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Biomedical subjects

B Bush

Publications and source records attributed to B Bush.

At least 19 recordsLinked to original sources

High friction from a stiff polymer using microfiber arrays.

High dry friction requires intimate contact between two surfaces and is generally obtained using soft materials with an elastic modulus less than 10 MPa. We demonstrate that high-friction properties similar to rubberlike materials can also be obtained using microfiber arrays constructed from a stiff thermoplastic (polypropylene, 1 GPa). The fiber arrays have a smaller true area of contact than a rubberlike material, but polypropylene's higher interfacial shear strength provides an effective friction coefficient of greater than 5 at normal loads of 8 kPa. At the pressures tested, the fiber arrays showed more than an order of magnitude increase in shear resistance compared to the bulk material. Unlike softer materials, vertical fiber arrays of stiff polymer demonstrate no measurable adhesion on smooth surfaces due to high tensile stiffness.

Journal Article↗

Hyperactivity and impulsiveness in rats fed diets supplemented with either Aroclor 1248 or PCB-contaminated St. Lawrence river fish.

We examined whether exposure to polychlorinated biphenyls (PCBs) around puberty would produce hyperactivity and impulsiveness in adult Sprague-Dawley rats. Randomly assigned groups consumed food containing environmental concentrations of Aroclor 1248, PCB-contaminated St. Lawrence River carp, or corn oil (control). All received operant training to a final multiple (mult) 120-s, fixed interval (FI), 5-min extinction (EXT) schedule. Pressing rates of both exposed groups for drops of water averaged more than 1.5 times that of controls, especially toward the end of the 120-s interval. This overactivity included bursts with short (< or =0.5 s) interresponse times (IRTs), behavior characteristic of hyperactive boys and genetically hyperactive rats. The exposed groups also overreacted to the decreases in reinforcement density associated with transition to the final schedule. The results were interpreted in terms of the possible alterations in the animals' reinforcement mechanisms and the possible neurotoxic effects of PCB exposure.

Animals↗

Nonpeptide tachykinin receptor antagonists. II. Pharmacological and pharmacokinetic profile of SB-222200, a central nervous system penetrant, potent and selective NK-3 receptor antagonist.

The pharmacological and pharmacokinetic profile of SB-222200 [(S)-(-)-N-(alpha-ethylbenzyl)-3-methyl-2-phenylquinoline-4-car boxami de], a human NK-3 receptor (hNK-3R) antagonist, was determined. SB-222200 inhibited (125)I-[MePhe(7)]neurokinin B (NKB) binding to Chinese hamster ovary (CHO) cell membranes stably expressing the hNK-3 receptor (CHO-hNK-3R) with a K(i) = 4.4 nM and antagonized NKB-induced Ca(2+) mobilization in HEK 293 cells stably expressing the hNK-3 receptor (HEK 293-hNK-3R) with an IC(50) = 18.4 nM. SB-222200 was selective for hNK-3 receptors compared with hNK-1 (K(i) > 100,000 nM) and hNK-2 receptors (K(i) = 250 nM). In HEK 293 cells transiently expressing murine NK-3 receptors (HEK 293-mNK-3R), SB-222200 inhibited binding of (125)I-[MePhe(7)]NKB (K(i) = 174 nM) and antagonized NKB (1 nM)-induced calcium mobilization (IC(50) = 265 nM). In mice oral administration of SB-222200 produced dose-dependent inhibition of behavioral responses induced by i.p. or intracerebral ventricular administration of the NK-3 receptor-selective agonist, senktide, with ED(50) values of approximately 5 mg/kg. SB-222200 effectively crossed the blood-brain barrier in the mouse and rat. The inhibitory effect of SB-222200 against senktide-induced behavioral responses in the mouse correlated significantly with brain, but not plasma, concentrations of the compound. Pharmacokinetic evaluation of SB-222200 in rat after oral administration (8 mg/kg) indicated sustained plasma concentrations (C(max) = about 400 ng/ml) and bioavailability of 46%. The preclinical profile of SB-222200, demonstrating high affinity, selectivity, reversibility, oral activity, and central nervous system penetration, suggests that it will be a useful tool compound to define the physiological and pathophysiological roles of NK-3 receptors, in particular in the central nervous system.

Animals↗

Assessment of prenatal exposure to PCBs from maternal consumption of Great Lakes fish: an analysis of PCB pattern and concentration.

The current study was designed to assess the pattern and concentration of prenatal PCB exposure in the newborns of women who consumed Great Lakes fish. We compared the pattern and concentration of umbilical cord blood PCBs of 145 women who reported never having consumed Great Lakes fish to 134 women who reported consuming at least 40 PCB-equivalent fish lbs of Great Lakes fish in their lifetime (Lonky et al., 1996). Although the average levels of total PCBs in cord blood were exceedingly low (approximately 1.0 ppb), the data clearly indicated that both the proportion (mol%) and the absolute concentration (ppb) of the most heavily chlorinated and persistent PCB homologues (homologues C17-C19) were markedly elevated in the cord blood of fish eaters. This effect grew markedly as a function of the total PCBs detected in the sample. Moreover, the concentration of the most heavily chlorinated PCB homologues was significantly dependent on how recently the fish were consumed relative to pregnancy. The order of highly chlorinated PCB concentration was consumed fish throughout pregnancy > consumed fish up until pregnancy > stopped consuming fish in 1984 > never consumed Lake Ontario fish. In contrast, PCB homologues of light (Cl1-Cl3) or moderate (Cl4-Cl6) chlorination were unrelated to fish consumption. Analysis of the relationship between the PCB homologues in cord blood and their homologues in breast milk provided further converging evidence of these findings. While PCB homologues of light (Cl1-Cl3) or moderate (Cl4-Cl6) chlorination did not correlate with their breast milk homologues, the most persistent and heavily chlorinated PCB homologues (Cl7-Cl9) were significantly and positively correlated with breast milk levels. These data indicate that the most heavily chlorinated PCBs provide valid and reliable exposure information in a lean medium such as cord blood. We conclude that maternal consumption of Great Lakes fish increases the risk of prenatal exposure to the most heavily chlorinated PCB homologues.

Adult↗

Local fish consumption and serum PCB concentrations among Mohawk men at Akwesasne.

A study was conducted to assess local fish consumption patterns and their relationship to concentrations of total polychlorinated biphenyls (PCBs) in the serum of Mohawk men residing near three hazardous waste sites. From 1992 to 1995, 139 men were interviewed and donated a 20-ml venous blood sample. The results indicated that the men ate a mean of 21.2 local fish meals during the past year, compared with annual means of 27.7 meals 1-2 years before and 88.6 meals more than 2 years before (P<0.001 for test of trend). This change is probably a consequence of advisories issued against the consumption of local fish, since 97% of the men were aware of the advisories and two-thirds had changed their behavior as a result. Multiple regression analysis revealed that serum PCB levels increased with age (beta=0.036, P<0.001) and local fish consumption (beta=0.088, P=0.006). The data suggest that local fish consumption has contributed to body burdens in this population and that the advisories have been effective in modifying local fish consumption habits.

Adolescent↗

Induction of hepatic cytochromes P450 in dogs exposed to a chronic low dose of polychlorinated biphenyls.

Induction of cytochrome P450 isoforms, specifically CYP1A1, and their catalytic activities are potential biomarkers of environmental contamination by polychlorinated biphenyls (PCBs). In this study, dogs were exposed to 25 ppm or 5 ppm Aroclor 1248 (PCB mixture) daily in their diet for 10 or 20 weeks, respectively. Relative to controls, hepatic microsomes from dogs dosed with PCBs had higher levels of CYP1A1 detected in immunoblots and higher levels of EROD activity, but low levels of induction for CYP2B and PROD activity. Concentrations of 96 PCB congeners in serum and liver were evaluated using capillary chromatography. Results showed that all dogs exposed to PCB mixtures had higher levels of PCB in serum and liver. Dogs preferentially sequestered highly chlorinated PCB congeners in liver relative to serum. With these experiments, we demonstrated that EROD activity was a potentially sensitive marker of PCB exposure at 5 and 25 ppm. Furthermore, CYP1A1 and EROD activity were maximally induced in dogs consuming dietary concentrations only 2.5 times the maximal permissible level for human food (FDA). The value of CYP1A1 induction as a biomarker of PCB exposure was tenuous because neither CYP1A1 levels nor EROD activity correlated with total PCB body burden. However, a small subset of congeners were identified in liver that may strongly influence EROD and PROD induction. Finally, two dogs in the 25 ppm dose group were fasted for 48 h. After 24 h of fasting, several new congeners appeared in the serum and remained in the serum for the remainder of the fast. The fast caused a 293% increase in PCB concentration in serum. This increase has strong implications regarding mobilization of toxic PCBs in wildlife during fasting (e.g., migration, hibernation).

Animals↗

Fish consumption and breast milk PCB concentrations among Mohawk women at Akwesasne.

A study was conducted to determine the relation between the consumption of contaminated local fish and concentrations of total polychlorinated biphenyls (PCBs) and 68 PCB congeners in the milk of nursing Mohawk women residing near three hazardous waste sites. From 1986 to 1992, 97 Mohawk women were interviewed and donated at least 50 ml of breast milk. The comparison population consisted of 154 Caucasians. After adjustment for potential confounders, Mohawk mothers who gave birth in 1986-1989 had a geometric mean milk total PCB concentration of 0.602 ppm (fat basis) compared with 0.375 ppm for the control group (p = 0.009). These Mohawk women also had significantly higher geometric mean concentrations of nine congeners. Beginning in 1990, however, there were no significant differences between the Mohawk women and the comparison group. Estimated cumulative lifetime exposure from local fish consumption was significantly related to milk total PCB and to three congeners only among those Mohawks who gave birth from 1986 to 1989. The reduction in breast milk PCB concentrations parallels a corresponding decrease in local fish consumption and may be the result of the advisories that have been issued over the past decade recommending against the consumption of local fish by pregnant and nursing Mohawk women.

Adult↗

PCBs reduce long-term potentiation in the CA1 region of rat hippocampus.

Prenatal exposure to polychlorinated biphenyls (PCBs) has been associated with a lower IQ in childhood. We have examined the effects of acute exposure to PCB mixtures and two single congeners on synaptic transmission between Schaffer collaterals and CA1 neurons of the rat hippocampus as well as posttetanic potentiation (PTP), paired pulse facilitation (PPF), and long-term potentiation (LTP). PTP and PPF represent transient increases in transmitter release immediately after stimulation, while LTP is a measure of long-term changes in synaptic plasticity that has been related to learning and memory. LTP, but neither PTP nor PPF, was reduced by Aroclor 1016 in a dose-dependent fashion at concentrations that had little effect on general synaptic transmission. The more highly chlorinated Aroclor 1254 at low concentrations specifically blocked LTP, but at higher concentrations also reduced synaptic transmission. The mono-ortho PCB congener 2,4,4'-trichlorobiphenyl and the coplanar congener 3,3',4,4'-tetrachlorobiphenyl also blocked LTP without effect on PTP or PPF. We conclude that PCBs selectively impair the process of LTP in CA1 neurons of the hippocampus.

Animals↗

Congener-specific distribution of polychlorinated biphenyls in brain regions, blood, liver, and fat of adult rats following repeated exposure to Aroclor 1254.

Our previous in vitro studies with both isolated organelles and primary neuronal cell cultures found that intracellular signal transduction can be perturbed by some noncoplanar PCBs at exposure levels of </=10 microM. However, it is not clear whether such concentrations are achievable in brain in vivo. Also, the pattern of congener disposition and quantities of the PCB accumulation in tissues of animals exposed to commercial PCB mixtures is not well studied. In the present study, we have conducted PCB congener-specific analysis in different brain regions, liver, blood, and fat of adult male Long-Evans rats dosed orally with Aroclor 1254 (0 or 30 mg/kg/day; once per day, 5 days/week for 4 weeks) in corn oil. Twenty-four hours after the last dose, rats were euthanized, and the brains were removed and dissected to obtain cerebellum, frontal cortex, and striatum. Liver, blood, and fat samples were also collected at the same time. Congener-specific analysis of PCBs was performed by high-resolution gas chromatography with electron capture detection. While PCB concentrations in control rat brain regions were less than 0.02 ppm, total PCB congeners in treated animals accumulated to much higher levels. Total levels in the frontal cortex, cerebellum, and striatum were 15.1 +/- 0.3, 13.1 +/- 1.7, and 8.2 +/- 2.6 ppm, respectively. The levels of PCBs in the fat, liver, and blood were 0.041, 0.002, and 0.001 ppm in control rats and 552, 38.3, and 1.6 ppm in treated rats, respectively. In addition to the differential total uptake between tissues, there was differential accumulation of PCBs with respect to the number of chlorines. In all the tissues, the more lightly chlorinated (tetra- and penta-) congeners accumulated less than their respective proportions in the parent Aroclor 1254 mixture. On the other hand, heavily chlorinated (hexa- to nona-) congeners accumulated more than the proportion of these congeners found in Aroclor 1254 mixture. This shift toward accumulation of heavily chlorinated congeners seems to be more pronounced in the brain than liver and fat. Predominant congeners (5-32% of total PCBs) detected in different brain regions, blood, liver, and fat are: 2,3,3',4',5,6- (no. 163) + 2,2',3,4,4',5- (no. 138) (coeluted); 2,2',4,4',5,5'- (no. 153) + 2, 2',3,3',4,6'- (no. 132) (coeluted); 2,3,3',4,4',5- (no. 156) + 2,2', 3,3',4,4',6- (no. 171) (coeluted); 2,3',4,4',5- (no. 118); 2,2',4,4', 5-(no. 99); and 2,3,3',4,4'- (no. 105). These congeners together accounted for about two thirds of the total PCB load in brain. All these predominant congeners are ortho-substituted and therefore are noncoplanar in nature. The total PCB concentrations accumulated in brain were as high as 50 microM (based on average molecular weight of 326.4 for Aroclor 1254) and, at these concentrations, intracellular second messengers were significantly affected in neuronal cultures and brain homogenate preparations in vitro. These results indicate that concentrations that altered Ca2+ disposition and second messenger systems in vitro are achievable in brain in vivo following repeated exposure.

Adipose Tissue↗

Environmental occurrence and potential toxicity of planar, mono-, and di-ortho polychlorinated biphenyls in the biota.

Four non-ortho-, eight mono-ortho-, and two di-ortho-chlorinated congeners have been determined in fresh water and salt water mussels, fish, snapping turtles, mallard, seals, and in human milk and adipose tissue. The planar PCB congeners are separated from the remainder of PCBs by activated carbon chromatography or HPLC on porous graphitic carbon followed by gas chromatography with electron capture detection. PCB toxic equivalency factors (TEFs) recommended by WHO [1] for 3 non-ortho, 8 mono-ortho, and 2 di-ortho PCBs and a TEF for congener 81 suggested by Harris et al. [2] were used for calculation of the contribution to dioxin-like toxicity to each life form. In all the biota examined, PCB congener IUPAC number 126 was the major contributor to PCB toxic equivalents. Congeners IUPAC number 118, 114, 105, 156, 157, 77, 81, and 170 also contributed significantly to PCB toxic equivalents. The ability to separate out planar 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 various species from different locations.

Adipose Tissue↗

Kinetics and products of the TiO2 photocatalytic degradation of 2-chlorobiphenyl in water.

The light-induced degradation of 2-chlorobiphenyl (2-CB) under simulated solar irradiation has been investigated in aqueous solutions containing TiO2 suspensions as photocatalysts. The apparent quantum yield for an initial 2-CB concentration C0 = 3.8 micrograms/mL at the natural pH was ca. 0.005 The oxidation kinetics of 2-CB follows the Langmuir-Hinshelwood kinetic model at natural pH. The primary degradation of 2-CB follows a pseudo-first-order kinetics. Several reaction intermediates were identified using GC/FTIR/MS and ion chromatography. The products at the initial stage of the reaction were seven isomers of 2-chlorobiphenyl-ol and biphenyl-2-ol. These intermediates underwent further photocatalytic oxidation via aldehydes, ketones, and acids finally into CO2 and HCl. The formation and fate of some of these compounds under irradiation were also investigated. A reaction scheme involving hydroxyl radicals has been proposed.

Adsorption↗

Electronic communication and collaboration in a health care practice.

Using cognitive evaluation techniques, this study examines the effects of an electronic patient record and electronic mail on the interactions of health care providers. We find that the least structured communication methods are also the most heavily used: face-to-face, telephone, and electronic mail. Positive benefits of electronically-mediated interactions include improving communication, collaboration, and access to information to support decision-making. Negative factors include the potential for overloading clinicians with unwanted or unnecessary communications.

Communication↗

Do large-scale remedial and dredging events have the potential to release significant amounts of semivolatile compounds to the atmosphere?

Laboratory studies suggest that substantial amounts of polychlorinated biphenyls are rapidly volatilized from wet contaminated solids during water evaporation. If significant losses also occur during field activities, potential analytical, global, and health implications should be considered in the design and monitoring of remedial actions and the handling of contaminated solids.

Air Pollutants↗

Human health and chemical mixtures: an overview.

Unlike laboratory animals, people are rarely exposed to a single hazardous chemical. However, most of the information documenting adverse human health effects from environmental and occupational contaminants has come from studies focused on exposure to single chemicals, and there is little information available on how two or more contaminants affect humans. Most information on the effects of mixtures comes from animal systems and limited investigations of isolated human cells in culture, even though the study of mixtures in such systems has also been neglected. Two or more compounds may show additive, antagonistic, or synergistic interactions or may act on totally different systems and thus not interact. Furthermore, even a single chemical may have multiple effects and affect more than one organ system. Effects may vary with age, and metabolites may have totally different actions from the parent compound. This paper will review the variety of health effects in humans that may result from environmental contaminants and discuss how such contaminants may interact with each other. We will also present examples on how different contaminants interact from toxicologic studies of polychlorinated biphenyls performed as part of our Albany, New York, Superfund Basic Research Program project.

Animals↗

Human exposure to PCBS: modeling and assessment of environmental concentrations on the Akwesasne reservation.

The Mohawk Nation at Akwesasne, comprised of approximately 10,000 people, is located along the St. Lawrence River in upstate New York. The Akwesasne reservation has been contaminated by local industries, which are located on the St. Lawrence River and its tributaries, and by upstream sources on the Great Lakes. The closest known source of contamination to the reservation is General Motors (GM) Foundry, which is located less than 100 feet from the reservation's border. This facility is listed on the Environmental Protection Agency's National Priority List and the New York State's Department of Environmental Conservation's (NYSDEC) inactive hazardous waste disposal site list. Contamination to the reservation arising from discharge and secondary transport mechanisms has caused concern to the Mohawk people of Akwesasne. The characterization of the environment at Akwesasne required a historical review of existing environmental data, generation of a database, review of existing data, sampling to augment existing data, data analysis, data modeling and data generation based on a chosen model for all environmental pathways of interest. The objectives this work were to: 1) assess the quality of existing data, 2) create a database which will manage the over 6000 samples recorded taken from the local area, 3) augment the existing data with additional sampling, 4) determine the degradation or attenuation of PCBs and specific congeners in various environmental media over time, and 5) create a model that estimates environmental concentrations of PCBs retro- and pro-spectively for times that sampling had not occurred. The results of this process yielded concentrations of PCBs, congener specific and total, in several environmental medium. Modeling of environmental concentrations through a thirteen-year time period was performed for a fish, wildlife and surface soil. Other media were not modeled due to limited information or non-detectable concentrations reported in past work. Additionally, the study participants activity, consumption and residential information was considered when limiting this modeling effort. The results of this work were used to estimate environmental concentrations through time and space. The results of this work were extremely valuable when determining areas of concern and provided the basis for a detailed exposure assessment of 97 women who reside at the Reservation.

Animals↗

Photocatalytic degradation of PCBs in TiO2 aqueous suspensions.

A generator-column technique was used to prepare aqueous solutions of PCBs. The degradation of 2-chlorobiphenyl, Aroclor 1248, Aroclor mixture (1221, 1016, 1254, and 1260) and St. Lawrence River water by simulated sunlight or sunlight has been investigated in the presence of aqueous suspensions of TiO2. The effect of TiO2 concentration and pH on the degradation rate of PCBs have been studied. The reaction rate followed apparent first-order kinetics and increased with increasing TiO2 concentration. The half-life of the degradation process for 2-chlorobiphenyl is 20 minutes at pH 10 and 9 minutes at pH 3 in the presence of 25 mg/L of TiO2. Less chlorinated PCBs decomposed faster than higher chlorinated ones. The rate constants and half-lives of individual PCBs in the commercial PCB mixture and St. Lawrence River water were also measured.

Catalysis↗

Gas phase infrared spectra of 209 polychlorinated biphenyl congeners using gas chromatography with Fourier transform infrared detection: internal standardization with a 13C-labelled congener.

The gas phase infrared spectra of biphenyl and 209 polychlorinated biphenyls (PCB) are observed; 30 are presented in graphical form so that their uniqueness can be appreciated. The spectra were observed with a gas chromatograph linked via a light pipe with a Fourier transform infrared spectrometer. Unequivocal library matches (with match factors > 990 in 1000) can be performed with 50 ng of a congener injected into the chromatograph. Quantitation with the technique was briefly investigated with 2,2',5,5'-tetrachlorobiphenyl (BZ no. 52). Selective wavelength chromatograms of the most intense absorption (1457cm-1) were integrated. Septuplicate injections showed that 20 ng of the compound could be determined with +/- 4% precision. The resolution of the spectrometer was sufficient to distinguish between the 13C-labelled trichlorobiphenyl and the unlabelled material, indicating the possibility of internal or surrogate standardization of PCB analysis.

Carbon Isotopes↗