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Biomedical subjects

A Kappas

Publications and source records attributed to A Kappas.

At least 235 records · Page 13Linked to original sources
PubMed1979

Manganese and zinc blockade of enzyme induction: studies with microsomal heme oxygenase.

Heme oxygenase (decyclizing) [heme,hydrogen-donor:oxygen oxidoreductase (alpha-methene-oxidizing, hydroxylating), EC 1.14.99.3] is greatly induced in the kidney by the administration of nickel or tin. Manganese, when administered simultaneously with nickel or tin in an equimolar amount, substantially inhibited the induction of heme oxygenase. The extent of inhibition was 80% and 98%, respectively. In rats pretreated up to 8 hr with manganese, the level of induction of heme oxygenase by nickel or tin was markedly reduced in a time-dependent fashion. Manganese treatment after the inducing metal was relatively ineffective in preventing the induction of heme oxygenase. Manganese in vitro did not inhibit heme oxygenase in the microsomes isolated from either control or tin-induced rats and in vivo did not increase the rate of catabolism of the induced enzyme. Magnesium was unable to block nickel or tin induction of heme oxygenase. Zinc in equimolar amounts could also substantially reduce the extent of induction of renal heme oxygenase when administered simultaneously with nickel or tin. In addition, simultaneous zinc administration blocked to a considerable extent the induction of hepatic heme oxygenase by nickel, cobalt, or cadmium. These findings indicate the existence of metal-metal interactions that can greatly influence the regulatory mechanism for the induced synthesis of heme oxygenase, the rate-limiting enzyme in heme degradation.

Animals↗
PubMed1979

Studies in porphyria IX: Detection of the gene defect of erythropoietic protoporphyria in mitogen-stimulated human lymphocytes.

We have demonstrated in this study that mitogen-stimulated lymphocytes from EPP subjects accumulate substantially greater amounts of protoporphyrin IX than do normal lymphocytes when incubated with ALA. Protoporphyrin IX formation by normal lymphocytes is stimulated by CaMgEDTA, an inhibitor of ferrochelatase, and is decreased by ferrous iron which facilitates the utilization of protoporphyrin IX for heme synthesis. In contrast, protoporphyrin IX formation by EPP lymphocytes is less stimulated by CaMgEDTA than is the case with normal lymphocytes and is only slightly affected by iron. Clinically manifested EPP subjects and completely latent gene carriers of EPP can be identified using this lymphocyte culture technique. The data from this study provide clear evidence of a functional deficiency of ferrochelatase activity in human EPP lymphocytes. EPP thus represents the third of the three dominant porphyric disorders of man, including acute intermittent porphyria and hereditary coproporphyria, which can now be diagnosed using lymphocytes.

Adolescent↗
PubMed1978

Diagnosis of pseudomembranous colitis.

Twenty-eight patients with histologically proved pseudomembranous colitis have been seen in one hospital since July 1975. All patients with the disease had received antibiotics, six for infections not requiring operations; the other 22 cases all occurred after major surgery. All the patients had diarrhoea; six patients also had fever with clinical signs of sepsis, and three had abdominal pain thought to be due to anastomotic dehiscence after colonic resection. Pseudomembranous colitis was associated with white blood counts over 15 000/mm3 in 17 patients and albumin concentrations of less than 30 g/1 in 18. Pseudomembranous colitis was an incidental finding at necropsy in two of six patients who had not had an operation. Of the 22 patients who had had major surgery, nine died from this complication; in all except two of these cases the diagnosis was made only at necropsy. If pseudomembranous colitis is suspected on clinical grounds or if there is an unexplained complication after colorectal surgery repeat sigmoidoscopy and testing for faecal toxins should be carried out to establish the diagnosis so that prompt supportive treatment can be given.

Adolescent↗
PubMed1978

Effect of charcoal-broiled beef on antipyrine and theophylline metabolism.

Eight healthy volunteers were sequentially fed a control diet, a charcoal-broiled beef--containing diet, and the control diet a second time. The mean plasma half-lives (t1/2) of antipyrine and theophylline were each decreased by 22% after the subjects were fed the charcoal-broiled beed--containing diet. The main plasma t1/2s for these drugs returned to control values when the subjects were fed the control diet for a second time. Considerable individuality occurred in the responsiveness of the subjects to the charcoal-broiled beef--containing diet. The decreases in antipyrine plasma t1/2s among the 8 subjects ranged from 5% to 39%, and the decreases in theophylling t1/2s ranged from 0% to 42%.

Adult↗
PubMed1978

On the mechanisms of induced somatic recombination by certain fungicides in Aspergillus nidulans.

Four fungicides interfered with the segregation of chromosomes at mitosis of Aspergillus nidulans by increasing the somatic recombination, shown as colour sectors in green colonies, in a strain heterozygous for spore colour mutations. In an attempt to discover the mechanisms by which these fungicides increased the somatic recombination, a prototrophic diploid strain, heterozygous for colour and several other appropriate markers in all chromosomes, was used which enabled the detection and classification of all colour recombinants to be made by genetic analysis. The fungicides investigated were: benomyl (methyl-1-(butylcarbamoyl)-2-benzimidazole carbamate) a benzimidazole derivative, botran (2,6-dichloro-4-nitroaniline) and chloroneb (1,4-dichloro-2,5-dimethoxybenzene) of the aromatic hydrocarbon group of fungicides, and the antibiotic actinomycin D. At least three different mechanisms, non-disjunction, mitotic crossing-over and breakage-deletion, were found to be responsible for the recombinogenic activity of the compounds studied.

Aniline Compounds↗
PubMed1978

Studies on porphyrin-heme biosynthesis in organotypic cultures of chick dorsal root ganglion. I. Observations on neuronal and non-neuronal elements.

Living, mature organotypic cultures of chick dorsal root ganglion maintained in culture for 3 weeks were incubated in medium containing various levels of a precursor of porphyrin and heme formation, delta-aminolevulinic acid (ALA), (0.5 mM to 10 mM) or a combination of ALA (10 MM) and a metal chelator, CaMg-EDTA (5 mM) for up to 48 hours. Although no morphologic changes occurred in the cultures incubated with these compounds as observed by bright-field or dark-field microscopy, fluorescence microscopic study at 12, 24, and 48 hours demonstrated an intense red fluorescence with in the non-neuronal cells of the cultures (Schwann cells, fibroblasts, and macrophages) but not in the nerve cells. Spectrofluorometric analysis of perchloric acid-methanol extracts of the cultures revealed an emission spectrum characteristic of porphyrins. Autoradiographic studies, using 14C-labelled ALA, indicated that ALA was taken up by all cells (nerve cells as well as non-neuronal cells) in the cultures. The cultures incubated with ALA plus the metal chelator CaMg-EDTA showed the same distribution of porphyrin fluorescence, but a 2-fold increase in the amount of porphyrins was generated, when compared to cultures incubated with ALA alone. This observation suggests that a considerable fraction of porphyrins may be utilized to form heme in these cells since CaMa-EDTA blocks ferrochelatase activity, the terminal enzyme in the heme biosynthetic pathway. This is the first demonstration of active porphyrin-heme biosynthesis from ALA in cultured nervous system cells. Our results indicate that this biosynthetic pathway remains active in 3-week old cultures of chick dorsal root ganglion, and further, that the pathway appears to be predominantly present in the non-neuronal cellular elements of the ganglion rather than in nerve cells.

Aminolevulinic Acid↗
PubMed1978

Studies in porphyria. VII. Induction of uroporphyrinogen-I synthase and expression of the gene defect of acute intermittent porphyria in mitogen-stimulated human lymphocytes.

A 50% reduction in the activity of uroporphyrinogen-I (URO) synthase in liver, erythrocytes, and cultured skin fibroblasts characterizes all patients with clinically active acute intermittent porphyria (AIP). The same enzyme defect has also been demonstrated in the erythrocytes and skin fibroblasts of completely latent gene carriers of this disorder and presumably exists in the liver as well. In this study, we examined whether or not the formation of URO-synthase is impaired in AIP cells using lymphocytes treated with mitogens or infected with Epstein-Barr virus. Both mitogens (phytohemagglutinin and pokeweed mitogen) and Epstein-Barr virus induced the synthesis of URO-synthase in lymphocytes, but the induction of URO-synthase in AIP lymphocytes was only 50% as compared with that in normal lymphocytes. The impaired induction of URO-synthase in AIP lymphocytes reflects a specific gene defect because AIP lymphocytes showed normal [(3)H] thymidine uptake into DNA, [(3)H] uridine uptake into RNA, and normal delta-aminolevulinic acid (ALA) synthase, ALA-dehydratase, catalase activities, and heme content. Utilizing the same methodology, the ferrochelatase deficiency of hereditary erythropoietic protoporphyria could also be identified. The K(m) of the induced URO-synthase in AIP cells was identical to that of the enzyme in normal cells. The induced URO-synthase of mitogen-treated AIP lymphocytes was not accompanied by a concurrent enhanced level of ALA-synthase. Moreover, the URO-synthase deficiency in lymphocytes from actively ill AIP patients was not different from the level of enzyme activity when they were in clinical remission, or when compared with the enzyme activity of cells from completely latent AIP gene carriers. The results of this study indicate that the URO-synthase deficiency in AIP may be the result of a gene mutation regulating the rate of synthesis of a normal enzyme rather than a mutation causing a structural abnormality of this enzyme protein.

Acute Disease↗
PubMed1978

Human skin aryl hydrocarbon hydroxylase. Induction by coal tar.

Coal tar products, which are widely used in treating dermatologic disease, contain numerous polycyclic aromatic hydrocarbons, including 3,4-benzo[a]pyrene (BP). BP is among the most potent environmental chemical carcinogens and is known to evoke tumors in the skin of experimental animals and perhaps also of man. In this study the effect of cutaneous application of coal tar solution (U. S. Pharmacopeia) on aryl hydrocarbon hydroxylase (AHH) activity in the skin of patients usually treated with this drug was investigated. AHH, a cytochrome P-450 dependent carcinogen-metabolizing enzyme appears to play an important role in the activation of polycyclic hydrocarbons into reactive moieties that can bind to DNA and that may directly induce cancer. Application of coal tar solution to human skin caused a two to five-fold induction of cutaneous AHH in nine subjects. In further studies, the incubation of human skin with coal tar solution in vitro also caused variable induction of cutaneous AHH. Maximum responses in both systems occurred after 24 h and enzyme activity in vitro was time- and tissue- and substrate-concentration dependent. Studies in experimental animals showed that topical application of coal tar solution caused induction of AHH in skin and, after percutaneous absorption, in liver as well. Assay of several defined constituents of coal tar for AHH induction showed that BP was the most potent inducer of AHH tested. These studies indicate that topical application of coal tar solution in doses ordinarily used in treating dermatologic disease causes induction of AHH in human skin and suggest that such induced enzymatic activity could relate to carcinogenic responses to this agent in skin or, after percutaneous absorption, in other tissues as well.

Animals↗