Search PubMed⌕ Search

Biomedical subjects

A Poland

Publications and source records attributed to A Poland.

71 records · Page 4Linked to original sources
PubMed1977

Chloracne from manufacture of a new herbicide.

Forty-one chemical company workers had chloracne as a result of exposure to 3,4,3',4'-tetrachloroazoxybenzene (TCAB), an extraneous intermediate produced during the manufacture of a new herbicide. There was no laboratory evidence of significant hepatotoxicity or porphyria during the short time the herbicide was produced. An acnegenic when applied to the rabbit ear, TCAB is also a potent inducer of the microsomal enzyme aryl hydrocarbon hydroxylase. Prevention of chlorance is a difficult industrial engineering task and treatment of the disease is even more perplexing.

Acne Vulgaris↗
PubMed1976

3,4,3',4'-Tetrachloro azoxybenzene and azobenzene: potent inducers of aryl hydrocarbon hydroxylase.

Two unwanted contaminants, 3,4,3',4'-tetrachloroazoxybenzene (TCAOB) and 3,4,3',4'-tetrachloroazobenzene (TCAB), formed in the commercial synthesis of 3,4-dichloroaniline or of herbicides made from 3,4-dichloroaniline, were responsible for three outbreaks of acne among chemical workers. TCAOB and TCAB are approximately isosteric to 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,3,7,8-tetrachlorodibenzofuran, two well-known contaminants that cause acne. All four of these agents are potent inducers of hepatic aryl hydrocarbon hydroxylase activity and compete for stereospecific binding sites in the hepatic cytosol, which are thought to be the receptor sites for the induction of this enzyme. Among the chlorinated azoxy and azobenzenes, the potency of a congener to induce aryl hydrocarbon hydroxylase activity correlates with its binding affinity for the hepatic cytosol specific binding sites and its capacity to induce acne; this relation between structure and activity parallels that observed for the chlorinated dibenzo-p-dioxins and dibenzofurans.

Acne Vulgaris↗
PubMed1976

Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol. Evidence that the binding species is receptor for induction of aryl hydrocarbon hydroxylase.

We previously hypothesized that the genetic trait of aromatic hydrocarbon nonresponsiveness (the failure in certain inbred strains of mice of polycyclic hydrocarbons to induce aryl hydrocarbon hydroxylase activity, and the diminished sensitivity to the more potent inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is due to mutation which results in an induction receptor with a diminished affinity for the inducing compound. Following the intraperitoneal administration of [14C]TCDD (6 nmol/kg), hepatic accumulation of the radiolabel was greatest in C57BL/6J mice, intermediate in the hybrid B6D2F1/J mice, and least in DBA/2J mice, a pattern which mirrors the strain sensitivity to hydroxylase induction by TCDD (C57BL/6J greater than B6D2F1/J greater than DBA/2J). These data are compatible with receptor mutation theory and suggested that the hepatic uptake of TCDD is determined by the affinity of the receptor. In vitro experiments on the binding of [3H]TCDD to hepatic cytosol from C57BL/6J mice revealed a small pool of high affinity sites which stereospecifically and reversibly bind TCDD. The specific binding of [3H]TCDD to hepatic cytosol had an equilibrium dissociation constant KD of 0.27 nM and a maximum binding capacity of 84 fmol/mg of cytosol protein. Much less high affinity specific binding of [3H]TCDD was observed in hepatic cytosol from DBA/2J mice, but the KD was not estimated because of the limited aqueous solubility of the ligand. The binding affinity of 23 halogenated dibenzo-p-dioxins and dibenzofurans for this hepatic cytosol-binding species closely correlated with the potencies of these compounds as inducers of hepatic aryl hydrocarbon hydroxylase activity. The polycyclic hydrocarbons that induce hepatic hydroxylase activity competed with [3H]TCDD for hepatic cytosol binding, but phenobarbital, pregnenolone-16alpha-carbonitrile, and the steroid hormones had no specific binding. The data suggest that the hepatic cytosol species which binds TCDD is the receptor for the induction of hepatic aryl hydrocarbon hydroxylase activity, and that the mutation in nonresponsive mice results in an altered receptor with a diminished affinity for inducing compounds.

Animals↗
PubMed1976

2,3,7,8-Tetrachlorodibenzo-p-dioxin: environmental contaminant and molecular probe.

The chlorinated dibenzo-p-dioxins and dibenzofurans are formed as trace contaminants during the synthesis of a number of commercially important chemicals. The prototype compound of this group, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is one of the most potent low molecular weight toxins and teratogens known, and its inadvertent dispersion in the environment has caused concern about the potential hazard to human health. In studying the biochemical effects of TCDD, it was found to be extraordinarily potent as an inducer of two hepatic enzymes: 1) delta-aminolevulinic acid synthetase, the initial and rate-limiting enzyme in heme synthesis, and 2) aryl hydrocarbon hydroxylase, a cytochrome P-450-mediated microsomal monooxygenase. Among a series of halogenated dibenzo-p-dioxins there is an excellent correlation between their toxic potency and their potency as inducers of these two enzymes. The administration of polycyclic aromatic hydrocarbons (e.g., 3-methylcholanthrene (MC)) to certain inbred strains of mice induces aryl hydrocarbon hydroxylase, while other inbred strains fail to respond; and the trait of aryl hydrocarbon responsiveness is inherited as an autosomal dominant. TCDD, about 30,000 times as potent as MC, induces all strains whether responsive or nonresponsive to MC; however, the responsive strains are more sensitive (ED 50 approximately 1 X 10(-9) mole/kg) to TCDD than are the nonresponsive strains (ED50 larger than or equal to 1 X 10(-8) mole/kg). The results suggest that the mutation in the nonresponsive strains results in a ligand binding site (an induction receptor) that has a diminished affinity for MC and TCDD. The correlation among the halogenated dibenzo-p-dioxins, between their potency as toxins and their potency as inducers of aryl hydrocarbon hydroxylase, is discussed in relationship to various proposed mechanisms of toxicity.

5-Aminolevulinate Synthetase↗
PubMed1973

2,3,7,8-Tetrachlorodibenzo-p-dioxin: a potent inducer of -aminolevulinic acid synthetase.

2,3,7,8-Tetrachlorodibenzo-p-dioxin, a toxic contaminant frequently formed during the synthesis of the herbicide 2,4,5-trichlorophenoxyacetic acid, was shown to be a potent inducer of hepatic delta-aminolevulinic acid synthetase in the chick embryo. As little as 4.66 x 10(-12) mole of the contaminant per egg produces a significant increase in the activity of the enzyme. Induction of the enzyme is related to the dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin and, in contrast to that produced with other drugs, is prolonged in time, with 70 percent of the maximum induced activity present 5 days after a single dose. This contaminant is implicated as the likely causative agent in an outbreak of porphyria cutanea tarda in workers in a factory where 2,4,5-trichlorophenoxyacetic acid was being synthesized.

5-Aminolevulinate Synthetase↗
PubMedDate not supplied

Photoaffinity labelling of the Ah receptor.

A series of halodibenzo-p-dioxins bearing the arylazide photolabile functional group were synthesized and tested as photoaffinity labels for the Ah receptor. 2-Azido-3-iodo-7,8-dibromodibenzo-p-dioxin (KD = 0.76 X 10(-9) M) was selected for radiosynthesis. Analysis of the 125I-photoaffinity-labelled proteins in mouse-liver cytosol by denaturing gel electrophoresis revealed two peptides which had apparent molecular masses of 95,000 and 70,000 daltons respectively, were labelled in an approximately 1:1 ratio and were selectively labelled at low concentrations of the photoaffinity ligand (0.05 KD = 0.04 X 10(-9) M). In addition, their labelling was inhibited by co-incubation with an excess of unlabelled ligand. On chromatographic separation under non-denaturing conditions, these two peptides co-migrated. These studies suggest that the Ah receptor in mouse liver cytosol is a heterodimer composed of two non-covalently bound peptides (95 K and 70 K) which each have a ligand binding site.

Affinity Labels↗
PubMedDate not supplied

Diagnostic features of clinical neurologic feline infectious peritonitis.

Feline infectious peritonitis (FIP) is a fatal Arthus-type immune response of cats to infection with FIP virus, a mutant of the ubiquitous feline enteric coronavirus (FECV). The disease may occur systemically or in any single organ system, and primary neurologic disease is a common subset of such manifestations. We examined 16 domestic cats with clinical neurologic FIP and 8 control cats with nonneurologic FIP, with the intention of identifying the ante- and postmortem diagnostic tests that most contribute to accurate diagnosis. Of the 16 cats with neurologic FIP, 15 were less than 2 years of age and all 16 originated from large multiple-cat households. The most useful antemortem indicators of disease were positive anti-coronavirus IgG titer in cerebrospinal fluid, high serum total protein concentration, and findings on magnetic resonance imaging suggesting periventricular contrast enhancement, ventricular dilatation, and hydrocephalus. Postmortem diagnosis was facilitated by FIP monoclonal antibody staining of affected tissue and coronavirus-specific polymerase chain reaction. Most cats with neurologic and ocular forms of FIP had patchy, focal lesions, suggesting that recently developed technologies described in this report may be useful for evaluation of cats with suspected FIP.

Age Factors↗