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Biomedical subjects

B Bush

Publications and source records attributed to B Bush.

At least 19 recordsLinked to original sources
PubMed1992

Coplanar PCBs in fish and mussels from marine and estuarine waters of New York State.

Thirty samples of striped bass from marine and estuarine waters of New York State, six samples of mussels from Long Island Sound, and one composite sample of freshwater mussels from Troy were analyzed by a recently developed method which combines sulfuric acid cleanup, carbon chromatography, and high-resolution gas chromatography for the determination of non-ortho- and mono-ortho-substituted polychlorinated biphenyls (PCBs), which are biologically active congeners of PCBs and approximate isostereomers of 2,3,7,8-tetrachlorodibenzo-P-dioxin of (2,3,7,8-TCDD). Non-ortho coplanar PCBs ranged from 0.2 to 37.1 ppb in fish. The highest concentrations of 37.1 ng/g of 3,3',4,4'-tetrachlorobiphenyl (77) and 7.5 ng/g of 3,3',4,4',5-pentachlorobiphenyl (126) were detected in a fish caught near Troy/Albany, New York. Mono-ortho-substituted PCBs ranged from 0.4 to 790 ppb in fish, with the major components identified as 2,3',4,4',5-penta-(118) and 2,3,3',4,4'-pentachlorobiphenyls (105). When concentrations were converted to 2,3,7,8-TCDD picogram equivalents, 99% of the equivalents were derived from three congeners (77, 105, and 126), 3,3',4,4',5-pentachlorobiphenyl (126) accounting for approximately 80% of the activity. At Troy pg/g TCDD equivalents derived from PCB were approximately 3000, whereas the actual 2,3,7,8-TCDD concentration was only 20 pg/g; hence, accurate coplanar PCB measurement is important.

Animals↗
PubMed1991

Neurotoxicity of polychlorinated biphenyls: structure-activity relationship of individual congeners.

Neurotoxicity of Polychlorinated Biphenyls: Structure-Activity Relationship of Individual Congeners, Shain, W., Bush, B., Seegal, R. (1991). Toxicol. Appl. Pharmacol. 111, 33-42. Experimental and epidemiological data indicate that polychlorinated biphenyls (PCBs) may function as neurotoxicants. The mechanism(s) of action of PCBs in the brain is not well understood. One reason for our lack of understanding of PCB action in the central nervous system is that, in general, commercial mixtures of PCBs have been used for these experiments. We used a homogeneous cell line, PC12 cells, to investigate the relative potency of 43 individual PCB congeners. The neurotoxicant action of PCB congeners was measured as a decrease in cell dopamine content. We first described the potency of individual congeners; 2,2'-dichlorobiphenyl was the most potent congener (EC50 = 65 microM). The structure-activity relationships described in these experiments indicated that (i) congeners with ortho- or ortho-, para-chlorine substitutions were most potent; (ii) chlorination in a meta position decreased cell dopamine content in ortho-substituted congeners, but had little effect in ortho-, para-substituted congeners; and (iii) increasing congener chlorination did not correlate with a decrease in potency, though total chlorination of a ring appeared to reduce potency. Second, we determined that potency did not correlate with either cellular PCB content or gas chromatographic retention time. Finally, experiments with 2,2'-dichlorobiphenyl indicated that PCBs and not their metabolites were the toxicants. Thus, PCB congeners decrease cell dopamine content by interaction at specific sites that have preference for ortho- or ortho-, para-substituted congeners. The neurotoxic action of PCBs may occur by a different mechanism than PCB hepato- and immunotoxicity since these effects are most sensitive to non-ortho-substituted, dioxin-like, congeners.

Animals↗
PubMed1991

Comparison of effects of Aroclors 1016 and 1260 on non-human primate catecholamine function.

Adult male non-human primates, Macaca nemestrina, were orally-exposed to corn oil or corn oil containing either Aroclor 1016 or 1260 at doses of 0.8, 1.6 or 3.2 mg/(kg.day) for 20 weeks. Brain concentrations of biogenic amines and individual PCB congeners were determined following exposure. Aroclor 1016 significantly decreased concentrations of dopamine and its metabolites in the caudate, putamen, substantia nigra and hypothalamus but did not alter neurotransmitter or metabolite concentrations in the globus pallidus and hippocampus. Total PCB concentrations ranged from 1 to 5 ppm with only three congeners detected (2,4,4'; 2,4,2',4' and 2,5,2',5') making up, on average, 72%, 18% and 7% respectively of the total residue in brain. There were no discernible differences in the congener make-up between brain regions. Aroclor 1260 reduced dopamine concentrations in the caudate, putamen and hypothalamus but produced no effects in the substantia nigra, globus pallidus or hippocampus. Aroclor 1260 concentrations ranged from 18 to 28 ppm with the highest levels found in the hippocampus. Of the congeners that made up more than 5% of the total residue in brain, all were hexa- and heptachlorinated di-ortho-substituted congeners. There were no discernible differences in congener make-up between brain regions. We conclude that: (1) ortho-substituted non-planar congeners are responsible for the observed changes in neurochemical function; (2) both Aroclor 1016 and Aroclor 1260 decrease dopamine concentrations by similar mechanisms; and (3) based on differences in brain concentrations of Aroclor 1260 congeners compared to Aroclor 1016 congeners, lightly-chlorinated congeners are more effective in reducing central dopamine concentrations than are the more highly chlorinated congeners.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Sub-chronic exposure of the adult rat to Aroclor 1254 yields regionally-specific changes in central dopaminergic function.

Laboratory rats were exposed to chow adulterated with either 500 or 1000 ppm Aroclor 1254 for 30 days. Analysis of biogenic amines and their metabolites in the dorsal frontal cortex, lateral olfactory tract, striatum, basal hypothalamus, hippocampus and brainstem revealed significant decreases in dopamine concentrations and metabolism in only the striatum and lateral olfactory tract. Concentrations of individual PCB congeners in the striatum, lateral olfactory tract and hippocampus were measured by gas chromatography with electron capture detection. Neither total concentration nor variations in concentrations of individual congeners between regions could explain this regional specificity. The susceptibility of the striatum and lateral olfactory tract to insult by PCBs may be due to their innervation by midbrain dopaminergic neurons which have been shown to be particularly sensitive to insult from environmental, infectious and pharmacologic agents.

Acetone↗
PubMed1990

Lightly chlorinated ortho-substituted PCB congeners decrease dopamine in nonhuman primate brain and in tissue culture.

Exposure of the nonhuman primate, Macaca nemestrina, to Aroclor 1016, a commercial mixture of 26 lightly chlorinated PCB congeners, decreased dopamine concentrations in the caudate, putamen, substantia nigra, and hypothalamus. Only three ortho-substituted nonplanar PCB congeners (2,4,4', 2,4,2',4', and 2,5,2',5') were detected in these brain regions, suggesting that these congeners may be responsible for the observed decreases in dopamine. The ability of these and other PCB congeners to alter dopamine function was tested directly by applying them to dopamine-synthesizing cells in culture, PC-12 pheochromocytoma cells. In vitro testing demonstrated that these three congeners reduced cellular dopamine concentrations while planar, dioxin-like congeners, e.g., 3,4,3',4' and 3,4,5,3',4', did not. Thus, these ortho-substituted nonplanar congeners may be directly responsible for the observed changes in in vivo neurochemistry. Furthermore, these results suggest that the observed decreases in both in vivo and in vitro dopamine concentrations may occur through a novel mechanism and not through the Ah-receptor complex thought to mediate immunotoxic and hepatotoxic changes following exposure to dioxin and dioxin-like PCBs.

Animals↗
PubMed1989

Accumulation of polychlorobiphenyl congeners and p,p'-DDE at environmental concentrations by corn and beans.

The uptake of polychlorinated biphenyl (PCB) congeners present at low concentrations in the environment was investigated in leaf composites of four crop species and final fruits at two sites. All four species preferentially accumulated the same eight congeners, although not in the same degree or rank. No bean species demonstrated a significant increase in accumulation over time, and corn significantly reduced its PCB load over time. Mechanisms are suggested for such behavior. Fruits were 100 times less contaminated than plant leaves.

Dichlorodiphenyl Dichloroethylene↗
PubMed1989

Effects of Aroclor 1254 on dopamine and norepinephrine concentrations in pheochromocytoma (PC-12) cells.

Pheochromocytoma (PC-12) cells synthesize, store, release and metabolize dopamine (DA) and norepinephrine (NE) in a manner analogous to that observed in the mammalian central nervous system. These cells were used to develop and validate an alternate method to animal testing to assess the effects of a complex environmental mixture of polychlorinated biphenyls (Aroclor 1254) on cellular catecholamine function. Aroclor 1254, at concentrations of 1 to 100 ppm, significantly decreased cellular catecholamine concentrations after 6 hrs. Exposure at 100 ppm for periods of less than an hr increased cellular catecholamine concentrations while longer exposure times (i.e., 1 to 24 hr) decreased cellular catecholamine concentrations. This in vitro depletion of catecholamines is similar to that seen in vivo. Thus, PC-12 cells may be useful for neurochemical evaluation of neurotoxicants with particular reference to effects on catecholaminergic systems.

Adrenal Gland Neoplasms↗
PubMed1988

Anaerobic biodegradation of polychlorinated biphenyls by bacteria from Hudson River sediments.

Anaerobic biodegradation of monochlorobiphenyls; a tetrachlorobiphenyl; Aroclor 1221, a polychlorinated biphenyl (PCB) mixture; and sediment PCBs was investigated by using mixed bacterial populations from Hudson River sediments obtained by PCB enrichment. When the bacteria were incubated with Aroclor 1221, the disappearance of congeners was in general inversely related to GC retention time and thus indirectly to the octanol/water partition coefficient. When incubated with 14C-labeled monochlorobiphenyls, 14CO2 was detected, but methane was not. Radioactivity was also found in the cell material and the aqueous fraction. 2,4,2',4'-Tetrachlorobiphenyl produced little evidence of biodegradation or reductive dechlorination. Inoculation of anaerobic sediments from the Hudson River with the mixed population produced a marked decrease in sediment PCBs, whereas uninoculated sediments were observed to have little change. This decrease was also related to the partition coefficient.

Anaerobiosis↗
PubMed1987

Screening for alcohol abuse using the CAGE questionnaire.

A prospective study of 518 patients admitted to the orthopedic and medical services of a community-based teaching hospital during a six-month period was performed to test the hypothesis that a short, easily administered questionnaire would improve the detection rate by physicians of alcohol abuse. The CAGE questionnaire--a mnemonic for attempts to cut back on drinking, being annoyed at criticisms about drinking, feeling guilty about drinking, and using alcohol as an eye opener--was utilized as a screening instrument. The mean corpuscular volume of red blood cells, liver transaminase levels, and the gamma-glutamyl transpeptidase level were also evaluated as screening tests. The presence or absence of alcoholism and alcohol abuse for a consecutive sample of CAGE-negative patients and all patients answering "yes" to one or more of the CAGE questions was established through the administration of the Michigan Alcoholism Screening Test, a detailed chart review, and analysis of quantity of alcohol consumed. Diagnostic criteria were those described in the Diagnostic and Statistical Manual III. The prevalence of alcohol abuse was 20 percent. The mean corpuscular volume, gamma-glutamyl transpeptidase value, and liver transaminase levels were very insensitive as screening tests. In contrast, the CAGE questionnaire had a sensitivity of 85 percent and a specificity of 89 percent. Only 63 percent of the alcoholic subjects and alcohol abusers were detected by their physicians, and in only 24 percent of these cases did a physician address the problem with the patient. The CAGE questionnaire is a simple, sensitive, and specific screening test for alcohol abusers.

Alcoholism↗
PubMed1987

Neurobehavioral and somatic effects of perinatal PCB exposure in rats.

Developing rats were exposed to PCBs via provision of diets containing 0.02 (no PCB added), 2.5, 26, or 269 ppm Aroclor 1254 to sperm-positive female rats from mating to weaning of their pups. Provision of the 269 ppm diet decreased the number of impregnated rats that delivered a litter and lowered pup birth weight, and most pups died within 7 days of birth. Pregnancy success, pup birth weight, and dam body weight and food intake were not altered in the 2.5 and 26 ppm conditions. Preweaning pup growth was reduced in the 26 ppm condition and slightly reduced in the 2.5 ppm condition. The ontogeny of negative geotaxis, auditory startle, and air righting was delayed in pups from the 26 ppm condition. Pups in the 2.5 ppm condition had slightly delayed development of auditory startle. PCB exposure did not affect the duration of forepaw suspension or age at eye opening. Maximal electroshock seizure tests on postweaning rats showed that perinatal PCB exposure decreased seizure severity of both the 2.5 and 26 ppm groups as indicated by increased durations of forelimb and hindlimb flexion and decreased duration of hindlimb extension. PCB exposure increased pup liver weights at birth and dam and pup liver weights at weaning. Spleen and thymus weights were lower in PCB-exposed pups, while brain weights were unaffected. Analytical determination of PCB levels in brain showed greater maternal transfer of PCBs during lactation than during gestation. Elevated PCB levels were detectable in brains of perinatally exposed adult rats. The results indicate that perinatal PCB exposure of rats alters neurobehavioral and somatic ontogeny.

Animals↗
PubMed1986

High-performance liquid chromatography of biogenic amines and metabolites in brain, cerebrospinal fluid, urine and plasma.

A method for high-performance liquid chromatographic separation and electrochemical detection of biogenic amines and metabolites in a variety of biological matrices is described. The method employs either homogenization, precipitation or dilution followed by direct injection of the samples and permits the chromatographic resolution of dopamine, norepinephrine, epinephrine, serotonin (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in brain; 3-methoxy-4-hydroxyphenylglycol, DOPAC, 5-HIAA and HVA in cerebrospinal fluid; 5-HIAA, HVA and 5-HT in plasma; and 5-HIAA and HVA in urine. Alterations in chromatographic conditions, voltammetry and in vivo pharmacological manipulations are employed to verify the identity of the putative neurotransmitter and metabolite peaks in the biological samples.

Animals↗
PubMed1986

Polychlorinated biphenyls produce regional alterations of dopamine metabolism in rat brain.

Adult male rats were gavaged with a mixture of polychlorinated biphenyls (PCBs; Aroclors 1254 and 1260) at either 500 or 1000 mg/kg body weight. Concentrations of dopamine (DA) and its major metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were determined in caudate nucleus and lateral olfactory tract on postgavage Days 1, 3, 7 and 14. DA and DOPAC concentrations in caudate decreased after exposure to PCBs, as did HVA/DA ratios. DA concentrations in the lateral olfactory tract were unaffected, although DOPAC/DA ratios decreased. These results demonstrate that the mature mammalian nervous system is sensitive to a brief exposure to PCBs and that regional differences exist in the neurochemical sequelae of exposure to PCBs.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Alcohol abuse in women seeking gynecologic care.

In several retrospective studies, alcoholic women have reported menstrual problems significantly more often than nonalcoholic women. There is no information, however, comparing the prevalence of alcohol abuse in women who receive periodic gynecologic care and those who seek care for menstrual disorders such as the premenstrual syndromes. This question was studied in two private practice settings. Women seeking periodic care were obtained from a suburban, general gynecology practice. Women seeking treatment for premenstrual syndrome (PMS) were obtained from a practice that specialized in the care of PMS. Ninety-five patients with PMS and 147 patients seeking periodic care were screened with the CAGE questions--a mnemonic for attempts to Cut back on drinking, being Annoyed at criticism about drinking, feeling Guilty about drinking, and using alcohol as an Eye-opener. Women who gave affirmative responses to one or more of the CAGE questions were evaluated for the presence of alcohol abuse. In the women seeking periodic care, 33% were CAGE positive and 12% were alcohol abusers. In the PMS practice, 51% were CAGE positive and 21% were alcohol abusers. Alcohol abuse is a common problem in gynecologic practice. Women who seek medical care for PMS are at much greater risk to be alcohol abusers.

Adolescent↗
PubMed1986

Regional alterations in serotonin metabolism induced by oral exposure of rats to polychlorinated biphenyls.

Adult male rats were gavaged with a mixture of Aroclors 1254 and 1260 at a dose level of either 500 or 1000 mg/kg and were killed on post-gavage days 1, 3, 7 and 14. Total PCB concentrations and concentrations of serotonin and its major central metabolite, 5-hydroxyindoleacetic acid, were determined in the dorsal frontal cortex, lateral olfactory tract, hippocampus, medial-basal hypothalamus and brainstem. Differences in the initial concentrations and redistribution patterns of PCBs were observed in the brain regions examined. Serotonin concentrations were reduced in frontal cortex and hippocampus, unaffected in hypothalamus and brainstem and elevated in lateral olfactory tract. Serotonin metabolism, estimated by determination of the metabolite to neurotransmitter ratio, was elevated in all brain areas except for the lateral olfactory tract. These results demonstrate that following a single exposure to PCBs, there are significant changes in serotonin concentrations and metabolism in the adult rat. Furthermore, there are regional brain differences with regard to PCB concentrations and the direction and magnitude of neurochemical change induced by the PCBs.

Animals↗