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Biomedical subjects

B Bush

Publications and source records attributed to B Bush.

At least 37 records · Page 2Linked to original sources
PubMed1995

Environmental polychlorinated biphenyls: acute toxicity of landfill soil extract to female prepubertal rats.

Subsurface soil from a National Priorities List landfill containing about 2.5% polychlorinated biphenyls (PCBs) was extracted and the extract cleaned by Florisil slurry and alumina column chromatography. The refined extract contained 48 mg/mL PCB, mainly trichlorobiphenyls and tetrachlorobiphenyls, traces of polychlorinated naphthalenes, 125 micrograms/mL 2,2-bis-p-chlorophenyl-1,1-dichloroethylene (DDE), and low levels of chlorinated dibenzofurans. The refined extract was dissolved in corn oil and administered intraperitoneally to weanling (day 20) female rats on days 20 and 21; rats were terminated on day 22. Limited data indicated possible hematopoietic effects, including neutrophilia. There were no changes in relative uterus, kidney, or adrenal gland weights between total doses of 3 to 96 mg/kg total PCB. Relative liver weights increased significantly at 36 mg/kg and activities of P450s 1A1 (as ethoxyresorufin O-dealkylase) and 2B (as pentoxyresorufin O-dealkylase) increased at 12 mg/kg and plateaued at 36 (P450 1A1) or 48 (P450 2b) mg/kg. Serum total thyroxine (T4) declined significantly at doses of 36 mg/kg and greater; thyroid follicular epithelial cells were significantly larger within the same dose range, but the follicular colloid area decreased to less than 60% control values at 12 mg/kg and remained at this size through 72 mg/kg. Maximum mobilization of T4 apparently occurred at 12 mg/kg and attenuated measured declines in circulating levels. Even though a large proportion of proven and probable estrogenic chlorobiphenyls (CBs) were present, the lower amounts of more potent antiestrogenic aryl hydrocarbon (Ah) receptor agonists and/or decreased responsiveness because of low serum T4 levels may have antagonized the uterotropic response.

Adrenal Glands↗
PubMed1994

Decreases in dopamine concentrations in adult, non-human primate brain persist following removal from polychlorinated biphenyls.

Adult male non-human primates, Macaca nemestrina, were orally exposed for 20 weeks to 3.2 mg/kg per day of either Aroclor 1016 or Aroclor 1260 made up in corn oil. Following cessation of exposure, the animals were observed for either an additional 24 or 44 weeks. After killing, regional brain concentrations of biogenic amines and polychlorinated biphenyls were determined by high-performance liquid chromatography (HPLC) and gas chromatography (GC), respectively. Brain dopamine (DA) concentrations were significantly decreased, compared to controls, in all polychlorinated biphenyl-exposed animals. Most importantly, in spite of significant decreases in brain polychlorinated biphenyl concentrations observed following removal from exposure (an average decline of 60%), there was no statistically discernible relationship of the changes in brain DA concentrations to either time following removal from polychlorinated biphenyls or brain polychlorinated biphenyl concentrations. These findings demonstrate that sub-chronic exposure of the adult non-human primate to polychlorinated biphenyls results in long-lasting changes in brain DA concentrations.

Animals↗
PubMed1994

Mono-ortho- and non-ortho-substituted polychlorinated biphenyls in human milk from Mohawk and control women: effects of maternal factors and previous lactation.

Fifty-four individual human milk samples from 50 mothers (20 Mohawks and 30 controls) were analyzed for four non-ortho- and eight mono-ortho-substituted polychlorinated biphenyls (PCBs). Mean total coplanar PCBs concentrations were 49 ng/g and 55 ng/g lipid for Mohawk and control women, respectively. A statistical evaluation of all analytical data reveals no significant difference of total coplanar PCB level between Mohawk and control women. The level of these contaminants is influenced by the age of the mother, number of breastfed children, and length of nursing period. Older women, primiparae, and cigarette smokers had higher levels of coplanar PCBs. In general, women had higher levels of coplanar PCBs in the first lactation and in the earlier samples of a given lactation, while levels declined both with duration of breast-feeding and with number of children nursed. The contribution of individual non-ortho- and mono-ortho-substituted PCB congeners to the total calculated toxic equivalent values (sigma TEQ) was assessed for the breast milk samples. The levels of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in human milk of pooled specimens from Los Angeles, California and Binghamton, New York, widely separate cities in the United States (Schecter et al. 1989), were presented for reference purpose. The main contributions to the sigma TEQ were PCB congeners #118 (25.8 pg/g lipid), #126 (25 pg/g lipid), #105 (10.8 pg/g lipid), and #156 (7.4 pg/g lipid). Collectively, these compounds accounted for 70% of the sigma TEQ values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

INTEGRATION OF POSITIVE AND NEGATIVE FEEDBACK LOOPS IN A CRAYFISH MUSCLE

It is now well established that in arthropods movement-related feedback may produce positive, as well as negative, feedback reflexes (Bassler, 1976; DiCaprio and Clarac, 1981; Skorupski and Sillar, 1986; Skorupski et al. 1992; Vedel, 1980; Zill, 1985). Usually the same motor neurones are involved in both negative feedback (resistance) reflex responses and positive feedback reflexes. Reflex reversal involves a shift in the pattern of central inputs to a motor neurone, for example from excitation to inhibition. In the crayfish, central modulation of reflexes has been described in some detail for two basal limb proprioceptors, the thoracocoxal muscle receptor organ (TCMRO) and the thoracocoxal chordotonal organ (TCCO) (Skorupski et al. 1992; Skorupski and Bush, 1992). Leg promotor motor neurones are excited by stretch of the TCMRO (which, in vivo, occurs on leg remotion) in a negative feedback reflex, but when this reflex reverses they are inhibited by the same stimulus. Release of the TCCO (which corresponds to leg promotion) excites some, but not all, promotor motor neurones in a positive feedback reflex. There are at least two ways in which the reflex control of a muscle may be modulated in this system. Firstly, inputs to motor neurones may be routed via alternative reflex pathways to produce different reflex outputs. Secondly, the pattern of inputs to a motor pool may be inhomogeneous, so that activation of different subgroups of the motor pool causes different outputs. Different crayfish promotor motor neurones are involved in different reflexes. On this basis, the motor neurones may be classified into at least two subgroups: those that are excited by the TCCO in a positive feedback reflex (group 1) and those that are not (group 2). Do these motor neurone subgroups have different effects on the promotor muscle, or is the output of the two promotor subgroups summed at the neuromuscular level? To address this question we recorded from the promotor nerve and muscle in a semi-intact preparation of the crayfish, Pacifastacus leniusculus. Adult male and female crayfish, 8-11 cm rostrum to tail, were decapitated and the tail, carapace and viscera removed. The sternal artery was cannulated and perfused with oxygenated crayfish saline, as described previously (Sillar and Skorupski, 1986).

Journal Article↗
PubMed1993

Toxic potential of non-ortho and mono-ortho coplanar polychlorinated biphenyls in Aroclors, seals, and humans.

Mono-ortho and non-ortho coplanar polychlorinated biphenyls (PCBs) were analyzed in Aroclors, seals, and humans by graphitized carbon, a recently developed HPLC method (Hong et al. 1992b) and high-resolution gas chromatography with electron capture detection (HRGC/ECD). The concentration data were multiplied by potency factors derived from aryl hydrocarbon hydroxylase (AHH) induction to give 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents. The ability to separate coplanar PCBs from the majority of PCBs has allowed the use of TCDD toxicity equivalence to compare the relative dioxin-like potency of PCB residues in the complex mixtures. The most active mixtures, Aroclors 1254, 1248, and 1242, contained 42-54% by weight of chlorine. The results demonstrate that the apparent dioxin-like potency of PCB residues in Aroclors, seals, and humans is dominated by three congeners, 3,3',4,4'-tetra-, 2,3,3'-4,4'-, and 3,3',4,4',5-pentachlorobiphenyl (IUPAC nos. 77, 105, 126).

Adipose Tissue↗
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

Fuel loads in U.S. cities.

Sources of burnable material within U.S. cities are analyzed. Based on a detailed evaluation of construction practices, storage of burnable contents, building function and layout, and density of buildings in city districts, we derive urban fuel load densities in terms of land use type and geographic location. Residential building fuel loads vary regionally from 123 to 150 kg m-2; nonresidential building classes have loads from 39 to 273 kg m-2. The results indicate that average U.S. urban area fuel loads range from 14 to 21 kg m-2.

Construction Materials↗
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↗