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Biomedical subjects

J R Foster

Publications and source records attributed to J R Foster.

At least 55 records · Page 3Linked to original sources
PubMed1992

Methylene chloride--an inhalation study to investigate pathological and biochemical events occurring in the lungs of mice over an exposure period of 90 days.

Male B6C3F1 mice were exposed to 4000 ppm methylene chloride (MC) for 6 hr/day, 5 days/week for up to 13 weeks. Groups of mice were killed at intervals from Day 2 to Week 13. Whole lungs were examined morphologically, immunocytochemically, and biochemically. Biochemical and morphological examination was also performed on isolated Clara cells. The major initial morphological effect seen in lungs was acute Clara cell damage after one exposure to MC. However, this damage appeared to resolve after five consecutive daily exposures to MC. After a 2-day interval the Clara cell lesion reappeared on subsequent reexposure to MC. However, the severity of the lesion decreased over the duration of the study. The appearance and disappearance of the lesion in the Clara cell correlated well with the activity of cytochrome P450 monooxygenase in the Clara cell as assessed immunocytochemically (cytochromes P450IIB 1 and 2) in the whole lung and biochemically in the freshly isolated Clara cell (determined by ethoxycoumarin O-dealkylation and aldrin epoxidation). When there was a marked decrease in cytochrome P450 monooxygenase activity the lesion was not present. This suggested that with time the lung (Clara cell) has developed tolerance to MC possibly due to the inactivation of a cytochrome P450 isozyme. The glutathione S-transferase metabolism of MC by the lung cytosol remained virtually unaltered throughout the study. Events accompanying the discussed changes include (1) a significant increase in nonprotein sulfhydryl in the lungs of all exposed animals, (2) altered plating characteristics of the isolated Clara cells from exposed lungs after 24 hr in culture, and (3) an increase in the number of bronchiolar cells in the S-phase after the first exposure to MC. The study also demonstrates the advantages of target cell isolation and study over whole lung biochemical investigation alone.

Administration, Inhalation↗
PubMed1992

Photosynthesis and water relations of the floodplain tree, boxelder (Acer negundo L.).

During summer, gas exchange and water relations were measured in mature boxelder (Acer negundo L.) trees growing on a floodplain in central Indiana, USA. A shallow (< 1.25-m deep) water table and repeated flooding kept the soil water potential above -0.5 MPa at all times. Net photosynthesis and stomatal conductance were influenced primarily by light and, to a lesser extent, by leaf temperature, but showed no relationships with leaf-to-air water vapor gradient or leaf water potential. Throughout the summer, there was no midday stomatal closure on any measurement day, and leaf water potential at dawn and minimum daily leaf water potential remained above -0.4 and -1.4 MPa, respectively. Nevertheless, there was a seasonal decline in leaf osmotic potentials at saturation and turgor-loss point. Seasonal changes in maximum daily net photosynthesis and stomatal conductance, minimum daily leaf water potential and soil-to-leaf hydraulic conductance were not related to seasonal changes in soil water potential, air or soil temperature, or water table depth. Seasonal responses of net photosynthesis to intercellular CO(2) indicated that net photosynthesis was controlled primarily by nonstomatal factors. High soil water and a shallow water table may have kept soil-to-leaf hydraulic conductance large (5-9 mmol m(-1) s(-1) MPa(-1)) throughout the summer, permitting the trees to keep their stomata open, yet maintain leaf turgor and high net photosynthesis during the hot, low-humidity afternoons. This could also account for the dominance of nonstomatal influences on net photosynthesis.

Journal Article↗
PubMed1992

Diquat-induced intestinal secretion in the anaesthetized rat.

1. Diquat (1,1'-ethylene-2,2'-bipyridilium) is a non-selective desiccant herbicide which, when administered orally to mammalian species, causes significant secretion of fluid into the lumen of the gastrointestinal tract. In order to characterize this secretory response in more detail the effect of sublethal doses of diquat dibromide (DQBr2) on intestinal secretion was investigated in vivo in the jejunum of anaesthetized rats. 2. Ligated segments of jejunum (10 cm) which were prepared in groups of up to five animals were filled with 500 microliters of isosmotic DQBr2 solutions with concentrations ranging from 1-100 mM and maintained in the anaesthetized rat for 1, 2 or 3 h; in control experiments a solution of 100 mM NaBr was used. 3. It was found that while all of the fluid instilled into the segments was absorbed in the control experiments, there was both a dose- and time-dependent secretory response to DQBr2. Maximal fluid secretion occurred after treatment with 50 mM DQBr2 for 3 h. 4. Histological assessment of the jejunum revealed an increase in cell exfoliation and evidence of luminal distension after incubation with DQBr2. However, no structural damage to the mucosa could be seen to account for the fluid secretion. 5. The model described provides a quantitative means of evaluating intestinal secretion and may be used for elucidating the mechanism by which diquat alters fluid transport processes.

Animals↗
PubMed1991

Selective impairment of T lymphocyte activation following contact sensitization with oxazolone.

We have previously reported that topical exposure of mice to oxazolone results in the appearance of regulatory mechanisms which markedly depress lymph node cell (LNC) proliferative responses to subsequent challenge with the same chemical. In the present study, we have sought to identify the cellular targets for such immunoregulation. Autoradiographic analyses revealed that although pre-exposure to oxazolone caused a substantial reduction of paracortical hyperplasia following challenge, the frequency of proliferating cells in lymphoid follicles was slightly increased. That B lymphocyte responses are unaffected by oxazolone-induced immunoregulation was confirmed by investigation of anti-hapten antibody formation by draining LNC. Challenge with oxazolone resulted in an accelerated antibody response in mice previously exposed to the same chemical. These data reveal that the active immunoregulation induced following sensitization with oxazolone is selective for T lymphocytes. Evidence is presented that CD4+ and CD8+ T lymphocytes possess equivalent sensitivity to these mechanisms.

Administration, Topical↗
PubMed1991

Nephrotoxicity of 4-aminophenol glutathione conjugate.

4-Aminophenol (p-aminophenol, PAP) causes selective necrosis to the pars recta of the proximal tubule in Fischer 344 rats. The basis for this selective toxicity is not known, but PAP can undergo oxidation in a variety of systems to form the 4-aminophenoxy free radical. Oxidation or disproportionation of this radical will form 1,4-benzoquinoneimine which can covalently bind to tissue macromolecules. Recent studies have shown that certain benzoquinol-glutathione conjugates can cause renal necrosis in rats. We have synthesized a putative glutathione conjugate of PAP. The effect on the kidney of this conjugate and the sulphate and N-acetyl conjugates, known metabolites of PAP, have been examined in Fischer 344 rats. 4-Amino-3-S-glutathionylphenol produced a dose-dependent (92-920 mumol kg-1) necrosis of the proximal tubular epithelium and altered renal excretory function. The lesion at the low dose was restricted to the pars recta of the proximal tubule in the medullary rays, while at the higher doses it affected the pars recta region of all nephrons. In contrast, PAP-O-sulphate and N-acetyl-4-aminophenol (paracetamol) caused no histological or functional alteration to the kidney at 920 mumol kg-1. The renal necrosis produced by 4-amino-3-S-glutathionylphenol was very similar to that produced by PAP (367-920 mumol kg-1), both functionally and histologically, except that smaller doses of the glutathione conjugate were required. These studies indicate that glutathione conjugation of PAP generates a metabolite that is more toxic to the kidney than the parent compound. A possible mechanism of toxicity (analogous to that reported for glutathione conjugates of certain quinones) involving oxidation to form a 1,4-benzoquinoneimine thioether that could redox cycle is discussed.

Acetaminophen↗
PubMed1990

Perchloroethylene-induced rat kidney tumors: an investigation of the mechanisms involved and their relevance to humans.

Lifetime exposure to perchloroethylene by inhalation has been shown to cause a low incidence of renal tumors in male rats. The mechanisms responsible for the induction of these tumors have been investigated following exposure of rats to perchloroethylene by oral gavage (1500 mg/kg for up to 42 days) or by inhalation (400 ppm for 28 days). Comparisons have been made between rats and mice in vivo and between rats, mice, and humans in vitro. High doses of perchloroethylene given by gavage have been shown to be toxic to the rat kidney, causing increases in urinary markers of kidney damage. A marked accumulation of protein droplets (alpha-2u-globulin) was seen in the P2 segment of the kidney proximal tubules. This response were not seen after inhalation exposure to 400 ppm perchloroethylene for 28 days and hence may not be associated with the tumors seen at this dose level. Protein droplet formation was seen after exposure to 1000 ppm perchloroethylene, suggesting that 400 ppm is below the threshold dose required to induce this response. Perchloroethylene has been shown to be metabolized by glutathione conjugation in the liver, resulting in the formation of a mutagenic cysteine conjugate which is activated by the kidney enzyme beta-lyase. Levels of the mercapturic acid of perchloroethylene have been compared in rat and mouse urine. The enzyme kinetics of hepatic glutathione conjugation and renal beta-lyase activation have been compared in rat, mouse, and human tissues in vitro. Results of these studies are consistent with the rat being the species susceptible to kidney tumors. Although human kidney was shown to contain beta-lyase, glutathione conjugation of perchloroethylene could not be detected in human liver. Perchloroethylene-induced male rat kidney tumors may be a result of chronic toxicity, protein droplet nephropathy, and genotoxicity from the beta-lyase pathway. These mechanisms appear to have little relevance to humans.

Administration, Inhalation↗
PubMed1990

Influence of two growing seasons of experimental ozone fumigation on photosynthetic characteristics of white oak seedlings.

White oak (Quercus alba L.) seedlings were exposed to charcoal-filtered air or to above-ambient ozone concentrations for 19-20 weeks during each of two growing seasons in continuously stirred tank reactors in greenhouses. Ozone treatments were 0.15 ppm (300 microg m(-3)) for 8 h day(-1), 3 days week(-1) in 1988, and continuous 15% above ambient in 1989. The seedlings were grown in forest soil watered twice weekly with simulated rain of pH 5.2. Responses of net photosynthesis to photosynthetically active radiation and intercellular CO(2) concentration were measured three times each year. There were no significant differences in light-saturated net photosynthesis or stomatal conductance, dark respiration, quantum or carboxylation efficiencies, and light or CO(2) compensation points on any date between control and ozone-exposed seedlings.

Journal Article↗
PubMed1990

Effects produced by the non-genotoxic hepatocarcinogen methylclofenapate in dwarf mice: peroxisome induction uncoupled from DNA synthesis and nuclearity changes.

Both Snell dwarf mice (dw/dw) and their phenotypically normal heterozygotes (dw/+) were dosed with methylclofenapate (MCP) at daily intervals by gavage (25 mg/kg). Animals were killed at 12, 24, 36 and 72 h after the initial dose and the parameters of ploidy, nuclearity and DNA synthesis were measured in hepatocytes isolated by collagenase perfusion. The occurrence of peroxisome proliferation was assessed by electron microscopy after daily administration of 25 mg/kg MCP by gavage for 28 days. The hepatocytes from both phenotypes exhibited similar degrees of peroxisome proliferation but hyperplasia occurred only in the heterozygous animals. The incidence of binulceated hepatocytes in heterozygotes was approximately 50%, and at the end of acute hyperplasia this had reduced to approximately 20%; by contrast the livers of dwarf animals contained approximately 20% binucleated cells and this remained unchanged throughout the period of dosing. The hyperplasia in the wild-type mice, as measured by the occurrence of S-phase, occurred predominantly in binucleated hepatocytes. These observations are further confirmation that acute hyperplasia induced by MCP and similar liver growth inducers occurs predominantly in a sensitive sub-population of binucleated hepatocytes. The results also indicate that peroxisome proliferation and hyperplasia can occur as independent phenomena.

Animals↗
PubMed1990

Cytochemical localization of mercury in Saccharomyces cerevisiae treated with mercuric chloride.

We describe a cytochemical method for localizing mercury at the electron microscopic level in the yeast Saccharomyces cerevisiae. After addition of a lethal concentration of mercuric chloride to growing yeast cells, mercury was associated with the cell wall and cytoplasmic membrane. Little or no mercury was present in the cytoplasm. Electron probe X-ray microanalysis (EPMA) confirmed that the cytochemical reaction, visualized as mercury-silver complexes, was localized in dense bodies consisting of a core of mercury sulfide polymers surrounded by a shell of silver atoms.

Electron Probe Microanalysis↗
PubMed1990

Target cell toxicity of inhaled spermidine in rat lungs.

Rats were exposed for a single 6-h period to varying concentrations of aerosols of the polyamine, spermidine trihydrochloride. They were subsequently killed at 6 h, 1, 2, 5, 9 and 14 days after the start of exposure. The lungs were examined for histopathological alterations at both light and electron microscopic level and assays of lung spermidine burdens performed. In rats killed at the 6-h termination period, lung spermidine levels had increased approximately 1.5-fold although concentrations in animals killed on days 1 and 2 showed only marginal increases. Concentrations peaked again on day 5 and henceforth decreased until control spermidine levels were again achieved on day 14. Exposure of rat lungs to spermidine resulted in a specific dose-dependent necrosis of Clara cells of the bronchiolar epithelium and alveolar Type II cells. At the lowest dose used (6 mg/m3) specific necrosis of the Clara cells was seen at the earliest time interval studied, i.e. 6 h, but these cells were rapidly lost and subsequently replaced without evidence of significant cell proliferation by the 2-day sacrifice period. At all higher dose levels additional necrosis of the alveolar Type II cells occurred which was not reversible but which progressed through alveolitis to a fully developed subchronic pneumonitis by 14 days.

Administration, Inhalation↗
PubMed1990

Application of Piagetian measures of cognition in severe Alzheimer's disease.

Conventional psychometric measures uniformly yield zero or near zero scores (i.e., "bottom-out") as patients with Alzheimer's disease (AD) progress to the more severe stages of the illness. Consequently, there are no psychometric measures which objectively assess the mental abilities of AD patients with very severe cognitive impairment. We explored the hypothesis that mental function in AD patients with very severe cognitive impairment can be effectively assessed using test measures developed to assess the earliest stage of cognitive development as proposed by Piaget. We also investigated the relationship between decline on these experimental cognitive measures and progressive functional disability in patients with severe cognitive impairment. The results indicate that modified instruments derived from measures developed to assess Piaget's sensorimotor stage of cognitive development provide useful information about the cognitive abilities of very severely impaired AD patients. These modified instruments provide a measure of cognition in these extremely impaired patients that has acceptable validity and demonstrable reliability.

Aged↗
PubMed1989

Immunohistochemical localization of cytochrome P450b/e in hepatic and extrahepatic tissues of the rat.

The cellular distribution of cytochrome P450b/e has been studied in the liver and a number of extrahepatic tissues in the Wistar rat by immunocytochemistry, using two monoclonal antibodies, 10/1 and 1/4, raised against the major phenobarbitone-inducible form of cytochrome P450. The specificity of these antibodies was verified by a number of techniques. In Western blotting, both antibodies recognised a single band of Mr 52,000 in liver microsomes from rats pre-treated with phenobarbitone, acetone and isosafrole, which co-migrated with a purified preparation of cytochrome P450b. In untreated rats, a weak specific immunostain was visible across the whole of the liver lobule, with stronger staining in a few hepatocytes around the central vein. Immunoreactive cytochrome P450b/e was also found in the Clara cells of the lung and in the enterocytes of the small intestine, with maximal staining at the tips of the villi. No immunoreactive cytochrome P450b/e was detected in kidney, testis or pancreas. Phenobarbitone treatment resulted in a strong, specific immunostain of all hepatic centrilobular cells, antibody titration indicating that induction of cytochrome P450b/e had occurred. Marked induction was also found in the enterocytes of the small intestine, a strong immunostain being apparent in cells along the length of the villus, from crypt to tip. No induction was apparent in lung, kidney, testis or pancreas. Immunoquantification of cytochrome P450b/e, by densitometric scanning of dot blots probed with a monoclonal antibody, 10/1, confirmed these observations. Thus, there are very marked, specific inter- and intra-tissue differences in both the expression and inducibility of cytochrome P450b/e in the rat.

Animals↗
PubMed1989

Cysteine conjugate beta-lyase of rat kidney cytosol: characterization, immunocytochemical localization, and correlation with hexachlorobutadiene nephrotoxicity.

Cysteine conjugate beta-lyase (beta-lyase) was purified to electrophoretic homogeneity from the kidney cytosol of male Wistar rats. The highly purified enzyme exhibited a monomeric molecular weight of 50,000 Da and was active in the alpha-beta elimination of cysteine conjugates including S-(1,2-dichlorovinyl)-L-cysteine (DCVC), S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC), and S-(2-benzothiazolyl)-L-cysteine, particularly toward DCVC and TFEC. The purified enzyme also exhibited glutamine transaminase K activity with phenylalanine and alpha-keto-gamma-methiolbutyrate as substrates. An antibody was raised to the purified rat protein in sheep and the crude immune serum affinity purified, yielding a specific antibody that recognized only the beta-lyase protein in whole kidney homogenates. Immunocytochemical studies on rat kidney sections stained with the purified antibody revealed that the cytosolic beta-lyase enzyme was mainly localized in the pars recta of the proximal tubule in untreated rats. This localization is coincident with the site-specific kidney necrosis produced by hexachloro-1,3-butadiene (HCBD). These results indicate that the tissue localization of beta-lyase in the proximal tubule plays an important role in determining the specific nephrotoxicity produced by halogenated alkenes such as HCBD.

Animals↗
PubMed1989

Dendritic cell accumulation in draining lymph nodes during the induction phase of contact allergy in mice.

Draining lymph node cells isolated from mice 24 h following topical exposure to a variety of contact-sensitizing chemicals, including the dinitrobenzene derivatives, 2,4-dinitrochlorobenzene and 2,4-dinitrothiocyanobenzene, contained increased numbers of dendritic cells (DCs). The increase in frequency of DCs was time-dependent and preceded significant changes in either lymph node cellularity or lymph node cell proliferative activity. The degree of DC accumulation was also influenced by the chemical used and the concentration employed for sensitization. In the context of contact allergy, the biological relevance of this phenomenon to the induction of hapten-specific responses is indicated by the fact that relatively small numbers of DC--enriched fractions of lymph node cells (comprising approximately 70% DCs), but not unfractionated or DC--depleted populations, transferred sensitization to naive animals. Moreover, using the skin-sensitizing fluorochrome, fluorescein isothiocyanate, it was observed that 24 h following exposure the majority of lymph node cells bearing high concentrations of antigen were within the DC-rich fraction.

Animals↗