect, Resp & Enter Viruses Br, Atlanta, GA USA. Natl Ctr Infect Dis, Off Director, Div Viral & Rickettsial Dis, Atlanta, GA USA. CDC, Vaccine Safety Datalink Team, Atlanta, GA 30333 USA. CDC, Stat Anal Br, Data Management Div, Atlanta, GA 30333 USA. CDC, Vaccine Safety & Dev Activ, Atlanta, GA 30333 USA. CDC, Child Vaccine Prevent Dis Br, Epidemiol & Surveillance Div, Natl Immunizat Program, Atlanta, GA 30333 USA. RP Ehresman, K (reprint author), Minnesota Dept Hlth, Minneapolis, MN 55414 USA. NR 1 TC 17 Z9 17 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 11 PY 1999 VL 282 IS 6 BP 520 EP 521 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 224UV UT WOS:000081919100010 ER PT J AU Meng, QX Henderson, RF Chen, T Heflich, RH Walker, DM Bauer, MJ Reilly, AA Walker, VE AF Meng, QX Henderson, RF Chen, T Heflich, RH Walker, DM Bauer, MJ Reilly, AA Walker, VE TI Mutagenicity of 1,3-butadiene at the Hprt locus of T-lymphocytes following inhalation exposures of female mice and rats SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE 1,3-butadiene; Hprt; lymphocyte; mutagenicity; mouse; rat ID LACI TRANSGENIC MICE; ETHYL-N-NITROSOUREA; IN-VIVO; MUTATIONAL SPECTRA; B6C3F1 MICE; 6-THIOGUANINE-RESISTANT LYMPHOCYTES; FISCHER-344 RATS; BONE-MARROW; CARCINOGENICITY; FREQUENCY AB The species specific response to 1,3-butadiene (BD), an important industrial chemical, was investigated by determining the influence of exposure duration and exposure concentration on the mutagenicity of BD in mice and rats and by defining the spectra of mutations in the Hprt gene T-cell mutants from control and BD-exposed mice. Female B6C3F1 mice and F344 rats (4-5 weeks old) were exposed by inhalation to 0, 20, 62.5, or 625 ppm of BD for up to 4 weeks (6 h/day, 5 days/week). Groups of control and exposed animals (n = 4-12/group) were necropsied at multiple time points after exposure and the T-cell cloning assay was used to measure Hprt mutant frequencies in lymphocytes isolated from spleen. Mutant clones collected from control and BD-exposed mice were propagated and analyzed by RT-PCR to produce Hprt cDNA for sequencing. In animals necropsied 4 weeks after 2 or 4 weeks of BD exposure (0 or 625 ppm), the rate of accumulation of mutations was greater in mice than in rats. Supra-linear dose-response curves were observed in BD-exposed mice, indicating a higher efficiency of mutant induction at lower concentrations of BD. The mutagenic potency estimates (represented by the differences in the areas under the mutant T-cell 'manifestation' curves of treated vs. control animals) in mice were 11 and 61 following 4 weeks of exposures to 62.5 and 625 ppm of BD, respectively, while mutant frequencies (Mfs) in rats were significantly increased only at 625 ppm BD (mutagenic potency of 7). Molecular analysis of Hprt cDNA from expanded T-cell clones from control and BD-exposed mice demonstrated an increased frequency of mutants in exposed animals that likely contain large deletions in the Hprt gene (P = 0.016). These data indicate that both exposure duration and exposure concentration are important in determining the magnitude of mutagenic response to BD, and that mutagenic and carcinogenic properties of BD in mice may be related more to the ability of its metabolites to cause chromosomal deletions than to produce point mutations. (C) 1999 Elsevier Science B.V. All rights reserved. C1 New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. SUNY Albany, Sch Publ Hlth, Dept Environm Hlth & Toxicol, Albany, NY 12203 USA. Lovelace Resp Res Inst, Albuquerque, NM 87185 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Walker, VE (reprint author), New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. FU NICHD NIH HHS [R01HD33648-02] NR 36 TC 26 Z9 29 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD AUG 11 PY 1999 VL 429 IS 1 BP 107 EP 125 DI 10.1016/S0027-5107(99)00104-9 PG 19 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 232HY UT WOS:000082366300008 PM 10434027 ER PT J AU Imam, SZ Crow, JP Newport, GD Islam, F Slikker, W Ali, SF AF Imam, SZ Crow, JP Newport, GD Islam, F Slikker, W Ali, SF TI Methamphetamine generates peroxynitrite and produces dopaminergic neurotoxicity in mice: protective effects of peroxynitrite decomposition catalyst SO BRAIN RESEARCH LA English DT Article DE methamphetamine; peroxynitsite; dopamine; 3-nitrotyrosine; striatum; oxidative stress ID NEURONAL NITRIC-OXIDE; DISMUTASE TRANSGENIC MICE; EXCITATORY AMINO-ACIDS; BEHAVIORAL SENSITIZATION; TYROSINE-HYDROXYLASE; LIPID-PEROXIDATION; SUPEROXIDE; SYNTHASE; 7-NITROINDAZOLE; INHIBITION AB Methamphetamine (METH)-induced dopaminergic neurotoxicity is believed to be produced by oxidative stress and free radical generation. The present study was undertaken to investigate if METH generates peroxynitrite and produces dopaminergic neurotoxicity. We also investigated if this generation of peroxynitrite can; be blocked by a selective peroxynitrite decomposition catalyst, 5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato iron III (FeTMPyP) and protect against METH-induced dopaminergic neurotoxicity. Administration of METH resulted in the significant formation of 3-nitrotyrosine (3-NT), an in vivo marker of peroxynitrite generation, in the striatum and also caused a significant increase in the body temperature. METH injection also caused a significant decrease in the concentration of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) by 76%, 53% and 40%, respectively, in the striatum compared with the control group. Treatment with FeTMPyP blocked the formation of 3-NT by 66% when compared with the METH group. FeTMPyP treatment also provided significant protection against the METH-induced hyperthermia and depletion of DA, DOPAC and HVA. Administration of FeTMPyP alone neither resulted in 3-NT formation nor had any significant effect on DA or its metabolite concentrations. These findings indicate that peroxynitrite plays a role in METH-induced dopaminergic neurotoxicity and also suggests that peroxynitrite decomposition catalysts may be beneficial for the management of psychostimulant abuse. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Hamdard Univ, Dept Med Elementol & Toxicol, Neurotoxicol Lab, New Delhi, India. Univ Alabama, Dept Anesthesiol, Birmingham, AL USA. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 41 TC 63 Z9 63 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 7 PY 1999 VL 837 IS 1-2 BP 15 EP 21 DI 10.1016/S0006-8993(99)01663-7 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 226FK UT WOS:000082009500003 PM 10433983 ER PT J AU Schmued, L Slikker, W AF Schmued, L Slikker, W TI Black-Gold: a simple, high-resolution histochemical label for normal and pathological myelin in brain tissue sections SO BRAIN RESEARCH LA English DT Article DE Black-Gold; myelin; demyelination; kainic acid; 3-nitropropionic acid; isoniazid; domoic acid ID NEURONAL DEGENERATION; ACID AB A novel haloaurophosphate complex called Black-Gold has been synthesized and applied to localize myelin within the central nervous system. The technique is tailored to studies using formalin fixed non-solvent processed tissue. The technique stains large myelinated tracts dark red-brown, while the individual myelinated axons appear black. This study demonstrates how this novel tracer can be used to localize both normal and pathological myelin. Specific myelin changes associated with exposure to diverse neurotoxicants including kainic acid, domoic acid, 3-nitropropionic acid, Fluoro-Gold and isoniazid are demonstrated and characterized. This study also demonstrates how Black-Gold can be combined with other histochemical markers including Nissl stains, retrogradely transported fluorescent tracers and fluorescent markers of neuronal degeneration. Advantages associated with the Black-Gold technique include high resolution, high contrast, short histochemical processing time, and consistent reproducibility. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Natl Ctr Toxicol Res, FDA, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Schmued, L (reprint author), Natl Ctr Toxicol Res, FDA, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. FU FDA HHS [FDA 7013.01]; NIEHS NIH HHS [Y01-ES-10187] NR 18 TC 52 Z9 53 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 7 PY 1999 VL 837 IS 1-2 BP 289 EP 297 DI 10.1016/S0006-8993(99)01624-8 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 226FK UT WOS:000082009500034 PM 10434014 ER PT J AU Miyazaki, Y Geber, A Miyazaki, H Falconer, D Parkinson, T Hitchcock, C Grimberg, B Nyswaner, K Bennett, JE AF Miyazaki, Y Geber, A Miyazaki, H Falconer, D Parkinson, T Hitchcock, C Grimberg, B Nyswaner, K Bennett, JE TI Cloning, sequencing, expression and allelic sequence diversity of ERG3 (C-5 sterol desaturase gene) in Candida albicans SO GENE LA English DT Article DE Darlington; ergosterol; GAL1; heterozygosity; yeast ID SACCHAROMYCES-CEREVISIAE; YEAST; MUTANTS; ERGOSTEROL; DNA; COMPLEMENTATION; DISRUPTION; VIABILITY; STRAINS AB The C-5 sterol desaturase gene (ERG3), essential for yeast ergosterol biosynthesis, was cloned and sequenced from Candida albicans by homology with the Saccharomyces cerevisiae ERG3. The ERG3 ORF contained 1158 bp and encoded 386 deduced amino acids. The clone was used to transform a gall mutant derived from the Darlington strain of C. albicans, using galactose selection. The Darlington strain is known to lack Delta(5,6) sterols, i.e. to have an erg3 phenotype (Howell, S.A., et al., 1990. J. Appl. Bacteriol. 69, 692-696). The transformant (CDTR1) contained six tandem integrated ERG3GAL1 repeats, had double the abundance of ERG3 transcript found in the host strain, and synthesized ergosterol, a Delta(5,6) sterol. The Darlington strain was noted to have an abundance of ERG3 transcript. Both ERG3 alleles in Darlington were cloned and sequenced in order to look for changes that might explain the erg3 phenotype. One allele, called Dar-2, contained a stop codon in place of tryptophan-292. The other ERG3 allele, called Dar-l, had changes in three amino acids, two of which were conserved in three fungal and one plant species. EcoRI genomic fragments containing ERG3 from the Dar-l allele and from B311, the wildtype strain, were inserted into the plasmid pRS316 and used to transform a Saccharomyces cerevisiae erg3,ura3 mutant using uracil selection. The 4.1 kb ERG3 fragments from the B311 and Dar-l both contained 1.4 kb 5' and 1.5 kb 3' flanking sequences around the coding region. Transformants with ERG3 from B311 but not from Dar-l showed restored ergosterol synthesis. One or more of these three deduced amino acids in the Dar-l allele of ERG3 appeared critical for function. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 NIAID, Clin Mycol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Pfizer Cent Res, Dept Discovery Biol, Sandwich, Kent, England. RP Bennett, JE (reprint author), NIAID, Clin Mycol Sect, Clin Invest Lab, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. RI Grimberg, Brian/I-1251-2013 OI Grimberg, Brian/0000-0002-6015-4912 NR 32 TC 38 Z9 40 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD AUG 5 PY 1999 VL 236 IS 1 BP 43 EP 51 DI 10.1016/S0378-1119(99)00263-2 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 225QF UT WOS:000081971700006 PM 10433965 ER PT J AU Lewis, CJ Crane, NT Wilson, DB Yetley, EA AF Lewis, CJ Crane, NT Wilson, DB Yetley, EA TI Estimated folate intakes: data updated to reflect food fortification, increased bioavailability, and dietary supplement use SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE folate; synthetic folic acid; intakes; food composition; Continuing Survey of Food Intakes by Individuals; CSFII; third National Health and Nutrition Examination Survey; NHANES III; humans; estimated average requirements; neural tube defects ID TRI-ENZYME EXTRACTION; PRODUCTS; VITAMIN; WOMEN; ASSAY AB Background: There is a critical need to estimate dietary folate intakes for nutrition monitoring and food safety evaluations, but available intake data are seriously limited by several factors. Objective: Our objective was to update 2 national food consumption surveys to reflect folate intakes as a result of the recently initiated food fortification program and to correct folate intakes for the apparently higher bioavailability of synthetic folic acid (SFA; ie, folate added to foods or from dietary supplements) than of naturally occurring folate so as to express intakes as dietary folate equivalents. Design: It was not possible to chemically analyze foods, so adjustments were made to food-composition data by using information about food ingredients and characteristics. Total folate intakes were estimated for several sex and age groups by using the modified data coupled with dietary supplement use. Results: Within the limitations of the data, our findings suggested that 67-95% of the population met or surpassed the new estimated average requirement, depending on the sex and age group and survey. Nonetheless, some subgroups had estimated intakes below these standards. Estimated SFA intakes suggested that approximate to 15-25% of children aged 1-8 y, depending on the survey, had intakes above the newly established tolerable upper intake level. We estimated that 68-87% of females of childbearing age had SFA intakes below the recommended intake of 400 mu g/d, depending on the age group and survey. Conclusion: There is a need to explore ways to improve folate intakes in targeted subgroups, including females of childbearing age, while not putting other population groups at risk of excessive intakes. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Lewis, CJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-451,200 C St SW, Washington, DC 20204 USA. NR 25 TC 114 Z9 116 U1 3 U2 5 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 1999 VL 70 IS 2 BP 198 EP 207 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 219RT UT WOS:000081621400005 PM 10426695 ER PT J AU O'Neill, RT Szarfman, A AF O'Neill, RT Szarfman, A TI Bayesian data mining in large frequency tables, with an application to the FDA spontaneous reporting system - Discussion SO AMERICAN STATISTICIAN LA English DT Editorial Material ID ADVERSE C1 US FDA, Ctr Drug Evaluat & Res, Off Biostat, Rockville, MD 20857 USA. RP O'Neill, RT (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Biostat, 5600 Fishers Lane,15B-45, Rockville, MD 20857 USA. NR 16 TC 21 Z9 21 U1 0 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0003-1305 J9 AM STAT JI Am. Stat. PD AUG PY 1999 VL 53 IS 3 BP 190 EP 196 DI 10.2307/2686094 PG 7 WC Statistics & Probability SC Mathematics GA 230YM UT WOS:000082279300002 ER PT J AU Holland, RD Duffy, CR Rafii, F Sutherland, JB Heinze, TM Holder, CL Voorhees, KJ Lay, JO AF Holland, RD Duffy, CR Rafii, F Sutherland, JB Heinze, TM Holder, CL Voorhees, KJ Lay, JO TI Identification of bacterial proteins observed in MALDI TOF mass spectra from whole cells SO ANALYTICAL CHEMISTRY LA English DT Article ID FAST-ATOM-BOMBARDMENT; ASSISTED LASER DESORPTION/IONIZATION; ESCHERICHIA-COLI; RAPID IDENTIFICATION; H-NS; NUCLEOID PROTEIN; SPECTROMETRY; EXPRESSION AB Characteristic ions in the MALDI TOF mass spectra from bacterial cells have been associated with four known proteins. The proteins, observed both from cells and in filtered cellular suspensions, were isolated by HPLC and identified on the basis of their mass spectra and their partial amino acid sequence, determined using the Edman method (10-15 residues). The acid resistance proteins HdeA and HdeB give rise to ions near m/z 9735 and 9060 iu MALDI TOF mass spectra from cells and from extracts of both Escherichia coli 1090 and Shigella flexneri PHS-1059. However, the proteins associated with proteolytic cleavage by the peptidase Lep, rather than the precursor proteins, were observed, both using cells and from cellular extracts. A cold-shock protein, CspA, was associated with the ion near m/z 7643 from Pseudomonas aeruginosa. Similarly, a cold-acclimation protein, CapB, was identified as the source of the ion near m/z 7684 in P. putida, This last protein was homologous with a known CapB from P. fragi. While these experiments involved the detection of known or homologous proteins from typical bacteria, this same approach could also be applied to the detection of unique proteins or biomarker proteins associated with other bacteria of public health significance. C1 US FDA, Natl Ctr Toxicol Res, Div Chem & Microbiol, Jefferson, AR 72079 USA. Colorado Sch Mines, Dept Chem, Golden, CO 80401 USA. RP Lay, JO (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem & Microbiol, Jefferson, AR 72079 USA. RI Lay, Jackson/G-1007-2011 OI Lay, Jackson/0000-0003-3789-2527 NR 24 TC 96 Z9 99 U1 4 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD AUG 1 PY 1999 VL 71 IS 15 BP 3226 EP 3230 DI 10.1021/ac990175v PG 5 WC Chemistry, Analytical SC Chemistry GA 224BW UT WOS:000081877100052 PM 10450164 ER PT J AU Cho-Chung, YS Beaucag, S Marquez, V Neckers, L Torrence, PF AF Cho-Chung, YS Beaucag, S Marquez, V Neckers, L Torrence, PF TI Abstracts from the Third Annual NIH Symposium on Therapeutic Oligonucleotides: Discovery and Milestone Achievements - December 4, 1998 - Bethesda, Maryland SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Editorial Material C1 NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, DBS, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. NCI, Med Chem Lab, DBS, Bethesda, MD 20892 USA. NCI, Tumor Cell Biol Sect, Med Branch, DCS, Rockville, MD 20850 USA. NIDDK, Biomed Chem Sect, Med Chem Lab, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, DBS, Bldg 10,Room 5B05,10 Ctr Dr,MSC 1750, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD AUG PY 1999 VL 9 IS 4 BP 359 EP 359 DI 10.1089/oli.1.1999.9.359 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 226RR UT WOS:000082035800005 ER PT J AU Wilk, A Grajkowski, A Srinivasachar, K Beaucage, SL AF Wilk, A Grajkowski, A Srinivasachar, K Beaucage, SL TI Improved chemistry for the production of synthetic oligodeoxyribonucleotides SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article; Proceedings Paper CT 3rd Annual NIH Symposium on Therapeutic Oligonucleotides - Discovery and Milestone Achievements CY DEC 04, 1998 CL BETHESDA, MARYLAND SP NIH ID OLIGONUCLEOTIDES; DEPROTECTION; SUPPORTS; CLEAVAGE; ADDUCTS; DNA C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Beaucage, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29A,Room 3B-06,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 17 TC 9 Z9 9 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD AUG PY 1999 VL 9 IS 4 BP 361 EP 366 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 226RR UT WOS:000082035800006 ER PT J AU Chaurasia, CS AF Chaurasia, CS TI In vivo microdialysis sampling: theory and applications SO BIOMEDICAL CHROMATOGRAPHY LA English DT Review ID FREELY-MOVING RATS; BLOOD-BRAIN-BARRIER; PERFORMANCE LIQUID-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY; IN-VIVO; INVIVO MICRODIALYSIS; CAPILLARY ELECTROPHORESIS; QUANTITATIVE MICRODIALYSIS; ELECTROCHEMICAL DETECTION; AMINO-ACIDS AB During the last two decades, a number of methods have been developed for in vivo collection, separation and characterization of biological samples and analytes. The capability acid reliability of the microdialysis technique for measuring endogenous substances (such as neurotransmitters and their metabolites) as well as exogenous therapeutic agents in various tissue systems have brought it to the forefront of the in vivo tissue sampling methods. The usability of this technique is demonstrated by its application as reported in almost 3600 scientific papers (as of January 1998). This paper describes the general aspects and various applications of this fast growing technique. Emphasis has been given to analytical considerations with regards to microdialysis probe recovery and newer HPLC techniques. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 US FDA, Div Bioequivalence, Rockville, MD 20855 USA. RP Chaurasia, CS (reprint author), US FDA, Div Bioequivalence, MPN 2,Rm 123E,7500 Standish Pl, Rockville, MD 20855 USA. NR 158 TC 99 Z9 104 U1 1 U2 14 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0269-3879 J9 BIOMED CHROMATOGR JI Biomed. Chromatogr. PD AUG PY 1999 VL 13 IS 5 BP 317 EP 332 DI 10.1002/(SICI)1099-0801(199908)13:5<317::AID-BMC891>3.0.CO;2-I PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA 225MW UT WOS:000081966200001 PM 10425021 ER PT J AU Suydam, LA AF Suydam, LA TI FDA and the promise of FDAMA SO BIOPHARM-THE APPLIED TECHNOLOGIES OF BIOPHARMACEUTICAL DEVELOPMENT LA English DT Article AB Everyone agrees that federal agencies must keep up with the times - both technologically and methodologically. Landmark legislation mandates that FDA revise, streamline, and update its processes, regulations, and procedures. Can the agency afford to modernize? C1 Care Of Kubic M, US FDA, Rockville, MD 20847 USA. RP Suydam, LA (reprint author), Care Of Kubic M, US FDA, Rockville, MD 20847 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 1040-8304 J9 BIOPHARM-APPL T BIO JI Biopharm-Appl Technol. Biopharm. Dev. PD AUG PY 1999 VL 12 IS 8 BP 43 EP 45 PG 3 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 225MX UT WOS:000081966300012 ER PT J AU Plata-Salaman, CR Ilyin, SE Gayle, D Romanovitch, A Carbone, KM AF Plata-Salaman, CR Ilyin, SE Gayle, D Romanovitch, A Carbone, KM TI Persistent Borna disease virus infection of neonatal rats causes brain regional changes of mRNAs for cytokines, cytokine receptor components and neuropeptides SO BRAIN RESEARCH BULLETIN LA English DT Article DE interleukin; tumor necrosis factor; growth factor; cerebellum; hippocampus; hypothalamus; cortex; neurotrophic; nervous system ID NECROSIS-FACTOR-ALPHA; MESSENGER-RNAS; ACCESSORY PROTEIN; IN-VIVO; FEEDBACK-SYSTEMS; IL-1-BETA SYSTEM; NERVOUS-SYSTEM; SCHWANN-CELLS; TNF-ALPHA; INTERLEUKIN-1 AB Borna disease virus (BDV) replicates in brain cells. The neonatally infected rat with BDV exhibits developmental-neuromorphological abnormalities, neuronal cytolysis, and multiple behavioral and physiological alterations. Here, we report on the levels of interleukin-1 beta (IL-1 beta), IL-1 receptor antagonist (IL-1Ra), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta 1 (TGF-beta 1), IL-1 receptor type I (IL-1RI), IL-1 receptor accessory protein (IL-1R AcP) I and II, glycoprotein 130, and various neuropeptide mRNAs in the cerebellum, parieto-frontal cortex, hippocampus and hypothalamus of BDV-infected rats at 7 and 28 days postintracerebral BDV inoculation. The data show that cytokine and neuropeptide mRNA components are abnormal and differentially modulated in brain regions. IL-1 beta, TNF-alpha and TGF-beta 1 mRNA levels were up-regulated in all brain regions following BDV inoculation. The same cerebellar samples from BDV-infected animals exhibited the highest levels of IL-1 beta, IL-1Ra, TNF-alpha, IL-1RI, and IL-1R AcP II mRNA expression. The profiles of IL-1 beta, IL-1Ra, TNF-alpha, and TGF-beta 1 mRNA induction in the cerebellar samples were highly intercorrelated, indicating an association among cytokine ligand mRNAs. Cytokine mRNA induction was differentially upregulated among brain regions, except for TGF-beta 1. Specificity of transcriptional changes in response to BDV infection is also suggested by the up-regulation of cytokine and neuropeptide Y mRNAs associated with down-regulation of pro-opiomelanocortin, and with no change of IL-1R AcP I, dynorphin and leptin receptor mRNAs in the same brain region samples. Other data also show a differential mRNA component modulation in distinct brain regions obtained from the same rats depending on the stage of BDV infection. The conclusion of these studies is that cytokines may play a role in the neuropathophysiology of neonatally BDV-infected rats. (C) 1999 Elsevier Science Inc. C1 Univ Delaware, Sch Life & Hlth Sci, Div Mol Biol, Newark, DE 19716 USA. US FDA, Lab Pediat & Resp Viral Dis, Div Viral Prod, Off Vaccine Res & Review,Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Plata-Salaman, CR (reprint author), RW Johnson Pharmaceut Res Inst, Cent Nervous Syst Res, Welsh & McKean Rd, Spring House, PA 19477 USA. FU NIMH NIH HHS [MH 48948] NR 59 TC 44 Z9 47 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD AUG PY 1999 VL 49 IS 6 BP 441 EP 451 DI 10.1016/S0361-9230(99)00081-7 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 230QK UT WOS:000082261700009 PM 10483922 ER PT J AU Gross, M Kruisselbrink, T Anderson, K Lang, N McGovern, P Delongchamp, R Kadlubar, F AF Gross, M Kruisselbrink, T Anderson, K Lang, N McGovern, P Delongchamp, R Kadlubar, F TI Distribution and concordance of N-acetyltransferase genotype and phenotype in an American population SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER RISK; CIGARETTE-SMOKING; ACETYLATION PHENOTYPE; MOLECULAR-GENETICS; BLADDER-CANCER; NAT2; POLYMORPHISMS; SUSCEPTIBILITY; GENES; CARCINOGENESIS AB Polymorphic arylamine N-acetyltransferase 2 (NAT2) status varies widely between individuals and ethnic groups and has been associated with susceptibility to several cancers. Few studies have reported the distribution of NAT2 status for Caucasian-American populations or evaluated the concordance between methods of assessment for cancer cases and controls. In our study, distribution of NAT2 status was classified by genotype and phenotype measurements in PANCAN, a population-based case-control study of pancreatic cancer, and concordance between measurements was evaluated for 33 cases and 222 controls. Major genotypes and alleles among controls were *5B/*6A, *5B/*5B, *4/*6A, and *5B/*4. One putative new allele was found in a single individual, Genotypes and phenotypes were classified as rapid or slow, according to a bimodal model. Presence of the *4 (wild-type) allele defined a NAT2 genotype as rapid. The NAT2 phenotype was analyzed by the caffeine assay. Ratios of 5-acetylamino-6-formylamino-3-methyluracil to 1-methylxanthine were determined, and individuals with values of greater than or equal to 0.66 were identified as having a rapid phenotype. In our population, 58.1 and 59.5% of control subjects were classified as slow acetylators by phenotype and genotype, respectively. Concordance of NAT2 genotype and phenotype classification was 97.8% in the bimodal model. A similar analysis was completed for a trimodal model. Concordance of genotype and phenotype was high in cases (90.9%) and similar to controls; genotyping alone provided an efficient, accurate method of analysis for acetylator status. A comparison with two previous reports revealed subtle differences in genotype and allele distribution but exhibited overall similarity with other Caucasian-American populations. C1 Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55454 USA. Mayo Clin, Rochester, MN 55905 USA. Univ Arkansas Med Sci, Dept Surg, Little Rock, AR 72205 USA. John L McClellan Vet Affairs Hosp, Dept Surg, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Gross, M (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. FU NCI NIH HHS [R01CA58697] NR 47 TC 88 Z9 91 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 AUG PY 1999 VL 8 IS 8 BP 683 EP 692 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 256BN UT WOS:000083705300006 PM 10744128 ER PT J AU Collins, JM Klecker, RW Katki, AG AF Collins, JM Klecker, RW Katki, AG TI Suicide prodrugs activated by thymidylate synthase: Rationale for treatment and noninvasive imaging of tumors with deoxyuridine analogues SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 89th Annual Meeting of the American-Association-for-Cancer-Research CY MAR 27-APR 01, 1998 CL NEW ORLEANS, LOUISIANA SP Amer Assoc Canc Res ID CELLS; DNA; CHEMOTHERAPY; EXPRESSION; PREDICTOR; CANCER AB Most tumors are resistant to therapy by thymidylate synthase (TS) inhibitors due to their high levels of TS, Instead of inhibiting TS, we hypothesized that it was possible to use this enzyme to activate suicide prodrugs (deoxyuridine analogues) to more toxic species (thymidine analogues). Tumors with high levels of TS could be particularly sensitive to deoxyuridine analogues because they would be more efficient in producing the toxic methylated species. Furthermore. the accumulation of methylated species within tumors could be visualized externally if a tracer dose of the deoxyuridine analogue was tagged with an isotope, preferably a positron emitter, such as F-18. Higher accumulation of isotope indicates higher activity of TS and lower sensitivity of the tumor to TS inhibitors, but perhaps more sensitivity to therapy with deoxyuridine analogues as suicide prodrugs, 2'-F-ara-deoxyuridine (FAU) was used as a prototype to demonstrate these concepts experimentally. FAU readily entered cells and was phosphorylated, methylated, and subsequently incorporated into cellular DNA, Among different cell lines, FAU produced varying degrees of growth inhibition. Greater DNA incorporation (e.g., for CEM and U-937 cells) was reflected as increased toxicity. FAU produced less DNA incorporation in Raji or L1210 cells, and growth rate was minimally decreased. As the first demonstration that cells with high levels of TS activity can be more vulnerable to therapy than cells with low TS activity, this preliminary work suggests a new therapeutic approach for common human tumors that were previously resistant. Furthermore, it appears that the TS activity of tumors could be noninvasively imaged in situ by tracer doses of [F-18]FAU and that this phenotypic information could guide patient therapy. C1 US FDA, Lab Clin Pharmacol, Rockville, MD 20850 USA. RP Collins, JM (reprint author), US FDA, Lab Clin Pharmacol, Room 314,4 Res Court, Rockville, MD 20850 USA. NR 16 TC 25 Z9 27 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 AUG PY 1999 VL 5 IS 8 BP 1976 EP 1981 PG 6 WC Oncology SC Oncology GA 228KL UT WOS:000082135600005 PM 10473074 ER PT J AU Lee, LH Graman, PS AF Lee, LH Graman, PS TI Congenital tuberculosis in a neonatal intensive care unit - Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 Univ Rochester, Sch Med, Dept Pediat, Div Pediat Infect Dis,Infect Dis Unit, Rochester, NY 14642 USA. Univ Rochester, Sch Med, Dept Med, Infect Dis Unit, Rochester, NY USA. RP Lee, LH (reprint author), US FDA, HFM-475,Suite 370 N,1401 Rockville Pike, Rockville, MD 20852 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 1999 VL 29 IS 2 BP 468 EP 468 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 227YE UT WOS:000082106900063 ER PT J AU Berger, VW Exner, DV AF Berger, VW Exner, DV TI Detecting selection bias in randomized clinical trials SO CONTROLLED CLINICAL TRIALS LA English DT Article DE allocation concealment; blocking; treatment allocation ID FOLLOW-UP; STRATEGIES; CHALLENGES; QUALITY AB Lack of concealment of allocation in randomized clinical trials can invite selection bias, which is the preferential enrollment of specific patients into one treatment group over another. For example, patients more likely to respond may be enrolled only when the next treatment to be assigned is known to be the active treatment, and patients less likely to respond may be enrolled only when the next treatment to be assigned is known to be the control. Despite the fact that selection bias can compromise both the internal and external validity of trials, little methodology has been developed for its detection. An investigator may test the success of the randomization by comparing baseline characteristics across treatment groups, but such test is limited by the potential inability of the measured baseline variables to predict response. A new method for detecting selections bias, based on response data only, is developed for the case in which a small block size, and either unmasking of treatment codes or an open-label design, have compromised the concealment of allocation. This new method complements baseline comparisons, and is sensitive to detect selection bias even in situations in which baseline comparisons are not. Control Clin Trials 1999;20:319-327 (C) Elsevier Science Inc. 1999. C1 NHLBI, Clin Trials Res Grp, Bethesda, MD 20892 USA. RP Berger, VW (reprint author), US FDA, CBER, HFM-215,1401 Rockville Pike,Suite 200S, Rockville, MD 20852 USA. NR 25 TC 88 Z9 88 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD AUG PY 1999 VL 20 IS 4 BP 319 EP 327 DI 10.1016/S0197-2456(99)00014-8 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 218MG UT WOS:000081555900002 PM 10440559 ER PT J AU Willy, ME Henderson, DK Magnuson, WG AF Willy, ME Henderson, DK Magnuson, WG TI Bacteremia in the intensive care unit: A predicament propagated by progress SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE bacteremias; intensive care units; nosocomial infections ID NOSOCOMIAL INFECTION; TRENDS; STATES C1 US FDA, Off Postmkt Drug Risk Assessment, Bethesda, MD 20014 USA. NIH, Warren G Magnuson Clin Ctr, Off Deputy Director Clin Care, Bethesda, MD 20892 USA. RP Willy, ME (reprint author), US FDA, Off Postmkt Drug Risk Assessment, Bethesda, MD 20014 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD AUG PY 1999 VL 27 IS 8 BP 1648 EP 1650 DI 10.1097/00003246-199908000-00048 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 229WG UT WOS:000082218300038 PM 10470780 ER PT J AU Andersen, ME Conolly, RB Faustman, EM Kavlock, RJ Portier, CJ Sheehan, DM Wier, PJ Ziese, L AF Andersen, ME Conolly, RB Faustman, EM Kavlock, RJ Portier, CJ Sheehan, DM Wier, PJ Ziese, L TI Quantitative mechanistically based dose-response modeling with endocrine-active compounds SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Workshop on Characterizing the Effects of Endocrine Disruptors on Human Health at Environmental Exposure Levels CY MAY 11-13, 1998 CL RALEIGH, NORTH CAROLINA DE endocrine-active compounds; endocrine disruptors; linkage models mechanistic dose-response modeling; pharmacodynamics; pharmacokinetics; risk assessment extrapolations ID DEPENDENT SEX DETERMINATION; RISK ASSESSMENT; DEVELOPMENTAL TOXICITY; POLYCHLORINATED-BIPHENYLS; STRUCTURAL INFORMATION; PHARMACOKINETIC MODELS; METHYLENE-CHLORIDE; GENE-TRANSCRIPTION; ESTROGEN-RECEPTOR; EXPOSURE AB A wide range of toxicity lest methods is used or is being developed for assessing the impact of endocrine-active compounds (EACs) on human hearth. Interpretation of these data and their quantitative use in human and ecologic risk assessment will be enhanced by the availability of mechanistically based dose-response (MBDR) models to assist tow-dose, interspecies, and in vitro to in vivo extrapolations. A quantitative dose-response modeling work group examined the state of the art for developing MBDR models for EACs and the near-term needs to develop, validate, and apply these models for risk assessments. Major aspects of this report relate to current status of these models, the objectives/goals in MBDR model development for EACs, low-dose extrapolation issues, regulatory inertia impeding acceptance of these approaches, and resource/data needs to accelerate model development and model acceptance by the research and the regulatory community. C1 Colorado State Univ, Dept Environm Hlth, Ft Collins, CO 80523 USA. Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA. Univ Washington, Dept Environm Hlth, Seattle, WA 98195 USA. US EPA, Natl Hlth & Environm Effects Res Labs, Res Triangle Pk, NC 27711 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. SmithKline Beecham Pharmaceut, King Of Prussia, PA 19406 USA. Calif Protect Agcy, RCHAS, Off Environm Hlth Hazard Assoc, Berkeley, CA USA. RP Andersen, ME (reprint author), KS Crump Grp Inc, 3200 Chapel Hill,Nelson Highway,Suite 101,POB 143, Res Triangle Pk, NC 27709 USA. RI Portier, Christopher/A-3160-2010; OI Portier, Christopher/0000-0002-0954-0279; Andersen, Melvin/0000-0002-3894-4811 NR 55 TC 15 Z9 16 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 1999 VL 107 SU 4 BP 631 EP 638 DI 10.2307/3434556 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 227RU UT WOS:000082094400007 PM 10421774 ER PT J AU Parshikov, IA Freeman, JP Lay, JO Beger, RD Williams, AJ Sutherland, JB AF Parshikov, IA Freeman, JP Lay, JO Beger, RD Williams, AJ Sutherland, JB TI Regioselective transformation of ciprofloxacin to N-acetylciprofloxacin by the fungus Mucor ramannianus SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE N-acetylation; biotransformation; ciprofloxacin; fluoroquinolone; Mucor ramannianus ID FLUOROQUINOLONE ENROFLOXACIN; DEGRADATION; METABOLITES; SOIL AB A strain of the saprobic fungus Mucor ramannianus, isolated from a forest, was used to demonstrate the potential for ciprofloxacin biotransformation by zygomycetes in the environment. The fungus carried out the regioselective N-acetylation of ciprofloxacin to a single product, which was purified from culture extracts by high-performance liquid chromatography. The metabolite was identified by mass and nuclear magnetic resonance spectrometry as 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-acetyl-1-piperazinyl)-3-quinolinecarboxylic acid. (C) 1999 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RI Lay, Jackson/G-1007-2011; OI Lay, Jackson/0000-0003-3789-2527; Parshikov, Igor/0000-0003-1466-1128 NR 19 TC 39 Z9 39 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD AUG 1 PY 1999 VL 177 IS 1 BP 131 EP 135 DI 10.1016/S0378-1097(99)00302-X PG 5 WC Microbiology SC Microbiology GA 222HC UT WOS:000081777600019 PM 10436931 ER PT J AU Fritsche, J Rickert, R Steinhart, H Yurawecz, MP Mossoba, MM Sehat, N Roach, JAG Kramer, JKG Ku, Y AF Fritsche, J Rickert, R Steinhart, H Yurawecz, MP Mossoba, MM Sehat, N Roach, JAG Kramer, JKG Ku, Y TI Conjugated linoleic acid (CLA) isomers: formation, analysis, amounts in foods, and dietary intake SO FETT-LIPID LA English DT Article; Proceedings Paper CT 52nd International Congress and Expo of the DGF CY SEP 13-15, 1998 CL MAGDEBURG, GERMANY ID PERFORMANCE LIQUID-CHROMATOGRAPHY; LACTATING DAIRY-COWS; TRANS-FATTY-ACIDS; MILK-FAT; GAS-CHROMATOGRAPHY; ADIPOSE-TISSUE; GERMAN FOODS; BOVINE-MILK; PRODUCTS; IDENTIFICATION AB The analysis, content, and daily intake of conjugated linoleic acid isomers (CLA) are presented in the following review. Modern analytical techniques such as capillary gas chromatography (GC), silver-ion high performance liquid chromatography (Ag+-HPLC) combined with different detection methods (flame ionisation, mass spectroscopic, ultra violet) are mandatory for the unequivocal determination of geometric and positional CLA isomers. An overview is given on the CLA contents in 139 German foods. e.g. milk/dairy products, meat/meat products, edible oils. margarines, fish, and deep fried products. The dietary intake for men and women is estimated using consumption data. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Food Labeling, Washington, DC 20204 USA. Univ Hamburg, Inst Biochem & Food Chem, Dept Food Chem, D-20146 Hamburg, Germany. Agr & Agri Food Canada, Food Res Ctr, Guelph, ON N16 2W1, Canada. RP Fritsche, J (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Labeling, 200 C St SW, Washington, DC 20204 USA. NR 42 TC 57 Z9 61 U1 0 U2 12 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0931-5985 J9 FETT-LIPID JI Fett-Lipid PD AUG PY 1999 VL 101 IS 8 BP 272 EP 276 PG 5 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 234AN UT WOS:000082460700002 ER PT J AU Yurawecz, MP Sehat, N Mossoba, MM Roach, JAG Kramer, JKG Ku, Y AF Yurawecz, MP Sehat, N Mossoba, MM Roach, JAG Kramer, JKG Ku, Y TI Variations in isomer distribution in commercially available conjugated linoleic acid SO FETT-LIPID LA English DT Article; Proceedings Paper CT 52nd International Congress and Expo of the DGF CY SEP 13-15, 1998 CL MAGDEBURG, GERMANY ID FATTY-ACIDS; DAIRY-PRODUCTS; MILK; ATHEROSCLEROSIS; IDENTIFICATION; METHYLATION; CONVERSION; CHEESES; TISSUE; RATS AB Conjugated linoleic acid (CLA) has been reported to have anticarcinogenic and antiatherogenic properties, to repartition body fat, to build bone mass, to normalize glucose tolerance, and to reduce hyperglycemia and diabetes. CLA products are now commercially available. and there is considerable interest in studying CLA because of this range of reported beneficial effects. However, little is known about the composition of these preparations. Representative commercial CLA products in capsule or liquid (aqueous or oily) form were analyzed for their CLA content and isomer composition using gas chromatography (GC), silver ion-high performance liquid chromatography (Ag+-HPLC) and spectroscopic techniques. The content of CLA in the preparations varied widely. Based on the GC-internal standard technique, total CLA varied from 20 to 89% by total weight and 28 to 94% of total fat. One product contained no CLA. The isomer distributions were generally of two types: those with two major CLA positional isomers, and those with four major CLA positional isomers. All the CLA preparations in capsule form contained the four isomer mixture, while the liquid preparations contained from two to four CLA positional isomers. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Agr & Agri Food Canada, Food Res Ctr, Guelph, ON N1G 2W1, Canada. RP Yurawecz, MP (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 32 TC 29 Z9 32 U1 1 U2 3 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0931-5985 J9 FETT-LIPID JI Fett-Lipid PD AUG PY 1999 VL 101 IS 8 BP 277 EP 282 PG 6 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 234AN UT WOS:000082460700003 ER PT J AU Klinman, DM Verthelyi, D Takeshita, F Ishii, KJ AF Klinman, DM Verthelyi, D Takeshita, F Ishii, KJ TI Immune recognition of foreign DNA: A cure for bioterrorism? SO IMMUNITY LA English DT Review ID TUMOR-NECROSIS-FACTOR; CPG-CONTAINING OLIGODEOXYNUCLEOTIDES; INDUCE AUTOIMMUNE-DISEASE; CYTOKINE GENE-EXPRESSION; B SURFACE-ANTIGEN; BACTERIAL-DNA; IMMUNOSTIMULATORY DNA; PLASMID DNA; PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES; CUTTING EDGE C1 US FDA, Sect Retroviral Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Sect Retroviral Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RI Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 90 TC 93 Z9 94 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD AUG PY 1999 VL 11 IS 2 BP 123 EP 129 DI 10.1016/S1074-7613(00)80087-4 PG 7 WC Immunology SC Immunology GA 232RH UT WOS:000082383400001 PM 10485647 ER PT J AU Hu, L Kopecko, DJ AF Hu, L Kopecko, DJ TI Campylobacter jejuni 81-176 associates with microtubules and dynein during invasion of human intestinal cells SO INFECTION AND IMMUNITY LA English DT Article ID HUMAN EPITHELIAL-CELLS; CULTURED ANIMAL-CELLS; CHLAMYDIA-TRACHOMATIS; HELA-CELLS; YERSINIA-ENTEROCOLITICA; INTRACELLULAR SURVIVAL; NEISSERIA-GONORRHOEAE; ACTIN POLYMERIZATION; SHIGELLA-FLEXNERI; ESCHERICHIA-COLI AB Campylobacter jejuni uptake into cultured INT407 cells was analyzed kinetically over a wide range of starting multiplicities of infection (MOI; from 0.02 to 20,000 bacteria/epithelial cell). The efficiency of internalization was the highest at MOI of 0.02 and decreased steadily at higher MOIs, presumably due to reported C. jejuni autoagglutination at higher densities. Total internalized Campylobacter CFU increased gradually from an MOI of 0.02 to a peak at an MOI of 200 (reaching an average of two bacteria internalized per epithelial cell) and decreased at higher MOIs. The invasion process was apparently saturated within 2 h at an MOI of 200, indicating stringent host cell limitations on this entry process. Furthermore, whereas control Salmonella typhi invaded all monolayer cells within 1 h, only two-thirds of monolayer cells were infected after 2 h with C. jejuni at MOIs of 200 to 2,000. The percentage of Campylobacter-infected host cells gradually increased to 85% after 7 h of infection, suggesting that C. jejuni entry may be host cell cycle dependent. Direct evidence of the involvement of microtubules in C. jejuni internalization, suggested previously by biochemical inhibitor studies, was obtained by time course immunofluorescence microscopic analyses. Bacteria initially bound to the tips of host cell membrane extensions containing microtubules, then aligned in parallel with microtubules during entry, colocalized specifically with microtubules and dynein but not with microfilaments, and moved over 4 h, presumably via min rotubules to the perinuclear region of host cells. Orthovanadate, which inhibits dynein activity, specifically reduced C. jejuni 81-176 entry, suggesting that this molecular motor is involved in entry and endosome trafficking during this novel bacterial internalization process. Collectively, these data suggest that C. jejuni enters host cells in a targeted and tightly controlled process leading to uptake into an endosomal vacuole which apparently moves intracellularly along microtubules via the molecular motor, dynein, to the perinuclear region. C1 US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Kopecko, DJ (reprint author), US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bldg 29-420,NIH Campus, Bethesda, MD 20892 USA. NR 65 TC 110 Z9 115 U1 1 U2 8 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 AUG PY 1999 VL 67 IS 8 BP 4171 EP 4182 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 219ZA UT WOS:000081637400063 PM 10417189 ER PT J AU Bhushan, R Frasch, CE AF Bhushan, R Frasch, CE TI Measurement of human antibodies to type III group B Streptococcus - Reply SO INFECTION AND IMMUNITY LA English DT Letter ID POLYSACCHARIDE C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Bethesda, MD 20892 USA. RP Bhushan, R (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1999 VL 67 IS 8 BP 4304 EP 4305 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 219ZA UT WOS:000081637400086 ER PT J AU Reddy, PA Atreya, CD AF Reddy, PA Atreya, CD TI Identification of simian cyclophilin A as a calreticulin-binding protein in yeast two-hybrid screen and demonstration of cyclophilin A interaction with calreticulin SO INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES LA English DT Article DE chaperone; immunophilin; peptidyl prolyl cis-trans isomerases (PPIases) ID GENE-EXPRESSION; CHAPERONE FUNCTION; GLYCOPROTEINS; MODULATION; RECEPTOR; DOMAIN; STRESS; LECTIN AB Cyclophilin A (CyPA) was identified as one of the calreticulin (CR)-binding proteins in a yeast two-hybrid screen utilizing simian cDNA expression-library. The simian CyPA protein had 96% identity with that of human, differing only at eight amino acid residues. We further established CyPA-CR interaction by incubation of glutathione transferase-fused CyPA (GST-CyPA) and CR proteins with CV-1 cyto-lysates, followed by CR and CyPA-specific immune-blot analysis. The immunosuppressive drug cyclosporin A, a CyPA ligand, did not inhibit CyPA-CR interaction. Our results established a new property of CyPA binding activity to CR. Since CR is a Ca2+-binding protein, CR-CyPA interactions may be important in signaling pathways for induction of Ca2+-dependent cellular processes. (C) 1999 Elsevier Science B.V. All rights reserved. C1 US FDA, Sect Viral Pathogenesis & Adverse React, Lab Pediat & Resp Viral Dis, Div Viral Prod,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Atreya, CD (reprint author), 8800 Rockville Pike,Bldg 29A,HFM-460, Bethesda, MD 20892 USA. NR 29 TC 12 Z9 13 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 AUG PY 1999 VL 25 IS 4 BP 345 EP 351 DI 10.1016/S0141-8130(99)00053-7 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 222JA UT WOS:000081780100005 PM 10456775 ER PT J AU Ozawa, S Shimizu, M Katoh, T Miyajima, A Ohno, Y Matsumoto, Y Fukuoka, M Tang, YM Lang, NP Kadlubar, FF AF Ozawa, S Shimizu, M Katoh, T Miyajima, A Ohno, Y Matsumoto, Y Fukuoka, M Tang, YM Lang, NP Kadlubar, FF TI Sulfating-activity and stability of cDNA-expressed allozymes of human phenol sulfotransferase, ST1A3*1 ((213)Arg) and ST1A3*2 ((213)His), both of which exist in Japanese as well as Caucasians SO JOURNAL OF BIOCHEMISTRY LA English DT Article DE genetic polymorphism; molecular cloning; phenol sulfotransferase; recombinant enzyme; thermostability ID HUMAN-LIVER; PARTIAL-PURIFICATION; DRUG-METABOLISM; FORM; PHENOLSULFOTRANSFERASE; PHARMACOGENETICS; POLYMORPHISM; DERIVATIVES; ACTIVATION; ASSAY AB We recently found single amino acid; substitutions ((213)Arg/His and (223)Met/Val) in polymorphic human phenol-sulfating phenol sulfotransferase (SULT: cDNAs encoding ST1A3, P PST or HAST1/2) among Caucasians and African-Americans. In a Japanese population (n = 143), allele frequencies of (213)Arg and (213)His were 83.2 and 16.8%, respectively, but the (223)Val allele was not found. (213)His homozygosity was reportedly associated with both very low (>7-fold) sulfating activities of p-nitrophenol (at 4 mu M) and low thermostability in platelets. Sulfating-activity determinations using recombinant (213)Arg- and (213)His-forms (ST1A3*1 and ST1A3*2, respectively) did not, however, reveal appreciable deficiency in [S-35]3'-phosphoadenosine 5'-phosphosulfate (PAPS)-dependent sulfation of p-nitrophenol (4 mu M) by ST1A3*2 (7.5 vs. 10.2 nmol/min/nmol SULT for ST1A3). Kinetic parameters for p-nitrophenol for p-nitrophenol sulfation supported the slight decrease in sulfating activities at 4 mu M (K-m, 0.82 vs. 1.75 mu M; V-max, 13.2 vs. 13.1 nmol/min/nmol SULT, respectively, for ST1A3*1 and *2), p-Nitrophenyl sulfate-dependent 2-naphthol sulfation by ST1A3*2 was 69% of that by ST1A3*1 (p < 0.05). However, ST1A3*2 was remarkably unstable at 45 and 37 degrees C as compared to ST1A3*1, The lower p-nitrophenol sulfating activity of ST1A3*2 may explain the lower platelet p-nitrophenol sulfation in ST1A3*2 homozygotes, Protein instability and ST1A3 gene regulation may be both involved in the polymorphism of p-nitrophenol sulfation in human tissues. C1 Natl Inst Hlth Sci, Div Pharmacol, Setagaya Ku, Tokyo 1588501, Japan. Showa Coll Pharmaceut Sci, Dept Clin Pharmacol & Toxicol, Tokyo 1948543, Japan. Univ Occupat & Environm Hlth, Sch Hlth Sci, Dept Hlth Sci Informat, Kitakyushu, Fukuoka 807, Japan. Natl Ctr Toxicol Res, Div Mol Epidemiol HFT100, Jefferson, AR 72079 USA. Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. John L McClellan Vet Adm Hosp, Little Rock, AR 72205 USA. RP Ozawa, S (reprint author), Natl Inst Hlth Sci, Div Pharmacol, Setagaya Ku, 1-18-1 Kamiyoga, Tokyo 1588501, Japan. NR 21 TC 31 Z9 34 U1 0 U2 1 PU JAPANESE BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F, 25-16 HONGO-5-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0021-924X J9 J BIOCHEM-TOKYO JI J. Biochem. (Tokyo) PD AUG PY 1999 VL 126 IS 2 BP 271 EP 277 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226GJ UT WOS:000082011700003 PM 10423517 ER PT J AU Arakere, G Flores, AE Ferrieri, P Frasch, CE AF Arakere, G Flores, AE Ferrieri, P Frasch, CE TI Inhibition enzyme-linked immunosorbent assay for serotyping of group B streptococcal isolates SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID STRAINS; DISEASE AB Group B Streptococcus (GBS) is one of the most common organisms causing neonatal sepsis as well as serious infections in adults. Serotyping the organism is important in studying the epidemiology of the disease as well as deciding a course of treatment. There are several methods available for serotyping, Most of them need high-titered sera and are not quantitative. We are reporting a new inhibition enzyme-linked immunosorbent assay (ELISA) for serotyping which is sensitive and specific compared to the conventional methods but does not need high-titered serotype-specific antisera, as the specificity is controlled by the polysaccharide coating on the ELISA plates. The method can also be quantitative, and we have measured polysaccharide elaborated by different serotype V strains. Thus, the inhibition ELISA method will be useful in serotyping for epidemiological studies, assessing virulence, and performing strain selection for vaccine production. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. RP Arakere, G (reprint author), Ctr Biol Evaluat & Res, Div Bacterial Prod, 1401 Rockville Pike,Mailstop HFM-428, Rockville, MD 20853 USA. EM arakereg@cber.fda.gov NR 17 TC 15 Z9 17 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD AUG PY 1999 VL 37 IS 8 BP 2564 EP 2567 PG 4 WC Microbiology SC Microbiology GA 216VR UT WOS:000081465600030 PM 10405402 ER PT J AU Khan, AS Sears, JF Muller, J Galvin, TA Shahabuddin, M AF Khan, AS Sears, JF Muller, J Galvin, TA Shahabuddin, M TI Sensitive assays for isolation and detection of simian foamy retroviruses SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID VIRUS TYPE-3 SFV-3; PURIFICATION; INFECTIONS; MONKEYS; CELLS AB Simian foamy viruses (SFVs) are highly prevalent in a variety of nonhuman primate species ranging from prosimians to apes, SFVs possess a broad host range, and human infections can occur by cross-species transfer (W, Heneine et al., Nat, Med, 4:403-407, 1998). Retrovirus screening of potential sources of infection, such as laboratory research animals and simian-derived biological products, could minimize human exposure to SFVs by reducing the risk of potential retrovirus infection in humans. We describe a variety of sensitive assays for SFV isolation and detection which were developed with a prototype strain of SFV serotype 2, The Mns dunni cell line (M, R, Lander and S. K, Chattopadhyay, J. Virol, 52:695-698, 1984) was found to be highly sensitive for SFV production on the basis of various general and specific retrovirus detection assays such as reverse transcriptase assay, transmission electron microscopy, immunofluorescence assay, and Western blotting. A highly sensitive PCR assay was developed on the basis of the sequences in primary SFV isolates obtained from pig-tailed macaques (Macaca nemestrina) and rhesus macaques (Macaca mulatta). Analysis of naturally occurring SFV infection in macaques indicated that analysis by a combination of assays, including both highly sensitive, specific assays and less sensitive, broadly reactive assays, is important for evaluation of retrovirus infection. C1 US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Lab Vector Borne Viral Dis, Rockville, MD 20852 USA. RP Khan, AS (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Lab Retrovirus Res, 1401 Rockville Pike,HFM-454, Rockville, MD 20852 USA. NR 48 TC 23 Z9 24 U1 0 U2 2 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 AUG PY 1999 VL 37 IS 8 BP 2678 EP 2686 PG 9 WC Microbiology SC Microbiology GA 216VR UT WOS:000081465600049 PM 10405421 ER PT J AU Furuke, K Burd, PR Horvath-Arcidiacono, JA Hori, K Mostowski, H Bloom, ET AF Furuke, K Burd, PR Horvath-Arcidiacono, JA Hori, K Mostowski, H Bloom, ET TI Human NK cells express endothelial nitric oxide synthase, and nitric oxide protects them from activation-induced cell death by regulating expression of TNF-alpha SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; NECROSIS-FACTOR-ALPHA; FAS-INDUCED APOPTOSIS; NF-KAPPA-B; MEDIATED CYTOTOXICITY; T-CELLS; DNA FRAGMENTATION; REDOX REGULATION; MESSENGER-RNA; BINDING AB Although NO appears important in rodent immune responses, its involvement in the human immune system is unclear, We report that human NK cells express constitutive endothelial NO synthase mRNA and protein, but not detectable levels of inducible NO synthase. They produce NO following activation by coculture with target cells or cross-linking with anti-CD16 mAb, and production is increased in the presence of IL-2, N-monomethyl-L-arginine (L-NMA), a NOS inhibitor, partially inhibited NK cell lysis of four different target cells (<40% inhibition at 500 mu M L-NMA), but not granule release following coculture with target cells, or Fas ligand induction following cross-linking with anti-CDl6 mAb, However, L-NMA augmented apoptosis of NK cells induced by activation through CD16 ligation or coculture with K562. An NO donor, S-nitroso-N-acetylpenicillamine (SNAP), suppressed apoptosis of NK cells induced by CD16 cross-linking or coculture with target cells, suggesting that endogenous NO production is involved in protection of NK cells from activation-induced apoptosis, thereby maintaining NK activity. SNAP also suppressed, and L-NMA enhanced, expression of TNF-alpha, reported to be involved in activation-induced NK cell death, in response to CD16 cross-linking. Suppression of anti-CD16-induced apoptosis by SNAP was reversed by the addition of rTNF-alpha, DNA-binding activity of the transcription factor, NF-AT, which is involved in TNF-alpha induction upon ligation of CD16, was inhibited by SNAP and enhanced by L-MMA, Our results suggest that down-regulation of TNF-alpha expression, possibly due to suppression of NF-AT activation, is a mechanism by which endogenous NO protects NK cells from activation-induced apoptosis, and maintains lytic capacity. C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Immunol HFM 518, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. RP Bloom, ET (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Cellular Immunol HFM 518, Div Cellular & Gene Therapies, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 57 TC 37 Z9 38 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1999 VL 163 IS 3 BP 1473 EP 1480 PG 8 WC Immunology SC Immunology GA 219ZX UT WOS:000081640000049 PM 10415049 ER PT J AU Rubin, SA Snoy, PJ Wright, KE Brown, EG Reeve, P Beeler, JA Carbone, KM AF Rubin, SA Snoy, PJ Wright, KE Brown, EG Reeve, P Beeler, JA Carbone, KM TI The mumps virus neurovirulence safety test in rhesus monkeys: A comparison of mumps virus strains SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 1998 FDA Science Forum CY DEC, 1998 CL WASHINGTON, D.C. SP FDA ID VACCINE; MENINGITIS AB Wild type mumps viruses are highly neurotropic and a frequent cause of aseptic meningitis in unvaccinated humans. To test whether attenuated mumps viruses used in the manufacture of mumps vaccines have neurovirulent properties, a monkey neurovirulence safety test (MNVT) is performed. However, results with several mumps virus MNVTs have raised questions as to whether the test can reliably discriminate neurovirulent from nonneurovirulent mumps virus strains, Here, various mumps virus strains representing a wide range of neuropathogenicity were tested in a standardized MNVT A trend of higher neurovirulence scores was observed in monkeys inoculated with wild type mumps virus versus vaccine strains, although differences were not statistically significant. Results indicated the need for further examination and refinement of the MNVT or for development of alternative MNVTs. C1 US FDA, DVP, OVRR, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON K1N 6N5, Canada. RP Carbone, KM (reprint author), US FDA, DVP, OVRR, Ctr Biol Evaluat & Res, Bldg 29A,Room 1A-21,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 14 TC 31 Z9 32 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG PY 1999 VL 180 IS 2 BP 521 EP 525 DI 10.1086/314905 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 222CZ UT WOS:000081767000039 PM 10395874 ER PT J AU Lira, R Sundar, S Makharia, A Kenney, R Gam, A Saraiva, E Sacks, D AF Lira, R Sundar, S Makharia, A Kenney, R Gam, A Saraiva, E Sacks, D TI Evidence that the high incidence of treatment failures in Indian kala-azar is due to the emergence of antimony-resistant strains of Leishmania donovani SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY OCT, 1998 CL SAN JUAN, PUERTO RICO SP Amer Soc Trop Med & Hygiene ID SODIUM STIBOGLUCONATE; VISCERAL LEISHMANIASIS; PENTAVALENT ANTIMONY; DRUG-RESISTANCE; IN-VITRO; AMASTIGOTES; BIHAR AB The possibility that the high frequency of treatment failures in Indian kala-azar might be due to infection with antimony-resistant strains of Leishmania donovani has not been experimentally addressed. L. donovani isolates were obtained from splenic aspiration smears of 24 patients in Bihar, India, who either did not respond (15) or did respond (9) to 1 or more full courses of treatment with sodium antimony gluconate (SAG), A strong correlation (P < .001) between clinical response and SAG sensitivity in vitro was observed only when strains were assayed as intracellular amastigotes: responsive isolates ED50 = 2.4 +/- 2.6, ED90 = 6.4 +/- 7.8 mu g SAG/mL; unresponsive isolates ED50 = 7.4 +/- 3.7 mu g SAG/mL, ED90 = 29.1 +/- 11.1 SAG/mL. No correlation with clinical response was found by use of extracellular promastigotes (ED50 = 48 +/- 22 vs. 52 +/- 29 mu g/mL). The emergence of antimony-resistant L. donovani strains appears to be a cause of treatment failures in India. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. US FDA, CBER, Lab Parasit Biol & Biochem, OVRR,DAPP, Rockville, MD 20857 USA. Benares Hindu Univ, Inst Med Sci, Varanasi, Uttar Pradesh, India. RP Sacks, D (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Rm 126,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA. NR 16 TC 240 Z9 249 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG PY 1999 VL 180 IS 2 BP 564 EP 567 DI 10.1086/314896 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 222CZ UT WOS:000081767000049 PM 10395884 ER PT J AU Melnyk, S Pogribna, M Pogribny, I Hine, RJ James, SJ AF Melnyk, S Pogribna, M Pogribny, I Hine, RJ James, SJ TI A new HPLC method for the simultaneous determination of oxidized and reduced plasma aminothiols using coulometric electrochemical detection SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE homocysteine; thiols; glutathione; methionine; HPLC; plasma; redox status; electrochemical detection ID PERFORMANCE LIQUID-CHROMATOGRAPHY; REDOX THIOL STATUS; TOTAL HOMOCYSTEINE; FOLATE-DEFICIENCY; MASS-SPECTROMETRY; VASCULAR-DISEASE; FOLIC-ACID; SERUM; GLUTATHIONE; METABOLISM AB A new method has been developed that is capable of providing a complete profile of the most common monothiols and disulfides present in plasma or tissue extracts. The method utilizes reversed phase ion-pairing high performance liquid chromatography coupled with coulometric electrochemical detection to simultaneously quantify free oxidized and reduced aminothiols or total aminothiols after chemical reduction. The method is extremely sensitive, with limits of detection in the 5 fmol/mL range for monothiols and 50 fmol/mL for dithiols. The interassay and intraassay coefficients of variation for total and free aminothiols ranged between 1.2 and 5.8%. The mean recoveries for total and plasma aminothiols ranged between 97.1 and 102.8%. The aminothiols are quantified directly, without derivatization, and include methionine, homocysteine, homocystine, cystathionine, cysteine, cystine, cysteinylglycine, and oxidized and reduced glutathione. Because a complete aminothiol profile of metabolites in both the remethylation (anabolic) and transulfuration (catabolic) pathways of homocysteine metabolism can be determined simultaneously, this new method should be useful in determining the metabolic etiology of homocysteinemia and in designing appropriate nutritional intervention strategies. Basic research applications of this method should lead to an increased understanding of the metabolic pathology of aminothiol imbalance. Published by Elsevier Science Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Nutr & Dietet, Little Rock, AR 72205 USA. RP James, SJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 26 TC 154 Z9 155 U1 1 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD AUG PY 1999 VL 10 IS 8 BP 490 EP 497 DI 10.1016/S0955-2863(99)00033-9 PG 8 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 230EW UT WOS:000082239700008 PM 15539328 ER PT J AU Purucker, M Malozowski, S AF Purucker, M Malozowski, S TI Inhaled corticosteroids and growth velocity in children with asthma SO JOURNAL OF PEDIATRICS LA English DT Letter C1 US FDA, Div Pulm Drug Prod, Rockville, MD 20857 USA. US FDA, Div Metab & Endocrine Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Purucker, M (reprint author), US FDA, Div Pulm Drug Prod, Rockville, MD 20857 USA. NR 5 TC 5 Z9 5 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD AUG PY 1999 VL 135 IS 2 BP 264 EP 265 PN 1 PG 2 WC Pediatrics SC Pediatrics GA 224FC UT WOS:000081885900026 PM 10431250 ER PT J AU Mahmood, I AF Mahmood, I TI Prediction of clearance, volume of distribution and half-life by allometric scaling and by use of plasma concentrations predicted from pharmacokinetic constants: a comparative study SO JOURNAL OF PHARMACY AND PHARMACOLOGY LA English DT Article ID HUMANS; CIPROFLOXACIN; DRUGS; RABBITS; ANIMALS; SM-1652; DOGS AB Pharmacokinetic parameters (clearance, CL, volume of distribution in the central compartment, Vdc, and elimination half-life, t(1/2 beta)) predicted by an empirical allometric approach have been compared with parameters predicted from plasma concentrations calculated by use of the pharmacokinetic constants A, B, alpha and beta, where A and B are the intercepts on the Y axis of the plot of plasma concentration against time and alpha and beta are the rate constants, both pairs of constants being for the distribution and elimination phases, respectively. The pharmacokinetic parameters of cefpiramide, actisomide, troglitazone, procaterol, moxalactam and ciprofloxacin were scaled from animal data obtained from the literature. Three methods were used to generate plots for the prediction of clearance in man: dependence of clearance on body weight (simple allometric equation); dependence of the product of clearance and maximum life-span potential (MLP) on body weight; and dependence of the product of clearance and brain weight on body weight. Plasma concentrations of the drugs were predicted in man by use of A, B, alpha and beta obtained from animal data. The predicted plasma concentrations were then used to calculate CL, Vd(C) and t(1/2 beta). The pharmacokinetic parameters predicted by use of both approaches were compared with measured values. The results indicate that simple allometry did not predict clearance satisfactorily for actisomide, troglitazone, procaterol and ciprofloxacin. Use of MLP or the product of clearance and brain weight improved the prediction of clearance for these four drugs. Except for troglitazone, Vd(C) and t(1/2 beta) predicted for man by use of the allometric approach were comparable with measured values for the drugs studied. CL, Vd(C) and t(1/2 beta) predicted by use of pharmacokinetic constants were comparable with values predicted by simple allometry. Thus, if simple allometry failed to predict clearance of a drug, so did the pharmacokinetic constant approach (except for actisomide). The results of this study indicate that caution should be employed in interpreting plasma concentrations predicted for a drug in man by use of pharmacokinetic constants obtained in animals. C1 US FDA, Div Pharmaceut Evaluat 1 HFD 860, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Div Pharmaceut Evaluat 1 HFD 860, Off Clin Pharmacol & Biopharmaceut, Woodmont Off Ctr 2,1451 Rockville Pike, Rockville, MD 20852 USA. NR 23 TC 28 Z9 29 U1 1 U2 4 PU ROYAL PHARMACEUTICAL SOC GREAT BRITAIN PI LONDON PA 1 LAMBETH HIGH ST, LONDON SE1 7JN, ENGLAND SN 0022-3573 J9 J PHARM PHARMACOL JI J. Pharm. Pharmacol. PD AUG PY 1999 VL 51 IS 8 BP 905 EP 910 DI 10.1211/0022357991773320 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 236NT UT WOS:000082606000006 PM 10504028 ER PT J AU Wear, KA Gagne, RM Wagner, RF AF Wear, KA Gagne, RM Wagner, RF TI Uncertainties in estimates of lesion detectability in diagnostic ultrasound SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID CONTRAST-DETAIL ANALYSIS; IMAGES; SPECKLE; STATISTICS; SCATTERERS; RESOLUTION; NUMBER AB Statistical properties of estimates of focal lesion detectability for medical ultrasonic imaging systems are investigated. Analytic forms for bias and variance of estimates of detectability of a lesion consisting of fully developed speckle embedded within a speckle background are derived. Bias and variance of estimates of detectability are investigated using a computer simulation and experiments on tissue-mimicking phantoms. This work offers a systematic methodology for interpreting measurements on phantoms in order to assess lesion detectability. In addition, it provides useful results which may be used to improve design of phantoms and experiments for imaging-system performance assessment. (C) 1999 Acoustical Sociery ofAmerica. [S0001-4966(99)01208-4]. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-142,12720 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 21 TC 3 Z9 3 U1 0 U2 1 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD AUG PY 1999 VL 106 IS 2 BP 1161 EP 1173 DI 10.1121/1.427124 PG 13 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 225YN UT WOS:000081993700066 PM 10462819 ER PT J AU Ratner, V Taylor, N Wein, AJ Hanno, PJ AF Ratner, V Taylor, N Wein, AJ Hanno, PJ TI Epidemiology of interstitial cystitis: A population based study SO JOURNAL OF UROLOGY LA English DT Letter C1 Interstitial Cystitis Assoc, Rockville, MD 20850 USA. Univ Penn, Med Ctr, Div Urol, Philadelphia, PA 19104 USA. US FDA, Div Reprod & Urol Drug Prod, Rockville, MD 20857 USA. RP Ratner, V (reprint author), Interstitial Cystitis Assoc, Suite 1402,51 Monroe St, Rockville, MD 20850 USA. NR 1 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 1999 VL 162 IS 2 BP 500 EP 500 DI 10.1016/S0022-5347(05)68608-9 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 214UA UT WOS:000081344900067 PM 10411074 ER PT J AU Feldman, SA Hendry, RM Beeler, JA AF Feldman, SA Hendry, RM Beeler, JA TI Identification of a linear heparin binding domain for human respiratory syncytial virus attachment glycoprotein G SO JOURNAL OF VIROLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; ENHANCED PULMONARY HISTOPATHOLOGY; IMMUNIZED BALB/C MICE; AMINO-ACID-SEQUENCE; PSEUDORABIES VIRUS; RSV CHALLENGE; SUBGROUP-B; FUNCTIONAL ATTACHMENT; SULFATE PROTEOGLYCANS; BHK CELLS AB Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract disease in infants and young children worldwide, Infection is mediated, in part, by an initial interaction between attachment protein (G) and a highly sulfated heparin-like glycosaminoglycan (Gag) located on the cell surface. Synthetic overlapping peptides derived from consensus sequences of the G protein ectodomain from both RSV subgroups A and B were tested by heparin-agarose affinity chromatography for their abilities to bind heparin, This evaluation identified a single linear heparin binding domain (HBD) for RSV subgroup A ((184)A-->T-198) and B (K-183-->K-197). The binding of these peptides to Vero cells was inhibited by heparin. Peptide binding to two CHO cell mutants (pgsD-677 and pgsA-745) deficient in heparan sulfate or total Gag synthesis was decreased 50% versus the parental cell line, CHO-K1, and decreased an average of 87% in the presence of heparin, The RSV-G HBD peptides were also able to inhibit homologous and heterologous virus infectivity of Vero cells. These results indicate that the sequence (184)A/K-183-->T-198/K-197 for RSV subgroups A and B, respectively, defines an important determinant of RSV-G interactions with heparin. C1 US FDA, Ctr Biol Evaluat & Res, Lab Pediat & Resp Virus Dis, Bethesda, MD USA. Calif Dept Hlth Serv, Viral & Rickettsial Dis Lab, Berkeley, CA 94704 USA. RP Feldman, SA (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29A,3B-05,HFM 463,1401 Rockville Pike, Rockville, MD 20852 USA. NR 52 TC 119 Z9 122 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 AUG PY 1999 VL 73 IS 8 BP 6610 EP 6617 PG 8 WC Virology SC Virology GA 215HZ UT WOS:000081377400049 PM 10400758 ER PT J AU Eulitz, K Yurawecz, MP Sehat, N Fritsche, J Roach, JAG Mossoba, MM Kramer, JKG Adlof, RO Ku, Y AF Eulitz, K Yurawecz, MP Sehat, N Fritsche, J Roach, JAG Mossoba, MM Kramer, JKG Adlof, RO Ku, Y TI Preparation, separation, and confirmation of the eight geometrical cis/trans conjugated linoleic acid isomers 8,10-through 11,13-18 : 2 SO LIPIDS LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; GAS-CHROMATOGRAPHY; FATTY-ACIDS; MILK; IDENTIFICATION; TISSUE; CHEESE AB Conjugated linoleic acid (CLA) mixtures were isomerized with p-toluenesulfinic acid or I-2 catalyst. The resultant mixtures of the eight cis/trans geometric isomers of 8,10-, 9,11-, 10,12-, and 11,13-octadecadienoic (18:2) acid methyl esters were separated by silver ion-high-performance liquid chromatography (Ag+-HPLC) and gas chromatography (GC). Ag+-HPLC allowed the separation of all positional CLA isomers and geometric cis/trans CLA isomers except 10,12-18:2. However, one of the 8,10 isomers (8cis,10trans-18:2) coeluted with the 9trans,11cis-18:2 isomer. There were differences in the elution order of the pairs of geometric CLA isomers resolved by Ag+-HPLC. For the 8,10 and 9,11 CLA isomers, cis,trans eluted before trans,cis, whereas the opposite elution pattern was observed for the 11,13-18:2 geometric isomers (trans,cis before cis,trans). All eight cis/trans CLA isomers were separated by GC on long polar capillary columns only when their relative concentrations were about equal. Large differences in the relative concentration of the CLA isomers found in natural products obscured the resolution and identification of a number of minor CLA isomers. In such cases, GC-mass spectrometry of the dimethyloxazoline derivatives was used to identify and confirm coeluting CLA isomers. For the same positional isomer, the cis,trans consistently eluted before the trans,cis CLA isomers by GC High resolution mass spectrometry (MS) selected ion recording (SIR) of the molecular ions of the 18:1, 18:2, and 18:3 fatty acid methyl esters served as an independent and highly sensitive method to confirm CLA methyl ester peak assignments in GC chromatograms obtained from food samples by flame-ionization detection. The high-resolution MS data were used to correct for the nonselectivity of the flame-ionization detector. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Food Labeling, Washington, DC 20204 USA. Agr & Agri Food Canada, Food Res Ctr, Guelph, ON N1G 2W1, Canada. ARS, No Reg Res Ctr, USDA, Peoria, IL 61604 USA. RP Yurawecz, MP (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Labeling, HFS-175,200 C St SW, Washington, DC 20204 USA. NR 11 TC 101 Z9 106 U1 0 U2 18 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PD AUG PY 1999 VL 34 IS 8 BP 873 EP 877 DI 10.1007/s11745-999-0435-z PG 5 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 236DT UT WOS:000082583500013 PM 10529099 ER PT J AU Miller, HI AF Miller, HI TI Nasty taste from G-8 GM food policy SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD AUG PY 1999 VL 17 IS 8 BP 730 EP 730 DI 10.1038/11613 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 221WX UT WOS:000081751400004 PM 10429217 ER PT J AU Epstein, S Bauer, S Miller, A Pilaro, A Noguchi, P AF Epstein, S Bauer, S Miller, A Pilaro, A Noguchi, P TI FDA comments on phase I clinical trials without vector biodistribution data SO NATURE GENETICS LA English DT Letter C1 US FDA, Div Cellular & Gene Therap, CBER, Rockville, MD 20852 USA. RP Epstein, S (reprint author), US FDA, Div Cellular & Gene Therap, CBER, 1401 Rockville Pike,HFM-521, Rockville, MD 20852 USA. NR 3 TC 3 Z9 3 U1 1 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 1999 VL 22 IS 4 BP 326 EP 326 DI 10.1038/11895 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 222FH UT WOS:000081772500012 PM 10431234 ER PT J AU Wilfert, CM Aronson, JE Beck, DT Fleischman, AR Kline, MW Mofenson, LM Scott, GB Wara, DW Whitley-Williams, PN Lindegren, ML Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Marcy, SM Murray, DL Overturf, GD Prober, CG Saari, TN Weiner, LB Whitley, RJ Baker, CJ Peter, G Pickering, LK Hirsch, A Jacobs, RF MacDonald, NE Myers, MG Orenstein, WA Patriarca, PA Rabinovich, NR Schwartz, B AF Wilfert, CM Aronson, JE Beck, DT Fleischman, AR Kline, MW Mofenson, LM Scott, GB Wara, DW Whitley-Williams, PN Lindegren, ML Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Marcy, SM Murray, DL Overturf, GD Prober, CG Saari, TN Weiner, LB Whitley, RJ Baker, CJ Peter, G Pickering, LK Hirsch, A Jacobs, RF MacDonald, NE Myers, MG Orenstein, WA Patriarca, PA Rabinovich, NR Schwartz, B CA Comm Pediat AIDS Comm Infect Dis TI Issues related to human immunodeficiency virus transmission in schools, child care, medical settings, the home, and community SO PEDIATRICS LA English DT Article ID HEPATITIS-B VIRUS; INFECTED CHILDREN; HIV-INFECTION; TYPE-1 HIV-1; WORKERS; BLOOD; RISK; SURVEILLANCE; PERSONNEL; EXPOSURE AB Current recommendations of the American Academy of Pediatrics (AAP) for infection control practices to prevent transmission of blood-borne pathogens, including human immunodeficiency virus (HIV) in hospitals, other medical settings, schools, and child care facilities, are reviewed and explained. Hand-washing is essential, whether or not gloves are used, and gloves should be used when contact with blood or blood-containing body fluids may occur. In hospitalized children, the 1996 recommendations of the Centers for Disease Control and Prevention (CDC) should be implemented as modified in the 1997 Red Book. The generic principles of Standard Precautions in the CDC guidelines generally are applicable to children in all health care settings, schools, child care facilities, and the home. However, gloves are not required for routine changing of diapers or for wiping nasal secretions of children in most circumstances. This AAP recommendation differs from that in the CDC guidelines. Current US Public Health Service guidelines for the management of potential occupational exposures of health care workers to HIV are summarized. As previously recommended by the AAP, HIV-infected children should be admitted without restriction to child care centers and schools and allowed to participate in all activities to the extent that their health and other recommendations for management of contagious diseases permit. Because it is not required that the school be notified of HIV infection, it may be helpful if the pediatrician notify the school that he or she is operating under a policy of nondisclosure of infection with blood-borne pathogens. Thus, it is possible that the pediatrician will not report the presence of such infections on the form. Because HIV infection occurs in persons throughout the United States, these recommendations for prevention of HIV transmission should be applied universally. C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Amer Thorac Soc, New York, NY USA. Canadian Paediat Soc, Ottawa, ON, Canada. Natl Vaccine Program Off, Atlanta, GA USA. US FDA, Rockville, MD 20857 USA. NIH, Bethesda, MD 20892 USA. RP Wilfert, CM (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 55 TC 4 Z9 4 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 AUG PY 1999 VL 104 IS 2 BP 318 EP 324 PG 7 WC Pediatrics SC Pediatrics GA 222EP UT WOS:000081770700039 ER PT J AU Shah, VP Elkins, JS Williams, RL AF Shah, VP Elkins, JS Williams, RL TI Evaluation of the test system used for in vitro release of drugs for topical dermatological drug products SO PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY LA English DT Article DE dermatological products; in vitro release; topical products ID CREAMS AB The purpose of this research was to evaluate different parameters that can influence in vitro drug release from topical dermatological drug products such as creams, gels, and ointments. In vitro release from topical dermatological drug products was carried out by using a static diffusion cell, a synthetic membrane, and an appropriate receptor medium. The receptor medium was mixed by means of a magnetic bar rotated at 400 rpm. Experiments were designed to evaluate the influence of (i) receptor media, (ii) different lots of synthetic membranes, and (iii) agitation on drug release. Release experiments were also carried out to study inter- and intralot variability. The in vitro release test was used to evaluate the marketed glucocorticoid products. Among the parameters studied, the receptor medium was found to be the most important and critical variable that influenced drug release. The release rate ranged between 0.61 and 2.68 mu g/cm(2)/min(0.5) for betamethasone dipropionate depending on the percentage of ethanol in the receptor medium. The drug release was not influenced by agitation or by different lots of synthetic membranes. Very small inter- and intralot variability was observed These experiments establish the ruggedness of the in vitro diffusion cell test system used for the drug release measurements. C1 US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. Dallas Dist Lab, Dallas, TX 75204 USA. RP Shah, VP (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, 1451 Rockville Pike WOC 2, Rockville, MD 20852 USA. NR 10 TC 23 Z9 24 U1 1 U2 6 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1083-7450 J9 PHARM DEV TECHNOL JI Pharm. Dev. Technol. PD AUG PY 1999 VL 4 IS 3 BP 377 EP 385 DI 10.1081/PDT-100101373 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 241UY UT WOS:000082902800010 PM 10434283 ER PT J AU Nawaz, MS Khan, AA Khan, SA Paine, DD Pothuluri, JV Cerniglia, CE AF Nawaz, MS Khan, AA Khan, SA Paine, DD Pothuluri, JV Cerniglia, CE TI Biochemical and molecular characterization of erythromycin-resistant avian Staphylococcus spp. isolated from chickens SO POULTRY SCIENCE LA English DT Article DE erythromycin resistance; avian Staphylococcus spp.; erm genes ID COAGULASE-NEGATIVE STAPHYLOCOCCI; STREPTOGRAMIN-B RESISTANCE; AUREUS; GENES; LINCOSAMIDES; MACROLIDES; EVOLUTION; EPIDEMIOLOGY; ANTIBIOTICS; EPIDERMIDIS AB The epidemiology of the two common erythromycin-resistant methylase (erm) genes ermC and ermA was analyzed in 12 coagulase-negative Staphylococcus spp. and 34 coagulase-positive Staphylococcus spp. isolated from chicken. Southern hybridization indicated that only 2 of the 12 coagulase-negative Staphylococcus spp. strains contained the ermC gene on the plasmid; 1 strain of Staphylococcus xylosus harbored the ermC gene on a 2.5-kb plasmid, and 1 strain of Staphylococcus cohnii harbored the gene on a 4.0-kb plasmid. Twelve of the 34 strains of Staphylococcus aureus contained the ermC gene. Eleven of these strains had the ermC gene on a 2.5-kb plasmid, and 1 strain had the gene on a 4.0-kb plasmid. Ten of the 12 coagulase-negative Staphylococcus spp. and 22 of the 34 coagulase-positive Staphylococcus spp. harbored the ermA gene exclusively on the chromosome. Two different ermA EcoRI restriction fragment length polymorphisms (RFLP) were identified. A majority of the isolates was found to have two chromosomal inserts (8.0- and 6.2-kb EcoRI fragments) of ermA. One strain of S. aureus had different chromosomal inserts (6.4- and 5.8-kb EcoRI fragments) of ermA. Our results indicate that either the ermC or ermA gene, homologous to those described in human isolates, was present in all avian Staphylococcus spp. and that ermA was the predominant gene in coagulase-negative and coagulase-positive avian Staphylococcus spp. The size and copy numbers of the ermA gene were different from its human counterpart. C1 US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Nawaz, MS (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 32 TC 16 Z9 19 U1 0 U2 0 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874 USA SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PD AUG PY 1999 VL 78 IS 8 BP 1191 EP 1197 PG 7 WC Agriculture, Dairy & Animal Science SC Agriculture GA 220ZF UT WOS:000081699200016 PM 10472846 ER PT J AU Siddiqui, O Mott, J Anderson, T Flay, B AF Siddiqui, O Mott, J Anderson, T Flay, B TI The application of Poisson random-effects regression models to the analyses of adolescents' current level of smoking SO PREVENTIVE MEDICINE LA English DT Article DE Poisson random-effects model; count data; smoking prevention; adolescents' current level of smoking ID CIGARETTE-SMOKING; GENDER DIFFERENCES; PARENTAL SMOKING; PREDICTORS; CESSATION; INITIATION; BEHAVIOR; FRIENDS; ONSET; TIME AB Background. In school-based smoking prevention research, it is still debatable whether parents or peers are most influential to maintained smoking among adolescents. As a result, this study examines the effects of parental and peer approval of smoking on adolescents' current levels of smoking. Methods. Poisson random-effects regression models were used to assess the effects of parental and peer approval of smoking on adolescents' (n = 913) current level of smoking. Results. Results of these analyses indicate that a stronger relationship between parental approval of smoking and current level of smoking was found for female adolescents than for male adolescents. Conversely, a stronger relationship between peer approval of smoking and current level of smoking was found for male adolescents than for female adolescents. With respect to race, the influence of parental approval of smoking on adolescents' current level of smoking was generally more pronounced for minority adolescents, relative to white adolescents. However, the influence of peer approval of smoking on current level of smoking was strongest for white adolescents and was less strong for black, Hispanic, and Asian adolescents. Conclusion. The findings of this study demonstrated that the effects of parental and peer approval of smoking on adolescents' current levels of smoking were var led by gender and race. These differential effects may have some implication for the development of future school-based smoking prevention and cessation programs, (C) 1999 American Health Foundation and Academic Press. C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Univ Illinois, Hlth Policy & Res Ctr, Chicago, IL USA. RP Siddiqui, O (reprint author), US FDA, 1451 Rockville Pike, Rockville, MD 20852 USA. OI Flay, Brian/0000-0002-5209-2766 FU NIDA NIH HHS [R01-DA06307, R01-DA0348] NR 34 TC 19 Z9 19 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD AUG PY 1999 VL 29 IS 2 BP 92 EP 101 DI 10.1006/pmed.1999.0517 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 229CN UT WOS:000082176100006 PM 10446034 ER PT J AU Collins, TFX Sprando, RL Shackelford, ME Hansen, DK Welsh, JJ AF Collins, TFX Sprando, RL Shackelford, ME Hansen, DK Welsh, JJ CA Revision Comm TI Food and Drug Administration proposed testing guidelines for reproduction studies SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID RAT SPERM MOTILITY; FOLLICLE COUNTS; TOXICITY AB In the United States, the Food and Drug Administration (FDA) is the agency responsible for ensuring that the direct food additives and color additives used in food are safe for all consumers. In order to determine the safety of these additives for consumption, appropriate information and results from a series of tests must be made available to the agency. In 1982, in an effort to provide guidance to the food industry concerning the appropriate tests for the determination of safety, the FDA issued the Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Foods, commonly referred to as the Redbook. In 1993, based on the expansion of technology and the use of food additives, as well as the refinement of the scientific criteria for establishing safety, the FDA updated its guidelines and issued the draft Redbook II. Since Redbook II: was issued, additional refinements have been made in the procedures for the multigeneration reproduction study and for the assessment of effects on male reproduction. The latest proposed guidelines for multigeneration studies are provided here. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Collins, TFX (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS 507,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 24 TC 11 Z9 13 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD AUG PY 1999 VL 30 IS 1 BP 29 EP 38 DI 10.1006/rtph.1999.1306 PG 10 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 239MN UT WOS:000082772100004 PM 10464044 ER PT J AU Collins, TFX Sprando, RL Shackelford, ME Hansen, DK Welsh, JJ AF Collins, TFX Sprando, RL Shackelford, ME Hansen, DK Welsh, JJ CA Revision Comm TI Food and Drug Administration proposed testing guidelines for developmental toxicity studies SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article AB The Food and Drug Administration (FDA) is the agency responsible for ensuring that the direct food additives and color additives used in food in the United States are safe for all consumers. In 1982, in an effort to provide guidance concerning appropriate tests, the FDA issued Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food, commonly known as the Redbook. The Redbook included detailed guidelines for testing the effects of direct and indirect food and color additives on mothers and their developing fetuses. Based on refinements in safety assessment and risk evaluation as well as expansion of knowledge concerning the metabolism and pharmacokinetics of food and color additives, the need to revise and update the 1982 document became apparent. In 1993, Redbook II in draft form was made available for public comment. Since then, test end points and developmental landmarks have been refined. The latest proposed guidelines for developmental toxicity studies are provided here. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Collins, TFX (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS 507,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 9 TC 10 Z9 10 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD AUG PY 1999 VL 30 IS 1 BP 39 EP 44 DI 10.1006/rtph.1999.1307 PG 6 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 239MN UT WOS:000082772100005 PM 10464045 ER PT J AU Fang, GC Chang, CN Wu, YS Fu, PPC Chang, KF Yang, DG AF Fang, GC Chang, CN Wu, YS Fu, PPC Chang, KF Yang, DG TI The characteristic study of TSP, PM2.5 similar to 10 and PM2.5 in the rural site of central Taiwan SO SCIENCE OF THE TOTAL ENVIRONMENT LA English DT Article ID PARTICULATE MATTER; AIR-POLLUTION; AUSTRALIA; BRISBANE; PM10 AB The total suspended particle (TSP), PM2.5 similar to 10 (aerodynamic diameter less than 10 mu m) and PM2.5 concentration (aerodynamic diameter less than 2.5 mu m) concentrations were sampled by PS-1 and Universal sampler on the roof (25 m) of the Medical and Engineering Building in the campus of Hungkuang Institute of Technology (HKIT) which is located at a height of 500 m on Da Du Mountain. The results indicated that average TSP, PM2.5 similar to 10 and PM2.5 concentrations are 0.42, 0.34 and 0.019 mg/m(3) in the day time, respectively and are 0.32, 0.26 and 0.017 mg/m(3) in the night time, respectively. The ratios of PM2.5 similar to 10/TSP were from 76% to 85% and from 50% to 91% for day and night period, respectively. It indicated that the major composition in the total suspended particles was PM2.5 similar to 10 in the rural site. The relationship between TSP and PM2.5 similar to 10 is TSP = 1.16PM(2.5 similar to 10) + 0.027 and TSP = 1.01PM(2.5 similar to 10), + 0.058 in the day and night time, respectively. The correlation coefficient (R-2) is 0.98 and 0.97 for day and night period, respectively. The relationship between PM2.5 similar to 10 and PM2.5 is PM2.5 = 0.0005PM(2.5 similar to 10) + 0.019 and PM2.5 = 0.037PM(2.5 similar to 10) + 0.0076 in the day and night period, respectively. The correlation coefficient (R-2) is 3E-5 and 0.67 for day and night period, respectively. The relationships between TSP, PM(2.5)similar to 10, PM2.5 particle concentrations and wind speed (R-2) in the day time are 0.71, 0.64, 0.43, respectively and are 0.83, 0.79, 0.57, respectively in the night time. The proposed reasons are that there are more activities caused by people (students) and natural living animals which absorbed some of the particles during the day time. Thus, the correlation coefficients for the night time are better than those of day time. The particle size distributions are both bimodel in the day and night time. The major peaks in the day time appear in the particle diameter between 0.031 similar to 0.056 mu m and 3.16 similar to 5.62 mu m in the day period and appear between 0.017 similar to 0.031 mu m and 1.78 similar to 3.16 mu m in the night period. The results indicate that the particle size distribution in the day time tends to be of larger particle size mode than the night time. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Hlth Hungkuang Inst Technol, Dept Environm Engn, Taichung 43307, Taiwan. Tunghai Univ, Dept Environm Sci, Tunghai, Peoples R China. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Fang, GC (reprint author), Hlth Hungkuang Inst Technol, Dept Environm Engn, Taichung 43307, Taiwan. NR 15 TC 15 Z9 16 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0048-9697 J9 SCI TOTAL ENVIRON JI Sci. Total Environ. PD AUG 1 PY 1999 VL 232 IS 3 BP 177 EP 184 DI 10.1016/S0048-9697(99)00092-3 PG 8 WC Environmental Sciences SC Environmental Sciences & Ecology GA 229MN UT WOS:000082198500004 PM 10481294 ER PT J AU Love, PE Shores, EW AF Love, PE Shores, EW TI Antigen receptor signalling in T cell development and selection - Introduction SO SEMINARS IN IMMUNOLOGY LA English DT Editorial Material C1 NICHHD, Sect Cellular & Dev Biol, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Love, PE (reprint author), NICHHD, Sect Cellular & Dev Biol, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD AUG PY 1999 VL 11 IS 4 BP 225 EP 226 DI 10.1006/smim.1999.0178 PG 2 WC Immunology SC Immunology GA 228CB UT WOS:000082117700001 ER PT J AU Mondoro, TH Ryan, BB Hrinczenko, B Schechter, A Vostal, J Vostal, J Alayash, A AF Mondoro, TH Ryan, BB Hrinczenko, B Schechter, A Vostal, J Vostal, J Alayash, A TI Biological action of no donor compounds on platelets from patients with sickle cell disease SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG PY 1999 SU S MA 728 BP 231 EP 232 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 290FP UT WOS:000085665900727 ER PT J AU Holada, K Mondoro, TH Gahl, WA Vostal, JG AF Holada, K Mondoro, TH Gahl, WA Vostal, JG TI Up-regulation of platelet prion protein after platelet activation does not correlate with up-regulation of lysosomal GP-53 SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. NICHD, Metab Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG PY 1999 SU S MA 1137 BP 358 EP 358 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 290FP UT WOS:000085665901138 ER PT J AU Cowan, EP Nemo, GJ Williams, AE Alexander, RK Vallejo, A Hewlett, IK Lal, RB Dezzutti, CS Gallahan, D George, K Pancake, BA Zucker-Franklin, D McCurdy, PR Tabor, E AF Cowan, EP Nemo, GJ Williams, AE Alexander, RK Vallejo, A Hewlett, IK Lal, RB Dezzutti, CS Gallahan, D George, K Pancake, BA Zucker-Franklin, D McCurdy, PR Tabor, E TI Absence of human T-lymphotropic virus type I tax sequences in a population of normal blood donors in the Baltimore, MD/Washington, DC, area: results from a multicenter study SO TRANSFUSION LA English DT Article ID MYCOSIS-FUNGOIDES; MYELOPATHY; PROVIRUS AB BACKGROUND: It was reported recently that sequences corresponding to the human T-lymphotropic virus type I (HTLV-I) tax gene were detected in peripheral blood mononuclear cells from 8 to 11 percent of healthy blood donors without detectable antibodies to HTLV-I. A multicenter blind study was conducted to determine if these results could be independently confirmed. STUDY DESIGN AND METHODS: Specimens were collected from 100 anti-HTLV-I-negative healthy blood donors and from 11 anti-HTLV-I- or anti-HTLV-II-positive individuals. All samples were coded and distributed to each of four independent testing laboratories for polymerase chain reaction analysis to detect sequences of the HTLV-I or HTLV-II fax gene, using detailed procedures specified by the laboratory reporting the original observation. Each laboratory also tested a dilution panel of a plasmid containing HTLV-I tax to determine the analytical sensitivity of the procedure. RESULTS: The analytical sensitivity of the screening methods permitted detection of as few as 1 to 10 copies of the fax gene. However, HTLV-I tax sequences could not be detected in any of the anti-HTLV-I-negative blood donors at more than one test site. CONCLUSION: HTLV-I tax sequences appear not to be present in this population of 100 blood donors negative for anti-HTLV-I. C1 NHLBI, Transfus Med Sci Res Grp, Bethesda, MD 20892 USA. US FDA, Div Transfus Transmitted Dis, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, HIV & Retrovirus Dis Branch, Atlanta, GA 30333 USA. Amer Red Cross, Jerome H Holland Lab, Transmissible Dis Dept, Rockville, MD USA. Retrovirus Epidemiol Donor Study, Rockville, MD USA. NYU Med Ctr, Dept Med, New York, NY 10016 USA. RP Cowan, EP (reprint author), 1401 Rockville Pike,HFM-320, Rockville, MD 20852 USA. RI Vallejo, Alejandro/I-5881-2015 OI Vallejo, Alejandro/0000-0001-5360-878X NR 15 TC 12 Z9 12 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 AUG PY 1999 VL 39 IS 8 BP 904 EP 909 DI 10.1046/j.1537-2995.1999.39080904.x PG 6 WC Hematology SC Hematology GA 226ZH UT WOS:000082052700018 PM 10504129 ER PT J AU Tabor, E Hewlett, I Yu, MYW Farshid, M Epstein, JS AF Tabor, E Hewlett, I Yu, MYW Farshid, M Epstein, JS TI Summary of a Food and Drug Administration workshop on nucleic acid testing to screen donations of blood and plasma for the hepatitis C virus SO TRANSFUSION LA English DT Letter C1 US FDA, Rockville, MD 20852 USA. RP Tabor, E (reprint author), US FDA, HFM-300, Rockville, MD 20852 USA. NR 0 TC 3 Z9 3 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 AUG PY 1999 VL 39 IS 8 BP 912 EP 913 DI 10.1046/j.1537-2995.1999.39080912.x PG 2 WC Hematology SC Hematology GA 226ZH UT WOS:000082052700020 PM 10504131 ER PT J AU Shames, D Garnick, MB AF Shames, D Garnick, MB TI Use of PC-SPES, a commercially available supplement for prostate cancer, in a patient with hormone-naive disease - Editorial comments SO UROLOGY LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Harvard Univ, Sch Med, Boston, MA USA. Praecis Pharmaceut Inc, Cambridge, MA USA. RP Shames, D (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD AUG PY 1999 VL 54 IS 2 BP 323 EP 324 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 221RL UT WOS:000081740000024 ER PT J AU Post, LO Keller, WC AF Post, LO Keller, WC TI An update of antidote availability in veterinary medicine SO VETERINARY AND HUMAN TOXICOLOGY LA English DT Article AB Lack of commercially available antidotes for animals is an issue of significant concern to the American Board of Veterinary Toxicology. A few antidotes are available for food animals through extra-label use, regulatory discretion and compounding. However, regulatory restrictions arising from human food safety concerns have limited the availability of food animal antidotes. Use of some antidotes in food animals requires establishment of an investigational new animal drug application. Antidotes are generally more available for non-food animals from several sources: approved animal drugs, extra-label use of approved animal and human drugs, regulatory discretion and compounding. Present alternatives are discussed as well as the need for legislation to increase antidote availability. Human food safety will always be an issue for food animal antidotes. Future availability of non-food animal and food animal antidotes will depend on several mechanisms and may include the establishment of veterinary antidote depots. Stakeholders are encouraged to participate in identifying and implementing these mechanisms. C1 US FDA, Div Epidemiol & Surveillance, Off Surveillance & Compliance, Ctr Vet Med, Rockville, MD 20855 USA. RP Post, LO (reprint author), US FDA, Div Epidemiol & Surveillance, Off Surveillance & Compliance, Ctr Vet Med, Rockville, MD 20855 USA. NR 1 TC 5 Z9 5 U1 0 U2 0 PU COMPARATIVE TOXICOLOGY LAB PI MANHATTAN PA KANSAS STATE UNIV, MANHATTAN, KS 66506-5606 USA SN 0145-6296 J9 VET HUM TOXICOL JI Vet. Human Toxicol. PD AUG PY 1999 VL 41 IS 4 BP 258 EP 261 PG 4 WC Toxicology; Veterinary Sciences SC Toxicology; Veterinary Sciences GA 220AN UT WOS:000081641900017 PM 10434385 ER PT J AU Colman, E AF Colman, E TI The first English medical journal: Medicina Curiosa SO LANCET LA English DT Article C1 US FDA, Div Metab & Endocrine Drug Prod, Rockville, MD 20857 USA. RP Colman, E (reprint author), US FDA, Div Metab & Endocrine Drug Prod, HFD-510 5600 Fishers Lane, Rockville, MD 20857 USA. NR 25 TC 4 Z9 4 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUL 24 PY 1999 VL 354 IS 9175 BP 324 EP 326 DI 10.1016/S0140-6736(98)11102-9 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 220CB UT WOS:000081646000046 PM 10440325 ER PT J AU Matsui, M Machida, S Feinstone, SM Akatsuka, T AF Matsui, M Machida, S Feinstone, SM Akatsuka, T TI Molecular analyses of five new chimpanzee MHC class I alleles: Implications for differences between evolutional mechanisms of HLA-A, -B, and -C loci SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID FREQUENCY; ANTIGEN; FAMILY; HUMANS AB In order to study the origin of the polymorphism of MHC class I molecules, we have cloned and sequenced five new Patr-A, -B, and -C loci alleles from two chimpanzees, Previous studies of sequence comparison between Patr and HLA Glass I alleles revealed that many of the sequence motifs were shared and the origin of class I molecules predated the divergence of chimpanzees and humans. These findings are confirmed by our current study, Additionally, our data suggest significant differences between mechanisms of evolution of the A, B, and C loci: (1) The B locus is characterized by frequent nucleotide substitutions, whereas the A and C loci are relatively more conserved; (2) However, unlike the A locus, the alpha 2 domains of the C locus sequenced appear to produce MHC polymorphism between these species. These differences might imply the distinctive contributions of each locus during the evolutionary history. (C) 1999 Academic Press. C1 Saitama Med Sch, Dept Microbiol, Moroyama, Saitama 3500495, Japan. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Akatsuka, T (reprint author), Saitama Med Sch, Dept Microbiol, Moroyama, Saitama 3500495, Japan. NR 17 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 22 PY 1999 VL 261 IS 1 BP 46 EP 52 DI 10.1006/bbrc.1999.0993 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 222DQ UT WOS:000081768500009 PM 10405321 ER PT J AU Lyn-Cook, BD Stottman, HL Yan, Y Blann, E Kadlubar, FF Hammons, GJ AF Lyn-Cook, BD Stottman, HL Yan, Y Blann, E Kadlubar, FF Hammons, GJ TI The effects of phytoestrogens on human pancreatic tumor cells in vitro SO CANCER LETTERS LA English DT Article DE phytoestrogens; chemoprotective; growth inhibition; K-ras expression; pancreatic cancer ID BREAST-CANCER CELLS; GROWTH-FACTOR RECEPTOR; ESTROGEN-RECEPTOR; BIOCHANIN-A; GENISTEIN; ISOFLAVONES; INHIBITION; LINES; WOMEN; PROTOONCOGENE AB Diet has been implicated as a possible link to the etiology, promotion and/or progression of many diseases, including cancer. Recently, interest has been focused on the cancer-protective role of several of the hormone-like diphenolic phytoestrogens, lignans, and isoflavonoids. This study examined the chemoprotective effects of genistein, biochanin A, equol, and coumestrol on human pancreatic adenocarcinoma cells in vitro. Two human adenocarcinoma cell lines, HPAF-11 from a male and Su 86.86 from a female, were used. HPAF-11 cells were exposed for 24 h to these agents at concentrations of 1 and 10 mu M Su 86.86 cells were exposed for 24 h at a concentration of 1 mu M. Coumestrol and equol at higher concentrations were toxic to the Su 86.86 cells. These agents displayed marked differences between cell lines in inhibition of growth. Equol and coumestrol inhibited the growth of the female pancreatic tumor cells by 95%; however, these agents stimulated the growth of pancreatic tumor cells from the male. Genistein also stimulated growth in the male pancreatic tumor cells, but had little effect on pancreatic tumor cells from the female. Biochanin A inhibited growth of both male and female tumor cells, but to a lesser extent than other agents. This study also indicated a difference in K-ras expression in pancreatic tumors cells treated with these agents. Equol and coumestrol decreased K-ras expression in the female tumor cell line. Genistein increased expression of K-ras in both male and female pancreatic tumor cells. Genistein also increased expressions of the multidrug resistant (mdr-1) gene in the male tumor-cell line, while coumestrol and biochanin A decreased expression. Equol had no effect on mdr-1 expression. Whether the chemoprotective potential of equol and coumestrol against pancreatic cancer is greater in females than males is being further studied. (C) 1999 Published by Elsevier Science Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Arkanas Tech Univ, Russellville, AR 72801 USA. RP Lyn-Cook, BD (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. NR 46 TC 19 Z9 20 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUL 19 PY 1999 VL 142 IS 1 BP 111 EP 119 DI 10.1016/S0304-3835(99)00157-3 PG 9 WC Oncology SC Oncology GA 211UR UT WOS:000081180700016 PM 10424789 ER PT J AU Singleton, JA Lloyd, JC Mootrey, GT Salive, ME Chen, RT AF Singleton, JA Lloyd, JC Mootrey, GT Salive, ME Chen, RT CA VAERS Working Grp TI An overview of the vaccine adverse event reporting system (VAERS) as a surveillance system SO VACCINE LA English DT Article DE vaccines; postmarketing surveillance; adverse effects ID SAFETY; IMMUNIZATION; PERTUSSIS AB We evaluated the Vaccine Adverse Event Reporting System (VAERS), the spontaneous reporting system for vaccine-associated adverse events in the United Slates, as a public health surveillance system, using evaluation guidelines from the Centers for Disease Control and Prevention. We found that VAERS is simple for reporters to use, flexible by design and its data are available in a timely fashion. The predictive value positive for one severe event is known to be high, but for most events is unknown. The acceptability, sensitivity and representativeness of VAERS are unknown, The study of vaccine safety is complicated by underreporting, erroneous reporting, frequent multiple exposures and multiple outcomes. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Ctr Dis Control & Prevent, Natl Immunizat Program, Vaccine Safety & Dev Author, Atlanta, GA 30333 USA. US FDA, Div Biostat & Epidemiol, Rockville, MD 20857 USA. RP Singleton, JA (reprint author), Ctr Dis Control & Prevent, Natl Immunizat Program, Adult Vaccine Prevent Dis Branch, 1600 Clifton Rd NE,Mail Stop E-61, Atlanta, GA 30333 USA. NR 43 TC 108 Z9 112 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUL 16 PY 1999 VL 17 IS 22 BP 2908 EP 2917 DI 10.1016/S0264-410X(99)00132-2 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 214FJ UT WOS:000081317700020 PM 10438063 ER PT J AU Feller, SE Pastor, RW AF Feller, SE Pastor, RW TI Constant surface tension simulations of lipid bilayers: The sensitivity of surface areas and compressibilities SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID MOLECULAR-DYNAMICS SIMULATION; PHASE DIPALMITOYLPHOSPHATIDYLCHOLINE BILAYER; COMPUTER-SIMULATION; LIQUID/LIQUID INTERFACES; PHOSPHOLIPID-BILAYER; BOUNDARY-CONDITIONS; FLUID MEMBRANES; LIQUID-CRYSTAL; PARAMETERS; PRESSURE AB Eight molecular dynamics simulations of a hydrated lipid bilayer have been carried out differing only in the applied surface tension, gamma, defining the boundary conditions of the periodic cell. The calculated surface area per molecule and deuterium order parameter profile are found to depend strongly on gamma. We present several methods to calculate the area compressibility modulus, K-A, from the simulations. Equivalence between the constant area and constant surface tension ensembles is investigated by comparing the present simulations with earlier work from our laboratories and we find simulation results to depend much more strongly on the specified surface area or surface tension than on the ensemble employed. (C) 1999 American Institute of Physics. [S0021-9606(99)71327-9]. C1 Wabash Coll, Dept Chem, Crawfordsville, IN 47933 USA. US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Feller, SE (reprint author), Wabash Coll, Dept Chem, Crawfordsville, IN 47933 USA. NR 34 TC 204 Z9 209 U1 4 U2 36 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 JUL 15 PY 1999 VL 111 IS 3 BP 1281 EP 1287 DI 10.1063/1.479313 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 214CB UT WOS:000081309100054 ER PT J AU Hu, RQ Bekisz, J Hayes, M Audet, S Beeler, J Petricoin, E Zoon, K AF Hu, RQ Bekisz, J Hayes, M Audet, S Beeler, J Petricoin, E Zoon, K TI Divergence of binding, signaling, and biological responses to recombinant human hybrid IFN SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN INTERFERON-ALPHA; EVOLUTIONARY IMPLICATIONS; RECEPTOR-BINDING; I INTERFERONS; COMPONENTS; PURIFICATION; CYTOKINES; DOMAINS; CELLS AB Three human IFN-alpha hybrids, HY-1 [IFN-alpha 21a(1-75)/alpha 2c(76-165)], HY-2 [IFN-alpha 21a(1-95)/alpha 2c(96-165)], and HY-3 [IFN-alpha 2c(1-95)/alpha 21a(96-166)], were constructed, cloned, and er;pressed, The hybrids had comparable specific antiviral activities on Madin-Darby bovine kidney (MDBK)(3) cells but exhibited very different antiproliferative and binding properties on human Daudi and WISH cells and primary human lymphocytes. Our data suggest that a portion of the N-terminal region of the molecule is important for interaction with components involved in binding of IFN-alpha 2b while the C-terminal portion of IPN is critical for antiproliferative activity, A domain affecting the antiproliferative activity was found within the C-terminal region from amino acid residues 75-166, The signal transduction properties of HY-2 and HY-3 were evaluated by ER ISA and RNase protection assays, Both HY-2 and HY-3 induced activation of STAT1 and 2, However, HY-2 exhibited essentially no antiproliferative effects at concentrations that activated STAT1 and 2. Additionally, at concentrations where no antiproliferative activity was seen, HY-2 induced a variety of IFN-responsive genes to the same degree as HY-3. RNase protection assays also indicate that, at concentrations where no antiproliferative activity was seen for HY-2, this construct retained the ability to induce a variety of IFN-inducible genes. These data suggest that the antiproliferative response may not be solely directed by the activation of the STAT1 and STAT2 pathway in the cells tested. C1 US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Off Therapeut Res & Review, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Off Vaccines Res & Review, Bethesda, MD 20892 USA. RP Hu, RQ (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Off Therapeut Res & Review, 1401 Rockville Pike, Bethesda, MD 20892 USA. NR 33 TC 20 Z9 21 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 JUL 15 PY 1999 VL 163 IS 2 BP 854 EP 860 PG 7 WC Immunology SC Immunology GA 215AY UT WOS:000081360800041 PM 10395679 ER PT J AU Rojas, E Herrera, LA Poirier, LA Ostrosky-Wegman, P AF Rojas, E Herrera, LA Poirier, LA Ostrosky-Wegman, P TI Are metals dietary carcinogens? SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Review DE environmental; genotoxicity; arsenic; cadmium; chromium; lead; mercury; nickel; selenium; tin; vanadium; zinc ID HAMSTER OVARY CELLS; SISTER-CHROMATID EXCHANGES; FREE-RADICAL GENERATION; FETAL LUNG FIBROBLASTS; SINGLE-STRAND BREAKS; SPRAGUE-DAWLEY RATS; ETHENO-DNA ADDUCTS; LIPID-PEROXIDATION; SODIUM ARSENITE; VANADIUM PENTOXIDE AB Humans have been in contact with metals almost since the beginning of our existence. In fact, one cannot even think on human evolution without considering the great role played by metals in mankind's development. Metals are common moieties of molecules involved in a wide variety of biological processes, and hence are found in virtually all Living organisms. Some metals are essential for human nutrition; others are found as contaminants in foodstuffs. One feature of the normal human diet which is frequently found is the simultaneous presence of both essential and toxic metals. Other factors important in the risk-evaluation analysis of metals are their pharmacokinetics, interactions among them and with other major components of the diet, and, especially, the great differences in the dietary habits of different populations and in the regional distribution of metals. In attempting to understand the role which dietary metals could play in human carcinogenesis, we found that the many factors involved and the lack of specific information made it difficult to reach firm conclusions on the hazards of dietary metals. We hope that this paper will raise the interest of genetic toxicologists in the subject and will consequently facilitate a risk analysis of the carcinogenic potential of dietary metals. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mexico City 04510, DF, Mexico. Natl Ctr Toxicol Res, Jefferson, AR 72132 USA. RP Ostrosky-Wegman, P (reprint author), Univ Nacl Autonoma Mexico, Inst Invest Biomed, Ciudad Univ,POB 70228, Mexico City 04510, DF, Mexico. OI ostrosky-wegman, patricia/0000-0002-8564-3472 NR 258 TC 122 Z9 130 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD JUL 15 PY 1999 VL 443 IS 1-2 BP 157 EP 181 DI 10.1016/S1383-5742(99)00018-6 PG 25 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 221XP UT WOS:000081753100012 PM 10415439 ER PT J AU Colman, E Stadel, BV AF Colman, E Stadel, BV TI Gabapentin for postherpetic neuralgia SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Colman, E (reprint author), US FDA, Rockville, MD 20857 USA. NR 2 TC 1 Z9 1 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 14 PY 1999 VL 282 IS 2 BP 134 EP 134 DI 10.1001/jama.282.2.134 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 215HT UT WOS:000081376800023 PM 10411191 ER PT J AU Lee, Y Shacter, E AF Lee, Y Shacter, E TI Oxidative stress inhibits apoptosis in human lymphoma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HYDROGEN-PEROXIDE; OXIDANT INJURY; ADENOSINE-TRIPHOSPHATE; ENDOTHELIAL-CELLS; DEATH; NECROSIS; BCL-2; DNA; ATP; OXYGEN AB Apoptosis and necrosis are two forms of cell death that are induced under different conditions and that differ in morphological and biochemical features. In this report, we show that, in the presence of oxidative stress, human B lymphoma cells are unable to undergo apoptosis and die instead by a form of necrosis. This was established using the chemotherapy drug VP-16 or the calcium ionophore A23187 to induce apoptosis in Burkitt's lymphoma cell lines and by measuring classical markers of apoptotic death, including cell morphology, annexin V binding, DNA ladder formation, and caspase activation. In the presence of relatively low levels of H2O2 (75-100 mu M), VP-16 and A23187 were unable to induce apoptosis in these cells. Instead, the cells underwent non-apoptotic cell death with mild cytoplasmic swelling and nuclear shrinkage, similar to the death observed when they were treated with H2O2 alone. We found that H2O2 inhibits apoptosis by depleting the cells of ATP, The effects of H2O2 can be overcome by inhibitors of poly(ADP)-ribosylation, which also preserve cellular ATP levels, and can be mimicked by agents such as oligomycin, which inhibit ATP synthesis. The results show that oxidants can manipulate cell death pathways, diverting the cell away from apoptosis, The potential physiological ramifications of this finding will be discussed. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. RP Shacter, E (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, HFM-538,Bldg 29A,Rm 2A-11, Bethesda, MD 20892 USA. NR 52 TC 179 Z9 180 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 9 PY 1999 VL 274 IS 28 BP 19792 EP 19798 DI 10.1074/jbc.274.28.19792 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 215HY UT WOS:000081377300042 PM 10391922 ER PT J AU Nightingale, SL AF Nightingale, SL TI Trovafloxacin public health advisory SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 7 PY 1999 VL 282 IS 1 BP 19 EP 19 DI 10.1001/jama.282.1.19 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 212BE UT WOS:000081195800007 PM 10404896 ER PT J AU Brown, SL Hansen, SL Langone, JJ AF Brown, SL Hansen, SL Langone, JJ TI Role of serology in the diagnosis of Lyme disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PROFICIENCY TESTING PROGRAM; BORRELIA-BURGDORFERI; OVERDIAGNOSIS; LABORATORIES; VACCINATION; ANTIBODY AB Numerous concerns regarding the potential for misdiagnosis of Lyme disease using commercial assays have been voiced by the US Food and Drug Administration (FDA). We attempted to clarify the clinical value of serologic testing for Lyme disease using the results of commonly marketed assays for detecting antibody to Borrelia burgdorferi, the organism that causes Lyme disease, We reviewed published studies on B burgdorferi test performance published through 1998, package insert labeling from FDA-cleared test kits for B burgdorferi, and Lyme Disease Survey Set LY-A from the College of American Pathologists. We assessed the sensitivity and specificity of commercial serologic tests (enzyme-linked immunosorbent assay [ELISA], immunofluorescence antibody [IFA], and immunodot) for diagnosis of Lyme disease. To reduce this risk of misdiagnosis, it is important that clinicians understand the performance characteristics and limitations of these tests. These tests, in common use in clinical or commercial laboratories, should be used only to support a clinical diagnosis of Lyme disease, not as the primary basis for making diagnostic or treatment decisions. Serologic testing is not useful early in the course of Lyme disease because of the low sensitivity of tests in early disease. Serologic testing may be more useful in later disease, at which time sensitivity and specificity of the test are improved. Positive or equivocal results on an ELISA, IFA, or immunodot assay requires supplemental testing with a Western blot assay. A negative result on the Western blot or ELISA indicates that there is no serologic evidence of infection by B burgdorferi at the time the sample was drawn. C1 US FDA, Off Surveillance & Biometr, Div Postmarket Surveillance, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. US FDA, Off Device Evaluat, Div Clin Lab Devices, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. US FDA, Off Sci & Technol, Div Life Sci, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Brown, SL (reprint author), 1350 Piccard Dr,HFZ-541, Rockville, MD 20850 USA. NR 30 TC 73 Z9 78 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 7 PY 1999 VL 282 IS 1 BP 62 EP 66 DI 10.1001/jama.282.1.62 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 212BE UT WOS:000081195800030 PM 10404913 ER PT J AU Patriarca, PA AF Patriarca, PA TI New options for prevention and control of influenza SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID EFFICACY; VIRUS; NEURAMINIDASE; INTRANASAL; ZANAMIVIR; INHIBITOR; VACCINES; DISEASE C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Patriarca, PA (reprint author), HFM-445,1401 Rockville Pike, Rockville, MD 20852 USA. NR 22 TC 10 Z9 11 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 7 PY 1999 VL 282 IS 1 BP 75 EP 77 DI 10.1001/jama.282.1.75 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 212BE UT WOS:000081195800032 PM 10404915 ER PT J AU Wolf, NS Li, Y Pendergrass, WR Schmeider, C Turturro, A AF Wolf, NS Li, Y Pendergrass, WR Schmeider, C Turturro, A TI Cataract as a biomarker of aging; Caloric restriction delays both. SO AGE LA English DT Meeting Abstract C1 Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER AGING ASSOC PI MEDIA PA SALLY BALIN MEDICAL CENTER, 110 CHESLEY DR, MEDIA, PA 19063 USA SN 0161-9152 J9 AGE JI Age PD JUL PY 1999 VL 22 IS 3 MA 48 BP 128 EP 128 PG 1 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 289RD UT WOS:000085635000049 ER PT J AU Goldin, LR Sgambati, M Marti, GE Fontaine, L Ishibe, N Caporaso, N AF Goldin, LR Sgambati, M Marti, GE Fontaine, L Ishibe, N Caporaso, N TI Anticipation in familial chronic lymphocytic leukemia SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID RELATIVES; HISTORY C1 NCI, Dov Canc Epidemiol & Genet, Genet Epidemiol Branch, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Westat Res Inc, Rockville, MD USA. RP Goldin, LR (reprint author), NCI, Dov Canc Epidemiol & Genet, Genet Epidemiol Branch, 6120 Execut Blvd,Room 7008,MSC 7236, Bethesda, MD 20892 USA. NR 19 TC 35 Z9 36 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 1999 VL 65 IS 1 BP 265 EP 269 DI 10.1086/302458 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 212NZ UT WOS:000081224300036 PM 10364544 ER PT J AU Setsuda, J Teruya-Feldstein, J Harris, NL Ferry, JA Sorbara, L Gupta, G Jaffe, ES Tosato, G AF Setsuda, J Teruya-Feldstein, J Harris, NL Ferry, JA Sorbara, L Gupta, G Jaffe, ES Tosato, G TI Interleukin-18, interferon-gamma, IP-10, and Mig expression in Epstein-Barr virus-induced infectious mononucleosis and posttransplant lymphoproliferative disease SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; NECROSIS IN-VIVO; LIVER-TRANSPLANTATION; INDUCIBLE PROTEIN-10; VIRAL INTERLEUKIN-10; T-CELLS; KAPPA-B; DISORDERS; RECIPIENTS; CYTOKINE AB T cell immunodeficiency plays an important role in the pathogenesis of posttransplant lymphoproliferative disease (PTLD) by permitting the unbridled expansion of Epstein-Barr virus (EBV)-infected B lymphocytes. However, factors other than T cell function may contribute to PTLD pathogenesis because PTLD infrequently develops even in the context of severe T cell immunodeficiency, and athymic mice that are T-cell-immunodeficient can reject EBV-immortalized cells. Here we report that PTLD tissues express significantly lower levels of IL-18, interferon-gamma (IFN-gamma), Mig, and RANTES compared to lymphoid tissues diagnosed with acute EBV-induced infectious mononucleosis, as assessed by semiquantitative RT-PCR analysis. Other cytokines and chemokines are expressed at similar levels. Immunohistochemistry confirmed that PTLD tissues contain less IL-18 and Mig protein than tissues with infectious mononucleosis. IL-18, primarily a monocyte product, promotes the secretion of IFN-gamma, which stimulates Mig and RANTES expression. Both IL-18 and Mig display antitumor activity in mice involving inhibition of angiogenesis, These results document greater expression of IL-18, IFN-gamma, Mig, and RANTES in lymphoid tissues with acute EBV-induced infectious mononucleosis compared to tissues with PTLD and raise the possibility that these mediators participate in critical host responses to EBV infection. C1 NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH, Bldg 10,Room 2A33,10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. NR 49 TC 43 Z9 46 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 1999 VL 155 IS 1 BP 257 EP 265 DI 10.1016/S0002-9440(10)65119-X PG 9 WC Pathology SC Pathology GA 212HE UT WOS:000081210600030 PM 10393857 ER PT J AU McLeod, LL Alayash, AI AF McLeod, LL Alayash, AI TI Detection of a ferrylhemoglobin intermediate in an endothelial cell model after hypoxia-reoxygenation SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE hemoglobin-based oxygen carriers; endothelium; antioxidants ID CROSS-LINKED HEMOGLOBIN; FREE-RADICAL REACTIONS; LIPID-PEROXIDATION; HYDROGEN-PEROXIDE; ANTIOXIDANT ROLE; NITRIC-OXIDE; OXIDATION; INJURY; GENERATION; ISCHEMIA AB A cell culture model of bovine aortic endothelial cells attached to microcarrier beads was used to study the interaction of diaspirin cross-linked hemoglobin (an oxygen-carrying blood substitute) with hypoxiareoxygenation. Hemoglobin (200 mu M) and hypoxia-volume restriction (3-5 h), together and separately, caused toxicity in this model, as measured by decreased cellular replating efficiency. Hemoglobin (60 mu M) caused a reduction in hydrogen peroxide concentration and an increase in lipid peroxidation above that induced by hypoxia alone. Incubation of hemoglobin with endothelial cells caused transient oxidation of hemoglobin to its highly reactive and toxic ferryl species after greater than or equal to 3 h of hypoxia, followed by 1 h of reoxygenation. Lipid peroxidation, which may occur in the presence of ferrylhemoglobin, also occurred after 1 h of reoxygenation. Hemoglobin caused a dose-dependent decrease in intracellular glutathione concentration, suggesting that it caused an oxidative stress to the cells. However, addition of ascorbate, a-tocopherol, or trolox did not decrease hemoglobin oxidation in the presence of normal or hypoxic cells. It is concluded that diaspirin cross-linked hemoglobin forms a ferryl intermediate in the absence of any exogenously added oxidant and contributes to the oxidative burden experienced by endothelial cells after hypoxia-reoxygenation, a condition that is likely to be encountered during trauma and surgery when hemoglobin solutions are used as perfusion agents. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), Bldg 29,Rm 112,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Alayash@cber.fda.gov NR 51 TC 39 Z9 39 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUL PY 1999 VL 277 IS 1 BP H92 EP H99 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 216KU UT WOS:000081442000013 PM 10409186 ER PT J AU Aksenova, TI Tetko, IV Ivakhnenko, AG Villa, AEP Welsh, WJ Zielinski, WL AF Aksenova, TI Tetko, IV Ivakhnenko, AG Villa, AEP Welsh, WJ Zielinski, WL TI Pharmaceutical fingerprinting in phase space. 1. Construction of phase fingerprints SO ANALYTICAL CHEMISTRY LA English DT Article ID ARTIFICIAL NEURAL NETWORKS; TRYPTOPHAN AB The present study proposes a general method for constructing pharmaceutical fingerprints in the analysis of HPLC trace organic impurity patterns, The approach considers signals in phase space and accounts for two different types of noise: additive and perturbative, The first type, additive noise, contributes to distortion of the absolute values of signal peaks. The second type, perturbative noise, contributes to variations of the retention times of signal peaks and distorts the time scale of the trace organic impurity patterns. The ability of the proposed approach to consider both types of noise significantly distinguishes it from existing methods of data analysis that are usually designed to treat only the additive noise. Analysis of the HPLC signals in phase space eliminates the problem of perturbation noise and enables detection and comparison of similar signal segments recorded at different retention times. The current study analyzes the chromatographic trace organic impurity patterns collected from six different manufacturers of L-tryptophan using three HPLC columns. For five manufacturers the variability of data recorded with the same column are in perfect agreement with the proposed model. A significant variance of parameters is detected for one manufacturer, thus indicating a possible change in its product consistency. The analysis in phase space is also used to explain the previously detected variability of HPLC signals across columns. The accompanying paper reports an application of the proposed approach for the pattern recognition of HPLC data. C1 Int Inst Appl Syst Anal, UA-252056 Kiev, Ukraine. Inst Bioorgan & Petr Chem, Dept Biomed Applicat, UA-253660 Kyiv, Ukraine. VM Glushkov Cybernet Inst, UA-252207 Kiev, Ukraine. Univ Missouri, Dept Chem, St Louis, MO 63121 USA. Univ Missouri, Ctr Mol Elect, St Louis, MO 63121 USA. US FDA, Div Drug Anal, St Louis, MO 63101 USA. Univ Lausanne, Inst Physiol, Lab Neuroheurist, CH-1005 Lausanne, Switzerland. RP Tetko, IV (reprint author), Univ Lausanne, Inst Physiol, Lab Neuroheurist, Rue du Bugnon 7, CH-1005 Lausanne, Switzerland. RI Villa, Alessandro/G-6220-2011; Tetko, Igor/B-1540-2010 OI Villa, Alessandro/0000-0002-4684-0027; Tetko, Igor/0000-0002-6855-0012 NR 22 TC 12 Z9 12 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JUL 1 PY 1999 VL 71 IS 13 BP 2423 EP 2430 DI 10.1021/ac981345r PG 8 WC Chemistry, Analytical SC Chemistry GA 213HA UT WOS:000081265600037 PM 10405608 ER PT J AU Tetko, IV Aksenova, TI Patiokha, AA Villa, AEP Welsh, WJ Zielinski, WL Livingstone, DJ AF Tetko, IV Aksenova, TI Patiokha, AA Villa, AEP Welsh, WJ Zielinski, WL Livingstone, DJ TI Pharmaceutical fingerprinting in phase space. 2. Pattern recognition SO ANALYTICAL CHEMISTRY LA English DT Article ID ARTIFICIAL NEURAL NETWORKS AB The current study introduces an approach for pattern recognition of drug manufacturers according to their HPLC trace impurity data. This method considers signals in phase space and accounts for two different types of noise: additive and perturbative. The pharmaceutical fingerprints are estimated as mean trajectories of HPLC trace impurity data and are used as reference models for recognition of new data by the minimal length classifier. The chromatographic trace organic impurity patterns collected from six different manufacturers of L-tryptophan are analyzed as an example. The prediction ability of the new method tested using three different cross-validation procedures remains about 95% even if the number of available data in the training sets decreases by 5 times. The accuracy of prediction in phase space is superior compared to results calculated using a Window Preprocessing method and artificial neural networks. The difference in performance between new and previous methods becomes more significant under particular conditions that are more adequate for practical application of the method. In addition, the current approach enables simple and comprehensive interpretation of the calculated results. C1 Inst Bioorgan & Petr Chem, Dept Biomed Applicat, UA-253660 Kyiv, Ukraine. Int Inst Appl Syst Anal, UA-252056 Kiev, Ukraine. Univ Missouri, Dept Chem, St Louis, MO 63121 USA. Univ Missouri, Ctr Mol Elect, St Louis, MO 63121 USA. US FDA, Div Drug Anal, St Louis, MO 63101 USA. ChemQuest, Steeple Morden SG8 0LP, Herts, England. Univ Portsmouth, Ctr Mol Design, Portsmouth PO1 2EG, Hants, England. RP Tetko, IV (reprint author), Univ Lausanne, Inst Physiol, Lab Neuroheurist, Rue du Bugnon 7, CH-1005 Lausanne, Switzerland. RI Villa, Alessandro/G-6220-2011; Tetko, Igor/B-1540-2010 OI Villa, Alessandro/0000-0002-4684-0027; Tetko, Igor/0000-0002-6855-0012 NR 13 TC 8 Z9 8 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JUL 1 PY 1999 VL 71 IS 13 BP 2431 EP + DI 10.1021/ac981346j PG 9 WC Chemistry, Analytical SC Chemistry GA 213HA UT WOS:000081265600038 PM 10405609 ER PT J AU Hendry, WJ DeBrot, BL Zheng, XL Branham, WS Sheehan, DM AF Hendry, WJ DeBrot, BL Zheng, XL Branham, WS Sheehan, DM TI Differential activity of diethylstilbestrol versus estradiol as neonatal endocrine disrupters in the female hamster (Mesocricetus auratus) reproductive tract SO BIOLOGY OF REPRODUCTION LA English DT Article ID MOUSE UTERUS; ESTROGEN STIMULATION; ALPHA-FETOPROTEIN; EXPOSURE; APOPTOSIS; LACTOFERRIN; SERUM; ENDOMETRIUM; BINDING; ADENOCARCINOMA AB The synthetic estrogen diethylstilbestrol (DES) is a potent neonatal endocrine disrupter in the hamster. To test the specificity of this phenomenon, newborn animals were treated with 100 mu g of either DES or the natural estrogen, estradiol-17 beta (E-2). Of the two, neonatal DES exposure caused greater morphological disruption throughout the female reproductive tract in prepubertal animals and in adults that either retained their ovaries or were ovariectomized and then given the same levels of chronic E-2 stimulation. In the uterus, a characteristic histopathological profile, including enhancement of both hyperplastic and apoptotic activity, was initiated prepubertally and exclusively in the endometrial epithelial cell compartment from the neonatally DES-treated animals and then was promoted by E-2 stimulation during adulthood. Interestingly, apoptotic activity was not detected in an area of endometrial epithelium that progressed to the neoplastic state in a DES-exposed animal. Lastly, chronic estrogen induction of lactoferrin was also restricted to the DES-exposed endometrium. We conclude that 1) DES is more active than E-2 as a perinatal endocrine disrupter in the hamster and 2) this experimental system should be generally useful as a means to screen compounds for such activity and then probe their mechanism of action. C1 Wichita State Univ, Dept Biol Sci, Wichita, KS 67260 USA. US FDA, Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. RP Hendry, WJ (reprint author), Wichita State Univ, Dept Biol Sci, 1845 Fairmount, Wichita, KS 67260 USA. FU NCI NIH HHS [CA60250] NR 53 TC 17 Z9 17 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 1999 VL 61 IS 1 BP 91 EP 100 DI 10.1095/biolreprod61.1.91 PG 10 WC Reproductive Biology SC Reproductive Biology GA 211FP UT WOS:000081150200013 PM 10377036 ER PT J AU Kuznetsov, VA Puri, RK AF Kuznetsov, VA Puri, RK TI Kinetic analysis of high affinity forms of interleukin (IL)-13 receptors: Suppression of IL-13 binding by IL-2 receptor gamma chain SO BIOPHYSICAL JOURNAL LA English DT Article ID CELL CARCINOMA-CELLS; PSEUDOMONAS EXOTOXIN; B-CELLS; SURFACE; GROWTH; INTERNALIZATION; AGGREGATION; BIOSENSORS; DIFFUSION; COMPLEXES AB Interleukin-13 (IL-13) is a pleiotropic cytokine that controls growth, differentiation, and apoptosis of immune and tumor cells. To understand the mechanisms of interaction between IL-13 and IL-13 receptors (IL-13R), and the role of the IL-2 receptor common gamma chain (gamma(c)) in IL-13 binding and processing, we have examined IL-13 binding kinetics, dissociation/shedding, and internalization in renal cell carcinoma (RCC) cell lines. We observed a new phenomena in that the apparent rate of association, but not the dissociation, was strongly related to IL-13 concentration. We also observed cooperativity phenomena in IL-13 and IL-13R interaction in control RCC (MLneo) cells, but not in cells transfected with gamma(c) chain (MLgamma c). The number of IL-13 binding sites, the effective rate of ligand association, and the dissociation rate constants were reduced in gamma(c)-transfected cells compared to control RCC cells. Two forms of IL-13R were detected in these cell lines, which differed in the kinetics of endocytosis and dissociation/exocytosis. Only a small fraction of bound receptors (14-24%) was rapidly internalized and the same fraction of the ligand-receptor complexes was shed and/or dissociated. The expression of gamma(c) chain did not change any of these processes. A two independent high-affinity and moderate-affinity receptor model fit the kinetic observations in gamma(c)-transfected cells. However, in control cells, the binding kinetics were more complicated. A mathematical model that fit a set of kinetic and steady state data in control cells was selected from a set of possible models. This best-fit model predicts that 1) two different IL-13R are expressed on the cell membrane, 2) a minor fraction of IL-13R exist as microclusters (homodimers and/or heterodimers) without exogenous IL-13, 3) high morphological complexity of the gamma(c) negative control cell membrane affects the cooperativity phenomena of IL-13 binding, and 4) a large number of co-receptor molecules is present, which helps keep the ligand on the cell surface for a long period of time after fast IL-13 binding and provides a negative control for ligand binding via production of the high affinity inhibitor bound to IL-13. Our data demonstrate that gamma(c) exerts dramatic changes in the kinetic mechanisms of IL-13 binding. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumour Biol, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. Russian Acad Sci, Inst Biochem Phys, Lab Math ImmunoBiophys, Moscow 117977, Russia. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumour Biol, Div Cellular & Gene Therapies, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. NR 45 TC 17 Z9 18 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 1999 VL 77 IS 1 BP 154 EP 172 DI 10.1016/S0006-3495(99)76879-7 PG 19 WC Biophysics SC Biophysics GA 214RQ UT WOS:000081341700013 PM 10388747 ER PT J AU Tobi, SE Levy, DD Seidman, MM Kraemer, KH AF Tobi, SE Levy, DD Seidman, MM Kraemer, KH TI Sequence-dependent mutations in a shuttle vector plasmid replicated in a mismatch repair deficient human cell line SO CARCINOGENESIS LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; SOMATIC FRAMESHIFT MUTATIONS; DYSPLASTIC NEVUS SYNDROME; XERODERMA-PIGMENTOSUM; COLON-CANCER; EXCISION-REPAIR; ULTRAVIOLET HYPERMUTABILITY; MICROSATELLITE INSTABILITY; ESCHERICHIA-COLI; MAMMALIAN-CELLS AB We utilized a shuttle vector plasmid (pLSC) to assess the role of DNA sequence and mismatch repair on mutagenesis in human cells. pLSC contains an interrupted 29 bp mononucleotide poly(G) run within a bacterial suppressor tRNA gene, which acts as a highly sensitive mutagenic target for detection of base substitution and frameshift mutations. The frequency of spontaneous mutations in pLSC was found to be similar after replication in either the hMSH6 (GT binding protein) mismatch repair-deficient MT1 line or its parental, mismatch repair-proficient line, TK6, However, the classes of plasmid mutations showed distinct differences in the two cell lines. Single base deletions comprised 48% of the mutations in the 56 independent pLSC plasmids sequenced from MT1 cells while these represented only 18% of the 40 independent pLSC mutants sequenced from the wild-type TK6 cells (P = 0.001). Virtually all the deletions included the mononucleotide run. In contrast, in pSP189, which contains the unmodified supF tRNA without the mononucleotide sequence, no single base deletions were observed for either cell line (P < 0.001), UV treatment of pLSC and pSP189 resulted in a 12-140-fold increase in mutations in TK6 and MT1 cells. These were predominately single base substitution mutations without a large increase in deletion mutations in the mononucleotide run in pLSC, These data indicate that a mononucleotide poly(G) run promotes single base deletion mutations. This effect is enhanced in a hMSH6 mismatch repair-deficient cell line and is independent of UV-induced mutagenesis. C1 NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NIA, Mol Genet Lab, Baltimore, MD 21224 USA. RP Kraemer, KH (reprint author), NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NR 57 TC 9 Z9 9 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 JUL PY 1999 VL 20 IS 7 BP 1293 EP 1301 DI 10.1093/carcin/20.7.1293 PG 9 WC Oncology SC Oncology GA 218JJ UT WOS:000081549200020 PM 10383903 ER PT J AU Mourato, LLG Beland, FA Marques, MM AF Mourato, LLG Beland, FA Marques, MM TI P-32-postlabeling of N-(deoxyguanosin-8-yl)arylamine adducts: A comparative study of labeling efficiencies SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID CARCINOGEN-DNA ADDUCTS; P-32 POSTLABELING ASSAY; NATURALLY-OCCURRING ALKENYLBENZENES; T4 POLYNUCLEOTIDE KINASE; HUMAN URINARY-BLADDER; AROMATIC-AMINES; HEMOGLOBIN ADDUCTS; CIGARETTE-SMOKE; TOBACCO-SMOKE; CANCER RISK AB P-32-Postlabeling is an extremely powerful technique for the detection of DNA adducts. Typically, the quantitation of DNA adducts by P-32-postlabeling is achieved by relative adduct labeling, via comparison of the radioactivity incorporated into the adducts to that associated with the normal nucleotides. This approach is based on a number of assumptions, the foremost being that normal and adducted nucleotide 3'-phosphates are converted to 3',5'-bisphosphates with similar efficiencies. To evaluate labeling efficiencies for specific DNA adducts, we conducted a comparative study of the kinetics of phosphorylation by T-4 polynucleotide kinase using 2'-deoxyguanosine 3'-phosphate (dG3'p) and a series of N-(deoxyguanosin-8-yl)arylamine 3'-phosphate adduct standards (dCT3'p-C8-Ar, Ar being 4-aminobiphenyl, 3- and 4-methylaniline, and 2,4- and 3,4-dimethylaniline). Phosphorylation of dG3'p and the dCT3'p-C8-Ar adducts followed Michaelis-Menten kinetics. The apparent turnover numbers were 40-240-fold lower when labeling dG3'p-C8-Ar adducts compared to that when labeling dG3'p. The apparent specificity constant calculated for dG3'p-C8-4-aminobiphenyl (1.4 mu M-1 min(-1)) was approximately 4-fold lower than that (5.4 mu M-1 min(-1)) found for dG3'p. Apparent specificity constants for the monoarylamine adducts were even lower (0.043-0.23 mu M-1 min(-1)) and decreased in the following order: 4-methylaniline > 3,4-dimethylaniline > S-methylaniline > 2,4-dimethylaniline. Similar experiments conducted with dG3'p-C8-Ar standards for 2-methylaniline and 2,3-dimethylaniline produced very poor and irreproducible labeling. These results indicate that P-32-postlabeling of dG3'p-C8-Ar adducts is less efficient than that of dG3'p and suggest that normal nucleotides will be labeled preferentially to the arylamine adducts under kinetically controlled conditions. The data also indicate a further decrease in labeling efficiency upon substitution ortho to the amino group (e.g., 2,4-dilmethylaniline). In addition, the ATP concentrations required for optimal labeling were found to be substantially higher than those used in typical 32P-postlabeling assays. Since the high specific activity of carrier-free [gamma-P-32]- ATP precludes increasing the ATP concentration to a significant extent, these data emphasize the need for using highly efficient adduct enrichment procedures when conducting P-32- postlabeling analyses of DNA adducts. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1049001 Lisbon, Portugal. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT-110, Jefferson, AR 72079 USA. EM fbeland@nctr.fda.gov; qmdmar@beta.ist.utl.pt RI Marques, M. Matilde/E-2535-2012; Goncalves, Luisa/A-4120-2016; OI Marques, M. Matilde/0000-0002-7526-4962; Goncalves, Luisa/0000-0002-3654-8612; Goncalves, Luisa/0000-0002-2385-7395 NR 59 TC 10 Z9 10 U1 0 U2 1 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 JUL PY 1999 VL 12 IS 7 BP 661 EP 669 DI 10.1021/tx990038t PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 219JC UT WOS:000081603300016 PM 10409407 ER PT J AU Yu, XH Sun, Y Frasch, C Concepcion, N Nahm, MH AF Yu, XH Sun, Y Frasch, C Concepcion, N Nahm, MH TI Pneumococcal capsular polysaccharide preparations may contain non-C-polysaccharide contaminants that are immunogenic SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID STREPTOCOCCUS-PNEUMONIAE; CELL-WALL; VACCINE; ANTIBODIES; ADULTS; SERUM; ASSAY; MICE AB We measured the capacity to opsonize Streptococcus pneumoniae serotype 6B and estimated the concentration of immunoglobulin G anti-6B capsular polysaccharide (PS) antibodies in 25 pre- and postimmune sera from adults immunized with a pneumococcal PS vaccine. We first studied two postvaccination serum samples displaying less opsonophagocytic capacity than expected. The majority of anti-6B antibodies in the two samples reacted with the capsular PSs of several unrelated serotypes (2, 4, 9V, 19F, and 23F) and with the lysate of noncapsulated S, pneumoniae bacteria but not with C-PS, The non-type-specific antibodies accounted for at least one-half of anti-6B antibodies in 40% of prevaccination sera and 10% of postvaccination sera from adults. The non-type-specific antibodies could be demonstrated in the enzyme-linked immunosorbent assays (ELISAs) for pneumococcal antibodies to other serotypes (4, 9V, 18C, 19F, and 23F), The nonspecific antibodies appear to bind a contaminant(s) in the current preparations of capsular PS, ELISA for antibodies to pneumococcal capsules may not be serotype specific for some samples. C1 Univ Rochester, Sch Med, Dept Pathol, Rochester, NY 14642 USA. Univ Rochester, Sch Med, Dept Med, Rochester, NY 14642 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Bethesda, MD 20853 USA. RP Nahm, MH (reprint author), Univ Rochester, Sch Med, Dept Pediat, 601 Elmwood Ave,Box 777, Rochester, NY 14642 USA. OI Nahm, Moon/0000-0002-6922-1042 FU NIAID NIH HHS [AI-85334, R56 AI031473, N01AI45248, AI-31473, N01 AI 45248, R01 AI031473] NR 19 TC 51 Z9 52 U1 0 U2 3 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 JUL PY 1999 VL 6 IS 4 BP 519 EP 524 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 215LA UT WOS:000081382100014 PM 10391854 ER PT J AU Sacks, LV Pendle, S Orlovic, D Blumberg, L Constantinou, C AF Sacks, LV Pendle, S Orlovic, D Blumberg, L Constantinou, C TI A comparison of outbreak- and nonoutbreak-related multidrug-resistant tuberculosis among human immunodeficiency virus-infected patients in a South African hospital SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ANTITUBERCULOSIS-DRUG-RESISTANCE; MYCOBACTERIUM-TUBERCULOSIS; NOSOCOMIAL TRANSMISSION; HIV-INFECTION; STRAIN; SUSCEPTIBILITY; EPIDEMIOLOGY; PATTERNS AB Nosocomial multidrug-resistant tuberculosis (MDR-TB) in human immunodeficiency virus (HIV)-infected people is recognized in Europe and America, We report the first such outbreak in South Africa. Six hospitalized women, identified by DNA fingerprinting, were infected with an outbreak strain of MDR-TB while receiving treatment for drug-susceptible tuberculosis. The putative source case was identified as an HIV-positive woman who underwent prolonged hospitalization for chronic cavitary tuberculosis. Compared with other HIV-positive patients in the hospital, outbreak patients were more immunocompromised, had fewer cavitary lung changes, and were less likely to have been treated before. They had high fevers, infiltrative patterns on chest radiographs, and a mean survival of 43 days. When individual isolation is not possible, separating highly immunocompromised patients with first-time tuberculosis from previously treated patients with cavitary lesions and from those with established drug resistance may reduce nosocomial transmission. C1 Sizwe Trop Dis Hosp, Johannesburg, South Africa. S African Inst Med Res, Johannesburg, South Africa. RP Sacks, LV (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Special Pathogens, Attn Document Control Room,5600 Fishers Lane, Rockville, MD 20857 USA. NR 28 TC 34 Z9 37 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL PY 1999 VL 29 IS 1 BP 96 EP 101 DI 10.1086/520189 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 220UF UT WOS:000081685300017 PM 10433570 ER PT J AU Sun, H Fadiran, EO Jones, CD Lesko, L Huang, SM Higgins, K Hu, CP Machado, S Maldonado, S Williams, R Hossain, M Ette, EI AF Sun, H Fadiran, EO Jones, CD Lesko, L Huang, SM Higgins, K Hu, CP Machado, S Maldonado, S Williams, R Hossain, M Ette, EI TI Population pharmacokinetics - A regulatory perspective SO CLINICAL PHARMACOKINETICS LA English DT Review ID DRUG DEVELOPMENT; PARAMETER-ESTIMATION; MODELS; PHARMACODYNAMICS; ERROR; PERFORMANCE; VALIDATION; GRAPHICS AB The application of population approaches to drug development is recommended in several US Food and Drug Administration (Fl)A) guidance documents. Population pharmacokinetic (and pharmacodynamic) techniques enable identification of the sources of inter- and intra-individual variability that impinge. upon drug Safety and efficacy. This article briefly discusses the 2-stage approach to the estimation of population pharmacokinetic parameters, which requires serial multiple measurements on each participant, and comprehensively reviews the nonlinear mixed-effects. modelling approach, which can be applied in situations where extensive sampling is not done on all or any of the participants. Certain preliminary information, such as the compartment model used in describing the pharmacokinetics of the drug, is required for a population pharmacokinetic study. The practical design considerations of the location of sampling times, number of samples/participants and the need to sample an individual more than once should be borne in mind. Simulation may be useful for choosing the study design that will best meet study objectives. The objectives of the population pharmacokinetic study can be secondary to the objectives of the primary clinical study lin which case an add-on population pharmacokinetic protocol may be needed) or primary (when a stand-alone protocol is required). Having protocols for population pharmacokinetic studies is an integral part of 'good pharmacometric practice'. Real-time data assembly and analysis permit an ongoing evaluation of site compliance with the study protocol and provide the opportunity to correct violations of study procedures. Adequate policies and procedures should be in place for study blind maintenance. Real-time data assembly creates the opportunity for detecting and correcting errors in concentration-time data, drug administration history and covariate data. Population pharmacokinetic analyses may be undertaken in 3 interwoven steps: exploratory data analysis, model development and model validation (i.e. predictive performance). Documentation for regulatory purposes should include a complete inventory of key runs in the analyses undertaken (with flow diagrams if possible), accompanied by articulation of objectives, assumptions and hypotheses. Use of diagnostic analyses of goodness of fit as evidence of reliability of results is advised. Finally, the use of stability testing or model validation may be warranted to support label claims. The opinions expressed in this article were revised by incorporating comments from various sources and published by the FDA as 'Guidance for Industry: Population Pharmacokinetics' (see the FDA home page http://www.fda.gov for further information). C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20850 USA. Solvay Pharmaceut, Marietta, GA USA. Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. Novartis Pharmaceut, E Hanover, NJ USA. Vertex Pharmaceut, Cambridge, MA USA. RP Sun, H (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, 9201 Corp Blvd, Rockville, MD 20850 USA. NR 59 TC 59 Z9 67 U1 0 U2 7 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PD JUL PY 1999 VL 37 IS 1 BP 41 EP 58 DI 10.2165/00003088-199937010-00003 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 223WB UT WOS:000081863600003 PM 10451782 ER PT J AU Yuan, R Parmelee, T Balian, JD Uppoor, RS Ajayi, F Burnett, A Lesko, LJ Marroum, P AF Yuan, R Parmelee, T Balian, JD Uppoor, RS Ajayi, F Burnett, A Lesko, LJ Marroum, P TI In vitro metabolic interaction studies: Experience of the Food and Drug Administration SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID HUMAN LIVER-MICROSOMES; IN-VITRO; SUBSTRATE CONCENTRATION; N-DEMETHYLATION; HUMAN CYP3A; KETOCONAZOLE; VIVO; INHIBITION; MIDAZOLAM; AMITRIPTYLINE AB A total of 194 new molecular entities approved by the Food and Drug Administration between 1992 and 1997 were surveyed to determine the role of in vitro metabolic interactions in the conduct of drug-drug interaction studies and to examine the methods used in these studies. Approximately 30% of the submissions were found to have in vitro metabolism-based interaction studies, most of which were inhibitory in nature. Chemical inhibition was the most commonly used approach in studying drug interactions in vitro. In this article, an attempt to assess the quality of the chemical inhibition approach was made. Pour areas were found to be often overlooked: (1) incubation time and concentrations of the drug, (2) the difference between inhibition constant (k(i)) and 50% inhibitory concentration (IC50) values, (3) the substrate-dependent inhibition potential, and (4) the metabolic genotype or phenotype of the liver donor. We discuss the pitfalls in estimating drug interactions when these four areas are overlooked. C1 US FDA, Ctr Drug Evaluat & Res, OPS, Off Clin Pharmacol & Biopharmaceut,DPE I, Rockville, MD 20857 USA. RP Yuan, R (reprint author), US FDA, Ctr Drug Evaluat & Res, OPS, Off Clin Pharmacol & Biopharmaceut,DPE I, HFD-860,5600 Fishers Lane,Woodmont 2 Bldg,Room 40, Rockville, MD 20857 USA. NR 18 TC 37 Z9 37 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUL PY 1999 VL 66 IS 1 BP 9 EP 15 DI 10.1016/S0009-9236(99)70048-2 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 220ER UT WOS:000081652000003 PM 10430104 ER PT J AU Fleming, A AF Fleming, A TI A task and problem focused approach to the development and regulation of drugs SO DRUG INFORMATION JOURNAL LA English DT Article DE Food and Drug Administration; drug development; drug regulation; electronic technology AB This paper describes an approach by which the pharmaceutical industry and the Food and Drug Administration (FDA) can communicate and interact more effectively in the drug development process. An electronic system is proposed that with constant updating would organize data and other information by issues. These issues-tasks and problems-would be carefully expressed, only as can be justified by available data. Using a shared task and problem list and an electronic space in which communication is captured, developers and evaluators would interactively resolve these issues in a stepwise fashion. This approach encompasses aspects of information and project management. It would also support the evolution of good review practice and increase understanding of the drug evaluation process. This proposal is intended to improve the effectiveness, efficiency, and speed of drug review at FDA without adding any burden to drug developers. C1 US FDA, Div Metab & Endocrine Drug Prod, Gaithersburg, MD 20878 USA. RP Fleming, A (reprint author), US FDA, Div Metab & Endocrine Drug Prod, 5600 Fishers Lane, Gaithersburg, MD 20878 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU DRUG INFORMATION ASSOCIATION PI FORT WASHINGTON PA 501 OFFICE CENTER DR, STE 450, FORT WASHINGTON, PA 19034-3212 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD JUL-SEP PY 1999 VL 33 IS 3 BP 939 EP 948 PG 10 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 228TE UT WOS:000082151100035 ER PT J AU Zoon, KC AF Zoon, KC TI Vaccines, pharmaceutical products, and bioterrorism: Challenges for the US Food and Drug Administration SO EMERGING INFECTIOUS DISEASES LA English DT Article C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Zoon, KC (reprint author), US FDA, Ctr Biol Evaluat & Res, Mailstop HFM-1,1401 Rockville Pike, Rockville, MD 20852 USA. NR 3 TC 11 Z9 11 U1 0 U2 1 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JUL-AUG PY 1999 VL 5 IS 4 BP 534 EP 536 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 225WE UT WOS:000081988300014 PM 10458960 ER PT J AU Li, QG Brueckner, RP Peggins, JO Trotman, KM Brewer, TG AF Li, QG Brueckner, RP Peggins, JO Trotman, KM Brewer, TG TI Arteether toxicokinetics and pharmacokinetics in rats after 25 mg/kg/day single and multiple doses SO EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS LA English DT Article DE arteether; toxicokinetics; pharmacokinetics; multiple doses; rats ID ANTIMALARIAL DRUG; FALCIPARUM-MALARIA; ARTEMETHER; BIOAVAILABILITY; ARTEMISININ AB Multiple doses of arteether (ARTE) at 25 mg/kg cause CNS and anorectic toxicities in rats. The same dose of ARTE was used to study the toxicokinetics (TK) after multiple injections and the pharmacokinetics (PK) following single administration. Animals were administered ARTE in sesame oil for 7 days, blood samples were collected using destructive sampling for up to 192 h after dosing and assayed by HPLC-ECD. Two other groups of rats were administered either a single 25 mg/kg i.v. or i.m. dose. In addition, the drug remaining in the i.m. injection site was measured. During the 7 day treatments, anorectic toxicity of ARTE was observed, and that caused significant reductions in food consumption and body weight after day 2. TK data on days 2-7 revealed marked changes compared to the PK parameters estimated on day 1. AUC (4367 ng.h/ml) on day 7 was 5-fold higher than AUC (905 ng.h/ml) on day 1. The volume of distribution at steady state (V-ss) on day 7 (41.81) was 40% of the day 1 value of the V-ss (104.31). Clearance (CL) was increased by 89% of the day 1 value, from 0.98 l/h to 1.85 l/h on day 7. The elimination t(1/2) of ARTE was also prolonged from 13.7 h (day 1) to 31.2 h (day 7). These data suggest that ARTE may have altered its distribution and elimination in rats as a result of the systemic toxicity. Analysis of the injection sites showed that 38% and 91% of the total amount of ARTE single dose remained in the muscles at 24 h (after first injection) and 168 h (at 24 h after 7 daily multiple doses), respectively. Fast and slow absorption phases from muscle were seen with t(1/2) Of 0.97 h and 26.3 h, respectively. The apparent elimination t(1/2) Of ARTE after i.m. injection (13.7 h) was much longer than that after i.v, dosing (0.67 h) due to the prolonged muscle absorption phase. Acute toxicity data of artemisinin drugs demonstrated that animals receiving a high single ARTE dose in sesame oil died between days 5-11, similar to artemether. When animals received dihydroartemisinin formulated in 50% DMAC/oil, or artesunic acid and artelinic acid in 0.9% saline vehicle, they died between days 1 and 2. This suggests that delayed onset toxicity and death in the ARTE rats may also be due to slow absorption and prolonged drug exposure. Therefore multiple i.m. administrations cause anorexia and drug accumulation, possibly affecting the toxicokinetics and efficacy of the drug. C1 Walter Reed Army Inst Res, Dept Pharmacol, Div Expt Therapeut, Washington, DC 20307 USA. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand. RP Li, QG (reprint author), Walter Reed Army Inst Res, Dept Pharmacol, Div Expt Therapeut, Washington, DC 20307 USA. NR 35 TC 19 Z9 19 U1 1 U2 2 PU MEDECINE ET HYGIENE PI GENEVA 4 PA 78 AVE ROSERALE, 1211 GENEVA 4, SWITZERLAND SN 0378-7966 J9 EUR J DRUG METAB PH JI Eur. J. Drug Metabol. Pharmacokinet. PD JUL-SEP PY 1999 VL 24 IS 3 BP 213 EP 223 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 280QA UT WOS:000085112400004 PM 10716059 ER PT J AU Hart, PH Bonder, CS Balogh, J Dickensheets, HL Vazquez, N Davies, KVL Finlay-Jones, JJ Donnelly, RP AF Hart, PH Bonder, CS Balogh, J Dickensheets, HL Vazquez, N Davies, KVL Finlay-Jones, JJ Donnelly, RP TI Diminished responses to IL-13 by human monocytes differentiated in vitro: role of the IL-13R alpha 1 chain and STAT6 SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE monocyte; macrophage; IL-13 receptor; STAT6; TNF-alpha ID RECEPTOR-ALPHA-CHAIN; INTERLEUKIN (IL)-13 BINDING; SYNOVIAL-FLUID MACROPHAGES; T-CELLS; GAMMA-CHAIN; B-CELLS; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; CYTOKINE; GENE AB The primary IL-13 receptor complex on human monocytes is believed to be a heterodimer comprised of the IL-4R alpha chain and the IL-2R gamma chain (gamma(c))-like molecule, IL-13R alpha 1. mRNA levels for IL-13R alpha 1, but not IL-4R alpha, were markedly decreased in in vitro monocyte-derived macrophages (MDMac), and with increasing time of monocytes in culture correlated with the loss of IL-13 regulation of lipopolysaccharide-induced TNF-alpha production. Analysis of cell lines Daudi and THP-1 that differentially express gamma(c) and IL-13R alpha 1 showed that IL-13 can activate STAT6 in IL-13R alpha 1-positive THP-1 cells but not in gamma(c)-positive, IL-13R alpha 1-negative Daudi cells. IL-13 activation of STAT6 was reduced in MDMac which was associated with diminished IL-13-induced expression of CD23 and MHC class II. However, with reduced IL-13R alpha 1 expression and low nuclear STAT6 activity, some IL-13-induced responses were unaltered in magnitude in MDMac. In the absence of functional IL-13R alpha 1 and gamma(c), IL-13 must signal through an alternative receptor complex on MDMac. Experiments with a blocking antibody to IL-4R alpha showed that this chain remains an essential component of the IL-13 receptor complex on MDMac. C1 Flinders Univ S Australia, Sch Med, Dept Microbiol & Infect Dis, Adelaide, SA 5001, Australia. US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. RP Hart, PH (reprint author), Flinders Univ S Australia, Sch Med, Dept Microbiol & Infect Dis, GPO Box 2100, Adelaide, SA 5001, Australia. RI Finlay-Jones, John/C-2421-2013 NR 33 TC 13 Z9 13 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 1999 VL 29 IS 7 BP 2087 EP 2097 DI 10.1002/(SICI)1521-4141(199907)29:07<2087::AID-IMMU2087>3.0.CO;2-J PG 11 WC Immunology SC Immunology GA 215ET UT WOS:000081369500005 PM 10427971 ER PT J AU Mossoba, MM Kramer, JKG Yurawecz, MP Sehat, N Roach, JAG Eulitz, K Fritsche, J Dugan, MER Ku, Y AF Mossoba, MM Kramer, JKG Yurawecz, MP Sehat, N Roach, JAG Eulitz, K Fritsche, J Dugan, MER Ku, Y TI Impact of novel methodologies on the analysis of conjugated linoleic acid (CLA). Implications of CLA feeding studies SO FETT-LIPID LA English DT Article; Proceedings Paper CT 52nd International Congress and Expo of the DGF CY SEP 13-15, 1998 CL MAGDEBURG, GERMANY ID PERFORMANCE LIQUID-CHROMATOGRAPHY; FATTY-ACIDS; DAIRY-PRODUCTS; GAS-CHROMATOGRAPHY; MILK-FAT; MASS-SPECTROMETRY; ADIPOSE-TISSUE; BOVINE-MILK; ISOMERS; IDENTIFICATION AB Interest in conjugated linoleic acid (CLA) has increased in the past decade as a result of repot ts of several health benefits related to its consumption. Naturally occurring CLA isomers are found in milk, dairy, and meat products from ruminants. Detailed isomeric composition of CLA in different chemical and biological matrices had been hindered by the lack of adequate analytical techniques. New methodologies were developed and used to determine the distribution of major and minor geometric and positional CLA isomers in cheese, beef, cow milk, human adipose, and human milk. Base-catalyzed methylation was used. A novel silver ion high-performance liquid chromatographic procedure was developed, which successfully resolved up to 16 isomers. The double bond configuration and position for CLA isomers were confirmed by gas chromatography (GC)-direct deposirion-Fourier transform infrared spectroscopy and CC-electron ionization mass spectrometry, respectively: The incorporation of CLA isomers in tissues of animals fed CLA diets was also determined. Currently available analytical data suggest the need to re-evaluate prior CLA studies and their nutritional and biological implications. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Agr & Agri Food Canada, So Crop Protect, Food Res Ctr, Guelph, ON, Canada. Agr & Agri Food Canada, Lacombe Res Ctr, Lacombe, AB, Canada. RP Mossoba, MM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 56 TC 8 Z9 9 U1 1 U2 4 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0931-5985 J9 FETT-LIPID JI Fett-Lipid PD JUL PY 1999 VL 101 IS 7 BP 235 EP 243 PG 9 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 224TE UT WOS:000081914600003 ER PT J AU Racoosin, JA Kessler, CM AF Racoosin, JA Kessler, CM TI Bleeding episodes in HIV-positive patients taking HIV protease inhibitors: a case series SO HAEMOPHILIA LA English DT Article ID METABOLISM AB In July 1996 the Food and Drug Administration (FDA) alerted healthcare providers about 15 case reports of spontaneous bleeding episodes in HIV-positive haemophiliacs taking HIV protease inhibitors. In order to characterize the bleeding associated with HIV protease inhibitor therapy, the FDA's spontaneous adverse event reporting system was searched through 28 February 1997. The bleeding episode reporting rate for persons with haemophilia was compared for HIV protease inhibitors and zidovudine, and the characteristics of haemorrhagic events were compared between individuals with and without haemophilia. There was a substantial predominance of bleeding episodes for haemophiliacs taking HIV protease inhibitors (39 of 67; 58%) as compared with zidovudine (two of 63; 3.2%). A comparison of 39 reports of bleeding in haemophiliacs with 28 in non-haemophiliacs revealed similarities in time to event and type of HIV protease inhibitor implicated, but differences were present concerning location of bleeding and outcome. A greater proportion of haemophiliacs had resolution of their bleeding following discontinuation of their HIV protease inhibitor and recurrence of bleeding following rechallenge, as compared with non-haemophiliacs. HIV-positive haemophiliacs appear to be at an elevated risk of bleeding while taking HIV protease inhibitors, but these medications may predispose all individuals to such complications. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Georgetown Univ, Med Ctr, Washington, DC 20057 USA. RP Racoosin, JA (reprint author), 5600 Fishers Lane,HFD-120, Rockville, MD 20857 USA. NR 8 TC 29 Z9 29 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD JUL PY 1999 VL 5 IS 4 BP 266 EP 269 PG 4 WC Hematology SC Hematology GA 288DC UT WOS:000085545700007 PM 10469181 ER PT J AU Ye, X Scallet, A Carp, RI AF Ye, X Scallet, A Carp, RI TI Abnormal periodic acid-Schiff (PAS)-positive substance in the islets of Langerhans, pituitaries and adrenal glands of 139H scrapie-infected hamsters SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Article DE scrapie; hamster; PAS-positive substance; pituitary; islet of Langerhans ID HISTOPATHOLOGICAL CHANGES; STRAIN; AMYLIN; CELLS; GENE; MICE AB Previous studies showed that the 139H strain of scrapie injected intra-cerebrally in hamsters caused obesity, and extensive histopathological changes in islets of Langerhans and pituitaries. In the current study, we report that an abnormal granular substance, which stained positively with periodic acid-Schiff (PAS-positive substance; PPS), was found in the islets of Langerhans, pituitaries, adrenal glands, in the lumens of blood vessel cores (BVCs) and in blood vessels in 139H-infected hamsters, but not in either 263K-infected or control hamsters. This substance was found in the endocrine organs, forming grape-like or plaque-like structures, which were small, round to ovoid, and homogenous measuring up to 7 mu m in diameter and usually grouped in clusters. PPS was not found in the brains of control or scrapie-infected hamsters. Using immunostaining for amyloid protein (PrP, beta A4), as well as Congo red and thioflavin-S stains, no evidence was found of amyloid plaque formation in the islets of Langerhans, the adrenal glands, or the pituitaries of 139H- or 263K-infected hamsters. PPS might relate to the pathological changes in the endocrine organs in 139H-infected hamsters. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA. RP Ye, X (reprint author), Washington State Univ, VCAPP, 205 Wegner Hall, Pullman, WA 99164 USA. FU NIA NIH HHS [AG09017] NR 21 TC 3 Z9 3 U1 0 U2 0 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD JUL PY 1999 VL 14 IS 3 BP 673 EP 678 PG 6 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 212WZ UT WOS:000081241800001 PM 10425534 ER PT J AU Waynant, RW Gannot, I AF Waynant, RW Gannot, I TI Introduction to the issue on lasers in medicine and biology SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Editorial Material C1 CDRH, FDA, Electro Opt Branch, Rockville, MD 20857 USA. Tel Aviv Univ, Fac Engn, Dept Biomed Engn, IL-69978 Tel Aviv, Israel. RP Waynant, RW (reprint author), CDRH, FDA, Electro Opt Branch, Rockville, MD 20857 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD JUL-AUG PY 1999 VL 5 IS 4 BP 893 EP 894 DI 10.1109/JSTQE.1999.796307 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 248CM UT WOS:000083257800003 ER PT J AU Ilev, IK Waynant, RW Kumagai, H Midorikawa, K AF Ilev, IK Waynant, RW Kumagai, H Midorikawa, K TI Double-pass fiber Raman laser - A powerful and widely tunable in the ultraviolet, visible, and near-infrared fiber Raman laser for biomedical investigations SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article ID DISPERSION MEASUREMENT; OPTICAL-FIBER AB We present the operating principle, general features, and advantages of a novel concept for the development of powerful and widely tunable fiber Raman lasers (FRL's), based on the high-power pumping of large-core low-loss multimode fibers using a simple double-pass laser arrangement with Littrow-prism-tuned emission. Basic experimental results obtained with various modification double-pass FRL schemes, which provide the generation of both discretely tunable emission in the UV/blue (360-493 nm) at lambda(p) = 355 nm and continuously tunable emission in the visible/near-IR (0.54-1.01 mu m) at lambda(p) = 532 nm, are reported. The double-pass FRL schemes permit powerful and widely tunable spectral components to be generated, due to the double passing of nonlinear-converted laser emission through the optical fiber, maximum cavity feedback, the use of multimode fibers, and high-power pumping. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RIKEN, Inst Phys & Chem Res, Laser Technol Lab, Wako, Saitama 35101, Japan. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-134, Rockville, MD 20857 USA. RI Midorikawa, Katsumi/B-6335-2015 OI Midorikawa, Katsumi/0000-0002-0588-519X NR 23 TC 5 Z9 5 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD JUL-AUG PY 1999 VL 5 IS 4 BP 1013 EP 1018 DI 10.1109/2944.796324 PG 6 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 248CM UT WOS:000083257800020 ER PT J AU Sagi-Dolev, AM Harris, GR Waynant, RW Gannot, I AF Sagi-Dolev, AM Harris, GR Waynant, RW Gannot, I TI Laser-induced acoustic stresses under submerged biological membranes SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article DE laser-tissue interaction; optical fiber; laser-induced stress; Er : YAG laser ID ERBIUM-YAG LASER; VITREORETINAL SURGERY; CLINICAL-EXPERIENCE; TISSUE ABLATION; RADIATION AB Er:YAG lasers are being widely studied as candidates for surgical procedures in liquid environments, such as in ophthalmology, However, while the Er:YAG laser can be a precise and efficient light scalpel, this surgical method includes accompanying stress waves that must be quantified and evaluated for potential harm. In this study, Er:YAG laser-induced stress waves for free running laser pulses were measured over various consecutive treatment periods. Using a spot-poled PVDF hydrophone, measurements were acquired beneath a biological membrane submerged in a saline bath, Results yielded pressures peaks of 300-600 mbar beneath the uncut membrane, which could be harmful for the optic nerve if located directly below the treatment area. Acoustic waves representative of direct laser-liquid interactions were observed immediately following membrane rupture, and yielded much larger pressures. The morphological changes in the acoustic wave can be used as a feedback signal to indicate when the membrane has been cut. C1 Tel Aviv Univ, Dept Biomed Engn, IL-69978 Tel Aviv, Israel. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Sagi-Dolev, AM (reprint author), Tel Aviv Univ, Dept Biomed Engn, IL-69978 Tel Aviv, Israel. NR 15 TC 1 Z9 1 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD JUL-AUG PY 1999 VL 5 IS 4 BP 1027 EP 1031 DI 10.1109/2944.796326 PG 5 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 248CM UT WOS:000083257800022 ER PT J AU Desaiah, D Pande, M Vig, PJS Cameron, JA Ali, SF AF Desaiah, D Pande, M Vig, PJS Cameron, JA Ali, SF TI In vitro and in vivo inhibition of rat brain nitric oxide synthase activity by phencyclidine SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE brain; phencyclidine; nitric oxide synthase ID RELAXING FACTOR; NERVOUS-SYSTEM; TREATED RATS; MESSENGER; INCREASES; NMDA AB Phencyclidine (PCP) is a widely abused psychoactive drug that perturbs many neurotransmitter systems studied to date. Nitric oxide (NO) has been established as a neuronal messenger and its rapid diffusibility across cell membranes makes NO an extensive and versatile messenger in brain development and functioning. The present study was initiated to investigate the effect of PCP on rat brain nitric or;ide synthase (NOS) activity both in vitro and in vivo, Brain cytosolic fractions from normal rats were used for in vitro and in vivo studies. The rats were treated with a single dose of PCP (10 mg/kg, intraperitoneally); the brains were removed at 0, 1, 2, 6, and 12 hours after PCP treatment and the cytosolic fractions were prepared by homogenization and centrifugation. NOS activity was assessed by quantifying the release of [H-3]-citrulline from [H-3]-arginine. PCP significantly inhibited rat brain NOS in vitro in a concentration (0.05-2 mM)-dependent manner. The kinetic evaluation of arginine, NADPH, and Ca2+ activation of NOS revealed that PCP (0.5 mM) inhibited NOS activity competitively with respect to arginine and NADPH and noncompetitively inhibited with respect to Ca2+. PCP also caused a time-dependent reduction of brain NOS activity in vivo as early as 1 hour after treatment. Even after 12 hours of PCP treatment, NOS activity did not reverse to its normal level as compared to the control group, suggesting sequestration and persistence of the drug in the central nervous system. These results suggest that inhibition of brain NOS by PCP might be one of the mechanisms through which PCP causes neurotoxicity. C1 Univ Mississippi, Med Ctr, Dept Neurol, Jackson, MS 39216 USA. Jackson State Univ, Dept Biol, Jackson, MS USA. US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Desaiah, D (reprint author), Univ Mississippi, Med Ctr, Dept Neurol, 2500 N State St, Jackson, MS 39216 USA. NR 34 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD JUL-AUG PY 1999 VL 18 IS 4 BP 245 EP 250 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 231HB UT WOS:000082301100003 ER PT J AU Duarte, CG Zhang, J Ellis, S AF Duarte, CG Zhang, J Ellis, S TI Effects of radiocontrast, mannitol, and endothelin on blood pressure and renal damage in the aging male spontaneously hypertensive rat SO INVESTIGATIVE RADIOLOGY LA English DT Article DE aging male spontaneously hypertensive rats; blood pressure; pentobarbital anesthesia; mannitol; radiocontrast medium; endothelin; renal damage ID WISTAR-KYOTO RATS; CONTRAST-MEDIA; INDUCED NEPHROPATHY; FAILURE; KIDNEY; NEPHROTOXICITY; RELEASE; AGENTS; INJURY; MODEL AB RATIONALE AND OBJECTIVES. The purpose of this research was to study the effects of the radiocontrast medium (CM) Hypaque-76 (diatrizoate meglumine sodium), equiosmolar mannitol, and endothelin on blood pressure and renal damage in a aging male spontaneously hypertensive rat, a small animal model for CM-induced renal damage. The importance of the presser effect and the high osmolality of CM in producing renal damage was investigated by first reducing the blood pressure with pentobarbital anesthesia, which suppresses sympathetic nervous system activity, then testing the effects of CM, saline, mannitol, and the potent vasoconstrictor endothelin alone and in combination with CM. METHODS. Systolic blood pressure was measured in 14-month-old male rats (1) when awake, (2) after pentobarbital anesthesia, (3) after the administration of saline, CM, mannitol, endothelin, or CM plus endothelin, (4) after awakening the same day, and (5) the following day while awake. Renal damage was quantified by evaluating histopathologically the left kidney removed the day after administration of test substances. RESULTS. The pentobarbital-lowered blood pressure remained depressed after saline and mannitol but rose dramatically after CM, endothelin, and CM plus endothelin. Renal damage, compared with the saline controls, occurred with CM, mannitol, endothelin, and endothelin plus CM. The order of increasing severity was mannitol = CM < endothelin < endothelin plus CM. CONCLUSIONS. The effect of CM on systolic blood pressure is not related to its osmolality. High osmolality, however, appears to be a factor in CM-induced renal damage. Ischemia and direct nephrotoxicity are factors contributing to the renal-damaging effects of CM, mannitol, and endothelin. C1 US FDA, Div Cardiorenal Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Laurel, MD USA. RP Duarte, CG (reprint author), US FDA, Div Cardiorenal Drug Prod, Ctr Drug Evaluat & Res, HFD-110,5600 Fishers Lane, Rockville, MD 20857 USA. NR 48 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JUL PY 1999 VL 34 IS 7 BP 455 EP 462 DI 10.1097/00004424-199907000-00003 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 211ZA UT WOS:000081190700003 PM 10399635 ER PT J AU Adam, LA AF Adam, LA TI Confirmation of azaperone and its metabolically reduced form, azaperol, in swine liver by gas chromatography/mass spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SOLID-PHASE EXTRACTION; MASS-SPECTROMETRY; WHOLE-BLOOD; TRANQUILIZERS; CARAZOLOL; HALOPERIDOL; IDENTIFICATION; BUTYROPHENONE; NEUROLEPTICS AB The method described confirms the use of the tranquilizer azaperone by detecting the parent compound and the metabolically reduced form, azaperol. Both are confirmed in swine liver at a target concentration of 10 ppb by gas chromatography/mass spectrometry (GC/MS) with electron ionization in the selected-ion-monitoring mode. Swine liver tissue is ground with dry ice. Acetonitrile is added to extract the drug from the tissue. Sodium chloride buffer is added to the extract in preparation for solid-phase extraction (SPE). The aqueous extract is loaded onto an SPE cartridge designed to extract acidic and neutral drug residues from biological matrixes. The cartridge is washed with methanol and conditioned with sodium phosphate buffer. Azaperone and azaperol residues are eluted with a 2% ammonium hydroxide in ethyl acetate. The extracts are evaporated to dryness under a stream of nitrogen and reconstituted in ethyl acetate for GC/MS analysis. A DB-I analytical column is used to separate the compounds prior to electron ionization. The parent ion, the base peak ion, and one diagnostic fragment ion are monitored for both compounds. The method was validated with fortified tissue samples containing both azaperone and azaperol. Azaperone-incurred tissues also were analyzed, and the presence of the parent drug and the metabolically reduced form, azaperol, was confirmed. C1 US FDA, Ctr Vet Med, Off Surveillance Compliance, Rockville, MD 20855 USA. RP Adam, LA (reprint author), US FDA, Ctr Vet Med, Off Surveillance Compliance, 7500 Standish Pl, Rockville, MD 20855 USA. NR 33 TC 4 Z9 4 U1 0 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1999 VL 82 IS 4 BP 815 EP 824 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 219GT UT WOS:000081600100005 PM 10444823 ER PT J AU Stehly, GR Gingerich, WH Kiessling, CR Cutting, JH AF Stehly, GR Gingerich, WH Kiessling, CR Cutting, JH TI A bridging study for oxytetracycline in the edible fillet of rainbow trout: Analysis by a liquid chromatographic method and the official microbial inhibition assay SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID FISH AB Oxytetracycline (OTC) is a drug approved by the U.S. Food and Drug Administration (FDA) to control certain diseases in salmonids and catfish. OTC is also a likely control agent for diseases of other fish species and for other diseases of salmonids and catfish not currently on the label. One requirement for FDA to extend and expand the approval of this antibacterial agent to other fish species is residue depletion studies. The current regulatory method for OTC in fish tissue, based on microbial inhibition, lacks sensitivity and specificity. To conduct residue depletion studies for OTC in fish with a liquid chromatographic method, a bridging study was required to determine its relationship with the official microbial inhibition assay. Triplicate samples of rainbow trout fillet tissue fortified with OTC at 0.3, 0.6, 1.2, 2.4, 4.8, and 9.6 ppm and fillet tissue with incurred OTC at approximately 0.75, 1.5, and 3.75 ppm were analyzed by high-performance liquid chromatography (HPLC) and the microbial inhibition assay. The results indicated that the 2 methods are essentially identical in the tested range, with mean coefficients of variation of 1.05% for the HPLC method and 3.94% for the microbial inhibition assay. C1 US Geol Survey, Upper Midwest Environm Sci Ctr, La Crosse, WI 54603 USA. US FDA, Denver Dist Lab, Denver, CO 80225 USA. RP Stehly, GR (reprint author), US Geol Survey, Upper Midwest Environm Sci Ctr, 2630 Fanta Reed Rd, La Crosse, WI 54603 USA. NR 14 TC 9 Z9 9 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1999 VL 82 IS 4 BP 866 EP 870 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 219GT UT WOS:000081600100011 PM 10444825 ER PT J AU Reina, RJ White, KD Firestone, D AF Reina, RJ White, KD Firestone, D TI Sterol and triterpene diol contents of vegetable oils by high-resolution capillary gas chromatography SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB An in-laboratory validated method for identification and quantitation of sterols and triterpene diols was used to determine the relative composition of identifiable sterols and triterpene diols in 13 vegetable oils and quantitate these components in multiple samples of 6 vegetable oils: extra virgin olive, pomace olive, corn, cottonseed, canola, and evening primrose oils. Erythrodiol, a triterpene diol present in all olive oils, was also found in cottonseed oil. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Reina, RJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 5 TC 8 Z9 8 U1 0 U2 4 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1999 VL 82 IS 4 BP 929 EP 935 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 219GT UT WOS:000081600100021 ER PT J AU Shaikh, B Schermerhorn, P Adam, LA von Bredow, JD AF Shaikh, B Schermerhorn, P Adam, LA von Bredow, JD TI Application of microbial receptor assay to quantitation of residues of spectinomycin in bovine milk and comparison with liquid chromatographic analysis SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Spectinomycin-contaminated bovine milk samples were assayed by liquid chromatographic (LC) and microbial receptor methods. LC involved a newly developed analytical method to quantitate the concentration of spectinomycin in the contaminated milk samples. The receptor assay used reagents and the reaction system used for the Charm II spectinomycin assay. Three standard curves (selected range, full range, and second-order polynomial) were plotted for the receptor assay and used to quantitate spectinomycin in contaminated milk samples. The levels of spectinomycin obtained by the receptor assay, using only the standard curve in the selected range, were comparable to the results obtained by LC analysis. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Shaikh, B (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 9 TC 2 Z9 2 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1999 VL 82 IS 4 BP 1002 EP 1005 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 219GT UT WOS:000081600100030 PM 10444837 ER PT J AU Royston, DD Richards, PQ AF Royston, DD Richards, PQ TI Comparison of fluence rate distributions made by side-firing fibers in an optical phantom SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE fluence rate distributions; optical phantom; side-firing fiber; exposure levels ID YAG LASER FIBER; BENIGN PROSTATIC HYPERPLASIA; NEODYMIUM; DOSIMETRY; PROSTATECTOMY; ABLATION; POWER; EXPERIENCE; DIFFERENCE; ANESTHESIA AB Side-firing fibers are used to provide coagulative therapy to the urologic tract. These fibers use different optical technologies to deflect the beam transverse to the fibers' optical axis. This produces emitted beams which differ in both beam direction and divergence angles. The relative optical performance of 13 fibers was studied in an optical phantom suspension. The fluence rate distribution created by each side-firing fiber was determined. The fluence rate distribution accounts for both the direct and spurious beams emitted from side-firing fibers as well as the light scattering produced by the target tissue. Based upon limited clinical dosimetry studies, the relative fluence rate distribution appears to indicate general exposure conditions for the evaluated fibers. (C) 1999 Society of Photo-Optical Instrumentation Engineers. [S1083-3668(99)00103-3]. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20850 USA. RP Royston, DD (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, HFZ-134,9200 Corp Blvd, Rockville, MD 20850 USA. NR 46 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JUL PY 1999 VL 4 IS 3 BP 352 EP 361 DI 10.1117/1.429943 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 229HY UT WOS:000082189400011 PM 23015256 ER PT J AU Herman, EH Zhang, J Lipshultz, SE Rifai, N Chadwick, D Takeda, K Yu, ZX Ferrans, VJ AF Herman, EH Zhang, J Lipshultz, SE Rifai, N Chadwick, D Takeda, K Yu, ZX Ferrans, VJ TI Correlation between serum levels of cardiac troponin-T and the severity of the chronic cardiomyopathy induced by doxorubicin SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; AMINO-ACID SEQUENCE; ADRIAMYCIN CARDIOTOXICITY; DIAGNOSTIC EFFICIENCY; HYPERTENSIVE RATS; RELEASE; ASSAY; MEMBRANES; DAMAGE; INJURY AB Purpose: To investigate, over a wide range of cumulative doxorubicin doses, the feasibility of using serum concentrations of cardiac troponin-T (cTnT) as a biomarker for doxorubicin-induced myocardial damage. Materials and Methods: Groups of spontaneously hypertensive rats (SHR) were given 1 mg/kg doxorubicin weekly for 2 to 12 weeks. Cardiomyopathy scores were assessed according to the method of Billingham and serum levels of cTnT were quantified by a noncompetitive immunoassay. Myocardial localization of cTnT was studied by immunohistochemical staining and confocal microscopy. Results: Increases in serum levels of cTnT (0.03 to 0.05 ng/mL) and myocardial lesions (cardiomyopathy scores of 1 or 1.5) were found in one out of five and two out of five SHR given 2 and 4 mg/kg doxorubicin, respectively. All animals given 6 mg/kg or more of doxorubicin had increases in serum cTnT and myocardial lesions. The average cTnT levels and the cardiomyopathy scores correlated with the cumulative dose of doxorubicin (0.13 v 0.4 ng/mL cTnT and scores of 1.4 v 3.0 in SHR given 6 and 12 mg/kg doxorubicin, respectively). Decreased staining for cTnT was observed in cardiac tissue from SHR receiving cumulative doses that caused only minimal histologic alterations (scores of 1 to 1.5), Staining for cTnT decreased simultaneously with increases in the severity of the cardiomyopathy scores. Conclusion: cTnT is released from doxorubicin-damaged myocytes. Measurements of serum levels of this protein seem to provide a sensitive means for assessing the early cardiotoxicity of doxorubicin. (C) 1999 by American Society of Clinical Oncology. C1 US FDA, Div Appl Pharmacol Res HFD910, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. Univ Rochester, Med Ctr, Div Pediat Cardiol, Rochester, NY 14642 USA. Boston Childrens Hosp, Dept Lab Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Herman, EH (reprint author), US FDA, Div Appl Pharmacol Res HFD910, Ctr Drug Evaluat & Res, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 33 TC 122 Z9 126 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1999 VL 17 IS 7 BP 2237 EP 2243 PG 7 WC Oncology SC Oncology GA 213GL UT WOS:000081264300038 PM 10561281 ER PT J AU Skinner, GE Solomon, HM Fingerhut, GA AF Skinner, GE Solomon, HM Fingerhut, GA TI Prevention of Clostridium botulinum type A, proteolytic B and E toxin formation in refrigerated pea soup by Lactobacillus plantarum, ATCC 8014 SO JOURNAL OF FOOD SCIENCE LA English DT Article DE biocontrol; Clostridium botulinum; storage stability; refrigerated food; Lactobacillus plantarum; pea soup ID LACTIC-ACID BACTERIA; EXTENDED DURABILITY; PROCESSED FOODS; INHIBITION; NITRITE; GROWTH; SAFETY; GRAVY; BACON; RISK AB The ability of Lactobacillus plantarum ATCC 8014 to inhibit Clostridium botulinum toxin production in pea soup was investigated, Soup containing C. botulinum spores (10(3)/g) with and without L. plantarum (10(6)/g) were evaluated. Soup containing only type A spores was toxic on days 1 and 2 when incubated at 35 degrees C and 25 degrees C, respectively. Soup containing only proteolytic type B spores was toxic on days 2 and 5 at 35 degrees C and 25 degrees C, respectively. Soup containing only type E spores was toxic at 25 degrees C, 15 degrees C, and 5 degrees C in 7, 7, and 63 days respectively. No toxin was found in soup containing C, botulinum spores plus L. plantarum at any temperature studied. C1 US FDA, Div Food Proc & Packaging, Food Proc Hazard Anal Branch, Natl Ctr Food Safety & Technol, Summit Agro, IL 60501 USA. US FDA, Washington, DC 20204 USA. IIT, Natl Ctr Food Safety & Technol, Summit Agro, IL 60501 USA. RP Skinner, GE (reprint author), US FDA, Div Food Proc & Packaging, Food Proc Hazard Anal Branch, Natl Ctr Food Safety & Technol, Summit Agro, IL 60501 USA. NR 25 TC 11 Z9 11 U1 0 U2 0 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA SUITE 300 221 N LASALLE ST, CHICAGO, IL 60601-1291 USA SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD JUL-AUG PY 1999 VL 64 IS 4 BP 724 EP 727 DI 10.1111/j.1365-2621.1999.tb15119.x PG 4 WC Food Science & Technology SC Food Science & Technology GA 229WD UT WOS:000082218000035 ER PT J AU Wilson, JA Margolin, AB AF Wilson, JA Margolin, AB TI The efficacy of three common hospital liquid germicides to inactivate Cryptosporidium parvum oocysts SO JOURNAL OF HOSPITAL INFECTION LA English DT Article DE Cryptosporidium parvum; infectivity; endoscopes ID DISINFECTION; ENDOSCOPES; MYCOBACTERIA; INFECTIONS AB We evaluated three commonly used hospital disinfectants against three concentrations of Cryptosporidium parvum oocysts (1.5 x 10(6), 1.5 x 10(5), 1.5 x 10(4)). A 10% phenol product, a 10% povidone-iodine product and a 2.5% glutaraldehyde product were tested against Cryptosporidium parvum oocysts without organic load. In-vitro excystation was used to determine viability and a cell culture assay was used to determine infectivity of germicide-treated oocysts. A 2.5% glutaraldehyde product was the most effective in halting excystation of sporozoites and infection in cell monolayers. However, this occurred only at the longest exposure time of 10 h and with the lowest concentration of oocysts (1.5 x 10(4)). The 10% phenol product and the 10% povidone-iodine product also decreased excystation, but were unable to halt infection. Although the ability of C. parvum to withstand chemical treatment is well known, the ability of oocysts to remain viable and infectious after a 10 h treatment in glutaraldehyde is cause for concern. Endoscopic equipment that may come into contact with these organisms cannot be immersed into glutaraldehyde for this length of time due to its corrosive nature. Thus, the results of this research are cause for concern in hospital disinfection units. C1 US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. Univ New Hampshire, Dept Microbiol, Durham, NH 03824 USA. RP Wilson, JA (reprint author), US FDA, Winchester Engn & Analyt Ctr, 109 Holton St, Winchester, MA 01890 USA. NR 21 TC 14 Z9 15 U1 0 U2 4 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-6701 J9 J HOSP INFECT JI J. Hosp. Infect. PD JUL PY 1999 VL 42 IS 3 BP 231 EP 237 DI 10.1053/jhin.1999.0553 PG 7 WC Infectious Diseases SC Infectious Diseases GA 218AQ UT WOS:000081531500008 PM 10439996 ER PT J AU Boykins, RA Mahieux, R Shankavaram, UT Gho, YS Lee, SF Hewlett, IK Wahl, LM Kleinman, HK Brady, JN Yamada, KM Dhawan, S AF Boykins, RA Mahieux, R Shankavaram, UT Gho, YS Lee, SF Hewlett, IK Wahl, LM Kleinman, HK Brady, JN Yamada, KM Dhawan, S TI Cutting edge: A short polypeptide domain of HIV-1-Tat protein mediates pathogenesis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TYPE-1 TAT PROTEIN; TUMOR-NECROSIS-FACTOR; ENDOTHELIAL-CELLS; T-CELLS; ACTIVATION; MONOCYTES; BINDING; KINASE; TRANSACTIVATION; TRANSCRIPTION AB HIV-1 encodes the transactivating protein Tat, which is essential for virus replication and progression of HIV disease. However, Tat has multiple domains, and consequently the molecular mechanisms by which it acts remain unclear. In this report, we provide evidence that cellular activation by Tat involves a short core domain, Tat(21-40), containing only 20 aa including seven cysteine residues highly conserved in most HIV-1 subtypes, Effective induction by Tat(21-40) of both NF-kappa B-mediated HIV replication and TAR-dependent transactivation of HIV-long terminal repeat indicates that this short sequence is sufficient to promote HIV infection, Moreover, Tat(21-40) possesses potent angiogenic activity, further underscoring its role in HIV pathogenesis. These data provide the first demonstration that a 20-residue core domain sequence of Tat is sufficient to transactivate, induce HIV replication, and trigger angiogenesis, This short peptide sequence provides a potential novel therapeutic target for disrupting the functions of Tat and inhibiting progression of HIV disease. C1 US FDA, Ctr Biol Evaluat & Res, Immunopathogenesis Sect, Mol Virol Lab, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Lab Parasit Biol & Biochem, Rockville, MD 20852 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. NIDCR, Immunopathol Sect, Bethesda, MD 20892 USA. NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Dhawan, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Immunopathogenesis Sect, Mol Virol Lab, 1401 Rockville Pike HFM-315, Rockville, MD 20852 USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 29 TC 34 Z9 37 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 JUL 1 PY 1999 VL 163 IS 1 BP 15 EP 20 PG 6 WC Immunology SC Immunology GA 208CY UT WOS:000080973700004 PM 10384093 ER PT J AU Balish, E Wagner, RD Vazquez-Torres, A Jones-Carson, J Pierson, C Warner, T AF Balish, E Wagner, RD Vazquez-Torres, A Jones-Carson, J Pierson, C Warner, T TI Mucosal and systemic candidiasis in IL-8Rh(-/-) BALB c mice SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE chemokines; Candida albicans; neutrophils; chemotaxis ID IL-8 RECEPTOR HOMOLOG; INTERLEUKIN-8 IL-8; ALBICANS HYPHAE; SCID MICE; NEUTROPHIL; RESISTANCE; MYELOPEROXIDASE; INVOLVEMENT; MACROPHAGES; MODEL AB Germ-free BALB/c mice, genetically engineered to be deficient for interleukin-8 (IL-8) receptor homolog (IL-8Rh(-/-)), were more susceptible to gastric candidiasis after oral challenge and to acute systemic candidiasis after intravenous challenge than IL-8Rh(+/+) controls. In comparison to IL-8Rh(+/+) mice, the IL-8Rh(-/-) mice had slower influx of polymorphonuclear neutrophils (PMN) into Candida albicans-infected tissues and a lo,ver percentage of PMN in peritoneal exudate cells (PEC) elicited with heat-killed C. albicans. PEC front IL-8Rh(-/)- mice exhibited less luminol-dependent chemiluminescence in response to C, albicans and did not kill C. albicans hyphae as well as PEC from IL-8Rh(+/+) mice. C. albicans-colonized IL-8Rh(-/-) mice showed no histological evidence of systemic candidiasis. These results suggest a role for the IL-8Rh iu murine resistance to gastric and acute systemic candidiasis, but not in resistance to systemic candidiasis of endogenous origin. C1 Univ Wisconsin, Sch Med, Dept Surg, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Dept Surg Pathol, Madison, WI 53706 USA. Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Denver, CO USA. Natl Jewish Med & Res Ctr, Dept Med, Denver, CO USA. RP Balish, E (reprint author), Univ Wisconsin, Sch Med, Dept Surg, 1300 Univ Ave,4638 MSC, Madison, WI 53706 USA. FU NIDCR NIH HHS [DE-09659] NR 31 TC 35 Z9 37 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 JUL PY 1999 VL 66 IS 1 BP 144 EP 150 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 215YW UT WOS:000081413900019 PM 10411002 ER PT J AU Suleiman, OH Spelic, DC Conway, B Hart, JC Boyce, PR Antonsen, RG AF Suleiman, OH Spelic, DC Conway, B Hart, JC Boyce, PR Antonsen, RG TI Radiographic trends of dental offices and dental schools SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID IMAGE QUALITY AB Background. A survey of private practise facilities in the United States that perform dental radiography was conducted in 1993 and repeated in dental schools in 1995-1996. Methods. Both surveys were conducted as part of the Nationwide Evaluation of X-ray Trends, or NEXT, survey program. A representative sample of dental facilities from each participating state were surveyed, and data on patient radiation exposure, radiographic technique, film-image quality, film-processing quality and darkroom fog were collected. Results. The authors found that dental schools use E-speed film more frequently than do private practising facilities. The use of E-speed film and better film processing by ental schools resulted in lower patient radiation exposures without sacrificing image quality. The authors also found that dental darkrooms had lower ambient fog levels than did those of private practise facilities. Conclusions. The distribution for the 1993 NEXT survey facilities was greater than that observed for dental schools for radiation exposure, film-processing quality and darkroom fog. Dental schools, in general, had better film quality and lower radiation exposures than did private practise facilities. Practise Implications. Facilities need to emphasize better quality processing and the use of E-speed film to reduce patient exposure and improving image quality. C1 Publ Hlth Serv, Radiat Programs, Div Mammog Qual, US Dept Hlth & Human Serv,US Food & Drug Adm, Rockville, MD 20850 USA. Minnesota Dept Publ Hlth, Radiat Control Sect, Div Environm Hlth, St Paul, MN USA. US FDA, Denver Dist Off, Denver, CO USA. RP Suleiman, OH (reprint author), Publ Hlth Serv, Radiat Programs, Div Mammog Qual, US Dept Hlth & Human Serv,US Food & Drug Adm, 1350 Picard Dr,HFZ-240, Rockville, MD 20850 USA. NR 18 TC 7 Z9 7 U1 0 U2 0 PU AMER DENTAL ASSOC 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 JUL PY 1999 VL 130 IS 7 BP 1104 EP 1110 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 216YV UT WOS:000081472800027 PM 10422407 ER PT J AU Payne, MA Baynes, RE Sundlof, SF Craigmill, A Webb, AI Riviere, JE AF Payne, MA Baynes, RE Sundlof, SF Craigmill, A Webb, AI Riviere, JE TI Drugs prohibited from extralabel use in food animals SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Editorial Material ID CLENBUTEROL; CHLORAMPHENICOL; ADENOCARCINOMA; NITROFURAZONE; RESIDUES; VAGINA; CALVES C1 Univ Calif Davis, Coll Agr & Environm Sci, Environm Toxicol Extens, FARAD, Davis, CA 95616 USA. N Carolina State Univ, Coll Vet Med, Ctr Cutaneous Toxicol & Residue Pharmacol, FARAD, Raleigh, NC 27606 USA. Univ Florida, Coll Vet Med, Dept Physiol Sci, FARAD, Gainesville, FL 32610 USA. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Payne, MA (reprint author), Univ Calif Davis, Coll Agr & Environm Sci, Environm Toxicol Extens, FARAD, Davis, CA 95616 USA. RI Riviere, Jim/A-9210-2008 OI Riviere, Jim/0000-0001-8412-9650 NR 49 TC 28 Z9 30 U1 0 U2 2 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 JUL 1 PY 1999 VL 215 IS 1 BP 28 EP 32 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA 211WL UT WOS:000081184800016 PM 10490381 ER PT J AU Hanno, PM AF Hanno, PM TI Activation of the kallikrein kinin system in interstitial cystitis - Comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 US FDA, Div Reprod & Urol Drug Prod, Rockville, MD 20857 USA. RP Hanno, PM (reprint author), US FDA, Div Reprod & Urol Drug Prod, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 1999 VL 162 IS 1 BP 134 EP 134 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 204FP UT WOS:000080753700030 ER PT J AU LaBorde, JB Wall, KS Bolon, B Kumpe, TS Patton, R Zheng, Q Kodell, R Young, JF AF LaBorde, JB Wall, KS Bolon, B Kumpe, TS Patton, R Zheng, Q Kodell, R Young, JF TI Haematology and serum chemistry parameters of the pregnant fat SO LABORATORY ANIMALS LA English DT Article DE clinical pathology; serum chemistry; haematology; pregnant rat; lactating rat; fetal serum; amniotic fluid ID CLINICAL PATHOLOGY; RAT AB This study describes the baseline haematology and serum chemistry values found in nonpregnant, pregnant (gestational days [GD] 2-21) and lactating (postnatal days 1-9) Sprague Dawley rats (n =3-10/day) from the NCTR breeding colony of Crl:COBS CD(SD)BR strain. Maternal body weights on GD0 ranged from 250 to 300 g. Multiple analytes were measured in both whole blood and serum of dams. Amniotic fluid, fetal serum, and postnatal pup serum analyte values were also acquired. Maternal blood was collected from the heart under subterminal carbon dioxide (CO2) anaesthesia. Most pregnant dam blood values were not appreciably different from values for non-pregnant dams until near term; near-term values for some analytes (red blood cells, haemoglobin, haematocrit, mean corpuscular haemoglobin concentration, alkaline phosphatase, albumin, total protein, glucose, total bilirubin, sodium, and chloride) decreased but returned to near-normal values soon after delivery. The most dramatic change was a three-fold elevation of serum triglyceride levels near term with a subsequent decrease at birth. Most serum chemistry analytes measured in progeny increased after birth except for alkaline phosphatase, calcium and potassium levels which decreased. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Pathol Associates Int, Jefferson, AR 72079 USA. RP Young, JF (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, 3900 NCTR Rd,HFT-20, Jefferson, AR 72079 USA. NR 14 TC 28 Z9 29 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1M 8AE, ENGLAND SN 0023-6772 J9 LAB ANIM JI Lab. Anim. PD JUL PY 1999 VL 33 IS 3 BP 275 EP 287 DI 10.1258/002367799780578156 PG 13 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 232EN UT WOS:000082357200012 PM 10780848 ER PT J AU Abbondanzo, SL Young, VL Wei, MQ Miller, FW AF Abbondanzo, SL Young, VL Wei, MQ Miller, FW TI Silicone gel-filled breast and testicular implant capsules: A histologic and immunophenotypic study SO MODERN PATHOLOGY LA English DT Article DE breast; capsule; immunohistochemistry; silicone implants; testicle ID SYNOVIAL METAPLASIA; GENE-EXPRESSION; BCL-X; TISSUE; AUGMENTATION; WOMEN; ACCUMULATION; CONTROVERSY; PROSTHESES; APOPTOSIS AB The immunophenotypic characteristics of silicone gel-filled breast and testicular implant capsules have not been well described. Therefore, we studied 17 paraffin-embedded tissue sections from 9 breast implant patients and 1 testicular implant patient to assess the type and extent of inflammatory responses present. Immunohistochemical analyses were performed on paraffin-embedded tissue sections for expression of CD20, CD45RO, beta F1, CD68, CD44, kappa and lambda immunoglobulin light chains, and bcl-X-L (a member of the bcl-2 family of proteins involved in apoptosis). The most common histologic features included prominent T-cell and foamy macrophage reactions with foreign body giant cells and granulomas in a dense fibrovascular connective tissue. Foci of polyclonal plasma cells and acute inflammatory cells were variably present. in one case, there was reactive germinal center formation, a novel finding. A "pseudosynovium" at the implant capsule interface was present in the majority of cases as previously described; it showed reactivity with CD68. Thin strands of highly refractile, nonpolarizable material, consistent with silicone, were regularly noted in intra- and extracellular locations. The immunohistochemical results included reactivity of the majority of lymphocytes with CD45RO and/or beta F1 (confirming an anamnestic reactive T-cell phenotype), and reactivity of the macrophages, giant cells, and "pseudosynovium" with the macrophage/histiocyte marker, CD68. The reactive germinal centers were positive for CD20. Reactivity for CD44, an activation and intracellular adhesion marker, was frequently observed in the foamy macrophages and foreign body giant cells and has not been previously reported. The plasma cells demonstrated polyclonal immunoglobulin light-chain reactivity, consistent with a reactive process. These findings suggest that silicone implants induce chronic inflammatory responses in many adjacent capsules, which consist of anamnestically responding T cells, reactive B-lymphocytes, and macrophages. C1 Armed Forces Inst Pathol, Dept Hematopathol, Washington, DC 20306 USA. Washington Univ, Sch Med, Dept Plast & Reconstruct Surg, St Louis, MO USA. US FDA, Ctr Biol Evaluat & Res, Lab Mol & Dev Immunol, Bethesda, MD USA. RP Abbondanzo, SL (reprint author), Armed Forces Inst Pathol, Dept Hematopathol, 6825 16th St NW, Washington, DC 20306 USA. OI Miller, Frederick/0000-0003-2831-9593 NR 30 TC 31 Z9 33 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JUL PY 1999 VL 12 IS 7 BP 706 EP 713 PG 8 WC Pathology SC Pathology GA 218NY UT WOS:000081559700007 PM 10430275 ER PT J AU Centeno, JA Mullick, FG Panos, RG Miller, FW Valenzuela-Espinoza, A AF Centeno, JA Mullick, FG Panos, RG Miller, FW Valenzuela-Espinoza, A TI Laser-Raman microprobe identification of inclusions in capsules associated with silicone gel breast implants SO MODERN PATHOLOGY LA English DT Article DE breast implants; capsular tissues; foreign materials; Raman microprobe; silicone gel ID CONNECTIVE-TISSUE DISEASE; INFRARED MICROSPECTROSCOPY; AUGMENTATION MAMMOPLASTY; FIBROUS CAPSULES; ANIMAL-MODEL; MICROANALYSIS; MICROSCOPY AB Raman spectroscopy (the analysis of scattered photons after excitation with a monochromatic light source) provides a nondestructive method for identifying organic and inorganic materials on the basis of the molecule's characteristic spectrum of vibrational frequencies. Although the technique has been predominantly applied in sciences other than pathology, the recent advent of high-quality microscope optics coupled to optical Raman spectrometers (a variation known as a Raman microprobe) rendered this technique amenable to applications in human pathology. In the Raman microprobe, a laser beam is focused on a spot approximately 1 mu m in diameter on the surface of the sample, e.g., tissue, and the scattered light is collected and analyzed. In this investigation, we used the Raman microprobe for the identification of foreign materials in breast implant capsular tissues. The characteristic silicone group frequencies associated with the silicon-oxygen stretch, the silicone-carbon stretch, the silicon-methyl and the methyl carbon-hydrogen stretch frequencies were used to identify polydimethylsiloxane and to define chemical differences among the various other implant-related inclusions. All of the inclusions were positively identified in a series of 44 capsules from silicone gel-filled implants: polydimethylsiloxane was found in 44 of 44 capsules surrounding silicone gel-filled implants; polyurethane was seen in 4 of 4 capsules around polyurethane foam-coated gel-filled implants; 4 of 4 capsules enveloping Dacron patch gel-filled implants revealed Dacron; and talc was identified in 8 of these 44 capsules. Raman microspectroscopy provides a rapid, accurate, and sensitive method for identifying inclusions associated with silicone and other implant materials in tissue. C1 Armed Forces Inst Pathol, Dept Environm & Toxicol Pathol, Div Environm Pathol, Washington, DC 20306 USA. USN, Med Ctr, Div Plast Surg, San Diego, CA 92152 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Hosp Gen Tijuana, Inst Serv Salud, Tijuana, Mexico. RP Centeno, JA (reprint author), Armed Forces Inst Pathol, Dept Environm & Toxicol Pathol, Div Environm Pathol, Washington, DC 20306 USA. OI Miller, Frederick/0000-0003-2831-9593 NR 24 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JUL PY 1999 VL 12 IS 7 BP 714 EP 721 PG 8 WC Pathology SC Pathology GA 218NY UT WOS:000081559700008 PM 10430276 ER PT J AU Husain, SR Kreitman, RJ Pastan, I Puri, RK AF Husain, SR Kreitman, RJ Pastan, I Puri, RK TI Interleukin-4 receptor-directed cytotoxin therapy of AIDS-associated Kaposi's sarcoma tumors in xenograft- model SO NATURE MEDICINE LA English DT Article ID CIRCULARLY PERMUTED INTERLEUKIN-4; HUMAN CHORIONIC-GONADOTROPIN; HUMAN-IMMUNODEFICIENCY-VIRUS; ENDOTHELIAL GROWTH-FACTOR; PSEUDOMONAS EXOTOXIN; CELL-LINE; CARCINOMA-CELLS; EXPRESSION; TOXIN; INFECTION AB The elusive and enigmatic origin of AIDS-associated Kaposi's sarcoma (AIDS-KS) makes it a complex tumor and therefore difficult to treat. Here we demonstrate that AIDS-KS cells express surface interleukin-4 (IL-4) receptors, and that IL-4 toxin (IL-4(38-37)-PE38KDEL) is specifically cytotoxic to these cells. Intratumoral, intraperitoneal and intravenous administration of IL-4 toxin in nude mice with established subcutaneous AIDS-KS tumors caused considerable antitumor activity in a dose-dependent manner, with highest dose producing durable complete responses. Metabolic changes, including cachexia and lymphopenia, induced by KS tumors were prevented by IL-4 toxin treatment. This report establishes IL-4(38-37)-PE38KDEL as an experimental therapeutic agent for the treatment of AIDS-KS. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. NCI, Div Basic Sci, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. NR 48 TC 47 Z9 49 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 JUL PY 1999 VL 5 IS 7 BP 817 EP 822 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 224YB UT WOS:000081926600038 PM 10395328 ER PT J AU Holson, RR Adams, J Ferguson, SA AF Holson, RR Adams, J Ferguson, SA TI Gestational stage-specific effects of retinoic acid exposure in the rat SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE retinoids; all-trans retinoic acid; cerebellum; dopamine ID MATERNAL HYPERVITAMINOSIS-A; VITAMIN-A; BEHAVIORAL TERATOLOGY AB Although, or perhaps because, retinoids are among the earliest known behavioral teratogens, there is still little agreement about the behavioral effects of stage-specific exposure to these compounds. In these studies, pregnant albino rats were gavaged once daily with retinoic acid (RA) for 3 consecutive gestational days (GD), GD 8-10, GD 11-13, or GD 14-16. Dose levels were maximal levels compatible with survival (10, 2.5, or 12.5 mg/kg RA, over GD 8-10, 11-13, and 14-16, respectively). Two studies were conducted. The first assessed the effects of RA exposure on GD 8-10 or 14-16 on regional brain weight and on a large behavioral test battery. The second study assessed the effects of RA exposure on GD 11-13 or GD 14-16 on many of the same variables. Taken together with an earlier study of the behavioral effects of GD 11-13 RA exposure, these studies permit the following conclusions. 1) RA exposure at the above doses at any of the three exposure periods produced an apparent reduction in amphetamine-induced open field activity. 2) RA exposure on GD 14-16 but not earlier produced a robust, replicable rotarod deficit in exposed offspring. 3) RA exposure on GD 11-13, but not earlier or later, increased daytime activity in residential running wheels. 4) RA exposure on GD 11-13 or GD 14-16 but not GD 8-10 reduced weight of cerebellum. 5) No RA effect at any exposure period was seen on maze learning, activity in novel open fields, or on auditory startle. (C) 1999 Elsevier Science Inc. All rights reserved. C1 New Mexico Tech, Dept Psychol, Socorro, NM 87801 USA. Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR USA. RP Holson, RR (reprint author), New Mexico Tech, Dept Psychol, 801 LeRoy Pl, Socorro, NM 87801 USA. NR 37 TC 22 Z9 22 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 1999 VL 21 IS 4 BP 393 EP 402 DI 10.1016/S0892-0362(99)00007-0 PG 10 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 219VD UT WOS:000081627100007 PM 10440483 ER PT J AU Amato, S Budihandojo, R Raybuck, B Vuolo-Schuessler, L AF Amato, S Budihandojo, R Raybuck, B Vuolo-Schuessler, L TI Technical report No. 31 - Validation and qualification of computerized laboratory data acquisition systems SO PDA JOURNAL OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY LA English DT Article C1 SmithKline Beecham Pharmaceut, Piscataway, NJ 08854 USA. Alcon Labs, Ft Worth, TX 76134 USA. Baxter Healthcare Corp, Deerfield, IL 60015 USA. Johnson & Johnson Inc, New Brunswick, NJ 08903 USA. US FDA, Rockville, MD 20857 USA. Amer Red Cross, Washington, DC 20006 USA. Whitehall Robins Hlth Care, Madison, NJ USA. G&W Labs, S Plainfield, NJ 07080 USA. Gilead Sci Inc, Foster City, CA 94404 USA. Genentech Inc, S San Francisco, CA 94080 USA. Berlex Labs Inc, Wayne, NJ 07470 USA. Berlex Biosci Inc, Richmond, CA USA. Schering Plough Corp, Madison, NJ 07940 USA. Cytogen Corp, Princeton, NJ 08540 USA. Bayer Corp, Pittsburgh, PA 15219 USA. Merck & Co Inc, Whitehouse Stn, NJ 08889 USA. Ciba Geigy Corp, Newport, DE 19804 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Hewlett Packard Co, Analyt Div, Palo Alto, CA 94304 USA. RP Amato, S (reprint author), SmithKline Beecham Pharmaceut, Piscataway, NJ 08854 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU PARENTERAL DRUG ASSOC INC PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 620, BETHESDA, MD 20814 USA SN 1076-397X J9 PDA J PHARM SCI TECH JI PDA J. Pharm. Sci. Technol. PD JUL-AUG PY 1999 VL 53 IS 4 SU S BP 1 EP + PG 13 WC Engineering, Biomedical; Pharmacology & Pharmacy SC Engineering; Pharmacology & Pharmacy GA 246XM UT WOS:000083190200001 ER PT J AU Jackson, AJ Ouderkirk, LA AF Jackson, AJ Ouderkirk, LA TI Truncated area under the curve as a measure of relative extent of bioavailability: Evaluation using experimental data and Monte Carlo simulations SO PHARMACEUTICAL RESEARCH LA English DT Letter C1 US FDA, CDER, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Jackson, AJ (reprint author), US FDA, CDER, Off Pharmaceut Sci, Rockville, MD 20857 USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD JUL PY 1999 VL 16 IS 7 BP 1144 EP 1145 DI 10.1023/A:1011920824159 PG 2 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 223JJ UT WOS:000081837700028 PM 10450946 ER PT J AU Pletnikov, MV Rubin, SA Schwartz, GJ Moran, TH Sobotka, TJ Carbone, KM AF Pletnikov, MV Rubin, SA Schwartz, GJ Moran, TH Sobotka, TJ Carbone, KM TI Persistent neonatal Borna disease virus (BDV) infection of the brain causes chronic emotional abnormalities in adult rats SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE Borna; anxiety; fear; hippocampus; cerebellum; rat ID SPONTANEOUSLY HYPERTENSIVE RATS; ACOUSTIC STARTLE RESPONSE; BEHAVIORAL REACTIVITY; MOTIVATED BEHAVIORS; LESIONS; FEAR; SENSITIZATION; SYSTEM; SCHIZOPHRENIA; ANXIETY AB Neonatal Borna disease virus (BDV) brain infection results in selective developmental damage to the hippocampal dentate gyrus and the cerebellum. When mature, neonatally BDV-infected rats show extreme locomotor hyperactivity and reduced freezing behavior in novel environments. Traditional interpretation of both of these behavioral abnormalities would suggest decreased anxiety in infected rats compared to normal animals. However, it also possible that the locomotor hyperactivity in infected rats reflects higher rather than reduced anxiety, and is the result of increased escape responses to aversive stimuli. The present experiments were undertaken to test a hypothesis about elevated anxiety in neonatally BDV-infected adult Lewis rats by studying their species-specific fear-related responses. Compared to normal subjects, BDV-infected rats exhibited locomotor hyperactivity and elevated defecation in a highly aversive, brightly lit open field. As expected, in a less aversive, dimly lit open field, uninfected controls increased ambulation, whereas infected rats significantly decreased locomotor activity and defecation. Unlike uninfected rats, BDV-infected rats exhibited an attenuated freezing response immediately after loud auditory stimuli. On the contrary, immediate freezing responses following footshock were comparable in the two groups of animals indicating an intact ability to freeze in BDV-infected rats. Despite a decreased baseline startle responsiveness, BDV-infected rats demonstrated increased sensitization of the startle response by preceding footshocks, suggesting a tendency toward elevated escape responses. Compared to normal subjects, BDV-infected rats showed decreased conditional freezing and elevated conditional defecation response in the context previously paired with aversive stimulation indicating sparing of an autonomic component of fear conditioning. The findings indicate that neonatally BDV-infected adult rats are hyperreactive to aversive stimuli, possibly as a result of chronic emotional abnormalities. (C) 1999 Elsevier Science Inc. C1 US FDA, Ctr Biol Evaluat & Res, Lab Pediat & Resp Viral Dis, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. US FDA, Neurobehav Toxicol Team, CFSAN, Laurel, MD 20708 USA. RP Pletnikov, MV (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Pediat & Resp Viral Dis, Bldg 29A,Rm 1A-21,HFM-460,8800 Rockville Pike, Bethesda, MD 20892 USA. FU NIMH NIH HHS [MH48948] NR 51 TC 43 Z9 43 U1 1 U2 2 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 JUL PY 1999 VL 66 IS 5 BP 823 EP 831 DI 10.1016/S0031-9384(99)00021-9 PG 9 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 210AL UT WOS:000081082900014 PM 10405111 ER PT J AU Zhang, J Duarte, CG Ellis, S AF Zhang, J Duarte, CG Ellis, S TI Contrast medium- and mannitol-induced apoptosis in heart and kidney of SHR rats SO TOXICOLOGIC PATHOLOGY LA English DT Article DE cardiotoxicity; nephrotoxicity; terminal deoxynucleotidyl transferase-mediated [TdT] dUTP nick-end labeling (TUNEL); Bcl-2; Bax; p53; osmolality ID SPONTANEOUSLY HYPERTENSIVE RATS; RENAL-DISEASE; RADIOCONTRAST; FAILURE; NEPHROTOXICITY; CARDIOMYOCYTES; NEPHROPATHY; ENDOTHELIN; EXPRESSION; PRESSURE AB The induction of apoptosis by contrast media (CM) and mannitol (M) was investigated in the hearts and kidneys of 12-mo-old male SHR rats. Ten groups of 3 SHR rats received a dose of 5 ml/kg of one of the following: Hypaque (H)-30, H-60, H-76, Omnipaque (O)-140, O-350, mannitol (M)-4%, M-9%, M-19%, M-27%, or saline (S). DNA fragmentation was detected using the terminal deoxynucleotidyl transferase-mediated [TdT] dUTP nick-end labeling (TUNEL) method, and the morphology characteristics of apoptosis were confirmed in cardiac and renal cells. The immunoreactivities of Bcl-2, Bax, and p53 were assessed immunohistochemically in the kidneys. Apoptosis occurred in cardiac myocytes and renal tubular and glomerular cells as well as in vascular endothelial and smooth muscle cells of the heart and kidneys. The high frequency of apoptosis correlated significantly with the increase in the osmolality of the H, O, and hi. The increased Bax, the increased p53, and the decreased Bcl-2 immunoreactivities were detected in H- or O-treated, but not in M-treated, rats. These findings suggest that CM and M activate cardiac and renal apoptosis by different mechanisms and that the apoptotic process may be implicated in acute heart and renal damage. C1 US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. RP Zhang, J (reprint author), US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, HFD-910,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 37 TC 28 Z9 29 U1 0 U2 1 PU SOC TOXICOLOGIC PATHOLOGISTS PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JUL-AUG PY 1999 VL 27 IS 4 BP 427 EP 435 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA 222AD UT WOS:000081759300006 PM 10485823 ER PT J AU Tomazic-Jezic, VJ Lucas, AD Lamanna, A Stratmeyer, ME AF Tomazic-Jezic, VJ Lucas, AD Lamanna, A Stratmeyer, ME TI Quantitation of natural rubber latex proteins: Evaluation of various protein measurement methods SO TOXICOLOGY METHODS LA English DT Article DE allergy; natural rubber latex; protein quantitation ID ALLERGEN AB The allergy to natural rubber latex (NRL) proteins is a significant occupational health hazard. The elimination or reduction of the water-soluble proteins from finished NRL products is one approach aimed at decreasing further sensitization and reactions to these allergens. To achieve this goal, a reliable protein measurement method is required. Several published and widely used methods for protein measurement in finished NRL products demonstrate major inconsistencies in the quantification of extractable NRL proteins in, comparison to the Kjeldahl nitrogen assay and the gravimetrically determined reference. Multiple protein assays and several reference proteins were examined to determine the most suitable method for the quantitation of soluble NRL proteins. Among the reference proteins evaluated (BSA, BGG, and OA), OA was found to correlate best with gravimetrically determined levels of NRL proteins. Of the protein assays evaluated (Bradford, BCA, and Lowry), the modified Lowry assay demonstrated the best uniformity and a good correlation with the Kjeldahl nitrogen assay. The commercial Lowry assay kit, Bio-Rad DC Protein Assay, was comparable to the laboratory-prepared reagents, and both demonstrated good sensitivity and precision. Altering a sample to reagent ratio increased the sensitivity of the test. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Tomazic-Jezic, VJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-112,12709 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 17 TC 7 Z9 7 U1 2 U2 7 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 1051-7235 J9 TOXICOL METHOD JI Toxicol. Method. PD JUL-SEP PY 1999 VL 9 IS 3 BP 153 EP 164 PG 12 WC Toxicology SC Toxicology GA 231AG UT WOS:000082283400003 ER PT J AU Duhart, BT Zhang, D Deck, J Freeman, JP Cerniglia, CE AF Duhart, BT Zhang, D Deck, J Freeman, JP Cerniglia, CE TI Biotransformation of protriptyline by filamentous fungi and yeasts SO XENOBIOTICA LA English DT Article ID CUNNINGHAMELLA-ELEGANS; MICROBIAL MODELS; MAMMALIAN METABOLISM; FUSARIUM-OXYSPORUM; AMITRIPTYLINE; FUROSEMIDE AB 1. The potential of various fungi to metabolize protriptyline tan extensively used antidepressant was studied to investigate similarities between mammalian and microbial metabolism. 2. Metabolites produced by each organism were isolated by high-pressure liquid chromatography and identified by nuclear magnetic resonance and mass spectrometry. The metabolites identified in one or more fungi were 2-hydroxyprotriptyline, N-desmethylprotriptyline, N-acetylprotriptyline, N-acetoxyprotriptyline, 14-oxo-N-desmethylprotriptyline, 2-hydroxy-acetoxyprotriptyline and 3-5-hydrodibenzo[bf][7]annulen-5-propanoic acid. 3. Among 27 filamentous fungi and yeast species screened, Fusarium oxysporum f. sp. pini 2380 metabolized 97% of the protriptyline added. Several other fungi screened gave significant metabolism of protriptyline, including Cunninghamella echinulata ATCC 42616 (67%), C. elegans ATCC 9245 (17%), C. elegans ATCC 36112 (22%,), C phaeospora ATCC 22110 (50%), F. moniliforme MRC-826 (33%) and F. solani 3179 (12%) 4. F. oxysporum f, sp. pini produced phase I and phase II metabolites and thus is a suitable microbial model for protriptyline metabolism. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 22 TC 14 Z9 15 U1 6 U2 10 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD JUL PY 1999 VL 29 IS 7 BP 733 EP 746 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 227MT UT WOS:000082084700005 PM 10456691 ER PT J AU Hay, A Gust, I Hampson, A Nerome, K Lim, W Chan, M Saw, TA Mak, KH Canas, L Guo, Y AF Hay, A Gust, I Hampson, A Nerome, K Lim, W Chan, M Saw, TA Mak, KH Canas, L Guo, Y TI Update: Influenza activity - United States and worldwide, 1998-99 season, and composition of the 1999-2000 influenza vaccine (Reprinted from MMWR, vol 48, pg 374, 1999) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 WHO Collaborating Ctr Reference & Res Influenza, Parkville, Vic, Australia. Natl Inst Infect Dis, WHO Collaborating Ctr Reference & Res Influenza, Tokyo, Japan. Dept Hlth Hong Kong, Special Adm Reg, Hong Kong, Peoples R China. Natl Ctr Prevent Med, Inst Virol, Beijing, Peoples R China. Armstrong Lab, Brooks AFB, TX 78235 USA. WHO, Natl Influenza Ctr, Div Emerging & Other Communicable Dis Surveilianc, CH-1211 Geneva, Switzerland. US FDA, Ctr Biol Evaluat & Res, Div Virol, Rockville, MD 20857 USA. CDC, Natl Resp Enter Virus Surveillance Syst Collabora, Atlanta, GA 30333 USA. CDC, WHO Collaborating Labs, Atlanta, GA 30333 USA. CDC, WHO Collaborating Ctr Reference & Res Influenza, Influenza Branch,Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. CDC, Sentinel Phys Influenza Surveillance Syst, Atlanta, GA 30333 USA. CDC, Sentinel Phys Influenza Surveillance Syst, Atlanta, GA 30333 USA. RP Hay, A (reprint author), Natl Inst Med Res, WHO Collaborating Ctr Reference & Res Influenza, Mill Hill, London NW7 1AA, England. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 16 PY 1999 VL 281 IS 23 BP 2178 EP 2180 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 204RB UT WOS:000080777000013 ER PT J AU Aoki, Y Jaffe, ES Chang, Y Jones, K Teruya-Feldstein, J Moore, PS Tosato, G AF Aoki, Y Jaffe, ES Chang, Y Jones, K Teruya-Feldstein, J Moore, PS Tosato, G TI Angiogenesis and hematopoiesis induced by Kaposi's sarcoma-associated herpesvirus-encoded interleukin-6 SO BLOOD LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Hematology CY DEC 05, 1998 CL MIAMI BEACH, FLORIDA SP Amer Soc Hematol ID ENDOTHELIAL GROWTH-FACTOR; MULTICENTRIC CASTLEMANS DISEASE; PRIMARY EFFUSION LYMPHOMA; B-CELL GROWTH; DNA-SEQUENCES; MYELOMA CELLS; EXPRESSION; MICE; CYTOKINE; VIRUS AB Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8 [HHV-8]) is a herpesvirus linked to the development of Kaposi's sarcoma (KS), primary effusion lymphoma, and a proportion of Castleman's disease. KSHV encodes viral interleukin-6 (vIL-6), which is structurally homologous to human and murine IL-6, The biological activities of vIL-6 are largely unknown. To gain insight into the biology of vIL-6, we expressed vIL-6 in murine fibroblasts NIH3T3 cells and inoculated stable vIL-6-producing clones into athymic mice. vIL-6 was detected selectively in the blood of mice injected with vIL-6-expressing clones. Compared with controls, vIL-6-positive mice displayed increased hematopoiesis in the myeloid, erythroid, and megakaryocytic lineages; plasmacytosis in spleen and lymph nodes; hepatosplenomegaly; and polyclonal hypergammaglobulinemia, vIL-6-expressing NIH3T3 cells gave rise to tumors more rapidly than did control cells, and vIL-6-positive tumors were more vascularized than controls. Vascular endothelial growth factor (VEGF) was detected at higher levels in the culture supernatant of vIL-6-expressing cells compared with controls, and immunohistochemical staining detected VEGF in spleen, lymph nodes, and tumor tissues from mice bearing vIL-6-producing tumors but not control tumors. Thus, vIL-6 is a multifunctional cytokine that promotes hematopoiesis, plasmacytosis, and angiogenesis, Through these functions, vIL-6 may play an important role in the pathogenesis of certain KSHV-associated disorders. (C) 1999 by The American Society of Hematology. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. NCI, Hematopathol Sect, NIH, Bethesda, MD USA. Columbia Univ, Sch Publ Hlth, Dept Pathol, New York, NY USA. RP Aoki, Y (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bldg 29A,Room 2DO6 HFM 535,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Chang, Yuan/F-4146-2011; Moore, Patrick/F-3960-2011 OI Moore, Patrick/0000-0002-8132-858X NR 50 TC 287 Z9 304 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1999 VL 93 IS 12 BP 4034 EP 4043 PG 10 WC Hematology SC Hematology GA 204TK UT WOS:000080780200002 PM 10361100 ER PT J AU Galon, J Sudarshan, C Ito, S Finbloom, D O'Shea, JJ AF Galon, J Sudarshan, C Ito, S Finbloom, D O'Shea, JJ TI IL-12 induces IFN regulating factor-1 (IRF-1) gene expression in human NK and T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSCRIPTION FACTOR IRF-1; INTERLEUKIN-1 RECEPTOR ANTAGONIST; NATURAL-KILLER-CELLS; INTERFERON-ALPHA; TYROSINE PHOSPHORYLATION; GAMMA PRODUCTION; IMMUNE-RESPONSE; TH2 CELLS; INDUCTION; ACTIVATION AB IL-12 is a critical immunoregulatory cytokine that promotes cell-mediated immune responses and the differentiation of naive CD4(+) cells to: Th1 cells; however, relatively few IL-12 target genes have been identified, To better clarify the molecular basis of IL-12 action, we set out to characterize genes up-regulated by IL-12, first by contrasting IL-12 and IFN-alpha-inducible genes. We identified several genes up-regulated by IL-12, namely, MIP-1 alpha, MIP-1 beta, IL-1RA, and IFN regulatory factor-1 (IRF-1), IRF-1 is a transcription factor regulated by IFNs that is also essential for Th1 responses, We demonstrated that IL-12 directly up-regulates IRF-1 to the same extent as IFN-alpha in normal human T cells and in NK cells. We showed that IL-12 had a direct effect on IRF-1, an effect not mediated indirectly by the induction of IFN-gamma production, Furthermore,: IL-2 and IL-12 synergistically induced IRF-1, whereas IFN-alpha and IL-12 did not. The participation of STAT4 in-the regulation of IRF-1 was demonstrated in two ways, First, STAT4 was required for the IL-12-dependent transactivation of an IRF-1 reporter construct, and second, STAT4 binding to the IRF-1 promoter was shown using EMSA. In contrast to IL-12, no up-regulation of IRF-1 was found in IL-4-stimulated cells, and IL-4 did not block IL-12-dependent up-regulation of IRF-1, Therefore, IRF-1 may be an important contributor to IL-12 signaling, and we speculate that the defective IL-12 responses seen in IRF-1(-/-) mice might be attributable, in part, to the absence of this transcription factor. C1 NIAMSD, Lymphocyte Cell Biol Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. US FDA, Div Cytokine Biol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Galon, J (reprint author), NIAMSD, Lymphocyte Cell Biol Sect, Arthrit & Rheumatism Branch, NIH, Bldg 10,Room 9N 252,10 Ctr Dr,MSC-1820, Bethesda, MD 20892 USA. NR 39 TC 75 Z9 76 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1999 VL 162 IS 12 BP 7256 EP 7262 PG 7 WC Immunology SC Immunology GA 205BT UT WOS:000080802000042 PM 10358173 ER PT J AU Pipkin, JL Hinson, WG James, SJ Shaddock, JG Lyn-Cook, LE Feuers, RJ Morris, SM Tolleson, WH Casciano, DA AF Pipkin, JL Hinson, WG James, SJ Shaddock, JG Lyn-Cook, LE Feuers, RJ Morris, SM Tolleson, WH Casciano, DA TI The relationship of p53 and stress proteins in response to bleomycin and retinoic acid in the p53 heterozygous mouse SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article ID HEAT-SHOCK PROTEINS; CALORIC RESTRICTED RATS; POLYACRYLAMIDE-GEL ELECTROPHORESIS; TUMOR-SUPPRESSOR PROTEIN; WILD-TYPE P53; CELL-CYCLE; MUTANT P53; NUCLEAR-PROTEIN; PHOSPHORYLATION; ISOFORMS AB A single, i.p. dose of bleomycin was administered simultaneously with [S-35]methionine to 4-month-old p53 wild type (+/+) and p53 heterozygous (+/-) C57BL/6 mice. Following a period of 3.5 h from dosing, the bone marrow nuclei were examined by two-dimensional PAGE and fluorography for induction of stress proteins (sps). Eight sps ranging from 22 000 to 100 000 M-r were synthesized in p53+/- and p53+/+ mice following elicitation by bleomycin. No quantitative or qualitative differences were observed in sp expression in these two groups of animals. In a second experiment, three doses of retinoic acid were given i.p. to p53+/- and p53+/+ mice over a 36 h period. The p53 isoforms in bone marrow nuclei from these mice were analyzed by PAGE for incorporation of [S-35]methionine following retinoic acid injections. Quantitative and qualitative alterations in p53 isotypes were substantially increased in p53+/+ as compared with p53+/- mice. The increased complexity in the synthesis patterns in both groups of dosed mice consisted of additional isoforms possessing more acidic isoelectric values. In an in vitro binding assay, individual p53 isoforms demonstrated varying degrees of association with sps 25a, 70i, 72c and 90 which was consistently greater in p53+/+ mice. Both the synthesis and binding of isoforms were greater in G(1) than in S+G(2) phase, in both groups of animals, reflecting a cell cycle regulated mechanism for these events. Collectively, these data implied that the synthesis and the binding characteristics of p53 isoforms with sps were enhanced in the p53+/+ mice relative to the p53+/- mouse; however, sp labeling was not affected by p53 genotype. (C) 1999 Elsevier Science B.V. All rights reserved. C1 US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Facil & Engn, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Pipkin, JL (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 72 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JUN 8 PY 1999 VL 1450 IS 2 BP 164 EP 176 DI 10.1016/S0167-4889(99)00044-0 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 205UU UT WOS:000080839600006 PM 10354508 ER PT J AU Zhong, SB Nguyen, NY Eggerman, TL AF Zhong, SB Nguyen, NY Eggerman, TL TI Detection of apolipoprotein B mRNA editing by peptide nucleic acid mediated PCR clamping SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE apolipoprotein B; peptide nucleic acid; PCR; primer extension; mutant; mRNA editing ID MESSENGER-RNA; PNA; RAT AB Apolipoprotein B (apoB) mRNA editing leads to a single base change in its mRNA and the production of apoB-48. Currently, the degree of apoB mRNA editing is analyzed by the RT-PCR primer extension method. While this method is quantitative, it is labor intensive, utilizes radioactivity for labeling and may not be sensitive enough to discriminate between low levels of editing and inherent assay background levels. Peptide nucleic acid (PNA) oligonucletides have been used in single point mutation detection through PCR. clamping. In the present work, we developed a PCR based assay which can detect the single base change responsible for the apoB-48 production. We found that as low as 0.5% of the edited form can be clearly detected by PNA mediated PCR clamping. When combined with the primer extension assay, an approximately 180-fold enrichment of the edited percentage is observed, reflecting selected PCR amplification of templates containing the edited base. (C) 1999 Academic Press. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Facil Biotechnol Resources, Bethesda, MD 20892 USA. RP Eggerman, TL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, NIH Bldg 29B,Room 2NN12, Bethesda, MD 20892 USA. NR 9 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 7 PY 1999 VL 259 IS 2 BP 311 EP 313 DI 10.1006/bbrc.1999.0687 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 207AB UT WOS:000080912200013 PM 10362504 ER PT J AU Nightingale, SL AF Nightingale, SL TI Hypotension and bedside leukocyte reduction filters SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 2 PY 1999 VL 281 IS 21 BP 1978 EP 1978 DI 10.1001/jama.281.21.1978 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 200NN UT WOS:000080546700006 PM 10359372 ER PT J AU Rekhi, GS Nellore, RV Hussain, AS Tillman, LG Malinowski, HJ Augsburger, LL AF Rekhi, GS Nellore, RV Hussain, AS Tillman, LG Malinowski, HJ Augsburger, LL TI Identification of critical formulation and processing variables for metoprolol tartrate extended-release (ER) matrix tablets SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE metoprolol tartrate; hydrophilic matrix tablet; HPMC; extended-release; experimental design; formulation; dissolution; mechanism; manufacturing; regulatory ID DOSAGE FORMS; DRUG RELEASE; SCALEUP AB The objective of this study, was to examine the influence of critical formulation and processing variables as described in the AAPS/FDA Workshop II report on scale-up of oral extended-release dosage forms, using a hydrophilic polymer hydroxypropyl methylcellulose (Methocel K100LV). A face-centered central composite design (26 runs+3 center points) was selected and the variables studied were: filler ratio (lactose:dicalcium phosphate (50:50)), polymer level (15/32.5/50%), magnesium stearate level (1/1.5/2%), lubricant blend time (2/6/10 min) and compression force (400/600/800 kg). Granulations (1.5 kg, 3000 units) were manufactured using a fluid-bed process, lubricated and tablets (100 mg metoprolol tartrate) were compressed on an instrumented Manesty D3B rotary tablet press. Dissolution tests were performed using USP apparatus 2, at 50 rpm in 900 ml phosphate buffer (pH 6.8). Responses studied included percent drug released at Q(1) (1 h), Q(4), Q(6), Q(12). Analysis of variance indicated that change in polymer level was the most significant factor affecting drug release. Increase in dicalcium phosphate level and compression force were found to affect the percent released at the later dissolution time points. Some interaction effects between the variables studied were also found to be statistically significant. The drug release mechanism was predominantly found to be Fickian diffusion controlled (n=0.46-0.59). Response surface plots and regression models were developed which adequately described the experimental space. Three formulations having slow-, medium- and fast-releasing dissolution profiles were identified for a future bioavailability/bioequivalency study. The results of this study provided the framework for further work involving both in vivo studies and scale-up. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Elan Holdings Inc, Gainesville, GA 30504 USA. Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. Roche Biosci, Palo Alto, CA 94304 USA. US FDA, Div Prod Qual Res, Rockville, MD 20857 USA. ISIS Pharmaceut, Carlsbad, CA 92008 USA. US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. RP Rekhi, GS (reprint author), Elan Holdings Inc, 1300 Gould Dr, Gainesville, GA 30504 USA. NR 25 TC 60 Z9 61 U1 3 U2 18 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 JUN 2 PY 1999 VL 59 IS 3 BP 327 EP 342 DI 10.1016/S0168-3659(99)00004-8 PG 16 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 205YL UT WOS:000080848400006 PM 10332064 ER PT J AU Lewis, CJ Yetley, EA AF Lewis, CJ Yetley, EA TI Health claims and observational human data: relation between dietary fat and cancer SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Workshop on the Role of Epidemiology in Determining When Evidence is Sufficient to Support Nutrition Recommendations CY OCT 07-08, 1997 CL WASHINGTON, D.C. SP ILSI N Amer DE observational data; health claims; dietary fat; cancer; epidemiologic studies; notice-and-comment rule making; Food and Drug Administration AB The US Food and Drug Administration review that provided the basis for authorizing a food-label health claim linking the risk of cancer to dietary fat intake illustrated several considerations in the use of epidemiologic data, and observational data in particular, to support dietary recommendations. The review suggested the need for clear and established criteria for judging the qualify of observational human data as well as the importance of making the evaluation process for individual studies transparent and organized. The review, which provided for a claim in the absence of controlled human studies, also suggested that observational data may play a greater role when the nature of the relation to be described by a health-claim statement is broad and general rather than targeted and specific. Of particular importance was the relevance of available data to the questions inherent in showing a diet-disease relation, the need to consider the totality of the evidence, and the key role that existing authoritative reports must play in establishing the basis for relation. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Lewis, CJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-451,200 C St SW, Washington, DC 20204 USA. NR 18 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 1999 VL 69 IS 6 BP 1357S EP 1364S PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 199UT UT WOS:000080503000054 PM 10359237 ER PT J AU Vena, JE Ambrosone, CB Kadlubar, FE Nasca, PC AF Vena, JE Ambrosone, CB Kadlubar, FE Nasca, PC TI "The legacy of epidemiology in the Department of Social and Preventive Medicine: A commemoration of the sesquicentennial of the State University of New York at Buffalo School of Medicine and Biomedical Sciences, " "Current problems that are likely to affect the future of epidemiology" and "Toward an integrated approach to molecular epidemology" - Reply SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. RP Vena, JE (reprint author), SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1999 VL 149 IS 11 BP 1072 EP 1073 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200DJ UT WOS:000080524100014 ER PT J AU Astor, BC Kaczmarek, RG Hefflin, B Daley, WR AF Astor, BC Kaczmarek, RG Hefflin, B Daley, WR TI The epidemiology of bioprosthetic and mechanical heart valve implantations in the United States. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1999 VL 149 IS 11 SU S MA 292 BP S73 EP S73 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200EK UT WOS:000080526500290 ER PT J AU Lytle, CD Routson, LB Jain, NB Myers, MR Green, BL AF Lytle, CD Routson, LB Jain, NB Myers, MR Green, BL TI Virus passage through track-etch membranes modified by salinity and a nonionic surfactant SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID SURROGATE VIRUSES; BARRIER MATERIALS; FILTRATION AB Why do viruses sometimes not pass through larger pores in track-etch filters? Increasing the salinity (0.8 to 160 mM Na+) decreased phi X174 and PRD1 passage through track-etch polycarbonate membranes (sodium dodecyl sulfate coated but not polyvinylpyrrolidone coated) and PRD1 passage through polyester membranes. Undiminished passage when 0.1% Tween 80 was added implied that nonionic virus adsorption occurred and indicated that high levels of salinity decreased virus passage by decreasing electrostatic repulsion that prevented adsorption. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Thomas Jefferson High Sch Sci & Technol, Alexandria, VA 22312 USA. Corning Inc, Acton, MA 01720 USA. RP Lytle, CD (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12709 Twinbrook Pkwy, Rockville, MD 20857 USA. NR 13 TC 7 Z9 8 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUN PY 1999 VL 65 IS 6 BP 2773 EP 2775 PG 3 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 201YF UT WOS:000080624300077 PM 10347078 ER PT J AU Gustafson, M AF Gustafson, M TI Blood safety - The Food and Drug Administration's role SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article; Proceedings Paper CT College-of-American-Pathologists Conference XXXIII on Transfusion Medicine Performance Improvement CY AUG 20-22, 1998 CL SAN FRANCISCO, CALIFORNIA SP Coll Amer Pathologists, Amer Assoc Blood Banks AB The federal government has a role in protecting consumers from threats to the blood supply. These threats range from the residual risks of known infection, to emerging infections that may contaminate the blood supply, to complacency in the area of adherence to product standards and Current Good Manufacturing Practices. The Food and Drug Administration is tasked with oversight of the safety of the nation's blood supply. The Food and Drug Administration's regulation of blood and blood components includes preapproval for products entering interstate commerce and adherence to Current Good Manufacturing Practices for all blood components. Oversight for Current Good Manufacturing Practices compliance includes inspection and reporting requirements. These regulatory programs are coupled with the Public Health Service's ongoing research and epidemiological surveillance. The goals of these programs are to prevent another infectious disease epidemic from infecting the blood supply as did the acquired immunodeficiency syndrome in the early 1980s and to further improve blood safety. C1 US FDA, Div Blood Applicat, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Gustafson, M (reprint author), US FDA, Div Blood Applicat, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-370, Rockville, MD 20852 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JUN PY 1999 VL 123 IS 6 BP 475 EP 477 PG 3 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 201YB UT WOS:000080623900008 PM 10383796 ER PT J AU Rider, LG Shamim, E Okada, S Pandey, JP Targoff, IN O'Hanlon, TP Kim, HA Lim, YS Han, H Song, YW Miller, FW AF Rider, LG Shamim, E Okada, S Pandey, JP Targoff, IN O'Hanlon, TP Kim, HA Lim, YS Han, H Song, YW Miller, FW TI Genetic risk and protective factors for idiopathic inflammatory myopathy in Koreans and American whites - A tale of two loci SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; CLASS-II ALLELES; RHEUMATOID-ARTHRITIS; HLA-DR; OLIGONUCLEOTIDE PROBES; MULTIPLE-SCLEROSIS; PCR AMPLIFICATION; SEQUENCE; DISEASE; SUSCEPTIBILITY AB Objective, To better understand genetic contributions to autoimmunity, immunogenetic markers were studied in two racially discrete and geographically isolated populations of patients with idiopathic inflammatory myopathy (IIM), Methods, Clinical characteristics, as well as clinical and autoantibody subsets, were defined in 151 American white patients and 50 Korean patients with IIM, HLA-DRB1 and DQA1 genotyping was performed on patients and racially matched controls by standard molecular techniques. Gm allotypes and phenotypes were determined by the hemagglutination-inhibition method, Results. HLA-DRB1*0301, the linked allele DQA1*0501, and DRB1 alleles sharing the first hypervariable region motif (EYSTS13)-E-9 were major genetic risk factors for the development of myositis in whites (corrected P [P-corr] < 0.0004, odds ratio [OR] 11.2, 4.5, and 3.1, respectively, for each factor versus controls). Although both the white and Korean patients had a similar distribution of clinical characteristics, autoantibody profiles, and clinical groups, no HLA-DRB1 nor DQA1 allele or motif was found to be a risk factor for IIM in the Korean patients. However, DRB1*14 was a protective factor in Korean patients without myositis-specific autoantibodies (P-corr = 0.004, OR 0.046), In addition, although no Gm phenotype or allotype was identified as a risk factor in whites, Gm 21 was a protective factor for the development of IIM in Koreans (P-corr = 0.024, OR 0.3), Conclusion. Although myositis patients in the US and Korea share similar clinical and serologic features, the immune response genes predisposing to and protecting from myositis in each of these ethnic groups differ at two chromosomal loci. These data suggest that multiple genetic loci should be studied to identify risk and protective factors for some autoimmune diseases in various ethnic populations. C1 US FDA, Lab Mol & Dev Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Univ Oklahoma, Med Sci Ctr, Vet Affairs Med Ctr, Oklahoma City, OK USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Seoul Natl Univ Hosp, Seoul 110744, South Korea. Catholic Univ, Coll Med, Seoul, South Korea. RP Rider, LG (reprint author), US FDA, Lab Mol & Dev Immunol, Ctr Biol Evaluat & Res, Bldg 29B,Room 2G11,HFM-561,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Song, Yeong Wook/J-2765-2012; OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 NR 37 TC 37 Z9 38 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1999 VL 42 IS 6 BP 1285 EP 1290 DI 10.1002/1529-0131(199906)42:6<1285::AID-ANR28>3.0.CO;2-1 PG 6 WC Rheumatology SC Rheumatology GA 204VU UT WOS:000080786000028 PM 10366124 ER PT J AU Swann, J AF Swann, J TI Prescription for profits: How the pharmaceutical industry bankrolled the unholy marriage between science and business. SO BULLETIN OF THE HISTORY OF MEDICINE LA English DT Book Review C1 US FDA, Rockville, MD 20857 USA. RP Swann, J (reprint author), US FDA, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 0007-5140 J9 B HIST MED JI Bull. Hist. Med. PD SUM PY 1999 VL 73 IS 2 BP 364 EP 366 DI 10.1353/bhm.1999.0065 PG 3 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 205XA UT WOS:000080844800048 ER PT J AU Ozawa, S Schoket, B McDaniel, LP Tang, YM Ambrosone, C Kostic, S Vincze, I Kadlubar, FF AF Ozawa, S Schoket, B McDaniel, LP Tang, YM Ambrosone, C Kostic, S Vincze, I Kadlubar, FF TI Analyses of bronchial bulky DNA adduct levels and CYP2C9, GSTP1 and NQO1 genotypes in a Hungarian study population with pulmonary diseases SO CARCINOGENESIS LA English DT Article ID ENVIRONMENTAL TOBACCO-SMOKE; LOS-ANGELES-COUNTY; LUNG-CANCER RISK; HUMAN CYTOCHROME-P450; GENETIC-POLYMORPHISM; CIGARETTE-SMOKING; DT-DIAPHORASE; AFRICAN-AMERICANS; ALLELIC VARIANT; BENZOPYRENE AB Carcinogen-DNA adducts may represent an intermediate end-point in the carcinogenic cascade and may reflect exposure to chemical carcinogens, as well as susceptibility and, ultimately, cancer risk. Interindividual variability in activity of enzymes involved in the metabolism of polycyclic aromatic hydrocarbons to mutagenic diol epoxides may predict adduct levels and, indirectly, lung cancer risk. Using P-32-postlabeling methods, the levels of bulky DNA adducts were determined in macroscopically normal bronchial tissues obtained from resected lobes of 143 Hungarian patients with lung malignancy and other pulmonary conditions. DNA from normal tissue was also evaluated for polymorphisms in cytochrome P450 2C9 (CYP2C9) at two sites, codons 144 (Arg/Cys) and 359 (Ile/Leu), for glutathione S-transferase P1 (GSTP1) at codon 105 and for NAD(P)H:quinone oxidoreductase (NQO1) at codon 187 (Pro/Ser), Using the Mann-Whitney U-test and analysis of variance, levels of adducts were evaluated in relation to variant genotypes, separately for smokers and nonsmokers. As previously reported, bulky DNA adduct levels in smokers (n = 104) were estimated to be 54% higher than in non-smokers (n = 39) (8.6 +/- 4.2 versus 5.6 +/- 3.3 per 10(8) nucleotides, respectively, P < 0.01), Adduct levels were 16-29% higher in individuals with the homozygous Ile359/Ile359 CYP2C9 allele than in those heterozygous for the variant allele (Ile359/Leu359) [8.8 +/- 4.3 (n = 84) versus 7.6 +/- 3.5 (n = 20) for smokers and 5.8 +/- 3.5 (n = 32) versus 3.5 +/- 1.3 (n = 7) for non-smokers], although differences were not statistically significant. There were no clear differences in adduct levels in relation to genotypes of NQO1 or GSTP1, Although numbers of patients in this study are large in relation to many studies of carcinogen-DNA adducts, it is still possible that significant differences were not noted for polymorphisms in xenobiotic metabolizing enzymes due to relatively small numbers in stratified data. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol HFT100, Jefferson, AR 72079 USA. Natl Inst Environm Hlth, Dept Biochem, H-1097 Budapest, Hungary. Koranyi Natl Inst Pulmnol, Thorac Surg Clin, H-1529 Budapest, Hungary. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol HFT100, Jefferson, AR 72079 USA. NR 44 TC 27 Z9 27 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 JUN PY 1999 VL 20 IS 6 BP 991 EP 995 DI 10.1093/carcin/20.6.991 PG 5 WC Oncology SC Oncology GA 205AF UT WOS:000080798500011 PM 10357778 ER PT J AU Cress, LW Owen, RD Desta, AB AF Cress, LW Owen, RD Desta, AB TI Ornithine decarboxylase activity in L929 cells following exposure to 60 Hz magnetic fields SO CARCINOGENESIS LA English DT Article ID COHERENCE TIME; MICROWAVES AB To determine whether there is a biological basis for epidemiological studies which suggest an association between exposure to magnetic fields and cancer, we have attempted to replicate earlier findings on cellular enzymes related to cell proliferation. Here we report on an effort to replicate the doubling of ornithine decarboxylase (ODC) activity in L929 murine fibroblasts following exposure to 60 Hz magnetic fields reported by Litovitz et nl, Efforts were made to reproduce the methods and exposure conditions used by the original investigators. Positive controls showed that our assay system responded to other known stimuli of ODC activity. We extended the previously reported investigations by testing a number of exposure conditions and other associated variables. Initial results suggested that cells exposed in the original investigators' laboratory demonstrated an enhanced enzyme activity, whereas cells exposed in our laboratory did not. Experiments in our laboratory using the most important elements of the original investigators' exposure system did not demonstrate any enhancement of ODC activity. Finally, a series of magnetic field exposure and sham exposure experiments conducted in the original investigators' laboratory failed to demonstrate an effect of magnetic fields on ODC activity. C1 US FDA, Ctr Devices & Radiol Hlth HFZ114, Rockville, MD 20850 USA. RP Cress, LW (reprint author), US FDA, Ctr Devices & Radiol Hlth HFZ114, 9200 Corp Blvd, Rockville, MD 20850 USA. FU NIEHS NIH HHS [Y1-ES-0006] NR 16 TC 22 Z9 23 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 JUN PY 1999 VL 20 IS 6 BP 1025 EP 1030 DI 10.1093/carcin/20.6.1025 PG 6 WC Oncology SC Oncology GA 205AF UT WOS:000080798500016 PM 10357783 ER PT J AU Doerge, DR Churchwell, MI Marques, MM Beland, FA AF Doerge, DR Churchwell, MI Marques, MM Beland, FA TI Quantitative analysis of 4-aminobiphenyl-C8-deoxyguanosyl DNA adducts produced in vitro and in vivo using HPLC-ES-MS SO CARCINOGENESIS LA English DT Article ID IONIZATION MASS-SPECTROMETRY; CARCINOGEN 4-AMINOBIPHENYL; CHROMATOGRAPHY; BLADDER; CAPTURE AB Electrospray mass spectrometry (ES-MS) is a powerful tool for analysis of carcinogen-adducted DNA. In this study, we developed a quantitative isotope dilution method for analysis of N-(deoxyguanosine-8-yl)-4-aminobiphenyl (dG-C8-4-ABP), the principal nucleoside adduct derived from enzymatic hydrolysis of 4-aminobiphenyl (4-ABP)-modified DNA. The method used column switching valves to perform on-line sample concentration and cleanup, which permitted direct analysis of enzymatic DNA hydrolysates using narrow-bore liquid chromatography (LC), ES-MS detection was performed using a single quadrupole instrument by monitoring M+H+ and two fragment ions characteristic for dG-C8-4-ABP, along with M+H+ and a fragment ion for the deuterated internal standard. The detection limit for dG-C8-4-ABP in DNA hydrolysates was similar to 10 pg on-column, equivalent to 0.7 dG-C8-4-ABP adducts in 10(7) normal nucleotides for a sample containing 100 mu g DNA. The method was applied to the analysis of calf thymus DNA modified in vitro through reaction with N-hydroxy-4-ABP and of hepatic DNA isolated from mice treated in I vivo with two dose levels of 4-ABP. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Tecn Lisboa, Inst Super Tecn, P-1049 Lisbon, Portugal. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM ddoerge@nctr.fda.gov RI Marques, M. Matilde/E-2535-2012 OI Marques, M. Matilde/0000-0002-7526-4962 NR 18 TC 43 Z9 43 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1999 VL 20 IS 6 BP 1055 EP 1061 DI 10.1093/carcin/20.6.1055 PG 7 WC Oncology SC Oncology GA 205AF UT WOS:000080798500021 PM 10357788 ER PT J AU Nowell, SA Massengill, JS Williams, S Radominska-Pandya, A Tephly, TR Cheng, ZQ Strassburg, CP Tukey, RH MacLeod, SL Lang, NP Kadlubar, FF AF Nowell, SA Massengill, JS Williams, S Radominska-Pandya, A Tephly, TR Cheng, ZQ Strassburg, CP Tukey, RH MacLeod, SL Lang, NP Kadlubar, FF TI Glucuronidation of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine by human microsomal UDP-glucuronosyltransferases: identification of specific UGT1A family isoforms involved SO CARCINOGENESIS LA English DT Article ID FOOD MUTAGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; HYDROXY HETEROCYCLIC AMINES; HUMAN-LIVER MICROSOMES; METABOLIC-ACTIVATION; EVOLUTIONARY DIVERGENCE; GENE SUPERFAMILY; DNA-ADDUCTS; COOKED FOOD; HUMAN COLON; 1A LOCUS AB 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine is a heterocyclic aromatic amine found in cooked meats and dietary exposure to PhIP has been implicated in the etiology of colon cancer in humans. PhIP, along with other heterocyclic aromatic amines, requires metabolic activation to exhibit genotoxic effects, PhIP is initially oxidized by the activity of cytochrome P4501A2 to produce 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP), a reaction occurring primarily in the liver. Whereas subsequent biotransformation of N-OH-PhIP via acetylation or sulfation can produce reactive electrophiles that readily bind to DNA, N-glucuronidation, catalyzed by UDP-glucuronosyltransferases (UGTs), functions as a detoxification mechanism. Although hepatic glucuronidation of N-OH-PhIP has been well characterized, the extrahepatic metabolism of this compound is poorly understood. Studies in our laboratory now indicate that the intestinal tract, and particularly the colon, is a significant site of glucuronidation of N-OH-PhIP, When assays were performed with microsomes prepared from the mucosa of the intestinal tract, it was determined that glucuronidation of N-OH-PhIP occurs throughout the intestinal tract, with activity approximately three times higher in the colon as that found in the upper intestine. Glucuronidation rates from colon microsomes showed considerable interindividual variability and incubation with N-OH-PhIP yielded two glucuronides, HPLC analysis showed that the predominant product formed is the N-OH-PhIP-N-2-glucuronide, while the N3-glucuronide accounts for <10% of the total glucuronidation product. These rates approach the rates found in human liver microsomes, demonstrating the significance of extrahepatic metabolism of this food-borne carcinogen. Subsequent assays with human recombinant UGTs demonstrated that at least four human UGT isoforms, all from the UGT1A subfamily, are capable of catalyzing the biotransformation of N-OH-PhIP, Members of the UGT2B family available for this study did not conjugate N-OH-PhIP, although immunoinhibition studies in human liver microsomes strongly suggest the involvement of a UGT2B isoform(s) in this organ. C1 Univ Arkansas Med Sci, Dept Surg Oncol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Biochem, Little Rock, AR 72205 USA. Univ Iowa, Dept Pharmacol, Iowa City, IA 52242 USA. Univ Calif San Diego, Ctr Canc, Dept Pharmacol, La Jolla, CA 92093 USA. John L McClellan Mem Vet Adm Med Ctr, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Nowell, SA (reprint author), Univ Arkansas Med Sci, Dept Surg Oncol, 4301 W Markham St,VA Res Slot 151, Little Rock, AR 72205 USA. FU NCI NIH HHS [CA55751, CA58697]; NIA NIH HHS [AG15722] NR 44 TC 90 Z9 91 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 JUN PY 1999 VL 20 IS 6 BP 1107 EP 1114 DI 10.1093/carcin/20.6.1107 PG 8 WC Oncology SC Oncology GA 205AF UT WOS:000080798500029 PM 10357796 ER PT J AU Stang, M Wysowski, DK Butler-Jones, D AF Stang, M Wysowski, DK Butler-Jones, D TI Incidence of lactic acidosis in metformin users SO DIABETES CARE LA English DT Article AB OBJECTIVE - The purpose of this study was to determine the incidence of lactic acidosis in a geographically defined population of metformin users. RESEARCH DESIGN AND METHODS - The study was based on a historical cohort from the Saskatchewan Health administrative databases. Individuals with a metformin prescription dispensed between 1980 and 1995 inclusive were eligible for the cohort. Person-years of exposure were calculated Cases were defined by hospital discharge with a diagnosis of acidosis (International Classification of Diseases, Ninth Revision code: 276.2) and confirmation by chart review of a blood lactate level greater than or equal to 5 mmol/l. Death registrations of individuals dying within 120 days of a metformin prescription were also reviewed. RESULTS - During the study period, 11,797 residents received one or more metformin prescriptions, resulting in 22,296 person-years of exposure. There were 10 subjects who had hospital discharges with a diagnosis of acidosis. However, primary record review revealed only two cases with laboratory findings of elevated blood lactate levels, for an incidence rate of 9 cases per 100,000 person-years of metformin exposure. In both cases, other factors besides metformin could have contributed to the lactic acidosis. No additional cases were found on review of death registrations. CONCLUSIONS - From 1980 through 1995, the incidence rate of lactic acidosis was 9 per 100,000 person-years (95% CI 0-21) in patients dispensed metformin in Saskatchewan, Canada. This incidence rate was derived from a population with complete ascertainment of hospitalizations and deaths associated with lactic acidosis in metformin users. It is similar to previously published rates based on passive reporting of cases, and it is well below the lactic acidosis rate of 40-64 per 100,000 patient-years in patients prescribed phenformin. C1 Saskatchewan Hlth, Regina, SK S4S 6X6, Canada. US FDA, Off Post Mkt Drug Risk Assessment, Rockville, MD 20857 USA. RP Stang, M (reprint author), Saskatchewan Hlth, 3475 Albert St, Regina, SK S4S 6X6, Canada. FU FDA HHS [FD-U-000976] NR 13 TC 152 Z9 153 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 1999 VL 22 IS 6 BP 925 EP 927 DI 10.2337/diacare.22.6.925 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 198WN UT WOS:000080447400009 PM 10372243 ER PT J AU Hooper, K Chuvakova, T Kazbekova, G Hayward, D Tulenova, A Petreas, MX Wade, TJ Benedict, K Cheng, YY Grassman, J AF Hooper, K Chuvakova, T Kazbekova, G Hayward, D Tulenova, A Petreas, MX Wade, TJ Benedict, K Cheng, YY Grassman, J TI Analysis of breast milk to assess exposure to chlorinated contaminants in Kazakhstan: Sources of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposures in an agricultural region of southern Kazakhstan SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE breast milk; coplanar PCBs; dioxins; exposure assessment; furans; Kazakhstan; TCDD ID TOXIC EQUIVALENCY FACTORS; DIOXIN-LIKE COMPOUNDS; POLYCHLORINATED-BIPHENYLS; PHENOXY HERBICIDES; CANCER MORTALITY; ORGANOCHLORINE PESTICIDES; OCCUPATIONAL EXPOSURE; PERINATAL EXPOSURE; BODY BURDEN; PCDF LEVELS AB High levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; up to 208 pg/g fat) were measured in samples of breast milk collected in 1997 from 64 donors [41 first-time mothers (primiparae)] living on state farms in southern Kazakhstan. TCDD was the major contributor (70%) to the toxic equivalents, matching the congener patterns found in breast milk and serum samples collected in 1994 and 1996 from donors in nearby villages. The highest TCDD levels were found in state farms adjacent to a reservoir (zone A), which receives agricultural runoff from cotton fields. TCDD levels in zone A were significantly higher than levels in a region more distant (zone B; > 10 miles) from the reservoir (zone A: mean 53 pg/g, n = 17; zone B: mean 21 pg/g, n = 24; p = 0.0017). Levels of TCDD in breast milk and animal-derived foodstuffs were 10 times U.S. levels. Body burden and dietary data suggest that exposures to TCDD are chronic, environmental, and long term and may be related to the use of chemicals in cotton agriculture. The data suggest that the most likely source is the use of cotton defoliants contaminated with TCDD, and the most likely pathway for human exposure is via the consumption of contaminated foodstuffs. C1 Calif Environm Protect Agcy, Hazardous Mat Lab, Berkeley, CA 94704 USA. Kazakhstan Minist Hlth, Phys Inst Postgrad Training, Alma Ata, Kazakhstan. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. United Nations High Commissioner Refugees, Astana, Kazakhstan. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Hooper, K (reprint author), Calif Environm Protect Agcy, Hazardous Mat Lab, 2151 Berkeley Way, Berkeley, CA 94704 USA. NR 63 TC 20 Z9 22 U1 2 U2 7 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1999 VL 107 IS 6 BP 447 EP 457 DI 10.2307/3434626 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 205QJ UT WOS:000080831800022 PM 10515712 ER PT J AU Gaylor, DW Kodell, RL Chen, JJ Krewski, D AF Gaylor, DW Kodell, RL Chen, JJ Krewski, D TI A unified approach to risk characterization SO INHALATION TOXICOLOGY LA English DT Article ID CANCER; NOAEL C1 US FDA, Natl Ctr Toxicol Res, Dept Hlth & Human Serv, Jefferson, AR 72079 USA. Univ Ottawa, Fac Med, Ottawa, ON, Canada. RP Gaylor, DW (reprint author), US FDA, Natl Ctr Toxicol Res, Dept Hlth & Human Serv, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 20 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PD JUN-JUL PY 1999 VL 11 IS 6-7 BP 575 EP 578 PG 4 WC Toxicology SC Toxicology GA 212UX UT WOS:000081236900013 PM 11202999 ER PT J AU Mahmood, I Mahayni, H AF Mahmood, I Mahayni, H TI A limited sampling approach in bioequivalence studies: application to long half-life drugs and replicate design studies SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE limited sampling approach (LSM); bioequivalence studies; long half-life drugs; replicate study designs ID MAXIMUM PLASMA-CONCENTRATION; CONCENTRATION C-MAX; UNDER-THE-CURVE; AREA; PHARMACOKINETICS; AUC; MODEL AB Objectives: The objectives of this study was to develop a limited sampling model (LSM) to predict the area under the curve (AUC) and the maximum plasma concentration (C-max) for the assessment of bioequivalence studies. Methods: Two drugs (A and B) were selected for this purpose. Drug A was chosen to test bioequivalence of two formulations with a long half-life (> 35 hours), whereas drug B was chosen to test the bioequivalence of two formulations (half-life = 12 hrs) with a replicate design study. The LSM for both drugs was developed using 5 blood samples each from 15 healthy subjects. The relationship between plasma concentration (independent variable) at selected time points with the AUC or C-max (dependent variable) was evaluated by multiple linear regression analysis, The multiple linear regression which gave the best correlation coefficient (r) for 5 sampling time vs AUC or C-max was chosen as the LSM. The predicted AUC and C-max from the LSM were then used to assess bioequivalence of two different formulations of each drug following a single oral dose. Results: The model provided good estimates of both AUC and C-max for both drugs. The 90% confidence intervals an log-transformed observed and predicted AUC and C-max were comparable for both drugs. Conclusions: The method described here may be used to estimate AUC and C-max for bioequivalence studies for drugs with long half-lives or for highly variable drugs which may require replicate design studies without detailed blood sampling. C1 US FDA, Div Pharmaceut Evaluat 1, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. US FDA, Div Pharmaceut Evaluat 3, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. RP Mahmood, I (reprint author), HFD 860,Room 4079,Woodmont Off Ctr 2,1451 Rockvil, Rockville, MD 20852 USA. NR 18 TC 10 Z9 10 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI MUNCHEN-DEISENHOFEN PA BAHNHOFSTRABE 9 POSTFACH 49, W-8024 MUNCHEN-DEISENHOFEN, GERMANY SN 0946-1965 J9 INT J CLIN PHARM TH JI Int. J. Clin. Pharmacol. Ther. PD JUN PY 1999 VL 37 IS 6 BP 275 EP 281 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 205QL UT WOS:000080832000003 PM 10395118 ER PT J AU Pegues, JC Kannan, B Stromberg, K AF Pegues, JC Kannan, B Stromberg, K TI ErbB receptor expression and growth response to heregulin beta 1 in five ovarian carcinoma lines SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article; Proceedings Paper CT 89th Annual Meeting of the American-Association-for-Cancer-Research CY MAR 27-APR 01, 1998 CL NEW ORLEANS, LOUISIANA SP Amer Assoc Canc Res DE erbB receptors; heregulin; ovarian; carcinoma ID NEU DIFFERENTIATION FACTOR; CANCER CELLS; HUMAN BREAST; SIGNAL-TRANSDUCTION; TUMOR-CELLS; HETERODIMERIZATION; ACTIVATION; NETWORK; DIVERSIFICATION; PROLIFERATION AB SKOV-3, NIH:OVCAR-3, NIH:OVCAR-8, OVCA 429 and OVCA 433 ovarian carcinoma cell lines were examined to correlate biological behavior (growth in monolayer and soft agar) with erbB family receptor expression levels and response to recombinant Heregulin beta 1 (Hrg). While all lines expressed variable amounts of each receptor, erbB-3 and to a lesser extent erbB-2 were constitutively tyrosine phosphorylated in all lines. Hrg beta 1 treatment enhanced only erbB-3 tyrosine phosphorylation; however, the addition of Hrg in low serum did not stimulate ovarian cell growth, unlike all three breast cancer cell lines examined. In addition, all five of the ovarian carcinoma cell lines expressed Hrg mRNA by RT-PCR, unlike two of the three breast cancer cell lines. These results suggest the apparent importance of erbB-3 and endogenous Hrg in ovarian carcinoma cell growth in vitro . C1 US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. RP Stromberg, K (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, HFM-511,8000 Rockville Pike, Bethesda, MD 20892 USA. NR 36 TC 10 Z9 10 U1 0 U2 0 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 JUN PY 1999 VL 14 IS 6 BP 1169 EP 1176 PG 8 WC Oncology SC Oncology GA 199UC UT WOS:000080500900023 PM 10339675 ER PT J AU Beezhold, DH Hickey, VL Slater, JE Sussman, GL AF Beezhold, DH Hickey, VL Slater, JE Sussman, GL TI Human IgE-binding epitopes of the latex allergen Hev b 5 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Hev b 5; latex allergy; antigens; IgE antibodies; recombinant allergens ID NATURAL-RUBBER LATEX; ACIDIC ALLERGEN; CELL EPITOPES; HEV-B-5; IDENTIFICATION; PEPTIDES; CLONING AB Background: Hev b 5 is an acidic protein (isoelectric point, 3.5) rich in glutamic acid with 9 repeated amino acid (AA) sequences of XEEX or XEEEX, Although its function in Hevea brasiliensis unknown, Hev b 5 has been identified as a major latex allergen. Immunoblot inhibition studies suggest Hev b 5 exists as multiple isoforms or contains a common epitope found in several other proteins. Objective: The purpose of this study was to further characterize Hev b 5 and to identify linear IgE-binding epitopes. Methods: Octapeptides spanning the entire Hev b 5 protein were synthesized on a derivatized cellulose membrane, The membrane was reacted with sera pooled from health care workers allergic to latex or rabbits immunized with latex proteins. B-cell epitopes were identified by subsequent incubations with the appropriate secondary antibodies and detected by using chemifluorescence. Results: Sera from patients allergic to latex recognized 6 IgE-binding regions located throughout the molecule. Two epitopes (2 and 4) had the common AA sequence of KTEEP. Epitopes 3 and 5 bad a similar AA sequence of EEXXA, where X was P, T, or K. Epitopes 1 and 6 appeared to be unrelated to the other epitopes, Database analysis could not identify other proteins with similar sequences. Neither of the XEEEX sequences bound IgE. Control sera failed to react to any peptides. Conclusions: Hev b 5 exists as multiple isoforms, but only small amounts are present in the nonammoniated latex preparations, such as those used for diagnostic tests, and this may help to explain the relatively poor sensitivity of some in vitro tests. C1 Guthrie Res Inst, Immunobiol Lab, Sayre, PA 18840 USA. US FDA, Lab Immunobiochem, Washington, DC 20204 USA. Univ Toronto, Div Clin Immunol & Allergy, Toronto, ON, Canada. RP Beezhold, DH (reprint author), Guthrie Res Inst, Immunobiol Lab, 1 Guthrie Sq, Sayre, PA 18840 USA. NR 24 TC 39 Z9 41 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 1999 VL 103 IS 6 BP 1166 EP 1172 DI 10.1016/S0091-6749(99)70194-6 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 207GT UT WOS:000080929500028 PM 10359901 ER PT J AU Ball, R Lehner, CE Parker, EC AF Ball, R Lehner, CE Parker, EC TI Predicting risk of decompression sickness in humans from outcomes in sheep SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE risk prediction; allometric scaling; decompression illness; hyperbaric; diving ID MODEL AB In animals, the response to decompression scales as a power of species body mass. Consequently, decompression sickness (DCS) risk in humans should be well predicted from an animal model with a body mass comparable to humans. No-stop decompression outcomes in compressed air and nitrogen-oxygen dives with sheep (n = 394 dives, 14.5% DCS) and humans (n = 463 dives, 4.5% DCS) were used with linear-exponential, probabilistic modeling to test this hypothesis. Scaling the response parameters of this model between species (without accounting for body mass), while estimating tissue-compartment kinetic parameters from combined human and sheep data, predicts combined risk better, based on log likelihood, than do separate sheep and human models, a combined model without scaling, and a kinetic-scaled model. These findings provide a practical tool for estimating DCS risk in humans from outcomes in sheep, especially in decompression profiles too risky to test with humans. This model supports the hypothesis that species of similar body mass have similar DCS risk. C1 USN, Med Res Inst, Bethesda, MD 20889 USA. Univ Wisconsin, Dept Surg Sci, Madison, WI 53706 USA. RP Ball, R (reprint author), US FDA, CBER, DBE, HFM 220, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 19 TC 12 Z9 12 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUN PY 1999 VL 86 IS 6 BP 1920 EP 1929 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 204TV UT WOS:000080781400029 PM 10368357 ER PT J AU Donoghue, AM Bakst, MR Drummond, P Haqque, S Smith, EJ Donoghue, DJ AF Donoghue, AM Bakst, MR Drummond, P Haqque, S Smith, EJ Donoghue, DJ TI Paternity efficiency in turkeys differs extensively after heterospermic insemination SO JOURNAL OF APPLIED POULTRY RESEARCH LA English DT Article DE DNA fingerprinting; fertility; paternity; semen evaluation; sire selection; sperm ID SEMEN DONOR SELECTION; SPERM MOTILITY; FERTILITY; MALES; SUCCESS; HEN AB All commercial turkey hens in the U.S. are bred by artificial insemination (AI). Since semen samples are pooled from 10 or more males (heterospermic inseminations), paternity of the progeny is rarely known. Whereas it is known that sperm competition exists, the degree to which any male's sperm fertilizes ova relative to other male's remains unknown. In this work, we determined individual male fecundity relative to that of other males in the study and attempted to establish a relationship between male fecundity and semen characteristics in turkeys. Fingerprinting of genomic DNA from parents and offspring was used to determine parentage efficiency. This work demonstrated that relatively few toms sired a high percentage of the progeny. Of the 26 toms contributing to the pooled ejaculates, six (23%) sired more than 60% of the 145 poults. Conversely, 14 toms (54%) sired three or fewer poults. We found that the semen parameters evaluated, some of which are used routinely by the turkey industry, were not good at predicting paternity. Under the conditions of this study, the majority of the progeny were derived from semen from one or two toms after heterospermic inseminations. C1 USDA ARS, Germplasm & Gamete Physiol Lab, Beltsville, MD 20705 USA. Tuskegee Univ, Sch Agr & Home Econ, Tuskegee, AL 36088 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Donoghue, AM (reprint author), USDA ARS, Germplasm & Gamete Physiol Lab, Bldg 200,BARC E, Beltsville, MD 20705 USA. NR 31 TC 5 Z9 5 U1 0 U2 0 PU APPLIED POULTRY SCIENCE INC PI ATHENS PA PO BOX 80286, ATHENS, GA 30608 USA SN 1056-6171 J9 J APPL POULTRY RES JI J. Appl. Poult. Res. PD SUM PY 1999 VL 8 IS 2 BP 214 EP 221 PG 8 WC Agriculture, Dairy & Animal Science SC Agriculture GA 228YA UT WOS:000082164100011 ER PT J AU Sears, JF Repaske, R Khan, AS AF Sears, JF Repaske, R Khan, AS TI Improved Mg2+-based reverse transcriptase assay for detection of primate retroviruses SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; DEPENDENT DNA POLYMERASE; VIRIONS; AIDS; TYPE-1; GENE AB The reverse transcriptase (RT) assay is a simple, relatively inexpensive, widely used assay that can detect all retroviruses (known and novel retroviruses as well as infectious and defective retroviruses) on the basis of the divalent cation requirement of their RT enzyme, i.e., Mg2+ or Mn2+. Descriptions of various RT assays have been published; however, they cannot be directly applied to the analysis of biological products or clinical samples without further standardization to determine the lower limit of virus detection (sensitivity), assay variability (reproducibility), or ability to detect different retroviruses (specificity). We describe the detection of type E and type D primate retroviruses, which may be pathogenic for humans, by a new P-32-based, Mg2+-containing RT assay. The results show that the sensitivity of detection is <3.2 50% tissue culture infective doses (TCID(50)s) for human immunodeficiency virus type 1 (HIV-1) and <1 TCID50 for simian immunodeficiency virus isolated from a rhesus macaque (SIVmac). Analysis of recombinant HIV-1 RT enzyme indicated that 10(-5) U, which is equivalent to 4.25 x 10(4) virions, could be detected. Additionally, genetically distinct type D retroviruses such as simian AIDS retrovirus and squirrel monkey retrovirus were also detected in the assay with similar sensitivities. Thus, the improved RT assay can be used to detect genetically divergent Mg2+-dependent retroviruses of human and simian origin that can infect human cells and that therefore pose a potential health risk to humans. C1 US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NIAID, Mol Med Lab, Bethesda, MD 20892 USA. RP Khan, AS (reprint author), US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, 1404 Rockville Pike,HFM-454, Rockville, MD 20852 USA. NR 27 TC 9 Z9 11 U1 0 U2 0 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 JUN PY 1999 VL 37 IS 6 BP 1704 EP 1708 PG 5 WC Microbiology SC Microbiology GA 197BN UT WOS:000080344900008 PM 10325311 ER PT J AU Jinneman, KC Wetherington, JH Hill, WE Omiescinski, CJ Adams, AM Johnson, JM Tenge, BJ Dang, NL Wekell, MM AF Jinneman, KC Wetherington, JH Hill, WE Omiescinski, CJ Adams, AM Johnson, JM Tenge, BJ Dang, NL Wekell, MM TI An oligonucleotide-ligation assay for the differentiation between Cyclospora and Eimeria spp. polymerase chain reaction amplification products SO JOURNAL OF FOOD PROTECTION LA English DT Article ID PCR; PATHOGEN; HUMANS AB An oligonucleotide-ligation assay (OLA) was developed and compared to a restriction fragment length polymorphism (RFLP) test for distinguishing between 294-bp polymerase chain reaction (PCR) amplification products of the 18S rRNA gene from Cyclospora and Eimeria spp. The PCR/OLA correctly distinguished between three Cyclospora, three E. tenella, and one E. mitis strains and the ratio of positive to negative spectrophotometric absorbance (A(490)) values for each strain ranged from 4.086 to 15.280 (median 9.5). PCR/OLA provides a rapid, reliable, spectrophotometric alternative to PCR/RFLP. C1 Seafood Prod Res Ctr, Bothell, WA 98041 USA. Food & Drug Adm, Seattle Dist Lab, Bothell, WA 98041 USA. Univ Washington, Dept Environm Hlth, Seattle, WA 98105 USA. RP Jinneman, KC (reprint author), Seafood Prod Res Ctr, Bothell, WA 98041 USA. NR 12 TC 21 Z9 24 U1 0 U2 0 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUN PY 1999 VL 62 IS 6 BP 682 EP 685 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 203ZE UT WOS:000080737700021 PM 10382662 ER PT J AU Eckert, D Merchlinsky, M AF Eckert, D Merchlinsky, M TI Vaccinia virus-bacteriophage T7 expression vector for complementation analysis of late gene processes SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID TEMPERATURE-SENSITIVE MUTANTS; DNA TOPOISOMERASE-I; RNA-POLYMERASE; ESCHERICHIA-COLI; IDENTIFICATION; SEQUENCE; SYSTEM; RECOMBINATION; REPLICATION; PROMOTERS AB A vaccinia virus-bacteriophage T7 RNA polymerase hybrid transient expression vector has been developed for complementation analysis of late gene functions in vaccinia virus. The conditionally defective virus ts21 was modified to express the bacteriophage T7 RNA polymerase, The derived virus, vtsT7, was conditionally defective in viral late gene expression but produced high levels of a target protein under the control of a T7 promoter at non-permissive temperatures. The level of P-galactosidase expression under the control of a T7 promoter was slightly lower in vtsT7 infections than those with the prototypical T7 RNA polymerase vector vTF7.3. However, the levels of expression for the human immunodeficiency virus envelope gene, a protein which undergoes post-translational modification, was slightly higher in vtsT7 infections, suggesting that some proteins may be expressed better in the absence of vaccinia virus late gene expression. Infections using vtsT7 at a low m.o.i. at 39 degrees C resulted in the accumulation of high molecular mass, non-linear replicative intermediates of vaccinia virus DNA replication and high levels of expression of a transfected gene proximal to a T7 promoter. The virus vtsT7 provides a means for the analysis of potential trans-acting factors participating in vaccinia virus late processes such as resolution of DNA replicative intermediates. C1 US FDA, Ctr Biol Evaluat & Res, Viral Dis Lab, Rockville, MD 20852 USA. RP Merchlinsky, M (reprint author), US FDA, Ctr Biol Evaluat & Res, Viral Dis Lab, HFM-457,1401 Rockville Pike, Rockville, MD 20852 USA. NR 24 TC 0 Z9 0 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 JUN PY 1999 VL 80 BP 1463 EP 1469 PN 6 PG 7 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 200LW UT WOS:000080542600016 PM 10374964 ER PT J AU Donnelly, RP Dickensheets, H Finbloom, DS AF Donnelly, RP Dickensheets, H Finbloom, DS TI The interleukin-10 signal transduction pathway and regulation of gene expression in mononuclear phagocytes SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Review ID TUMOR-NECROSIS-FACTOR; T-CELL PROLIFERATION; NF-KAPPA-B; HUMAN MONOCYTES; CYTOKINE PRODUCTION; INTERFERON-GAMMA; IFN-GAMMA; TYROSINE PHOSPHORYLATION; TRANSCRIPTION FACTOR; TNF-ALPHA AB Interleukin-10 (IL-10) activates a diverse array of functional responses in mononuclear phagocytes, Functional IL-10 receptor (IL-10R) complexes are tetramers consisting of two IL-10R1 polypeptide chains and two IL-10R2 chains, Binding of IL-10 to the extracellular domain of IL-10R1 activates phosphorylation of the receptor-associated Janus tyrosine kinases, JAK1 and Tyk2, These kinases then phosphorylate specific tyrosine residues (Y446 and Y496) on the intracellular domain of the IL-10R1 chain. Once phosphorylated, these tyrosine residues (and their flanking peptide sequences) serve as temporary docking sites for the latent transcription factor, STAT3 (signal transducer and activator of transcription-3). STAT3 binds to these sites via its SH2 (Src homology 2) domain, and is, in turn, tyrosine-phosphorylated by the receptor-associated JAKs, It then homodimerizes and translocates to the nucleus where it binds with high affinity to STAT-binding elements (SBE) in the promoters of various IL-10-responsive genes, One of these genes, SOCS-3 (Suppressor of Cytokine Signaling-3) is a member of a newly identified family of genes that inhibit JAK/STAT-dependent signaling. Moreover, the ability of IL-10 to induce de novo synthesis of SOCS-3 in monocytes correlates with its ability to inhibit expression of many genes in these cells, including endotoxin-inducible cytokines such as tumor necrosis factor-alpha (TNF-alpha) and IL-1, Thus, the ability of IL-10 to inhibit gene expression in monocytes is associated with its ability to rapidly induce synthesis of SOCS-3. C1 US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Rockville, MD 20852 USA. RP Donnelly, RP (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, 1401 Rockville Pike,HFM 505, Rockville, MD 20852 USA. NR 82 TC 262 Z9 270 U1 3 U2 14 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD JUN PY 1999 VL 19 IS 6 BP 563 EP 573 DI 10.1089/107999099313695 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 217QG UT WOS:000081510000003 PM 10433356 ER PT J AU Bej, AK Patterson, DP Brasher, CW Vickery, MCL Jones, DD Kaysner, CA AF Bej, AK Patterson, DP Brasher, CW Vickery, MCL Jones, DD Kaysner, CA TI Detection of total and hemolysin-producing Vibrio parahaemolyticus in shellfish using multiplex PCR amplification of tl, tdh and trh SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE Vibrio parahemolyticus; multiplex PCR; microorganism; shellfish; hemolysin ID THERMOSTABLE DIRECT HEMOLYSIN; POLYMERASE CHAIN-REACTION; KANAGAWA-PHENOMENON; THERMOLABILE HEMOLYSIN; ESCHERICHIA-COLI; UNITED-STATES; GENES; STRAINS; SEQUENCE; FRAGMENT AB Vibrio parahaemolyticus is an important human pathogen which can cause gastroenteritis when consumed in raw or partially-cooked seafood. A multiplex PCR amplification-based detection of total and virulent strains of V. parahaemolyticus was developed by targeting thermolabile hemolysin encoded by tl, thermostable direct hemolysin encoded by tdh, and thermostable direct hemolysin-related trh genes. Following optimization using oligonucleotide primers targeting tl, tdh and trh genes, the multiplex PCR was applied to V. parahaemolyticus from 27 clinical, 43 seafood, 15 environmental, 7 strains obtained from various laboratories and 19 from oyster plants. All 111 V. parahaemolyticus isolates showed PCR amplification of the tl gene; however, only 60 isolates showed amplification of tdh, and 43 isolates showed amplification of the trh gene. Also, 18 strains showed amplification of the tdh gene, but these strains did not show amplification of the trh gene. However, one strain exhibited amplification for the trh but not the tdh gene, suggesting both genes need to be targeted in a PCR amplification reaction to detect all hemolysin-producing strains of this pathogen. The multiplex PCR approach was successfully used to detect various strains of V. parahaemolyticus in seeded oyster tissue homogenate. Sensitivity of detection for all three target gene segments was at least between 10(1)-10(2) cfu per 10 g of alkaline peptone water enriched seeded oyster tissue homogenate. This high level of sensitivity of detection of this pathogen within 8 h of pre-enrichment is well within the action level (10(4) cfu per 1 g of shell stock) suggested by the National Seafood Sanitation Program guideline. Compared to conventional microbiological culture methods, this multiplex PCR approach is rapid and reliable for accomplishing a comprehensive detection of V. parahaemolyticus in shellfish. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Alabama, Dept Biol, Birmingham, AL 35294 USA. US FDA, Seafood Prod Res Ctr, Bothell, WA 98041 USA. RP Bej, AK (reprint author), Univ Alabama, Dept Biol, 1300 Univ Blvd, Birmingham, AL 35294 USA. NR 36 TC 318 Z9 367 U1 4 U2 45 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD JUN PY 1999 VL 36 IS 3 BP 215 EP 225 DI 10.1016/S0167-7012(99)00037-8 PG 11 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 202JV UT WOS:000080649600007 PM 10379807 ER PT J AU Guinard, JX Sechevich, PJ Meaker, K Jonnalagadda, SS Kris-Etherton, P AF Guinard, JX Sechevich, PJ Meaker, K Jonnalagadda, SS Kris-Etherton, P TI Sensory responses to fat are not affected by varying dietary energy intake from fat and saturated fat over ranges common in the American diet SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID DAIRY-PRODUCTS; HUMAN OBESITY; SUGAR; PREFERENCES; LIPOPROTEINS; CAPSAICIN; FOODS; DELTA; MILK AB Objective To examine the effects of manipulating dietary fat in foods on sensitivity and hedonic response to fat in selected foods. Design Twenty subjects were randomly assigned to a sequence of three 8-week experimental diets (average American diet, step 1 diet, low-saturated-fat diet) that varied in energy from fat (37%, 30%, and 26%, respectively) and saturated fat (17%, 10%, and 6%, respectively). Subjects participated in sensory tests designed to assess their sensitivity to and liking for fat in several foods, before the study (baseline), after consumption of each diet, and after the study (washout). Subjects/setting Subjects were participants in the Dietary Effects on Lipoprotein and Thrombogenic Activity (DELTA) study. Results No significant differences were found among diets for difference thresholds Cie, just noticeable differences) for fat in milk and pudding, ad libitum mixing of low- and high-fat samples of milk and soup, and hedonic scaling of fat concentrations in milk and muffins and of cheese, mayonnaise, hot dog, and pastry samples. Applications/conclusions Within the dietary fat ranges and for the fat stimuli tested in this study, dietary fat as percentage of energy from fat and saturated fat was not a significant determinant of sensitivity to and/or liking for fat. Sensory factors should not be a barrier to the implementation of low-fat diets such as the step 1 and low-saturated-fat diets. C1 Univ Calif Davis, Dept Food Sci & Technol, Davis, CA 95616 USA. Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. US FDA, Washington, DC 20204 USA. Georgia State Univ, Dept Nutr & Dietet, Atlanta, GA 30303 USA. Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. Penn State Univ, Dept Stat, University Pk, PA 16802 USA. RP Guinard, JX (reprint author), Univ Calif Davis, Dept Food Sci & Technol, Davis, CA 95616 USA. FU NHLBI NIH HHS [HL5U01-49659] NR 42 TC 3 Z9 3 U1 1 U2 1 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JUN PY 1999 VL 99 IS 6 BP 690 EP 696 DI 10.1016/S0002-8223(99)00167-4 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 201AA UT WOS:000080571400017 PM 10361531 ER PT J AU Vemulapalli, TH Mansouri, MES Oeller, MR Wilmot, LM Vaughn, SD AF Vemulapalli, TH Mansouri, MES Oeller, MR Wilmot, LM Vaughn, SD TI Proposals for increasing the availability of animal drugs for minor species and minor uses SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article C1 VAMD, Reg Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA. US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD USA. RP Vemulapalli, TH (reprint author), VAMD, Reg Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA. NR 0 TC 0 Z9 0 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 JUN 1 PY 1999 VL 214 IS 11 BP 1632 EP 1635 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 200EV UT WOS:000080527400010 PM 10363093 ER PT J AU Assaf, NA Pothuluri, JV Wang, RF Cerniglia, CE Moffitt, CM AF Assaf, NA Pothuluri, JV Wang, RF Cerniglia, CE Moffitt, CM TI Bioassay procedure for the evaluation of erythromycin activity in aquaculture environments SO JOURNAL OF THE WORLD AQUACULTURE SOCIETY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ELECTROCHEMICAL DETECTION; ASSAY; DRUGS AB A new bioassay procedure was developed for the detection of erythromycin in aquaculture samples using a strain of a Srenotraphomonas as an indicator organism. Conventional disk-plate and well-plate radial diffusion assay procedures were developed, as well as a third procedure using the same indicator organism in Luria-Bertani (LB) broth, supplemented with the indicator dye Brilliant Black (40 mu g/mL) in a multi-well microtiter plate. For both the disk-plate and well-plate radial diffusion assays, the response reflected in the size (width) of the growth inhibition zone, which was linear over the tested concentration range of 0.05 to 2.0 mu g erythromycin/mL. The limit of quantitation of the bioassay was at 0.05 mu g erythromycin/mL. Among the three methods of assay tested with Stenotrophomonas sp., the semiquantitative dye reduction method is easy to read and is not diffusion dependent. This method allows for processing of more samples and more replication on a single titer plate. This new indicator organism is specific for erythromycin when tested in the presence of other antibacterial agents, i.e., oxytetracycline (Terramycin((R))) and/or Romet-30((R)). This new bioassay procedure is suitable for quantitation of low concentrations of erythromycin in aquaculture water and sediment samples. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Univ Idaho, Dept Fish & Wildlife Resources, Moscow, ID 83844 USA. RP Pothuluri, JV (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 24 TC 2 Z9 4 U1 0 U2 0 PU WORLD AQUACULTURE SOCIETY PI BATON ROUGE PA LOUISIANA STATE UNIV, 143 J M PARKER COLISEUM, BATON ROUGE, LA 70803 USA SN 0893-8849 J9 J WORLD AQUACULT SOC JI J. World Aquacult. Soc. PD JUN PY 1999 VL 30 IS 2 BP 137 EP 146 DI 10.1111/j.1749-7345.1999.tb00860.x PG 10 WC Fisheries SC Fisheries GA 203VR UT WOS:000080729300001 ER PT J AU Hanno, PM AF Hanno, PM TI Potassium leak test predicts outcome in interstitial cystitis - Comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Hanno, PM (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 1999 VL 161 IS 6 BP 1794 EP 1794 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 194PJ UT WOS:000080202500011 ER PT J AU Williams, O Wolffe, EJ Weisberg, AS Merchlinsky, M AF Williams, O Wolffe, EJ Weisberg, AS Merchlinsky, M TI Vaccinia virus WR gene A5L is required for morphogenesis of mature virions SO JOURNAL OF VIROLOGY LA English DT Article ID MOLECULAR-WEIGHT PRECURSOR; COLI LAC REPRESSOR; EARLY TRANSCRIPTION; ESCHERICHIA-COLI; STRUCTURAL POLYPEPTIDE; PROTEOLYTIC MATURATION; EXTRACELLULAR VIRUS; ENVELOPE FORMATION; CORE PROTEINS; DNA-SEQUENCE AB The vaccinia virus WR A5L open reading frame (corresponding to open reading frame A4L in vaccinia virus Copenhagen) encodes an immunodominant late protein found in the core of the vaccinia virion. To investigate the role of this protein in vaccinia virus replication,,ve have constructed a recombinant virus, vA5Li, in which the endogenous gene has been deleted and an inducible copy of the A5 gene dependent on isopropyl-beta-D-thiogalactopyranoside (IPTG) for expression has been inserted into the genome. In the absence of inducer, the yield of infectious virus was dramatically reduced. However, DNA synthesis and processing, viral protein expression (except for A5), and early stages in virion formation were indistinguishable from the analogous steps in a normal infection. Electron microscopy revealed that the major vaccinia virus structural form present in cells infected with vA5Li in the absence of inducer was immature virions. Viral particles were purified from vA5Li-infected cells in the presence and absence of inducer. Both particles contained viral DNA and the full complement of viral proteins, except for A5, which was missing from particles prepared in the absence of inducer. The particles prepared in the presence of IPTG were more infectious than those prepared in its absence. The A5 protein appears to be required for the immature virion to form the brick-shaped intracellular mature virion. C1 US FDA, Ctr Biol Evaluat & Res, Viral Dis Lab, Rockville, MD 20852 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Merchlinsky, M (reprint author), US FDA, Ctr Biol Evaluat & Res, Viral Dis Lab, HFM-457,1401 Rockville Pike, Rockville, MD 20852 USA. NR 57 TC 24 Z9 24 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 JUN PY 1999 VL 73 IS 6 BP 4590 EP 4599 PG 10 WC Virology SC Virology GA 195UW UT WOS:000080271400009 PM 10233918 ER PT J AU Nony, PA Scallet, AC Rountree, RL Ye, X Binienda, Z AF Nony, PA Scallet, AC Rountree, RL Ye, X Binienda, Z TI 3-nitropropionic acid (3-NPA) produces hypothermia and inhibits histochemical labeling of succinate dehydrogenase (SDH) in rat brain SO METABOLIC BRAIN DISEASE LA English DT Article ID STRIATUM; LESIONS; DAMAGE AB 3-nitropropionic acid (3-NPA) is a toxin sometimes produced on moldy crops (sugarcane, peanuts, etc.) in amounts sufficient to cause severe neurological disorders when consumed by humans. In vitro, 3-NPA irreversibly inactivates SDH, a Complex II respiratory enzyme required for mitochondrial energy production. A single dose of 3-NPA (30 mg/kg S.C.) was given to singly-caged adult male Sprague-Dawley rats. Rectal temperature was measured after dosing as a potential biomarker of exposure to 3-NPA, and animals were sacrificed at various times after 3-NPA exposure for histochemical visualization of SDH activity. 3-NPA-treated rats experienced a progressive hypothermia, which reached a loss of 3 degrees C or more in core body temperature by 3 hours after dosing. The optical density of the SDH stain in brain was reduced according to a similar time-course, most prominently in the cerebellum and least sharply in the thalamus. The caudate nucleus had the greatest density of SDH staining that we measured in brain; it also has been reported to be the region most consistently lesioned by 3-NPA. However, within other areas of brain such as subdivisions of the hippocampus, neither endogenous SDH activity nor its sensitivity to inhibition by 3-NPA could predict the susceptibility to neurodegenerative changes. Although SDH activity remained significantly reduced in most areas of brain (except thalamus) for up to 5 days after dosing, core temperatures had returned to control values by 5 days suggesting that animals can utilize an alternate method of heat production to withstand insult by 3-NPA. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. RP Scallet, AC (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 18 TC 22 Z9 22 U1 1 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD JUN PY 1999 VL 14 IS 2 BP 83 EP 94 DI 10.1023/A:1020753629477 PG 12 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 232TB UT WOS:000082385100002 PM 10488910 ER PT J AU Khan, SA Nawaz, MS Khan, AA Cerniglia, CE AF Khan, SA Nawaz, MS Khan, AA Cerniglia, CE TI Direct in-gel hybridization of digoxigenin-labelled nonradioactive probes SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE PCR; Staphylococcus aureus; digoxigenin; in-gel hybridization ID DRIED AGAROSE GELS; DNA-FRAGMENTS; RAPID METHOD; GENE AB An improved, simple, cost-effective and non-radioactive procedure for in-gel hybridization is described for the detection of signal in dried agarose gels. Large and smalt digoxigenin-labelled DNA and oligonucleotide probes hybridized efficiently and specifically with the complementary DNA sequences in the gel. The signal-to-noise ratios for the gels dried at 55 degrees C at 1 atmospheric pressure were 3-3.5-fold higher than the gels dried at 25 degrees C under vacuum. The method shows an increased sensitivity over currently available non-radioactive methods for in-gel hybridization. A single copy of a gene insert could be detected by the use of this procedure. (C) 1999 Academic Press. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Nawaz, MS (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 16 TC 5 Z9 6 U1 1 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD JUN PY 1999 VL 13 IS 3 BP 233 EP 237 DI 10.1006/mcpr.1999.0241 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 210RG UT WOS:000081118000010 PM 10369749 ER PT J AU Alayash, AI AF Alayash, AI TI Hemoglobin-based blood substitutes: oxygen carriers, pressor agents, or oxidants? SO NATURE BIOTECHNOLOGY LA English DT Review DE blood substitutes; blood pressure; oxidants ID CROSS-LINKED HEMOGLOBIN; CELL-FREE HEMOGLOBIN; NITRIC-OXIDE; FREE-RADICALS; EFFICACY; POLYMERIZATION; METHEMOGLOBIN; MECHANISMS; FAILURE AB Hemoglobin-based blood substitutes are being developed as oxygen-carrying agents for the prevention of ischemic tissue damage and hypovolemic (low blood volume) shock. The ability of cell-free hemoglobin blood substitutes to affect vascular tone through the removal of nitric oxide has also prompted an evaluation of their usefulness for maintaining blood pressure in critically ill patients. Before the clinical potential of these substitutes can be fully realized, however, concerns remain as to the intrinsic toxicity of the hemoglobin molecule, particularly the interference of the heme prosthetic group with the tissue oxidant/antioxidant balance. This review provides some insights into the complex redox chemistry of hemoglobin and places an emphasis on how current knowledge may be exploited both to selectively enhance/suppress specific chemical reaction pathway(s) and to ultimately design safer hemoglobin-based therapeutics. C1 US FDA, Lab Plasma Derivat, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Lab Plasma Derivat, Ctr Biol Evaluat & Res, NIH Campus,Bldg 29,Room 112,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 53 TC 149 Z9 152 U1 0 U2 18 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUN PY 1999 VL 17 IS 6 BP 545 EP 549 DI 10.1038/9849 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 203PR UT WOS:000080716500024 PM 10385317 ER PT J AU Sathe, P Venitz, J Lesko, L AF Sathe, P Venitz, J Lesko, L TI Evaluation of truncated areas in the assessment of bioequivalence of immediate release formulations of drugs with long half-lives and of Cmax with different dissolution rates SO PHARMACEUTICAL RESEARCH LA English DT Article DE truncated AUC; long half-life; in vitro dissolution rate; Monte-Carlo simulations ID ABSORPTION; PERFORMANCE; EXTENT; AUC AB Purpose. To Evaluate truncated AUC in place of AUCt or extrapolated AUCinf. for drugs with long half-lives and to study the relationship between Cmax and in vitro dissolution rates. Methods. Monte-Carlo simulations were conducted using actual mean plasma concentrations of five long half-life drug products. The simulations were based on a catenary pharmacokinetic system in which the drug disposition in the body was represented by a one-or two-compartment model, characterizing the observed mean profiles. The influence of dramatic changes in the in vitro dissolution rate constant 'k(d)', was simulated in scenarios consisting of 20 crossover trials with 24 subjects per trial. comparing a fast dissolving reference and a hypothetical, slow dissolving test formulation. Results. The AUC's truncated after the completion of distribution phase were found surrogate to the AUCt or AUCinf measures. Except for Phenylbutazone. the Cmax measure was insensitive to the changes in the in vitro dissolution rate. The Cmax measure was found to be useful in the bioequivalence assessment since it reflected both the rate and extent of absorption. (Cmax/AUCt) measure was specific to absorption rate. Conclusions. For the bioequivalence determination of long half-life drug products. (1) the use of truncated AUC's after completion of the distribution phase instead of AUCinf, appears feasible. (2) Cmax measure may be insensitive to input rate changes, if the absorption rate is not constrained by the input rate in relation to the distribution or elimination rate. (3) (Cmax/AUCt) may be more specific to 'k(a)' differences. but Cmax reflects differences in both rate and extent of absorption. C1 CDER, USFDA, Off Pharmaceut Sci, Rockville, MD 20852 USA. Virginia Commonwealth Univ, Dept Pharm & Pharmaceut, Richmond, VA 23298 USA. RP Sathe, P (reprint author), CDER, USFDA, Off Pharmaceut Sci, Rockville, MD 20852 USA. NR 21 TC 15 Z9 15 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD JUN PY 1999 VL 16 IS 6 BP 939 EP 943 DI 10.1023/A:1018898624643 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 208KD UT WOS:000080989200024 PM 10397617 ER PT J AU Chen, GF Tang, YM Green, B Lin, DX Guengerich, FP Daly, AK Caporaso, NE Kadlubar, FF AF Chen, GF Tang, YM Green, B Lin, DX Guengerich, FP Daly, AK Caporaso, NE Kadlubar, FF TI Low frequency of CYP2A6 gene polymorphism as revealed by a one-step polymerase chain reaction method SO PHARMACOGENETICS LA English DT Article DE genetic polymorphism; restriction fragment length polymorphism; DNA sequencing; cytochrome P450 ID HUMAN LIVER-MICROSOMES; CYTOCHROME-P450 2A6 CYP2A6; COUMARIN 7-HYDROXYLATION; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; IDENTIFICATION; ACTIVATION; ENZYMES AB Human cytochrome P450 2A6 (CYP2A6) has been shown to metabolically activate carcinogens and mutagens, Genetic polymorphisms for CYP2A6 have been reported previously in different ethnic groups using a two-step polymerase chain reaction (PCR) method to identify CYP2A6*1, CYP2A6*2 and CYP2A6*3. Moreover, a new truncated allele has been recently identified in a Japanese population. We report here a one-step PCR amplification of the CYP2A6 gene from human genomic DNA and the detection of intact CYP2A6 alleles by restriction enzyme digestion. The diagnostic exon (exon 3) of the CYP2A6 gene was amplified from human genomic DNA with a primer pair. The forward primer is unique to the CYP2A6 gene, which eliminates previous problems in amplifying two highly homologous CYP2A genes, CYP2A7 and CYP2A13, in humans. The resulting PCR products (214 bp) were digested with XcmI or DdeI to detect the presence of CYP2A6*2 or CYP2A6*3 alleles, respectively. The allelic frequencies for CYP2A6*2 were 2.3% (n = 320) in the Caucasian and 0.7% (n = 71) in the Chinese populations, respectively, CYP2A6*3 allelic frequency in the Chinese population was 0.7%; while no CYP2A6*3 allele was detected in the Caucasian population, The allelic frequencies are relatively low and the reason for this discrepancy between different methods is discussed. Pharmacogenetics 9:327-332 (C) 1999 Lippincott Williams & Wilkins. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Chinese Acad Med Sci, Inst Canc, Dept Chem Etiol & Carcinogenesis, Beijing 100021, Peoples R China. Beijing Union Med Coll, Beijing, Peoples R China. Vanderbilt Univ, Ctr Mol Toxicol, Dept Biochem, Nashville, TN USA. Univ Newcastle Upon Tyne, Sch Med, Dept Pharmacol Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Natl Canc Inst, Genet Epidemiol Branch, Bethesda, MD USA. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, 3900 NCTR Dr Jefferson, Jefferson, AR 72079 USA. RI Daly, Ann/H-3144-2011 OI Daly, Ann/0000-0002-7321-0629 NR 17 TC 42 Z9 46 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD JUN PY 1999 VL 9 IS 3 BP 327 EP 332 DI 10.1097/00008571-199906000-00007 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 222AU UT WOS:000081760700007 PM 10471064 ER PT J AU Piechocki, JT AF Piechocki, JT TI Recent advances in pharmaceutical photostability testing. SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Meeting Abstract C1 US FDA, Div Cardiorenal Drugs, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 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 JUN PY 1999 VL 69 SI SI BP 11S EP 11S PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 220KB UT WOS:000081663200032 ER PT J AU Syed, S Bethea, D Godar, DE Maust, H Vonderheid, E Gasparro, FP AF Syed, S Bethea, D Godar, DE Maust, H Vonderheid, E Gasparro, FP TI Apoptosis in CTCL patients induced by PUVA therapy. SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Meeting Abstract C1 Thomas Jefferson Univ, Dept Dermatol, Philadelphia, PA 19107 USA. Med Coll Penn & Hahnemann Univ, Philadelphia, PA USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 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 JUN PY 1999 VL 69 SI SI BP 39S EP 40S PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 220KB UT WOS:000081663200117 ER PT J AU Timmer, WC DeCamp, WH Wilkin, JK AF Timmer, WC DeCamp, WH Wilkin, JK TI Regulatory issues in the photochemical behavior of topical drug products SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Meeting Abstract C1 US FDA, CDER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 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 JUN PY 1999 VL 69 SI SI BP 46S EP 47S PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 220KB UT WOS:000081663200138 ER PT J AU Brown, PC Jacobs, A Lipnicki, JD Wilkin, JK AF Brown, PC Jacobs, A Lipnicki, JD Wilkin, JK TI FDA considerations for sunscreen safety and efficacy: Sunscreen products. SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Meeting Abstract C1 US FDA, CDER, HFD 540, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 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 JUN PY 1999 VL 69 SI SI BP 52S EP 53S PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 220KB UT WOS:000081663200157 ER PT J AU Jacobs, A Brown, P Wilkin, J AF Jacobs, A Brown, P Wilkin, J TI FDA considerations for sunscreens: New UV filters. SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Meeting Abstract C1 US FDA, CDER, HFD 540, Rockville, MD 20857 USA. NR 0 TC 0 Z9 1 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 JUN PY 1999 VL 69 SI SI BP 53S EP 53S PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 220KB UT WOS:000081663200158 ER PT J AU Wamer, WG Wei, RR AF Wamer, WG Wei, RR TI Formation and repair of DNA damage photosensitized by titanium dioxide in vitro. SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 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 JUN PY 1999 VL 69 SI SI BP 87S EP 87S PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 220KB UT WOS:000081663200263 ER PT J AU Wolff, GL Kodell, RL Kaput, JA Visek, WJ AF Wolff, GL Kodell, RL Kaput, JA Visek, WJ TI Caloric restriction abolishes enhanced metabolic efficiency induced by ectopic agouti protein in yellow mice SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID HUMAN HOMOLOG; GENE; EXPRESSION; RECEPTOR; OBESITY AB Caloric restriction (CR), from approximately 3 months of age, at 70% of the ad libitum (AL) caloric intake prevented development of overt obesity in female "viable yellow" A(vy)/A (BALB/cStCrlfC3Hf/Nctr x VY/WffC3Hf/Nctr-A(vy)) F-1 hybrid mice, In adult yellow A(vy)/A mice, caloric restriction eliminated the increased metabolic efficiency associated with the presence of agouti protein in ectopic sites, At 4 weeks of age, the yellow A(vy)/A mice were approximate to 14% heavier and by 12 weeks of age, when caloric restriction began, they were approximate to 24% heavier than the congenic agouti A/a mice. Between 4 and 12 weeks, the yellow mice gained approximate to 63% in body weight, whereas the agouti mice gained only approximate to 44%, While the comparable AL A(vy)/A mice gained approximate to 128% and the AL A/a mice gained approximate to 41% between 12 and 51 weeks of age, the CR A(vy)/A and A/a mice gained only 16% and 15%, respectively. Mean brain weights of CR mice of both genotypes were lower than those of the comparable ad libitum-fed (AL) groups; however, CR A(vy)/A mice had slightly, but significantly (P < 0.0001), higher brain weights than CR A/a mice. The larger mean brain weight and retention, during caloric restriction, of the somewhat greater prerestriction A(vy)/A mean body weight compared with prerestriction A/a mice were consonant with the hypothesis that ectopic agouti protein affects somatic growth directly or indirectly. This may be related to altered developmental/metabolic programming in yellow mice, indicated by greater metabolic efficiency and by an early transient increase in circulating IGF-1 levels. The specific cellular processes modulated by the agouti protein in ectopic sites remain to be identified. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Biochem Mol Biol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pharmacol Interdisciplinary Toxicol, Little Rock, AR 72205 USA. Gemini Biotech Inc, The Woodlands, TX 77381 USA. Univ Illinois, Coll Med, Dept Internal Med, Urbana, IL 61801 USA. RP Wolff, GL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 19 TC 9 Z9 11 U1 0 U2 2 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 JUN PY 1999 VL 221 IS 2 BP 99 EP 104 DI 10.1046/j.1525-1373.1999.d01-61.x PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 198PW UT WOS:000080434000003 PM 10352119 ER PT J AU Cerniglia, CE Kotarski, S AF Cerniglia, CE Kotarski, S TI Evaluation of veterinary drug residues in food for their potential to affect human intestinal microflora SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Review ID HUMAN FECAL FLORA; ANTI-MICROBIAL AGENTS; ANTIMICROBIAL AGENTS; CLOSTRIDIUM-DIFFICILE; HUMAN GUT; SELECTIVE DECONTAMINATION; ANAEROBIC-BACTERIA; GNOTOBIOTIC MICE; DIGESTIVE-TRACT; TRANSIT-TIME AB The use of veterinary drugs in food-producing animals may result in trace quantities of the drugs or their metabolites being present as residues in food. The effects of veterinary drugs intended for use in food-producing animals on intestinal microflora are evaluated in drug registration since these residues may pose a risk due to their antibiotic activity. This article reviews the different in vivo and in vitro experimental test systems and approaches used by animal health industries, contract laboratories, and regulatory authorities to assess the safety of veterinary drug residues in foods for human consumption. Furthermore, we propose a systematic approach to assess the effects and safety of veterinary drug residues on the human intestinal microflora. (C) 1999 Academic Press. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Pharmacia & Upjohn Inc, Kalamazoo, MI 49001 USA. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 131 TC 41 Z9 50 U1 1 U2 20 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD JUN PY 1999 VL 29 IS 3 BP 238 EP 261 DI 10.1006/rtph.1999.1300 PG 24 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 217KQ UT WOS:000081498800002 PM 10388611 ER PT J AU West, RW Kodell, RL AF West, RW Kodell, RL TI A comparison of methods of benchmark-dose estimation for continuous response data SO RISK ANALYSIS LA English DT Article DE efficiency; nonquantal; probit; quantal ID QUANTITATIVE RISK ASSESSMENT; DEVELOPMENTAL TOXICITY AB Methods of quantitative risk assessment for toxic responses that are measured on a continuous scale are not well established. Although risk-assessment procedures that attempt to utilize the quantitative information in such data have been proposed, there is no general agreement that these procedures are appreciably more efficient than common quantal dose-response procedures that operate on dichotomized continuous data. This paper points out an equivalence between the dose-response models of the nonquantal approach of Kodell and West((1)) and a quantal probit procedure, and provides results from a Monte Carlo simulation study to compare coverage probabilities of statistical lower confidence limits on dose corresponding to specified additional risk based on applying the two procedures to continuous data from a dose-response experiment. The nonquantal approach is shown to be superior, in terms of both statistical validity and statistical efficiency. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Univ S Carolina, Dept Stat, Columbia, SC 29208 USA. RP Kodell, RL (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 21 TC 20 Z9 20 U1 0 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD JUN PY 1999 VL 19 IS 3 BP 453 EP 459 DI 10.1023/A:1007052729375 PG 7 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 231JA UT WOS:000082303800012 PM 10765417 ER PT J AU DeGeorge, JJ Meyers, LL Takahashi, M Contrera, JF AF DeGeorge, JJ Meyers, LL Takahashi, M Contrera, JF TI The duration of non-rodent toxicity studies for pharmaceuticals SO TOXICOLOGICAL SCIENCES LA English DT Article DE non-rodent toxicity studies; harmonization of international standards ID LONG-TERM TOXICITY; DATABASE; DOG AB At the present time, there are no uniform standards for the duration of non-rodent chronic toxicity studies. The European Union (EU) requires a 6-month non-rodent study. In Japan, a 6-month study is sufficient for most, but not all, compounds. The U.S. Food and Drug Administration (FDA) maintains its standard duration of 12 months for non-rodents, with ti-month studies accepted for some clinical indications on a case-by-case basis. To achieve harmonization on the duration of non-rodent toxicity studies, each member regulatory region (EU, U.S., and Japan) of the International Conference on Harmonization (ICH) collected non-rodent studies with significant new toxicological findings that had occurred after 6 months. An ICH expert working group was organized that included representatives from the regulatory authorities of each ICH region, to jointly review all available case studies for the purpose of arriving at a consensus on the best duration time for non-rodent toxicity studies. Eighteen case studies were identified and evaluated (16 original cases plus 2 additional FDA cases); most of the toxicities identified fell into the following categories: (1) toxicities identified at 6 months; (2) toxicities observed at 12 months, which were absent or considered isolated and not noteworthy findings at 6 months; (3) drug-related deaths or morbidity that occurred between 6 and 12 months, with a pattern of toxicity that permited the interpolation of findings to an intermediate interval between 6 and 12 months; and (4) a shift in the dose response for toxicity with increasing duration of drug exposure. Of the 18 cases evaluated, 11 supported a study-duration of 9-12 months, 4 supported a duration of 12 months, and the 3 remaining cases indicated that a 6-month study would be adequate. The working group concluded that there was sufficient evidence to support a harmonized 9-month duration for non-rodent toxicity studies, which would be applicable for most categories of pharmaceuticals. C1 US FDA, Ctr Drug Evaluat & Res, Off Review Management, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Rockville, MD 20857 USA. Natl Inst Hlth Sci, Tokyo 158, Japan. RP Contrera, JF (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Review Management, HFD-901,5600 Fishers Lane, Rockville, MD 20857 USA. NR 6 TC 8 Z9 8 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 1999 VL 49 IS 2 BP 143 EP 155 DI 10.1093/toxsci/49.2.143 PG 13 WC Toxicology SC Toxicology GA 251PY UT WOS:000083455100001 PM 10416259 ER PT J AU Gaylor, DW Kodell, RL AF Gaylor, DW Kodell, RL TI Dose-response trend tests for tumorigenesis, adjusted for body weight SO TOXICOLOGICAL SCIENCES LA English DT Article DE dose-response; tumorigenesis; trend test; body weight; p-nitrobenzoic acid; o-nitroanisole; doxylamine succinate ID TOXICITY AB Several studies have demonstrated a relationship between rodent body weight and tumor incidence for some tissue/organ sites. It is not uncommon for a chemical tested for carcinogenicity to also affect body weight. In such cases, comparisons of tumor incidence may be biased by body-weight differences across dose groups. A simple procedure was investigated for reducing this bias. This procedure divides the animals into a few groups based on body weight. Body weight at 12 months was used, before the appearance of a tumor was likely to affect body weight. Statistics for dose-response trend tests are calculated within body weight strata and pooled to obtain an overall dose-response trend test. This procedure is analogous to that currently used, of stratifying animals, based on their age at the time of removal from a study. Age stratification is used to account for differences in animal age across dose groups, which can affect comparisons of tumor incidence. Several examples were investigated where the high-dose group had reduced body weights and associated reductions in tumor incidence, When the data were analyzed by body-weight strata, some positive dose-response trends for tumor incidence were demonstrated. In one case, the weight-adjusted analysis indicated that a negative dose-response trend in tumor incidence was a real effect, in addition to a body weight reduction. These examples indicate that it is important to consider the effects of body weight changes as low as 10%, and perhaps below, that were caused by chemicals in 2-year bioassays for carcinogenesis. The simple procedure of analyzing tumor incidence within bodyweight strata can reduce the bias introduced by weight differences across dose groups. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Gaylor, DW (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 10 TC 10 Z9 10 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 1999 VL 49 IS 2 BP 318 EP 323 DI 10.1093/toxsci/49.2.318 PG 6 WC Toxicology SC Toxicology GA 251PY UT WOS:000083455100020 PM 10416278 ER PT J AU Cavaille-Coll, M AF Cavaille-Coll, M TI Impact of compliance on drug developments: An FDA perspective SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT International Symposium on Transplant Recipient Compliance CY APR 03-05, 1998 CL ARLINGTON, VIRGINIA C1 US FDA, CDER, Div Special Pathogens & Immunol Drug Prod, Rockville, MD 20857 USA. RP Cavaille-Coll, M (reprint author), US FDA, CDER, Div Special Pathogens & Immunol Drug Prod, 5600 Fishers Lane,HFD-590, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD JUN PY 1999 VL 31 IS 4A SU S BP 40S EP 41S DI 10.1016/S0041-1345(99)00124-4 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 205WQ UT WOS:000080843900014 PM 10372044 ER PT J AU Rezapkin, GV Fan, LJ Asher, DM Fibi, MR Dragunsky, EM Chumakov, KM AF Rezapkin, GV Fan, LJ Asher, DM Fibi, MR Dragunsky, EM Chumakov, KM TI Mutations in Sabin 2 strain of poliovirus and stability of attenuation phenotype SO VIROLOGY LA English DT Article ID GENETIC STABILITY; NUCLEOTIDE-SEQUENCE; NEUROVIRULENCE TEST; TRANSGENIC MICE; MONKEY TEST; VACCINE; VIRUS; POLIOMYELITIS; PCR AB In this study, we attempted to identify the molecular determinants in the genome of the attenuated Sabin 2 vaccine strain of poliovirus that may change during vaccine production and result in an increase in monkey neurovirulence. An extensive search for suitable vaccine lots identified six batches that had failed the monkey neurovirulence test (MNVT). On repeated tests, these batches were found to have acceptable levels of monkey neurovirulence. One of the batches was additionally passaged six times under conditions used in vaccine production, and the resulting high-passage sample was screened for the presence of mutations and tested in monkeys. In addition to the previously described A --> G reversion at nucleotide 481, high-passage stock also contained a mutation in the VP1-coding region (3364 = G --> A) that consistently accumulated in the course of passaging. However, despite the presence of substantial amounts of these mutations, high-passage stock passed the MNVT. Replication of Sabin 2 poliovirus in the central nervous system of transgenic mice susceptible to poliovirus or in cultures of mouse cells, resulted in another mutation (3363 = A --> G). Even though its presence correlated with paralysis in mice, the introduction of 3363-G into the Sabin 2 genome did not increase neurovirulence of the virus. Previous studies identified the 481-G mutation as an important determinant of monkey neurovirulence. We prepared virus samples with varying amounts of genetically defined single mutants at this nucleotide and tested them in monkeys. The results demonstrated that even a 100% substitution at this site introduced into Sabin 2 strain did not increase monkey neurovirulence. The determination of the nucleotide sequence of an alternative strain used for the production of type 2 OPV (Chung 2) showed that it contained 100% of the wild-type 481-G but possessed an extremely low level of neurovirulence. These results demonstrate the remarkable stability of the attenuated phenotype of the Sabin 2 strain and show that (1) no batch of OPV 2 has ever repeatedly failed the MNVT, (2) growing the virus beyond the passage level allowed in vaccine production did not result in increased neurovirulence in monkeys, (3) a test for neurovirulence in transgenic mice may be more sensitive than the MNVT, and (4) determination of the mutational profile of vaccine batches detects inconsistencies in vaccine manufacturing processing that would not be detected by the MNVT. (C) 1999 Academic Press. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Chiron Behring GMBH & Co, D-35001 Marburg, Germany. RP Chumakov, KM (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-470,1401 Rockville Pike, Rockville, MD 20852 USA. EM chumakov@cber.fda.gov NR 21 TC 23 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAY 25 PY 1999 VL 258 IS 1 BP 152 EP 160 DI 10.1006/viro.1999.9718 PG 9 WC Virology SC Virology GA 201JV UT WOS:000080592400015 PM 10329577 ER PT J AU Schnellmann, JG Pumford, NR Kusewitt, DF Bucci, TJ Hinson, JA AF Schnellmann, JG Pumford, NR Kusewitt, DF Bucci, TJ Hinson, JA TI Deferoxamine delays the development of the hepatotoxicity of acetaminophen in mice SO TOXICOLOGY LETTERS LA English DT Article DE acetaminophen; deferoxamine; hepatotoxicity; oxidative stress; iron; covalent binding ID INDUCED HEPATIC NECROSIS; LIPID-PEROXIDATION; COVALENT BINDING; CULTURED-HEPATOCYTES; OXIDATIVE STRESS; LIVER PROTEINS; IN-VIVO; IRON; DESFERRIOXAMINE; TOXICITY AB The hepatotoxicity of acetaminophen is conventionally ascribed to metabolism by CYP450 to N-acetyl-p-benzoquinone imine and covalent binding to proteins. We investigated a potential role for oxidative stress by determining the effect of the ferric chelator deferoxamine (Desferal) on acetaminophen (paracetamol)-induced hepatotoxicity in mice. Administration of deferoxamine (75 mg/kg) 1 h after a toxic dose of acetaminophen (300 mg/kg) significantly delayed the development of the toxicity without altering covalent binding. In saline-treated mice serum ALT was 18 +/- 2 IU/l. In acetaminophen-treated mice serum alanine aminotransferase (ALT) was 779 +/- 271 at 2 h, 7421 +/- 552 IU/l at 4 h, 5732 +/- 523 IU/l at 8 h, and 5984 +/- 497 IU/l at 24 h. In acetaminophen plus deferoxamine-treated mice, serum ALT was 80 +/- 10 at 2 h, 472 +/- 74 IU/l at 4 h, 2149 +/- 597 IU/l at 8 h, and 5766 + 388 at 24 h. Deferoxamine at 1 h after acetaminophen did not decrease serum ALT at 12 h; however, deferoxamine at 1 and 4 h, or deferoxamine at 1 h plus N-acetylcysteine at 4 h to replete hepatic glutathione, decreased the toxicity from 5625 +/- 310 IU/l to 3436 +/- 546 IU/l and 3003 +/- 282 IU/l, respectively. Deferoxamine plus N-acetylcysteine at 1.25 h after acetaminophen was more effective at decreasing the 24 h toxicity than N-acetylcysteine alone. In acetaminophen treated mice, higher doses of deferoxamine (150-300 mg/kg) at 1 h greatly increased the observed hepatotoxicity at 4 h in a dose responsive manner, but deferoxamine alone was nontoxic. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Pathol Associates Inc, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Hinson, JA (reprint author), Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. EM HinsonJackA@exchange.uams.edu FU NIGMS NIH HHS [GM48749] NR 40 TC 34 Z9 36 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD MAY 20 PY 1999 VL 106 IS 1 BP 79 EP 88 DI 10.1016/S0378-4274(99)00021-1 PG 10 WC Toxicology SC Toxicology GA 202NJ UT WOS:000080658700009 PM 10378453 ER PT J AU Crowe, L Lau, W McLeod, L Anand, CM Ciebin, B LeBer, C McCartney, S Easy, R Clark, C Rodgers, F Ellis, A Thomas, A Shields, L Tate, B Klappholz, A LaBerge, I Sato, H Lehnkering, E Mascola, L Waddell, J Waterman, S Suarez, J Hammond, R Hopkins, R Neves, P Horine, MS Kludt, P DeMaria, A Hedberg, C Wicklund, J Besser, J Boxrud, D Hubner, B Osterholm, M Wu, FM Beuchat, L AF Crowe, L Lau, W McLeod, L Anand, CM Ciebin, B LeBer, C McCartney, S Easy, R Clark, C Rodgers, F Ellis, A Thomas, A Shields, L Tate, B Klappholz, A LaBerge, I Sato, H Lehnkering, E Mascola, L Waddell, J Waterman, S Suarez, J Hammond, R Hopkins, R Neves, P Horine, MS Kludt, P DeMaria, A Hedberg, C Wicklund, J Besser, J Boxrud, D Hubner, B Osterholm, M Wu, FM Beuchat, L TI Outbreaks of Shigella sonnei infection associated with eating fresh parsley - United States and Canada, July-August 1998 (Reprinted from MMWR, vol 48, pg 285-289, 1999) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Calgary Reg Hlth Author, Calgary, AB, Canada. Prov Lab So Alberta, Calgary, AB, Canada. Ontario Minist Hlth, Toronto, ON M5W 1R5, Canada. Ottawa Carleton Hlth Unit, Ottawa, ON, Canada. Hlth Canada, Natl Enter Lab, Edmonton, AB, Canada. Canadian Food Inspect Agcy, Ottawa, ON, Canada. Los Angeles Cty Dept Hlth Serv, Los Angeles, CA USA. Calif Dept Hlth Serv, Berkeley, CA 94704 USA. Miami Dade Cty Hlth Dept, Miami, FL USA. Massachusetts Dept Publ Hlth, Boston, MA 02111 USA. Massachusetts Div Food & Drugs, Boston, MA USA. Florida Dept Hlth, Tallahassee, FL USA. Minnesota Dept Hlth, Minneapolis, MN 55414 USA. Univ Georgia, Ctr Food Safety & Qual Enhancement, Athens, GA 30602 USA. CDC, US FDA, Epidemiol Branch, Div Parasit Dis, Atlanta, GA 30333 USA. CDC, Hosp Environm Lab Branch, Hosp Infect Program, Atlanta, GA 30333 USA. CDC, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. RP Crowe, L (reprint author), Calgary Reg Hlth Author, Calgary, AB, Canada. NR 1 TC 1 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 19 PY 1999 VL 281 IS 19 BP 1785 EP 1787 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 196BH UT WOS:000080288800009 ER PT J AU Volkman, BF Wilkens, SJ Lee, AL Xia, B Westler, WM Beger, R Markley, JL AF Volkman, BF Wilkens, SJ Lee, AL Xia, B Westler, WM Beger, R Markley, JL TI Redox-dependent magnetic alignment of Clostridium pasteurianum rubredoxin: Measurement of magnetic susceptibility anisotropy and prediction of pseudocontact shift contributions SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID DENSITY-FUNCTIONAL CALCULATIONS; LIQUID-CRYSTALLINE MEDIUM; CHEMICAL-SHIFTS; PARAMAGNETIC METALLOPROTEINS; ENERGY MINIMIZATION; DIPOLAR COUPLINGS; FIELD DEPENDENCE; CYTOCHROME-C; N-15 SIGNALS; NMR-SPECTRA AB An analysis of the magnetic field dependence of one-bond couplings has yielded the magnetic susceptibility anisotropies for Clostridium pasteurianum rubredoxin (Rdx) in its oxidized Fe(III) and reduced Fe(II) states. Experimental one-bond (HN)-H-1-N-15 and (Halpha-13Calpha)-H-1 couplings were measured at two field strengths (corresponding to 400 and 750 MHz H-1 frequencies) and decomposed into their field-independent scalar ((1)J) and field-dependent dipolar (D-1) components. The total numbers of measured dipolar couplings (H-1(N)-N-15 plus (1)Ha-C-13(alpha)) were 50 for oxidized Rdx and 49 for reduced Rdx. The atom pairs giving rise to these signals are located >11 Angstrom from the iron; those closer to the iron are too broad to be resolved in two-dimensional NMR spectra and may exhibit large Fermi contact shifts. A five-dimensional grid search and Powell minimization of the difference between each set of measured dipolar couplings and those calculated from an X-ray crystal structure of Fe(III) Rdx yielded the magnitude and orientation of the magnetic susceptibility. anisotropy in each oxidation state. (The data for Fe(II) Rdx were analyzed in terms of the X-ray structure for Fe(III) Rdx because no X-ray coordinates were available for the reduced rubredoxin. The assumption underlying this approximation, that the conformations of the oxidized and reduced rubredoxin are very similar in protein regions >11 Angstrom from the iron, was validated by comparisons of experimental and calculated pseudocontact shifts.) The axial and rhombic magnetic susceptibility anisotropies were 5.3 x 10(-28) and 2.1 x 10(-28) cm(3)/molecule, respectively, for oxidized Rdx, and 20.3 x 10(-28) and 9.7 x 10(-28) cm(3)/molecule, respectively, for reduced Rdx. The derived susceptibility tensors were then used to calculate the pseudocontact contributions to the backbone H-1(alpha) and H-1(N) chemical shifts of Rdx in the two oxidation states. Oxidation-state-dependent pseudocontact shifts were found to account fully (within experimental,error) for the experimental chemical shift differences exhibited by these backbone signals. Thus, the results are consistent with the absence of appreciable conformational differences between Fe(III) Rdx and Fe(ll) Rdx in the protein regions represented by the NMR data (>11 Angstrom from the iron). C1 Univ Wisconsin, Dept Biochem, Natl Magnet Resonance Fac, Madison, WI 53706 USA. Univ Wisconsin, Grad Program Biophys, Madison, WI 53706 USA. Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Markley, JL (reprint author), Univ Wisconsin, Dept Biochem, Natl Magnet Resonance Fac, 433 Babcock Dr, Madison, WI 53706 USA. RI Xia, Bin/O-1160-2016 OI Xia, Bin/0000-0002-2197-6403 NR 46 TC 30 Z9 30 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAY 19 PY 1999 VL 121 IS 19 BP 4677 EP 4683 DI 10.1021/ja990079b PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA 198MP UT WOS:000080428200017 ER PT J AU Ilev, IK Waynant, RW AF Ilev, IK Waynant, RW TI Grazing-incidence-based hollow taper for infrared laser-to-fiber coupling SO APPLIED PHYSICS LETTERS LA English DT Article ID YAG LASER; TRANSMISSION AB Based on grazing incidence, a simple uncoated hollow glass taper as an alternative technique for efficient infrared laser-to-fiber coupling is presented. Because of the mutual action of the direct parallel laser excitation, the mode-coupling process, and mode filtering, the hollow taper serves as a mode converter that transforms the highly multimode intensity distribution of the input laser emission into a high-quality smooth profile at the taper output. When an uncoated Pyrex-glass hollow taper is used for direct launching, without any intermediate focusing elements, of a powerful infrared Er:YAG laser emission (lambda = 2.94 mu m), we obtain high laser-to-taper (81%), taper-to-fiber (96%), and total laser-to-fiber (78%) coupling efficiencies. (C) 1999 American Institute of Physics. [S0003-6951(99)05320-6]. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Tech Univ Sofia, Inst Appl Phys, BG-1156 Sofia, Bulgaria. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-134, Rockville, MD 20857 USA. NR 12 TC 22 Z9 22 U1 1 U2 2 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0003-6951 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD MAY 17 PY 1999 VL 74 IS 20 BP 2921 EP 2923 DI 10.1063/1.123966 PG 3 WC Physics, Applied SC Physics GA 197EU UT WOS:000080352700005 ER PT J AU Tonnetti, L Veri, MC Bonvini, E D'Adamio, L AF Tonnetti, L Veri, MC Bonvini, E D'Adamio, L TI A role for neutral sphingomyelinase-mediated ceramide production in T cell receptor-induced apoptosis and mitogen-activated protein kinase-mediated signal transduction SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE neutral sphingomyelinase; ceramide; T cell receptor; signaling; activation; apoptosis ID MAJOR HISTOCOMPATIBILITY COMPLEX; NEGATIVE SELECTION; TRANSGENIC MICE; PHOSPHOLIPASE C-GAMMA-1; CLONAL ELIMINATION; ANTIGEN RECEPTOR; SELF-TOLERANCE; ENTEROTOXIN-B; THYMOCYTES; DEATH AB Studying apoptosis induced by T cell receptor (TCR) cross-linking in the T cell hybridoma, 3DO, we found both neutral sphingomyelinase activation and production of ceramide upon receptor engagement. Pharmacological inhibition of ceramide production by the fungal toxin, fumonisin B1, impaired TCR-induced interleukin (IL)-2 production and programmed cell death. Addition of either exogenous ceramide or bacterial sphingomyelinase reconstituted both responses. Moreover, specific inactivation of neutral sphingomyelinase by antisense RNA inhibited IL-2 production and mitogen-activated protein kinase activation after TCR triggering. These results suggest that ceramide production by activation of neutral sphingomyelinase is an essential component of the TCR signaling machinery. C1 NIAID, Tcell Apoptosis Unit, Lab Cell & Mol Immunol, NIH, Bethesda, MD 20892 USA. Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Immunobiol Lab, Bethesda, MD 20892 USA. RP NIAID, Tcell Apoptosis Unit, Lab Cell & Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ldadamio@atlas.niaid.nih.gov NR 48 TC 68 Z9 69 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD MAY 17 PY 1999 VL 189 IS 10 BP 1581 EP 1589 DI 10.1084/jem.189.10.1581 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 198TT UT WOS:000080440900007 PM 10330437 ER PT J AU Malozowski, S Purucker, M Worobec, A AF Malozowski, S Purucker, M Worobec, A TI Cushing's syndrome induced by betamethasone nose drops - Children taking intranasal corticosteroids should be monitored for growth retardation SO BRITISH MEDICAL JOURNAL LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Malozowski, S (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 4 TC 7 Z9 7 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD MAY 15 PY 1999 VL 318 IS 7194 BP 1355 EP 1356 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 198HR UT WOS:000080418400060 PM 10383213 ER PT J AU Sur, S Wild, JS Choudhury, BK Sur, N Alam, R Klinman, DM AF Sur, S Wild, JS Choudhury, BK Sur, N Alam, R Klinman, DM TI Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDUCED EOSINOPHIL RECRUITMENT; RECOMBINANT INTERFERON-GAMMA; INDUCED AIRWAY HYPERRESPONSIVENESS; ANTI-IGE ANTIBODY; IMMUNOGLOBULIN (IG)-E; CUTTING EDGE; LATE-PHASE; MICE; INTERLEUKIN-12; CHALLENGE AB Asthma is an inflammatory disease of the airways that is induced by Th2 cytokines and inhibited by Th1 cytokines, Despite a steady increase in the incidence, morbidity, and mortality from asthma, no current treatment can reduce or prevent asthma for a prolonged period, We examined the ability of unmethylated CpG oligodeoxynucleotides (ODN), which are potent inducers of Th1 cytokines, to prevent the inflammatory and physiological manifestations of asthma in mice sensitized to ragweed allergen. Administration of CpG ODN 48 h before allergen challenge increased the ratio of IFN-gamma to IL-4 secreting cells, diminished allergen-induced eosinophil recruitment, and decreased the number of ragweed allergen-specific IgE-producing cells. These effects of CpG ODN were sustained for at least 6 wk after its administration, Furthermore, there was a vigorous Th1 memory response to the recall Ag, inhibition of peribronchial and perivascular lung inflammation, and inhibition of bronchial hyperresponsiveness 6 wk after administration of CpG ODN, Administration of CpG ODN in IFN-gamma -/- mice failed to inhibit eosinophil recruitment, indicating a critical role of IFN-gamma in mediating these effects. This is the first report of a treatment that inhibits allergic lung inflammation in presensitized animals for a prolonged period and thus has relevance to the development of an effective long term treatment for asthma. C1 Univ Texas, Med Branch, Dept Internal Med, Div Allergy & Immunol, Galveston, TX 77555 USA. US FDA, Ctr Biol Evaluat & Res, Retroviral Immunol Sect, Bethesda, MD 20892 USA. RP Sur, S (reprint author), Univ Texas, Med Branch, Dept Internal Med, Div Allergy & Immunol, Route 0762,409 CSB,301 Univ Blvd, Galveston, TX 77555 USA. NR 51 TC 296 Z9 307 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 15 PY 1999 VL 162 IS 10 BP 6284 EP 6293 PG 10 WC Immunology SC Immunology GA 195FP UT WOS:000080240200083 PM 10229876 ER PT J AU Sechler, JMG Rosenberg, AS AF Sechler, JMG Rosenberg, AS TI Genetic variation among 129 substrains: Practical consequences - Reply SO JOURNAL OF IMMUNOLOGY LA English DT Letter C1 US FDA, Dept Hlth & Human Serv, Rockville, MD 20852 USA. RP Sechler, JMG (reprint author), US FDA, Dept Hlth & Human Serv, Rockville, MD 20852 USA. NR 4 TC 0 Z9 0 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 15 PY 1999 VL 162 IS 10 BP 6295 EP 6295 PG 1 WC Immunology SC Immunology GA 195FP UT WOS:000080240200086 ER PT J AU Walchle, C Diwan, BA Shiao, YH Calvert, RJ AF Walchle, C Diwan, BA Shiao, YH Calvert, RJ TI Microsatellite instability is infrequent in azoxymethane-induced rat intestinal tumors: An assessment by capillary electrophoresis SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article; Proceedings Paper CT 89th Annual Meeting of the American-Association-for-Cancer-Research CY MAR 27-APR 01, 1998 CL NEW ORLEANS, LOUISIANA SP Amer Assoc Canc Res DE rat; colon cancer; microsatellite instability; azoxymethane; intestinal tumor; capillary electrophoresis ID P53 GENE-MUTATIONS; COLORECTAL-CANCER; MISMATCH REPAIR; METHYLAZOXYMETHANOL ACETATE; COLON CARCINOGENESIS; F344 RATS; 1,2-DIMETHYLHYDRAZINE; DNA; CELL; INVOLVEMENT AB A rat model of colon cancer in which tumors are induced by azoxymethane (AOM) is frequently used to study putative environmental agents that may modify the risk of human colon cancer development. In order to evaluate the usefulness of this model for human risk assessment, a comparison of the molecular changes associated with tumorigenesis in the rat model with those in human colon cancer is desirable. Microsatellite instability (MSI), an alteration in length of short repetitive DNA sequences associated with defective DNA mismatch repair, is an important molecular characteristic of many human colon tumors. Intestinal tumors were induced in male Fischer 344 rats injected with 15 mg/kg body wt AOM in four weekly doses. Thirteen intestinal tumors were examined for MSI at 10 different microsatellite loci, using a capillary electrophoresis (CE) method for accurate assessment of DNA length. This method was shown to have a resolution of 1 bp for a 140-bp PCR product and to be capable of detecting one mutant sequence within a background of 10 wild-type sequences. The CE method also readily distinguished a known MSI-positive human tumor sample from its matching control sample. Among the 13 rat intestinal tumors examined, only one had MSI, which was present at only a single locus. We conclude that, unlike sporadic human colon tumors in which 15-30% of tumors have MSI (usually at multiple loci), MSI is very rare in AOM-induced rat intestinal tumors. C1 NCI, Comparat Carcinogenesis Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC Frederick, Ft Detrick, MD 21702 USA. US FDA, Off Special Nutr, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Walchle, C (reprint author), NCI, Comparat Carcinogenesis Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. FU NCI NIH HHS [N01-CO-5600] NR 39 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY 15 PY 1999 VL 157 IS 1 BP 9 EP 15 DI 10.1006/taap.1999.8662 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 201DQ UT WOS:000080580100002 PM 10329502 ER PT J AU Friedman, MA Woodcock, J Lumpkin, MM Shuren, JE Hass, AE Thompson, LJ AF Friedman, MA Woodcock, J Lumpkin, MM Shuren, JE Hass, AE Thompson, LJ TI The safety of newly approved medicines - Do recent market removals mean there is a problem? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID APPETITE-SUPPRESSANT DRUGS; VALVULAR HEART-DISEASE; FEXOFENADINE; MIBEFRADIL; FENFLURAMINE; PHENTERMINE; TERFENADINE AB The removal of 5 pharmaceuticals from the market in a 12-month period because of unexpected adverse events raised concerns about the adequacy of the drug review process at the US Food and Drug Administration (FDA), Specifically, concerns were raised about improvements in drug review efficiency that significantly reduced FDA review times. We have reviewed the circumstances of the 5 removals to determine whether there was any relationship to the increased efficiencies in the drug review process. When the removed drugs were analyzed by date of approval, no increase in the number of drugs taken off the market was seen, demonstrating that reduced review processing time was not the reason for the cluster of removals, We conclude that the agency's drug review procedures and postmarketing surveillance system after a drug has been marketed are currently adequate but must continually adjust to future challenges. C1 US FDA, Off Commissioner, Rockville, MD 20857 USA. US FDA, Ctr Drug Res & Evaluat, Rockville, MD 20857 USA. US FDA, Off Policy, Rockville, MD 20857 USA. US FDA, Off Performance Evaluat, Rockville, MD 20857 USA. US FDA, Off Publ Affairs, Off Commissioner, Rockville, MD 20857 USA. RP Friedman, MA (reprint author), US FDA, Off Commissioner, 5600 Fishers Ln,Hf-28, Rockville, MD 20857 USA. NR 35 TC 143 Z9 149 U1 2 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 12 PY 1999 VL 281 IS 18 BP 1728 EP 1734 DI 10.1001/jama.281.18.1728 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 193WR UT WOS:000080161200031 PM 10328074 ER PT J AU Hori, K Burd, PR Kutza, J Weih, KA Clouse, KA AF Hori, K Burd, PR Kutza, J Weih, KA Clouse, KA TI Human astrocytes inhibit HIV-1 expression in monocyte-derived macrophages by secreted factors SO AIDS LA English DT Article DE astrocytes; cytokines; dementia; HIV AIDS; macrophages ID HUMAN-IMMUNODEFICIENCY-VIRUS; COLONY-STIMULATING FACTOR; CENTRAL-NERVOUS-SYSTEM; IMMUNE-DEFICIENCY-SYNDROME; GROWTH-FACTOR-BETA; CELL-LINES; INFECTION; BRAIN; REPLICATION; CYTOKINES AB Objective: To determine the effects of primary human fetal and adult astrocytes on HIV-1 replication in monocyte-derived macrophages (MDM). Design: HIV-2 can infect the brain in the early stage of systemic infection. The HIV-1-associated cognitive/motor complex develops later in the course of the disease, suggesting that brain cells may inhibit the early productive infection and the development of neurological disease. In this study, we established an in-vitro coculture system to determine whether astrocytes can modulate HIV-1 replication in MDM. Methods: Elutriated human monocytes were differentiated in culture, then infected with monocyte tropic HIV-1. One day after infection, MDM were co-cultured with primary astrocyte. Reverse transcriptase (RT) activity was used to monitor virus replication. RT-polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA) and bioassay were used to assess cytokine production. Results: Primary human astrocytes suppressed HIV-1 replication in MDM via the production of soluble factors. Cytokine inhibitors of HIV-1, such as IFN-gamma, IL-4, IL-10 and IL-13, were not detectable, whereas transforming growth factor beta (IGF-P) was constitutively produced only in its latent form. Paraformaldehyde-fixed astrocytes, unable to secrete cytokines, failed to inhibit HIV-1. These cells caused enhanced virus replication, however, which correlated with an increase in macrophage colony stimulating factor (M-CSF) production. Conclusions: Human astrocytes can increase and decrease HIV-1 expression in MDM. An imbalance between the positive and negative effects of astrocytes may contribute to the expression of virus in the brain, and the development of HIV-1-associated cognitive/motor complex. (C) 1999 Lippincott Williams & Wilkins.. C1 US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Rockville, MD 20852 USA. RP Clouse, KA (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, HFM-505,1401 Rockville Pike, Rockville, MD 20852 USA. EM clouse@cber.fda.gov NR 37 TC 13 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 7 PY 1999 VL 13 IS 7 BP 751 EP 758 DI 10.1097/00002030-199905070-00003 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 194CG UT WOS:000080174100003 PM 10357373 ER PT J AU Murray, JS Elashoff, MR Iacono-Connors, LC Cvetkovich, TA Struble, KA AF Murray, JS Elashoff, MR Iacono-Connors, LC Cvetkovich, TA Struble, KA TI The use of plasma HIV RNA as a study endpoint in efficacy trials of antiretroviral drugs SO AIDS LA English DT Article DE antiretroviral therapy; combination therapy; clinical trials; viral load; limit of assay quantification; clinical progression ID IMMUNODEFICIENCY-VIRUS INFECTION; ZIDOVUDINE COMBINATION THERAPY; PLACEBO-CONTROLLED TRIAL; CD4 CELL COUNTS; CUBIC MILLIMETER; DOUBLE-BLIND; LAMIVUDINE; ZALCITABINE; MONOTHERAPY; DIDANOSINE AB Objectives: To evaluate the utility of HIV RNA as an endpoint in antiretroviral efficacy studies. Design: Data collected from antiretroviral efficacy trials were analyzed to explore relationships between clinical progression and the magnitude, nadir and duration of HIV RNA reductions. The proportion of patients suppressing HIV RNA below assay quantification, time to maximal virologic response, and loss of virologic response in relation to pretreatment characteristics were also analyzed. Methods: Analyses were conducted using data from individual antiretoviral efficacy trials or groups of trials that studied similar types of drug regimens and used similar HIV RNA assays. Treatment regimens were pooled for most analyses. Clinical progression was defined as the occurrence of an AIDS-defining event (essentially Centers of Disease Control criteria) or death. Results: Treatment-induced reductions in HIV RNA approximating total assay variability of about 0.5 log(10) copies/ml were associated with decreases in the risk of clinical progression. Larger and more sustained reductions in HIV RNA were directly associated with lower risks for disease progression. Lower initial HIV RNA reductions were associated with more durable HIV RNA suppression. Conclusions: For antiretoviral efficacy studies, plasma HIV RNA is a suitable study endpoint that is likely to predict a decreased risk for AIDS progression and death. Because greater and more sustained reductions in HIV RNA appear to confer greater reductions in clinical risk, maintaining maximal suppression of plasma HIV RNA, particularly below the limits of assay quantification, appears to be a rigorous benchmark for assessing the efficacy of antiretroviral regimens. C1 US FDA, Ctr Drug Evaluat & Res, Div Antiviral Drug Prod, Rockville, MD 20857 USA. RP Murray, JS (reprint author), 1429 Swann St NW, Washington, DC 20009 USA. NR 24 TC 85 Z9 85 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 7 PY 1999 VL 13 IS 7 BP 797 EP 804 DI 10.1097/00002030-199905070-00008 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 194CG UT WOS:000080174100008 PM 10357378 ER PT J AU Nightingale, SL AF Nightingale, SL TI Electronic "Orange book" SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 5 PY 1999 VL 281 IS 17 BP 1580 EP 1580 DI 10.1001/jama.281.17.1580 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 191MJ UT WOS:000080025900008 PM 10235141 ER PT J AU Nightingale, SL AF Nightingale, SL TI Dietary supplement labeling more informative SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 5 PY 1999 VL 281 IS 17 BP 1580 EP 1580 DI 10.1001/jama.281.17.1580 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 191MJ UT WOS:000080025900009 PM 10235141 ER PT J AU Nightingale, SL AF Nightingale, SL TI Regularly updated drug product safety information on the Internet SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 5 PY 1999 VL 281 IS 17 BP 1580 EP 1580 DI 10.1001/jama.281.17.1580 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 191MJ UT WOS:000080025900007 PM 10235141 ER PT J AU Szabo, D Szabo, G Ocsovszki, I Aszalos, A Molnar, J AF Szabo, D Szabo, G Ocsovszki, I Aszalos, A Molnar, J TI Anti-psychotic drugs reverse multidrug resistance of tumor cell lines and human AML cells ex-vivo SO CANCER LETTERS LA English DT Article DE reversal; multidrug resistance; amitriptyline; fluphenazine; maprotiline; trimipramine; desipramine; imipramine; haloperidol; cyclosporin A; in vitro; in vivo; in patients ID P-GLYCOPROTEIN; CANCER; TRANSPORTER; DOXORUBICIN AB Anti-psychotic drugs are used in cancer patients undergoing chemotherapy frequently and the concomitantly used drugs may alter the pharmacokinetics of each other. One reason for the alteration of pharmacokinetics may be the modulation of the function of P-glycoprotein, whose efflux pump occurs in resistant cancer cells, in human intestine and in the blood-brain barrier. For this reason we tested the effect of several anti-psychotic drugs on the multidrug-resistant pump, P-glycoprotein. We found that in the MDR gene transfected L121C MDR, L5178 MDR and in the KB-V-1 cells selected for resistance some antipsychotic drugs block the function of P-glycoprotein. Blood cells of two treatment-resistant leukemic patients also showed increased uptake of daunorubicin if treated ex vivo with the anti-psychotic drugs. Our results suggest that pharmacokinetic studies should be performed prior to concomitant clinical use of such drugs which block P-glycoprotein function. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Albert Szent Gyorgyi Med Univ, Fac Med, Inst Microbiol, H-6720 Szeged, Hungary. Albert Szent Gyorgyi Med Univ, Inst Biochem, H-6701 Szeged, Hungary. Debrecen Univ Med, Inst Biophys, H-4012 Debrecen, Hungary. US FDA, Washington, DC 20204 USA. RP Szabo, D (reprint author), Albert Szent Gyorgyi Med Univ, Fac Med, Inst Microbiol, Dom Ter 10, H-6720 Szeged, Hungary. NR 19 TC 44 Z9 47 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAY 3 PY 1999 VL 139 IS 1 BP 115 EP 119 DI 10.1016/S0304-3835(99)00020-8 PG 5 WC Oncology SC Oncology GA 202NC UT WOS:000080658000016 PM 10408903 ER PT J AU Mann, M Piazza-Hepp, T Koller, E Struble, K Murray, J AF Mann, M Piazza-Hepp, T Koller, E Struble, K Murray, J TI Unusual distributions of body fat in AIDS patients: A review of adverse events reported to the Food and Drug Administration SO AIDS PATIENT CARE AND STDS LA English DT Review ID HIV-1 INFECTION; ACCUMULATION AB This report summarizes postmarketing adverse events reported to the Food and Drug Administration (FDA) that describe unusual or abnormal fat distribution in association with anti-retroviral therapies. Reports associated will protease inhibitors were compared to those associated with non-protease inhibitor antiretroviral therapies. The Spontaneous Reporting System (SRS) and Adverse Event Reporting System (AERS) of the FDA MEDWATCH postmarketing surveillance system served as the database. Four protease inhibitors (saquinavir, indinavir, nelfinavir, and ritonavir) and seven nonprotease inhibitors (zidovudine, didanosine, zalcitabine, stavudine, lamivudine, nevirapine, and delavirdine) were searched for reports relating to: weight increase, unusual fat deposition, Cushing's syndrome, or Cushingoid appearance. Each drug was searched for its "life" from time of initial approval through a uniform database cutoff of March 18, 1998. A total of 62 cases of abnormal fat accumulation were reported in association with one or several of the four approved protease inhibitors compared to three cases reported in association with the seven non-protease inhibitor based therapies. Case descriptions varied, and included abdominal fat accumulation, breast enlargement, thick necks, buffalo humps, multiple lipomatous growths, Cushingoid features, centralized fat redistribution, and mesenteric, omental, and retroperitoneal fat accumulation. Some subjects switched or stopped their antiretroviral therapy, others underwent surgery to remove the fat, and many considered their symptoms disabling. The pathophysiologic mechanism for these events remains unclear and a causal link to a specific drug or drug class is uncertain. Patients and clinicians reporting to the MEDWATCH system, however, have clearly associated the development of abnormal body fat with protease inhibitors as opposed to other antiretroviral therapies. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Mann, M (reprint author), 13712 Springdale Dr, Clarksville, MD 21029 USA. NR 14 TC 12 Z9 12 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD MAY PY 1999 VL 13 IS 5 BP 287 EP 295 DI 10.1089/apc.1999.13.287 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 199MN UT WOS:000080486100006 PM 10356808 ER PT J AU Temple, R AF Temple, R TI Role of government agencies regarding cost-effectiveness claims: FDA perspective SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT Symposium on Economics and Cost-Effectiveness in Evaluating the Value of Cardiovascular Therapies CY APR 17-20, 1997 CL ST PETERSBURG, FLORIDA C1 US FDA, Ctr Drugs Evaluat & Res, Rockville, MD 20857 USA. RP Temple, R (reprint author), US FDA, Ctr Drugs Evaluat & Res, 5600 Fisher Lane,HFD-101, Rockville, MD 20857 USA. NR 3 TC 2 Z9 2 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 1999 VL 137 IS 5 BP S75 EP S77 DI 10.1016/S0002-8703(99)70434-5 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 194AY UT WOS:000080171000041 PM 10220602 ER PT J AU Mondoro, TH Shafer, BC Vostal, JG AF Mondoro, TH Shafer, BC Vostal, JG TI Restoration of in vitro responses in platelets stored in plasma SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE hypotonic shock response; plasma storage; platelet aggregation; platelet storage; P-selectin expression ID FUNCTIONAL THROMBIN RECEPTOR; MONOCLONAL-ANTIBODY; ACTIVATED PLATELETS; HYPOTONIC STRESS; STORAGE; VIABILITY; TRANSFUSION; INVIVO; RECOVERY; PROTEIN AB Conventional platelet storage in a blood bank is up to 5 days at room temperature in plasma. I We investigated the optimal medium for assessing the quality of stored platelets by comparing in vitro test responses after resuspension in autologous plasma prepared from platelet-rich plasma after 5 days of storage at room temperature, autologous plasma stored cell-free for 5 days at room temperature, or autologous plasma stored cell-free for 5 days at -20 degrees C. Five-day-old platelets were prepared from aliquots of the same unit and resuspended in 1 of the 3 plasma preparations. The platelet-plasma mixtures were monitored for changes in pH, mean platelet volume, hypotonic shock response, P-selectin expression, and aggregation. There were statistically significant differences between platelets resuspended in original plasma and platelets resuspended in either plasma stored cell-free at room temperature or frozen, with regard to hypotonic shock response, agonist-induced aggregation, and P-selectin expression. Plasma stored with platelets for 5 days yielded inferior platelet function test responses when? compared with plasma stored cell-free at room temperature or frozen. Therefore, for direct comparison of platelet responses following novel storage methods, the resuspending plasma should be stored under the same conditions as the control platelet unit. C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD USA. RP Mondoro, TH (reprint author), Bldg 29,Rm 331,HFM-335,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 37 TC 20 Z9 21 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAY PY 1999 VL 111 IS 5 BP 693 EP 699 PG 7 WC Pathology SC Pathology GA 189RU UT WOS:000079920500015 PM 10230361 ER PT J AU Forti, N Salazar, LA Giannini, SD Hirata, RDC Diament, J Issa, JS Ozaki, AN Nguyen, NY Hirata, MH AF Forti, N Salazar, LA Giannini, SD Hirata, RDC Diament, J Issa, JS Ozaki, AN Nguyen, NY Hirata, MH TI Apolipoprotein E isoforms are apparently not related to lipid profile modification in Brazilian postmenopausal women SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 Univ Sao Paulo, Fac Pharmaceut Sci, Sao Paulo, Brazil. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RI Hirata, Mario/C-9718-2013 NR 0 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 1999 VL 144 SU 1 BP 106 EP 106 DI 10.1016/S0021-9150(99)80408-0 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 203BM UT WOS:000080687500409 ER PT J AU Salazar, LA Giannini, SD Forti, N Hirata, MH Diament, J Issa, JS Lima, TM Ozaki, AN Nguyen, NY Hirata, RDC AF Salazar, LA Giannini, SD Forti, N Hirata, MH Diament, J Issa, JS Lima, TM Ozaki, AN Nguyen, NY Hirata, RDC TI Polymorphisms of the candidate genes of atherosclerosis in Brazilian women with Coronary Artery Disease SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 Univ Sao Paulo, Fac Pharmaceut Sci, Sao Paulo, Brazil. Univ Sao Paulo, Inst Heart, Sao Paulo, Brazil. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RI Lima, Thais/C-2767-2012; Hirata, Mario/C-9718-2013 OI Lima, Thais/0000-0003-3175-5281; NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 1999 VL 144 SU 1 BP 185 EP 185 DI 10.1016/S0021-9150(99)80705-9 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 203BM UT WOS:000080687500707 ER PT J AU Gu, Y Branham, WS Sheehan, DM Webb, PJ Moland, CL Streck, RD AF Gu, Y Branham, WS Sheehan, DM Webb, PJ Moland, CL Streck, RD TI Tissue-specific expression of messenger ribonucleic acids for insulin-like growth factors and insulin-like growth factor-binding proteins during perinatal development of the rat uterus SO BIOLOGY OF REPRODUCTION LA English DT Article ID FACTOR-I; ESTROGEN-RECEPTOR; MYOBLAST DIFFERENTIATION; POSTNATAL ONTOGENY; COMPLEMENTARY-DNA; MOLECULAR-CLONING; UTERINE GROWTH; IGF-I; RNAS; REPRODUCTION AB Insulin-like growth factor (IGF)-I and IGF-II play a number of important roles in growth and differentiation, and IGF-binding proteins (IGFBPs) modulate IGF biological activity. IGF-l has been shown previously to be essential for normal uterine development. Therefore, we used in situ hybridization assays to characterize the unique tissue- and developmental stage-specific pattern of expression for each IGF and IGFBP gene in the rat uterus during perinatal development (gestational day [GD]-20 to postnatal day [PND]-24). IGF-I and IGFBP-1 mRNAs were expressed in all uterine tissues throughout this period. IGFBP-3 mRNA was not detectable at GD-20 but became detectable beginning at PND-5, and the signal intensity appeared to increase during stromal and muscle development. IGFBP-4 mRNA was abundant throughout perinatal development in the myometrium and in the stroma, particularly near the luminal epithelium. IGFBP-4 mRNA was abundantly expressed in myometrium throughout perinatal development. IGFBP-6 mRNA was detected throughout perinatal development in both the stroma and myometrium in a diffuse expression pattern. IGF-II and IGFBP-2 mRNAs were not detected in perinatal uteri. Our results suggest that coordinated temporal and spatial expression of IGF-I and its binding proteins (IGFBP-1,-3,-4,-5, and -6) could play important roles in perinatal rodent uterine development. C1 US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Streck, RD (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT-130, Jefferson, AR 72079 USA. NR 46 TC 24 Z9 24 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD MAY PY 1999 VL 60 IS 5 BP 1172 EP 1182 DI 10.1095/biolreprod60.5.1172 PG 11 WC Reproductive Biology SC Reproductive Biology GA 189VE UT WOS:000079926200016 PM 10208980 ER PT J AU Friedman, MA AF Friedman, MA TI Regulatory issues in the evaluation of antimetastatic and other novel anticancer therapies SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT 14th Bristol-Myers-Squibb Nagoya International Cancer Treatment Symposium on the Challenges in Cancer Metastasis CY SEP 11-12, 1998 CL NAGOYA, JAPAN SP Bristol Myers Squibb DE antimetastatic drugs; US food and drug administration; clinical trials; regulation AB This article outlines some of the complexities and challenges confronting researchers and the US Food and Drug Administration (FDA) in the area of evaluation of antimetastatic and other novel anticancer therapies. The scientific regulatory matrix utilized by the FDA is outlined. Subsequently, the complications encountered when designing and interpreting studies of antimetastatic drugs are described, and finally changes in the regulatory landscape both within the USA and internationally are considered. C1 US FDA, Rockville, MD 20857 USA. RP Friedman, MA (reprint author), US FDA, 5600 Fishers Lane,Rom 14-57, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 1999 VL 43 SU S BP S100 EP S103 DI 10.1007/s002800051106 PG 4 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 202DJ UT WOS:000080636600017 PM 10357567 ER PT J AU Clark, DL Andrews, PA Smith, DD DeGeorge, JJ Justice, RL Beitz, JG AF Clark, DL Andrews, PA Smith, DD DeGeorge, JJ Justice, RL Beitz, JG TI Predictive value of preclinical toxicology studies for platinum anticancer drugs SO CLINICAL CANCER RESEARCH LA English DT Article ID I CLINICAL-TRIAL; PHASE-I; PHARMACOKINETICS; PHARMACOLOGY; COMPLEX AB Rodent and nonrodent toxicology studies are currently expected to support Phase I trials of antineoplastic drugs in the United States. To determine the predictive value of these studies, we initiated a project to compare preclinical and clinical toxicity data within various drug classes. The first class analyzed was the platinum anticancer drugs. Twelve platinum analogues that had both preclinical (mice, rats and/or dogs) and clinical data from matching drug administration schedules were identified. The rodent LD,, (the dose that causes lethality in 10% of treated animals) or dog toxic dose high (a dose that when doubled causes lethality in dogs) correlated well with the human maximally tolerated dose on a mg/m(2) basis, For every platinum analogue investigated, one-third the rodent LD,, or one-third the dog toxic dose high in mg/m(2) gave a starting dose and a first escalation dose that did not exceed the clinical maximally tolerated dose. The dose-limiting toxicities in patients were previously observed in 7 of 7, 7 of 8, and 9 of 11 mouse, rat, and dog studies, respectively. Our data indicate that mice, rats, and dogs all had value in predicting a safe starting dose and the qualitative toxicities in humans for platinum anticancer compounds. The efficiency of Phase 1 trials could have been improved without sacrificing patient safety by allowing higher starting doses for this drug class than conventionally permitted. C1 US FDA, Div Oncol Drug Prod, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Div Biometr, Rockville, MD 20857 USA. US FDA, Off Review Management, Rockville, MD 20857 USA. RP Clark, DL (reprint author), US FDA, Div Oncol Drug Prod, 5600 Fisheries Lane,HFD 150, Rockville, MD 20857 USA. FU DRS NIH HHS [RSR-003A] NR 29 TC 18 Z9 18 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 1999 VL 5 IS 5 BP 1161 EP 1167 PG 7 WC Oncology SC Oncology GA 200FE UT WOS:000080528300028 PM 10353752 ER PT J AU Gutman, S AF Gutman, S TI The role of Food and Drug Administration regulation of in vitro diagnostic devices - Applications to genetics testing SO CLINICAL CHEMISTRY LA English DT Article AB The Food and Drug Administration (FDA) has been involved in the regulation of in vitro diagnostic devices (IVDs or laboratory tests) since the introduction of the Medical Device Amendments of 1976. IVDs developed as kits or systems intended for use in multiple laboratories require review by the FDA before being marketed to ensure appropriate performance and labeling. IVDs developed as in-house, or so-called "home-brew", tests or laboratory test services are considered medical devices, but historically have not been subject to premarket review as a matter of enforcement discretion. FDA recently established a new regulatory paradigm for in-house tests based on classification of the active ingredients or building blocks of these tests as analyte-specific reagents (ASRs). ASRs are exempt from premarket review but subject to both manufacturing and labeling controls. Currently, genetic tests are received and reviewed by the FDA in the same manner as other in vitro diagnostic tests. The FDA currently is in the process of chartering a new genetics advisory panel to provide the agency with outside expertise to deal with genetic testing issues. We are also continuing to work with other agencies within the Department of Health and Human Services to determine how we can cooperatively help foster this important new area of testing. (C) 1999 American Association for Clinical Chemistry. C1 US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Clin Lab Devices, Rockville, MD 20850 USA. RP Gutman, S (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Clin Lab Devices, Rockville, MD 20850 USA. NR 1 TC 19 Z9 19 U1 1 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAY PY 1999 VL 45 IS 5 BP 746 EP 749 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 194TP UT WOS:000080209900036 PM 10222377 ER EF