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Chlorinated benz[ a]anthracenes (Cl-BaA) are halogenated aromatic compounds (typified by dioxins) found in the environment at relatively high concentrations. Fischer 344 rats were intragastrically administered 0, 1, or 10 mg of Cl-BaA or its parent compound benz[ a]anthracene (BaA) per kg of body weight for 14 consecutive days. Both chemicals at 10 mg/kg/day inhibited the gain in body weight, and consequent increase in relative liver weight. Hepatic gene expression of cytochrome P450 (CYP) 1A1, 1A2, and 1B1 was significantly stimulated by administration of BaA (10 mg/kg/day) compared with the control. After administration of Cl-BaA, only the CYP1A2 gene was significantly induced, even at the lower dosage; CYP1A1 and 1B1 mRNA levels remained unchanged in Cl-BaA-treated rats compared with controls. To elucidate the role of such Cl-BaA exposure and induced CYPs at toxicity onset, we investigated the mutagenicity of BaA and Cl-BaA using Salmonella typhimurium TA98 and TA100. BaA and Cl-BaA at 10 μg/plate produced positive results in both strains in the presence of rat S-9. Incubation of Cl-BaA with recombinant rat CYP1A2 produced a significantly higher number of revertant colonies in TA98 and TA100 than in controls, but no such change was observed for BaA. In conclusion, BaA changes its own physiological and toxicological actions by its chlorination; (1) daily exposure to Cl-BaA selectively induces hepatic CYP1A2 in rats and (2) Cl-BaA induces frameshift mutations in the presence of CYP1A2, although BaA does not exert mutagenicity. This indicates that CYP1A2 may metabolize Cl-BaA to active forms. © 2011 Wiley Periodicals, Inc. Environ Toxicol 2013. [ABSTRACT FROM AUTHOR]

Background: The trimethadione (TMO) tolerance test was performed to evaluate its usefulness in the assessment of hepatic functional reserve in patients with biliary atresia. Method: Nineteen patients with biliary atresia after hepatic portoenterostomy (age range: 2 months to 25 years; sex: 6 males and 13 females) were studied. The study was performed in the morning after a 12-h fast. TMO was given orally, at a dose of 4 mg/kg, with 5 mL of 5% glucose 2 h before breakfast. Blood samples (0·5 mL) were collected to determine serum TMO and dimethadione (DMO), a metabolite of TMO, levels 4 h after the administration of TMO. TMO and DMO were measured by a gas-liquid chromatographic method. Results: A higher total bilirubin level (over 1 mg/dL) in patients with jaundice was reflected in the smaller serum DMO/TMO ratio 4 h after the oral administration of TMO. In addition, these patients with total bilirubin levels of 1 mg/dL or less had a significantly lower DMO/TMO ratio than the control group (healthy subjects). The serum DMO/TMO ratio showed a close correlation with the Child–Pugh score, which is used for overall evaluation of severity of cirrhosis and Mayo risk scores for primary biliary cirrhosis in adults (0·856, P < 0·01 and 0·788, P < 0·01, respectively). The TMO tolerance test shows the benefit of performing a relatively early test of dynamic liver function to evaluate hepatic functional reserve in pre- and post-operative biliary atresia patients. [ABSTRACT FROM AUTHOR]

Adult normal mice and those mice which had been thymectomized, X-irradiated, and reconstituted either with bone marrow cells and thymus cells (TxXBT) or with bone marrow cells alone (TxXB), were given varying amounts (0.1-5 mg) of deaggregated soluble bovine serum albumin (sBSA). They were challenged 10 days later with an immunogenic form of BSA. TxXB mice were supplemented with normal thymus cells 3 days before the challenge. With any dose of sBSA, TxXBT and normal mice were made tolerant. Only 5 mg of sBSA, the highest dose in these experiments, was effective in inducing the tolerance in TxXB mice. The simultaneous administration of 5 mg of sBSA and 0.1 mg of alumprecipitated BSA plus 0.01 mg of endotoxin resulted in the priming in TxXBT mice but induced tolerance in TxXB mice. These results indicate that: (a) B-cell tolerance could be induced independently of the influence of T cells; (b) the tolerogen susceptibility of B cells may be lower than that oft cells; (c) such a weakly immunogenic agent as the mixture of tolerogen and immunogen could either activate the antibody response in the presence oft cells or induce B-cell tolerance in the absence of T cells. [ABSTRACT FROM AUTHOR]

We examined the effects of cyclosporin A (CsA) administered in vivo on the capacity of peripheral blood mononuclear cells (PBMC) from kidney transplant recipients to express IL-2 receptor (IL-2R) gene at the level of mRNA after mitogen stimulation in vitro. There were no differences in the percentage of IL-2R cells among the groups of normal individuals, azathioprine-prednisolone treated, and CsA-prednisolone-treated recipients, using FITC-labelled monoclonal anti-IL-2R antibody (anti-α chain): 40.3±10.1% and 62-8±11.1% of normal PBMC (n=18), 37.0±493% and 61.7±5.8% of PRMC from azathioprine-prednisolone-treated recipients (n = 20), and 37.7±9.6% and 60.7+12.7% of PBMC from CsA prednisolone-treated recipients (n=20) expressed II.-2R after 24 h and 48 h of phytohaemagglutinin stimulation, respectively. However, in a study of Northern blotting using cDNA For IL-2R (anti-α chain specific), both the 3500 and 1400 bp families of IL-2R mRNA were remarkably decreased in PBMC from CsA-prednisolone-treated recipients compared with azathioprine-prednisolone-treated recipients and normal individuals. These studies demonstrated that CsA could inhibit IL-2R gene expression at the level of mRNA at physiological concentration. [ABSTRACT FROM AUTHOR]

The plaque-forming antibody response of C57BL/6 mice to rabbit gamma globulin (RGG) decreases as a function of age. RGG in tolerogenic form induces tolerance of young mice but sensitizes older animals. If antigen is administered together with lipopolysaccharide, the age-dependent decline in immune responsiveness is not observed, nor are older animals sensitized by tolerogen. The age-dependent decline in immune responsiveness is due to a loss of T helper capacity; sensitization by tolerogen is attributable to a subpopulation of B cells which becomes sensitized by the tolerogen. Older animals, treated with tolerogen, show a degree of central tolerance of T cells and a relatively slight, age-dependent diminution in colchicine- or cyclophosphamide-sensitive precursors of suppressor cells. [ABSTRACT FROM AUTHOR]

This study reports the establishment of cloned hybridomas between mouse myeloma cells (P3-X63-Ag8, 6·5·3) and spleen cells from BALB/c mice immunized with lung homogenates of nude mice (BALB/c nu/nu) heavily infected with Pneumocystis carinii. A hybridoma subclone, designated 1E12-8, produced antibodies of an IgG subclass. Using indirect immunofluorescent antibody techniques, the monoclonal antibody was found to be directed toward the pellicle antigen of air-dried P. carinii both in trophozoite and cyst forms, and to recognize the P. carinii antigen not only from nude mice but also from rats. The antibody did not cross-react with other components of the infected host lung tissue and showed little cross-reactivity with fungi examined. The monoclonal antibody should be useful in the isolation and identification of corresponding antigenic substances of P. carinii and may provide a useful tool in epidemiology, taxonomy, and diagnosis of this organism. [ABSTRACT FROM AUTHOR]

This study was aimed at finding microorganisms capable of biodegrading dioxins efficiently to develop a biotechnological , treatment for decomposition of dioxins. Dibenzofuran (DBF) was used as a test substance to cultivate and to screen microbes active in degrading dioxins.Two microbial species (Pseudomonas aeruginosa and Xanthomonas maltaphilia) which could degrade DBF were isolated from the sludge of a Kraft pulp mill wastewater treatment plant. The optimal conditions for biodegrading DBF were 30 and pH 7. Ps. aeruginosa, which had a high growth rate with DBF as carbon source showed high growth rates in the presence of such dioxins as dibenzo-p-dioxin, medium growth with I-chlorodibenzo-p-dioxin, 2chlorodibenzo-p-dioxin and 2,8-dichlorodibenzofuran, low growth with 2,6dichlorodibenzo-p-dioxin and 1,2,3,4tetrachlorodibenzo-p-dioxin and no growth with octachlorodibenzofuran. These results suggested that tile growth rate of Ps. aeruginosa using dioxins as carbon source decreased with the increase in the degree of chlorine substitution. Activity of Ps. aeruginosa biodegrading dioxins was high for DBF, dibenzo-p-dioxin and I-chlorodibenzo-p-dioxin and lowfor 2,8dichlorodibenzofuran, 3,6-dichlorodibenzofuran, 2-chlorodibenzo-p-dioxin and 2,6-dichlorodibenzo-p-dioxin. These results suggestedthat there is a correlation between growth and the ability to biodegrade dioxins. On the other hand, the efficiency in the biodegradationof 1,2,3,4-tetrachlorodibenzo-p-dioxin was comparatively high although the growth rate on this dioxin was low. Hydroxydibenzofuran, 2-hydroxy-3-allyl-benzofuran and 2-carboxyvinyloxy phenyl acetic acid wereidentified by gas chromatograph-mass spectrometry (GC/MS) as products of DBF biodegradation by Ps. aeruginosa, suggesting a possible biodegradation pathway for dioxins. [ABSTRACT FROM AUTHOR]