Biomedical subjects

S D Sleight

Publications and source records attributed to S D Sleight.

At least 19 recordsLinked to original sources

PubMed1995

Definition of chemiluminescence and superoxide production responses of bovine neutrophils to selected soluble and particulate stimulants, and comparisons with the responses to Pasteurella haemolytica.

We defined methods for use of luminol-dependent chemiluminescence (LDCL) and superoxide anion (O2-) production as parameters of the oxidative metabolism of neutrophils isolated from 1.5- to 5-week-old neonatal calves. We determined how variations in blood sample handling, agonist preparation, individual variability, and age of calves influenced the LDCL and O2- responses to certain agonists, and defined concentrations of soluble and particulate agonists that maximally stimulated the oxidative metabolism of bovine neutrophils. Oxidative responses, particularly LDCL, were characterized by marked day-to-day variability, differed greatly within and between calves, were partially age-dependent, and were partially dependent on the individual agonist. Superoxide anion production had substantially less variability. We compared the in vitro oxidative (LDCL and O2-) responses of neutrophils isolated from neonatal calves stimulated by defined concentrations of the agonists--latex, phorbol myristate acetate, calcium ionophore, and opsonized zymosan--with responses to formylated oligopeptides and zymosan-activated serum, and to live, dead, live opsonized, and dead opsonized Pasteurella haemolytica organisms. Opsonization of particulates, pathogenic or nonpathogenic, enhanced the LDCL and O2- responses of stimulated neutrophils although P haemolytica was a less potent stimulant of oxidative functions than were nonbiological agonists. We conclude that the generation of reactive oxygen species by bovine neutrophils in response to P haemolytica is highly dependent on the presence of opsonins and is greatly enhanced in live vs killed bacteria. Furthermore, the in vitro generation of reactive oxygen species, including O2- by stimulated neutrophils, may be of biologic importance if similar events occur in vivo, and could have a major role in the pathogenesis of the acute lung injury associated with pneumonic pasteurellosis.

Adjuvants, Immunologic↗

PubMed1995

Enzyme release by bovine neutrophils.

Release of enzymes from cytoplasmic granules has been postulated to have a major role in neutrophil-mediated tissue injury. Secretion or release of primary granules, specific granules, and cytosolic enzymes by bovine neutrophils was examined by quantifying the release of beta-glucuronidase, B12-binding protein, and lactate dehydrogenase, respectively, in response to predetermined amounts of phorbol myristate acetate, calcium ionophore, and opsonized zymosan. These responses were compared with the enzyme release induced by exposure to live or dead, unopsonized or opsonized Pasteurella haemolytica. The greatest release of beta-glucuronidase, B12-binding protein, and lactate dehydrogenase was observed in neutrophils exposed to live organisms partially because of neutrophil lysis. Bovine neutrophils respond markedly to particulate agonists, live or dead, pathogenic or nonpathogenic, by a selective release of specific granules, an effect enhanced by opsonization. Particulate agonists induce minimal primary granule release other than that induced by cell death. Because bovine neutrophils contain quantitatively high numbers of specific granules, the high rate of secretion/release in response to P haemolytica organisms could have a major role in the tissue responses that characterize the lesions of pneumonic pasteurellosis.

Analysis of Variance↗

PubMed1992

Development of preneoplastic lesions in the liver and nasal epithelium of rats initiated with N-nitrosodimethylamine or N-nitrosopyrrolidine and promoted with polybrominated biphenyls.

In rats, N-nitrosodimethylamine (NDMA) and N-nitrosopyrrolidine (NPYR) induce liver tumours and, to a lesser extent, nasal tumours. Polybrominated biphenyls (PBBs) are liver tumour promoters and are highly persistent in tissues of rats. To characterize the development of preneoplastic lesions in the liver and nasal cavity, female Sprague-Dawley rats were initiated with NDMA or NPYR and promoted with Firemaster (FM), a commercial mixture of PBBs. Rats were killed after 30, 120 or 180 days of promotion. Liver and nasal tissues were stained with haematoxylin and eosin and were tested immunohistochemically for glutathione S-transferase placental form (GST-P). Significantly more altered hepatocellular foci (AHF) were evident in rats initiated with NDMA or NPYR and promoted with FM compared with non-promoted groups or rats given only FM. Appreciable numbers of AHF were seen at 120 and 180 days in livers of rats in all other treatment groups, whereas the untreated control rats had no AHF. The percentage volume of the liver occupied by AHF was significantly higher in promoted rats given NDMA than in rats given only NDMA or FM. These results indicate that a single oral dose of PBB can significantly enhance development of AHF in rats initiated with NDMA or NPYR. Preneoplastic lesions in nasal tissues were not detected by staining with GST-P.

Animals↗

PubMed1992

Sequential study in rats of nasal and hepatic lesions induced by N-nitrosodimethylamine and N-nitrosopyrrolidine.

Female Sprague-Dawley rats were given an ip dose of N-nitrosodimethylamine (NDMA) and N-nitrosopyrrolidine (NPYR), singly or in combination, and the sequential development of lesions in the liver and nasal cavity was characterized. Liver and nasal tissues were collected from rats given either NDMA or NPYR and killed at 6 or 12 hr and 1, 3, 10, or 30 days. After combination exposure, rats were killed at 3 or 30 days. Olfactory epithelium and adjacent Bowman's glands were specifically targeted by each chemical. Lesions were seen as early as 6 hr and were most severe by 3 days. At the high doses (60 mg/kg NDMA or 100 mg/kg NPYR) regeneration was not complete by 30 days. Hepatic necrosis was seen at 1 and 3 days with NDMA but was not seen with NPYR. Combination exposure appeared to cause additive effects in both the liver and the nasal cavity. Results indicate that a single ip administration of NDMA or NPYR can induce severe and prolonged toxic effects on nasal tissues in rats.

Animals↗

PubMed1989

Effects of dietary retinyl acetate on the promotion of hepatic enzyme-altered foci by polybrominated biphenyls in initiated rats.

Vitamin A inhibits the development of some chemically-induced tumours. Since polybrominated biphenyls (PBBs) are hepatic tumour promoters and they affect vitamin A homeostasis in rats, we put forward the hypothesis that dietary levels of vitamin A would influence tumour promotion by PBBs. In the study described here, female Sprague-Dawley rats were initiated on day 1 by ip administration of diethylnitrosamine. On day 7 after initiation, the rats were fed a vitamin A-deficient basal diet that was supplemented with either 2000 IU (low-vitamin A) or 200,000 IU (high-vitamin A) retinyl acetate/kg feed. From day 30 after initiation until the end of the study the following PBBs were added to the diets: Firemaster BP-6 (10 ppm), 2,4,5,2',4',5'-hexabromobiphenyl (10 ppm) or 3,4,5,3',4',5'-hexabromobiphenyl (1 ppm). The control animals received low- or high-vitamin A diets containing no PBBs. On day 180, the rats were necropsied, sections of various tissues were stained for histopathological examination and an evaluation of hepatic enzyme-altered foci was performed. Numbers of gamma-glutamyl transpeptidase-positive foci/cm3 liver and the mean volumes of these foci were lower in the high-vitamin A groups than those in the corresponding low-vitamin A groups, but these differences were not significant. The percentage of the liver volume occupied by foci was significantly greater in the low-vitamin A with 345-HBB group than in the corresponding high-vitamin A group. Thus, high dietary levels of vitamin A had some inhibitory effect on the promotion of hepatic-altered foci by 345-HBB in initiated rats.

Animals↗

PubMed1989

Promoting effect of polybrominated biphenyls on tracheal papillomas in Syrian golden hamsters.

Male Syrian golden hamsters were used for an initiation-promotion study of respiratory tract carcinogenesis. Hamsters were given a single subcutaneous dose of 0 or 80 mg N-nitrosodiethylamine (NDEA)/kg body weight and were fed diets containing 0 or 100 mg polybrominated biphenyls (PBB)/kg diet for 140 d. Basal diet was fed from d 140 until the end of the experiment on d 273. The number of tracheal papillomas was significantly increased in hamsters given NDEA and PBB as compared to those in hamsters given only NDEA. Tracheal papillomas were not seen in untreated hamsters or in those not given NDEA and fed diets containing PBB. Nasal tumors occurred at approximately the same incidence in hamsters given NDEA as in those given NDEA and PBB. Results indicate that PBB may promote the development of tracheal papillomas in the hamster.

Adenoma↗

PubMed1988

Anchored cell analysis/sorting coupled with the scrape-loading/dye-transfer technique to quantify inhibition of gap-junctional intercellular communication in WB-F344 cells by 2,2',4,4',5,5'-hexabromobiphenyl.

Inhibition of intercellular communication has been hypothesized to play a role in tumor promotion. The compound 2,2',4,4',5,5'-hexabromobiphenyl (245-HBB) is a tumor promoter in vivo and blocks intercellular communication in vitro. The scrape-loading/dye-transfer (SL/DT) assay was used to assess this in vitro effect at varying concentrations of 245-HBB. The SL/DT technique is based on the intracellular loading of a fluorescent dye, lucifer yellow (LY), and monitoring its transfer into adjacent cells via patent gap junctions. Confluent WB-F344 (rat epithelial) cells were exposed to various noncytolethal concentrations of 245-HBB. Transfer of LY was then quantified with anchored cell analysis/sorting (ACAS 470, Meridian Instruments, Okemos, Mich.). The results indicate an inverse correlation between the degree of fluorescence in secondary LY-recipient cells and the treatment concentration. The coupling of these two new methods of cellular biology provided rapid quantitative analysis of dye transfer in measuring the concentration/response of modulation of gap-junctional permeability in cultured cells.

Animals↗

PubMed1987

Toxic effects of N-nitrosodiethylamine on nasal tissues of Sprague-Dawley rats and golden Syrian hamsters.

The acute necrogenic effects of N-nitrosodiethylamine (NDEA) on nasal tissues of female Sprague-Dawley rats and golden Syrian hamsters were determined. Rats and hamsters were given a single ip dose of 0, 10, 20, 40, or 80 mg NDEA/kg body wt. After 24 hr, the rats and hamsters were killed and tissues were collected. Sections of nasal cavity and liver were evaluated histologically. All doses of NDEA caused inhibition of glycoprotein synthesis in cells of Bowman's glands in the olfactory region of rats and hamsters as determined by the loss of Alcian blue-periodic acid-Schiff staining material. Glycoprotein synthesis in other glands including the lateral nasal glands, maxillary glands, medial nasal glands, and the acinous glands near the vomeronasal organ was not affected by NDEA. Necrosis of Bowman's glands in the olfactory region of the nasal cavity occurred in rats given 20, 40, or 80 mg NDEA/kg body wt whereas the same cells were not necrotic in hamsters given NDEA. The results demonstrate the unique susceptibility of cells of the Bowman's glands to the toxic effects of NDEA given ip and indicate that nasal tissues of the rat are more susceptible to the necrogenic effects of NDEA than those of the hamster.

Animals↗

PubMed1987

Short-term oral administration of polybrominated biphenyls enhances the development of hepatic enzyme-altered foci in initiated rats.

FireMaster BP-6 (FM), a commercial mixture of polybrominated biphenyls (PBB), has been shown to act as a tumor promoter in hepatocarcinogenesis assays in rats. Most hepatic tumor promoters must be administered for many weeks or months. Because FM is highly persistent in animal tissues, it was hypothesized that very short-term administration of FM would result in tumor promotion. Female Sprague-Dawley rats weighing 185-215 g were initiated by a two-thirds partial hepatectomy followed by 10 mg diethylnitrosamine/kg body weight (BW) 24 h later. Thirty days later, rats were gavaged with FM in corn oil, at total doses of 0, 13, or 130 mg FM/kg BW. Half the dose was given on d 30, and the remaining half was given 24 h later. At 120 d after gavage the rats were killed and necropsied. Five liver sections from each animal were histochemically stained for gamma-glutamyl transpeptidase-positive enzyme-altered foci (EAF). EAF were significantly increased over control values in initiated rats given 130 mg FM/kg. In animals given 13 mg FM/kg, EAF were increased to a lesser extent but not significantly above controls. Enhancement of these EAF in initiated rats reflects tumor-promoting activity. In this study, 24-h administration of FM in initiated rats was sufficient to enhance hepatic EAF measured 120 d later in an rats was sufficient to enhance hepatic EAF measured 120 d later in an initiation-promotion protocol, and a dose of 13 mg FM/kg was apparently close to a possible no-effect threshold level for enhancement of EAF.

Administration, Oral↗

PubMed1986

Sequential study on the synergistic effects of 2,2',4,4',5,5'-hexabromobiphenyl and 3,3',4,4',5,5'-hexabromobiphenyl on hepatic tumor promotion.

A sequential study was completed to determine the effect of polybrominated biphenyl (PBB) congeners on the enhancement of gamma-glutamyl transpeptidase (GGT)-positive altered hepatic foci (AHF) and the development of hepatic nodules (HN) and carcinomas. Female Sprague-Dawley rats were given a single dose of N-nitrosodiethylamine (NDEA) 24 h following a 70% partial hepatectomy. Thirty days later, rats were randomly assigned to groups and fed a basal diet or the basal diet containing 10 p.p.m. 2,2',4,4',5,5'-hexabromobiphenyl (245-HBB), 0.1 p.p.m. 3,3',4,4',5,5'-hexabromobiphenyl (345-HBB) or 10 p.p.m. 245-HBB plus 0.1 p.p.m. 345-HBB for 140 days followed by a basal diet for up to another 310 days. Rats from each group were killed 170, 240 or 480 days after partial hepatectomy. Dietary exposure to 245-HBB and 245-HBB plus 345-HBB enhanced the development of AHF and HN whereas 345-HBB alone did not. The combination of 245-HBB and 345-HBB caused a synergistic effect on the development of AHF and HN. The number of hepatocellular carcinomas was low and evenly distributed among the groups of rats fed diets containing PBB.

Animals↗

PubMed1985

Failure to induce mutations in Chinese hamster V79 cells and WB rat liver cells by the polybrominated biphenyls, Firemaster BP-6, 2,2',4,4',5,5'-hexabromobiphenyl, 3,3',4,4',5,5'-hexabromobiphenyl, and 3,3',4,4'-tetrabromobiphenyl.

Firemaster BP-6 (FM), a mixture of polybrominated biphenyls (PBB), and the congeners 2,2',4,4',5,5'-hexabromobiphenyl (2,4,5-HBB), 3,3',4,4',5,5'-hexabromobiphenyl (3,4,5-HBB), and 3,3',4,4'-tetrabromobiphenyl (3,4-TBB) were tested for their ability to induce mutations in mammalian cells in culture. A rat liver microsome-mediated (S 15) Chinese hamster V79 cell mutation assay was used to test the mutagenicity of PBB and 3,4-TBB. V79 cells and WB rat liver cells were used to detect the mutagenicity of 2,4,5-HBB and 3,4,5-HBB. No mutagenic effects were detected at the dose levels tested. The possibility that these compounds promote liver neoplasms via a nongenotoxic mechanism is discussed.

Animals↗

PubMed1985

Toxicity of 3,4,5,3',4',5'-hexabrominated biphenyl and 3,4,3',4'-tetrabrominated biphenyl.

Immature male rats were given a single equimolar dose (21.3 mumol/kg body wt) of 3,4,5,3',4',5'-hexabromobiphenyl (HBB) or 3,4,3',4'-tetrabromobiphenyl (TBB) and terminated at various times up to 14 days after treatment. Hepatic microsomal aryl hydrocarbon hydroxylase (AHH) activity for the TBB treatment group was maximal at Day 2 and then steadily decreased, whereas this activity was induced in 1 day and remained high for the HBB treatment group. Tissue concentrations of HBB appeared to be unchanged over time whereas tissue concentrations of TBB decreased in a biphasic manner. Rates of in vitro metabolism of TBB with hepatic microsomes from TBB-treated animals showed a similar time-course relationship to AHH induction. HBB caused moderate to severe hepatic changes while TBB-treated rats had only mild hepatic changes. The relative binding of TBB by the hepatic receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was about 10 times that of HBB. The results suggest that even though the receptor-binding affinities imply that TBB should be more toxic than HBB, it is less toxic than HBB because it is metabolized. Studies with the chlorinated analogs of TBB and HBB suggested that PCB behave similarly. These results also suggest that receptor binding and AHH induction do not accurately reflect toxicity for polyhalogenated aromatic hydrocarbons which are metabolized, presumably because continued occupation of the receptor and persistent induction of some enzyme activity are required for toxicity.

Adipose Tissue↗

PubMed1985

Photolysis products of 2,4,5,2',4',5'-hexabromobiphenyl: hepatic microsomal enzyme induction and toxicity in Sprague-Dawley rats.

The irradiation of 2,4,5,2',4',5'-hexabromobiphenyl (2,4,5-HBB) by ultraviolet light created a mixture of lower brominated polybrominated biphenyl (PBB) congeners. Three photoproducts, 2,4,5,3',4'-pentabromobiphenyl (-PBB), 2,4,5,2',5'-PBB, and 3,4,3',4'-tetrabromobiphenyl (3,4-TBB), as well as 2,4,5-HBB and the photolyzed 2,4,5-HBB mixture, were administered to rats as a single ip injection (90 mg/kg, except 3,4-TBB, which was given at 2 mg/kg) 2 weeks before sacrifice. All treatments except 3,4-TBB induced NADPH-cytochrome P-450 reductase and aminopyrine-N-demethylase activities while all treatments except 2,4,5-HBB induced ethoxyresorufin-O-deethylase and UDP-glucuronosyltransferase activities. Thymus to body weight and spleen to body weight ratios were unchanged compared to controls for all treatments whereas an increase in the liver weights was observed for all treatment groups. Histologic examination revealed that the photolyzed 2,4,5-HBB mixture caused moderate to severe hepatocyte enlargement. Results of tissue analysis for the pure PBB congeners indicated that 2,4,5,2',5'-PBB and 3,4-TBB were metabolized in vivo and this was confirmed by in vitro metabolism studies. The results revealed that the photolyzed 2,4,5-HBB mixture caused a mixed-type induction of hepatic drug-metabolizing enzymes. This is most likely due to the effect of 2,4,5-HBB and toxic congeners formed during the irradiation of 2,4,5-HBB. 2,4,5,3',4'-PBB, which is toxic and apparently not metabolized, is believed to be the major congener contributing to the increased toxicity of the photolyzed 2,4,5-HBB mixture since 3,4-TBB was metabolized and appeared not to be as potent as inducer of aryl hydrocarbon hydroxylase activity.

Adipose Tissue↗

PubMed1985

Assessment of pentachlorophenol toxicity in newborn calves: clinicopathology and tissue residues.

Newborn Holstein bull calves were fed either analytical pentachlorophenol (aPCP) or technical pentachlorophenol (tPCP) for 6 wk to establish and compare the clinical and pathologic manifestations of toxicity. Four groups of three calves/group were each fed either 1 or 10 mg X (kg body weight)-1 X d-1 of either aPCP or tPCP. A fifth group served as control. Dosages of both PCP preparations were normalized to contain equal concentrations of PCP. Toxic effects were observed only at the 10 mg/kg dose in the tPCP-treated calves. These effects included decreased body weight gain, anorexia, decreased serum protein concentration, elevated serum gamma glutamyl transferase, and decreased triiodothyronine (T3) and thyroxine (T4) concentrations. Histologic lesions included cortical atrophy in the thymus and squamous metaplasia and hyperkeratous changes in the Meibomian gland of the eyelid. Thyroid function, which was assessed in vivo by measuring the rate of T3 and T4 production over 4 h after thyrotropin-releasing hormone (TRH)-challenge, was not impaired suggesting an extrathyroidal site of toxic action. Although serum chemistry indicators were suggestive of hepatic injury there were no discernable lesions. Organ weight analyses were inconclusive but there was a tendency toward enlargement of liver, kidneys and thyroid and decreased weight of lungs, spleen and thymus. A toxic effect clearly related to PCP and not its contaminants was depressed active transport of p-aminohippurate measured in kidney slices in vitro. Steady state concentrations of PCP in serum were about 40 and 90 ppm for the 1 and 10 mg/kg groups, respectively. Concentrations of PCP among the major organs were comparable.

Animals↗

PubMed1984

Effect of sex hormone status on chloroform nephrotoxicity and renal mixed function oxidases in mice.

In mice, only males are susceptible to chloroform (CHCl3) nephrotoxicity and the susceptibility appears to be related to renal mixed function oxidase activity. There were sex-related differences of renal cytochrome P-450 and b5 concentrations and of ethoxycoumarin O-deethylase activity in mouse kidneys; in all cases activity was higher in males. Castration of male mice eliminated susceptibility to CHCl3 nephrotoxicity and reduced renal mixed function oxidases to concentrations observed in female mice. Treatment of male and female mice with testosterone increased the susceptibility to CHCl3 nephrotoxicity and increased renal mixed function oxidases to similar activities in both sexes. Previous data have suggested that CHCl3 is metabolized in situ by the kidney, possibly by a mechanism similar to that occurring in the liver. The data from this investigation are consistent with the concept that CHCl3 is metabolized by a cytochrome P-450-dependent mechanism in the kidney.

Animals↗

PubMed1984

Effect of varying the length of exposure to polybrominated biphenyls on the development of gamma-glutamyl transpeptidase enzyme-altered foci.

Female Sprague-Dawley rats were fed polybrominated biphenyls (PBBs) for 15 or 140 days after a 70% partial hepatectomy and diethylnitrosamine administration (10 mg/kg body weight) to determine the effect of varying the length of exposure to PBBs on the enhancement of gamma-glutamyl transpeptidase enzyme-altered foci. fireMaster BP-6R, a commercial mixture of PBBs, was fed to rats at a dietary concentration of 100 mg/kg for 15 days or 10 mg/kg for 140 days during the promotion phase of a two-stage hepatocarcinogenesis assay. Results indicate that short term exposure to PBBs is as effective as long term exposure in enhancing the development of enzyme-altered foci.

Adipose Tissue↗

PubMed1984

Effects of aminoglycosides on glomerular ultrastructure.

Effects of the aminoglycosides, gentamicin, netilmicin and tobramycin (30 mg/kg/day X 7, i.p.), on glomerular ultrastructure were determined in male Wistar rats. Glomerular ultrastructure was studied by scanning and transmission electron microscopy. The average number of capillary endothelial fenestrae per 5 microns of capillary wall decreased from a control value of 10.8 to 8.2 and 8.1 in gentamicin- and tobramycin-treated rats, respectively, as shown by transmission electron microscopy (TEM). Scanning electron microscopy (SEM) showed that the density of endothelial fenestrae decreased to about 80% of control in gentamicin- and tobramycin-treated rats. In addition, gentamicin and tobramycin produced a marked reduction in the number of granulated myoepithelioid++ cells of the juxtaglomerular apparatus. Netilmicin appeared to have no effect on glomerular ultrastructure. Both TEM and SEM, indicate that the nephrotoxic aminoglycosides gentamicin and tobramycin alter the ultrastructure of the fenestrated endothelia of the glomerular capillaries. These ultrastructural changes appear to be correlated to the impairment of the glomerular permeability for different compounds.

Aminoglycosides↗

PubMed1984

Effects of ascorbic acid deficiency on methyl mercury dicyandiamide toxicosis in guinea pigs.

Methylmercury dicyandiamide (MMD) when given intraperitoneally at a dosage of 4 mg/kg of body weight at weekly intervals for 3 weeks resulted in death of guinea pigs fed an ascorbic acid deficient diet. Controls fed an ascorbic acid deficient diet survived during this period as did guinea pigs given MMD and fed an ascorbic acid adequate diet. In a second experiment, guinea pigs fed an ascorbic acid deficient diet containing 22 ppm of MMD died within 26 days and had severe hemorrhagic and ulcerative gastroenteritis and coagulative necrosis of the liver. Ascorbic acid deficient controls died at 34 days. The MMD-containing ascorbic acid adequate diet killed guinea pigs in 150 days. Guinea pigs fed an ascorbic acid deficient diet with 44 ppm of MMD died within 20 days with acute neurologic signs. Pathologic changes were mostly in the gray matter. Guinea pigs fed MMD and a diet with adequate ascorbic acid survived for 38 days whereas the ascorbic acid deficient controls survived for 47 days. Results indicate that ascorbic acid deficiency can be a factor in the location and severity of clinical signs and lesions of MMD.

Animals↗