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Biomedical subjects

H Peter

Publications and source records attributed to H Peter.

At least 73 records · Page 4Linked to original sources

DNA-binding assay of methyl chloride.

Fischer-344 rats and B6C3F1 mice of both sexes were exposed in closed chambers to 14C-labeled methyl chloride. Different clearance values from the gas phase of the system indicated that, based on body weight, mice metabolized the test compound much faster than rats. After isolation of DNA and nucleoproteins from liver and kidneys radioactivity was found in all macromolecular samples; this was ascribed to metabolic C1-incorporation. Radioactivity incorporation was particularly high in DNA of mouse kidneys, suggesting a high turnover to active C1 bodies (formaldehyde, formate) in this tissue. Analyses of DNA samples from kidneys of female and male mice showed neither 7-N-methylguanine nor O6-methylguanine. Hence, the formation of tumors in B6C3F1 mice exposed to high concentrations of methyl chloride is not based on methylation of DNA in this tissue.

Animals↗

Effect of antidotes of the acute toxicity of methacrylonitrile.

When rats were exposed for 30 min to methacrylonitrile at concentrations between 3180 and 5700 ppm, the clinical symptoms observed suggested a toxic activity of metabolically formed cyanide. This is in contrast to the signs of toxicity observed in the same species after inhalation of acrylonitrile where metabolic cyanide formation plays only a minor role. The acute toxicity of methacrylonitrile could be antagonized with cyanide antidotes (4-dimethylaminophenol plus sodium thiosulfate) as well as with N-acetyl-cysteine which directly reacts with alpha,beta-unsaturated nitriles.

Acrylates↗

[N-Acetylcysteine as an antidote in accidental acrylonitrile poisoning].

Acute acrylonitrile intoxications are followed by loss of consciousness, convulsions, respiratory arrest, and may end fatally. Common cyanide antidotes have not proved to be effective. In previous animal experiments we could demonstrate that the cyanide antidotes show some protective effect only after oral acrylonitrile application. Only a minimal amount of inhaled acrylonitrile will be transformed into cyanide, in contrast to pharmacokinetics after oral intake. After acrylonitrile inhalation the toxic effect of the whole molecule ( cyanethylation ) is important, and sulfhydryl compounds show antidotal effects. Further animal experiments demonstrate the superior antidotal effects of N-acetyl-cysteine after acrylonitrile inhalation. Intravenous injection of N-acetyl-cysteine in high doses is recommended according to the treatment of paracetamol poisoning.

Acetylcysteine↗

Invasive dysgerminoma in a girl with 45,X/46,X; mar mosaicism.

We report a 16-year-old girl with features of Turner's syndrome from whom an invasive dysgerminoma was removed. Cytotoxic drugs were given for the next 12 months. Mosaicism of two karyotypes (45,X/46,X; mar) was found in various tissues. The literature is reviewed with special regard to cytogenetic findings and prognosis of malignant growth and differentiation of dysgenetic gonads.

Adolescent↗

Irreversible binding of acrylonitrile to nucleic acids.

1. [2,3-14C]Acrylonitrile was incubated with rat-liver microsomes, NADPH and either DNA, RNA or bovine serum albumin. Irreversible binding occurred to the macromolecular targets. Binding was lower when incubations were performed without microsomes. 2. Most of the 14C bound to DNA, RNA or polynucleotides (poly-A, poly-C, poly-G, poly-U) after incubation of [2,3-14C]acrylonitrile with rat-liver microsomes and 'conventional' re-isolation of the nucleic acids was removed from the macromolecular target when subsequently chromatographed on hydroxyapatite. 3. Radioactivity attached to DNA after prolonged non-enzymic incubations with [2,3-14C]acrylonitrile was also removed from the DNA by chromatography on hydroxyapatite. 4. When [2,3-14C]acrylonitrile was administered to rats (i.p.), incorporation of 14C into the natural bases of hepatic RNA was observed. In contrast with previous experiments with [1,2-14C]vinyl chloride, no radioactive [1-N6]etheno-adenine could be detected in RNA. 5. After administration of [2,3-14C]acrylonitrile to rats, hepatic DNA was isolated and hydrolysed by a modified enzymic procedure. Chromatography on PEI-cellulose showed two 14C peaks which did not co-chromatograph with any known standard. The amount of 14C in these presumed alkylation products was too low to allow chemical identification. 6. It is concluded that acrylonitrile, either itself or its metabolites, can alkylate nucleic acids. However, the extent of irreversible nucleic-acid binding is quantitatively much less than that observed with vinyl halides.

Acrylonitrile↗

A randomized trial of adjuvant chemotherapy and immunotherapy in cutaneous melanoma.

In a randomized trial of adjuvant chemotherapy, immunotherapy, or immunochemotherapy, 761 evaluable patients with pathological Stage II cutaneous melanoma anywhere on the body or with pathological Stage I melanoma of the trunk (Clark's level 3 to 5) were studied by the World Health Organization International Melanoma Group. Wide local excision and excisional regional lymphadenectomy alone were performed in 185 patients and the results were compared with those of surgery plus chemotherapy with dacarbazine (in 192 patients), surgery plus immunotherapy with bacille Calmette-Guérin vaccine (in 203), and surgery plus chemotherapy combined with immunotherapy (in 181). The rates of disease-free survival and overall survival at 36 months were 30.4 +/- 8.3 per cent (mean +/- S.E.) and 41.6 +/- 10.0 per cent, respectively, after surgical treatment alone; 37.2 +/- 7.9 per cent and 46.5 +/- 8.3 per cent after surgery plus chemotherapy; 34.8 +/- 7.9 per cent and 48.7 +/- 8.7 per cent after surgery plus immunotherapy; and 33.6 +/- 7.9 per cent and 50.0 +/- 8.8 per cent after surgery plus a combination of chemotherapy and immunotherapy. None of the differences between groups was significant, and thus no effect of adjuvant therapy could be demonstrated in this study.

BCG Vaccine↗

Interaction of acrylonitrile with hepatic microsomes of rats and men.

Acrylonitrile (AN) showed spectral interaction with hepatic microsomes from mouse, rat and man. Whereas human and rat liver microsomes resulted in ligand AN-binding spectra, mouse liver microsomes behaved differently. Hepatic microsomes from phenobarbital-treated mice with AN showed a type I substrate binding; ligand spectra are recorded with microsomes from benzo[a]pyrene-treated mice. Microsomes from untreated control mice showed a mixed type behaviour.

Acrylonitrile↗

Irreversible protein binding of acrylonitrile.

1. After i.p. injection of [2,3-14C]acrylonitrile to rats, a significant portion of radioactivity becomes irreversibly attached to proteins of liver, lung, spleen and other tissues. 2. When rat liver microsomes were incubated with [2,3-14C]acrylonitrile, a time-dependent irreversible binding of radioactivity occurred to microsomal proteins. This binding was not dependent on NADPH. A high extent of binding to heat-inactivated microsomes indicated that no enzymic metabolic step was involved. 3. The irreversible binding of [2,3-14C]acrylonitrile to rat liver microsomal protein in vitro was inhibited by thiols (cysteine, glutathione, mercaptoethanol). The greatest inhibitory potency was displayed by dithiocarb (diethyl dithiocarbamate).

Acrylonitrile↗

Pharmacokinetics of vinyl chloride in the Rhesus monkey.

The metabolic elimination of vinyl chloride in Rhesus monkeys is a dose-dependent, satruable process, as in rats. Below 200-300 ppm of vinyl chloride (VC) in atmosphere, elimination obeys a first-order law; the clearance rate is much closer to that found in man than the values for rats, mice and gerbils. The maximal velocity of metabolic elimination of VC at high concentrations in Rhesus monkeys is only about half that of rats when related to kg body weight. It s suggested that Rhesus monkeys mimic the quantitative aspects of VC metabolism better than rats or mice.

Animals↗

Experience with transnasal canthopexy.

The results are presented of a series of 14 canthopexies in recent trauma cases, 15 for correction of post-traumatic canthal dystopy, 12 for correction of hypertelorism and 8 in Le Fort III midface advancements. The overall results in traumatic cases are acceptable, in hypertelorism a considerable amount of relapse is noted and in Le Fort III osteotomies intercanthal distance enlarges slightly. The reasons for unsatisfactory results are discussed: Pressure ulcers of the skin, lateral pull of the soft tissues, and exaggerated pull on the ligaments seem to be the main factors. In Le Fort III osteotomies the anatomical situation has to be considered. As a conclusion it is suggested that the canthal ligaments should not be detached whenever possible in cases in which the topographical relationship between ligament and medial orbital wall does not have to be changed.

Eyelid Diseases↗