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Biomedical subjects

J Kusche

Publications and source records attributed to J Kusche.

At least 37 records · Page 2Linked to original sources
PubMed1986

Androgen receptors in experimentally induced colon carcinogenesis.

Sex hormones may play a role in colonic carcinogenesis, as evidenced by epidemiologic and experimental data showing different tumor rates in males and females. We investigated the effects of hormonal manipulation on tumor development and on androgen receptor binding in both colonic wall and experimentally induced tumors in male rats. Five of six groups, each with 40 animals, were given 10 weekly s.c. injections of azoxymethane (AOM), 7.5 mg/kg body weight. Group-I served as normal controls. Group-II received AOM only. Group-III was castrated 2 weeks prior to carcinogen treatment. Group-IV was castrated similarly and then hormone substituted with testosterone propionate. Group-V was chemically castrated with the anti androgen cyproterone acetate. Group-VI was castrated and given hormone vehicle. Scatchard analysis for androgen receptors in cytosol from normal colonic wall and tumor was performed with 3H-methyltrienolone as the ligand. Androgens were found to have an inhibitory effect on carcinogenesis: chemical castration increased colonic tumor development (P less than 0.05 for multiplicity), and testosterone administration produced a borderline statistically significant reduction in tumor incidence in surgically castrated rats (P less than 0.053), particularly in the right colon. Specific binding sites for androgen with high affinity and low capacity were found in the colonic wall of all groups. Receptor density was not altered by AOM administration, but increased after surgical castration. Receptor density was markedly lower in tumors than in normal colonic wall. Receptor binding sites in tumors were not altered by the various hormonal manipulations. Our study demonstrated that although cytoplasmic androgen receptors are present in colonic wall and in experimental tumors, AOM-induced colonic carcinogenesis appears to be only mildly affected by manipulation of androgens.

Animals↗
PubMed1986

Diamine oxidase as a marker of intestinal integrity in acute appendicitis.

In the operative treatment of appendicitis the so called negative appendectomy is an important issue because of its increased morbidity. From the hypothesis that the intestinal diamine oxidase activity is a suitable marker of mucosal integrity, the distribution pattern of the enzyme in appendices histologically classified as inflamed or not inflamed was studied. Histologically apparent inflammation of the appendix was connected with a significant reduction of diamine oxidase activity. The determination of this enzymic activity may be a simple and sensitive test for mucosal inflammation of the appendix even at a very early state. This could reduce the rate of negative appendectomies and influence thereby risk-cost-benefit calculations.

Acute Disease↗
PubMed1986

The effect of experimental carcinogenesis on intestinal diamine oxidase, a polyamine deaminating enzyme.

Intestinal mucosa hyperproliferation is an important risk factor of large bowel carcinoma development. Intestinal diamine oxidase (DAO) is suggested to be a proliferation terminating principle in the mature mucosa. Therefore, the influence of the carcinogen azoxymethane (AOM) on this enzyme was studied. The enzyme was measured with the 14C-putrescine assay. In vitro the enzyme was inhibited only by excessive high concentrations of AOM (89 mmol/liter). In vivo the enzymic activity was reduced in the duodenum but not in the colon during the first 48 hr after AOM application (15 mg/kg). Ten weekly injections of AOM reduced the DAO activity in the duodenum and colon significantly (alpha = 0.05). After the stop of the AOM application a significant (alpha = 0.05) increase of DAO activity over the control level was found which was interpreted as a defense reaction of the mucosa against the hyperproliferation that had occurred during the carcinogen treatment. Intestinal DAO is regarded as an antiproliferative principle protecting the integrity of the intestinal mucosa. An inhibition of this enzyme probably increases the risk of intestinal carcinoma promotion.

Amine Oxidase (Copper-Containing)↗
PubMed1985

Histamine reduces the deamination of putrescine in vitro--but also in vivo?

The diamine oxidase catalysed deamination of putrescine was reduced in vitro by histamine at concentrations occurring in the gut. An oral application of histamine, however, had no effect on the enzymic activity. When the histamine was injected i.p. a decrease of intestinal diamine oxidase activity was observed which, however, did not depend on histamine but probably on an unspecific irritation of the gut.

Amine Oxidase (Copper-Containing)↗
PubMed1985

[Stapler suture or single button suture? A controlled clinical study on the comparison of both skin closure methods].

In a controlled randomized clinical trial, skin closure with a skin-stapling technique was compared with interrupted sutures on 50 patients (26 sutured and 24 stapled). The two groups were similar in all important respects. The clinical side of the study was to compare 1) the cosmetic results, 2) the time taken to close the skin, and 3) advantages and disadvantages of the two techniques by a questionnaire completed by the clinical staff. The study suggested a cosmetic advantage for the stapling when the results at 6th postop. week were compared. The only significant difference was in cross hatching (22 out of 26 sutured wounds but none of the 24 stapled) which was predominantly visible in sutured wounds. A clear difference was found in operating time. Skin closure with interrupted sutures took 310s, compared with 122s for stapling (alpha = 0,001). Similarly time required to remove the closure material was less with the staples than with sutures. Staples are more expensive than sutures. However the advantage of the staples over the suture in avoiding cross hatching is significant as well as time saving.

Abdomen↗
PubMed1984

N-methyl-N-formylhydrazine: a toxic and mutagenic inhibitor of the intestinal diamine oxidase.

N-methyl-N-formylhydrazine is the first active intermediate of the poison gyromitrin of the mushroom: false morel. This compound is a non-competitive inhibitor of human intestinal diamine oxidase (ID50 = 1.6 X 10(-5) mol/l). This concentration corresponds to less than 5 g of wet weight of mushroom/l. The diamine oxidases from 5 other sources are inhibited in a similar manner. Semicarbazide and aminoguanidine are 10-respectively 1000-fold more potent inhibitors of the human intestinal diamine oxidase. An involvement of the diamine oxidase inhibitory property of N-methyl-N-formylhydrazine in toxic and mutagenic effects of the substance is considered.

Amine Oxidase (Copper-Containing)↗
PubMed1983

Distribution and properties of human intestinal diamine oxidase and its relevance for the histamine catabolism.

High activities of diamine oxidase (EC 1.4.3.6) were measured in the intestinal tract of human subjects and of several mammalian species. The enzyme was localized in the mucosa and was distributed primarily in the cytoplasm; the only exception being the guinea-pig where it was located in the particulate fraction. Despite its instability the enzyme from human colonic mucosa was purified 80-fold. During the purification a soluble monoamine oxidase (EC 1.4.3.4) was separated from diamine oxidase. The pH optima of diamine oxidase for putrescine and histamine were 6.6-7.0 and 6.4-6.6, respectively. Short-chain aliphatic diamines were deaminated with the highest reaction velocity, but histamine and N tau-methylhistamine were also excellent substrates. The Km for putrescine was 8.3 x 10(-5) M, for histamine 1.9 x 10(-5) M and for N tau-methylhistamine 9.7 x 10(-5) M. Typical substrates of monoamine oxidase were not deaminated by the enzyme. Aminoguanidine strongly inhibited human intestinal diamine oxidase (IC50 = 1.1 x 10(-8) M). Because of its properties the intestinal diamine oxidase is considered to play a protective role against histamine in diseases such as ischaemic bowel syndrome, mesenteric infarction and ulcerative colitis.

Adult↗
PubMed1983

Metabolism and function of gastric histamine in health and disease.

Histamine is not uniformly distributed in the human and animal organisms, but occurs in high concentrations in the gastric mucosa. The enzymes responsible for its metabolism--histidine decarboxylase, histamine N-methyltransferase and diamine oxidase--seem to be less predominantly localized in the stomach. Considerable effort was necessary to detect and measure histamine formation in the gastric mucosa. This was a controversial subject that only was solved recently. Histamine inactivation by histamine methyltransferase occurs in man in the fundic gastric mucosa that has reasonable enzymic activity. However, liver, spleen and intestine show much higher activities indicating less specificity of histamine catabolism in the gastric mucosa. Finally, diamine oxidase activity was once thought to be absent in the corpus mucosa, but more recently, moderate activities of this enzyme were found in several species, including man. Thus, histamine metabolism in the gastric mucosa is by no means unique in mammalian tissues, but the presence of these enzymes may be regarded as an indicator of its physiological function. To some extent enzymic activities involved in histamine formation and inactivation are regulated in the process of acid secretion. Histidine decarboxylase and histamine N-methyltransferase activities are enhanced by gastrin, but are not influenced by vagal stimulation. Hitherto, only histamine methylation was found to be diminished in duodenal ulcer disease. Vagotomy and histamine H2-receptor antagonists modulate histamine catabolism by histamine methyltransferase. The implication of these findings for treatment of duodenal ulcer are discussed.

Amine Oxidase (Copper-Containing)↗
PubMed1982

Plasma histamine levels in patients in the course of several standard operations: influence of anaesthesia, surgical trauma and blood transfusion.

A prospective controlled clinical trial was conducted on changes in plasma histamine and catecholamine levels during 5 standard operations. This communication, as the first part of the trial, deals only with the feasibility of such a trial and the changes in plasma histamine levels. Elevated histamine concentrations corresponding to histamine-release responses of greater than 1 ng/ml occurred in 8 of 25 operations. In an explorative analysis these responses were associated with distinct phases of anaesthesia or the surgical procedure. Blood transfusion carried the risk of infusion of "free histamine" into the patient--especially when administered under pressure. Since during operations "free histamine" enters the circulation with a rather high incidence and may cause harmful effects, premedication with H1-+H2-receptor antagonists seems worth consideration.

Adult↗
PubMed1982

Intestinal monoamine oxidase: does it have a role in histamine catabolism?

The importance of intestinal diamine oxidase in histamine catabolism was proved in several series of experiments. However, intestinal monoamine oxidase might also be involved in histamine degradation either by direct deamination or by the deamination of methylated products. The soluble fraction of intestinal monoamine oxidase was purified and tested for the properties and substrate specificity by three different methods which are described in detail. Using 0.15 M phosphate buffer the optimum pH was 7.4--7.6. The Km values for serotonin and tyramine were 0.2 and 0.3 X 10(-3) M. The most favoured substrates of the enzyme were tyramine, tryptamine and serotonin, but it was not possible to classify the enzyme as a type A or B monoamine oxidase only by its substrate specificity. Histamine and ring methylated derivatives were not attacked by intestinal monoamine oxidase. This means that in the intestinal mucosa by the oxidative pathway of histamine is completely catalysed by diamine oxidase.

Animals↗
PubMed1981

[The retrospective view of controlled clinical trials: is the subsequent formation of subgroups allowed? (author's transl)].

Additional data appearing in clinical trials can be evaluated only outside the protocol, i.e. retrospectively. An exclusion of patients before randomization is feasible, a withdrawal of patients after randomization is not allowed, but if unavoidable a "central blind review" should be introduced. No loss of patients should occur after the closing of the study. Differences in prognostic factors between groups of patients can be overcome by retrospective stratification. If there are different outcomes, a subsequent significance test at the 1% level is considered as well as a free interpretation.

Clinical Trials as Topic↗
PubMed1981

The start of a programme for measuring diamine oxidase activity in biopsy specimens of human renal mucosa.

In human subjects, apart from in the kidney, diamine oxidase occurs mainly in the gut. Therefore this enzyme can be used as an indicator of intestinal integrity. In biopsies of rectal mucosa the diamine oxidase activity was assayed in 55 patients, 41 having a histologically normal mucosa and 14 being diseased. The determinations of the enzymic activity were supervised by statistical quality control. In the unchanged rectal mucosa the diamine oxidase activity was 40 nmol/min X g on average. In 7 patients with rectal polyps the enzymic activity was significantly diminished in these benign tumors (mean = 7.7 nmol/min X g) apart from one, where it was elevated. A decrease in diamine oxidase activity was further observed in rectal carcinoma and ulcerative colitis. Whether the reduction of intestinal diamine oxidase activity accompanies premalignant or malignant states or whether it is a general sign of a disturbance of intestinal integrity remains questionable.

Adult↗
PubMed1981

Intestinal diamine oxidase and histamine release in rabbit mesenteric ischemia.

It has been suggested that histamine contributes to lethal circulatory collapse after acute superior mesenteric artery occlusion. The activity of the histamine inactivating enzyme diamine oxidase, the release of the amine, and the effect of histamine receptor antagonists was therefore studied in rabbits. The main results were: (a) Diamine oxidase activity decreased by 60% after intestinal ischemia and reperfusion. A monoexponential dose-response relationship was found between the specific diamine oxidase inhibitor aminoguanidine and reduced survival time. (b) Plasma histamine levels in the right atrium rose only slightly after ischemia, but considerably during reperfusion of the gut, and remained high for at least 20 min. In sham-operated animals the plasma histamine concentration was unchanged throughout the experiment. The histamine content in the intestinal wall did not fall significantly at any time after mesenteric artery occlusion and reperfusion. (c) The aminoguanidine-induced reduction in survival time was completely reversed by pre-treatment of the animals with the H1-receptor antagonist dimethylpyridine and the H2-receptor antagonist cimetidine. This study provides strong evidence for the protective role of intestinal diamine oxidase in intestinal ischemia.

Amine Oxidase (Copper-Containing)↗
PubMed1981

[Antibiotic prophylaxis in colorectal surgery: is there a drug of choice?].

It is possible to reduce the rate of septic complications following colorectal operations by a prophylactic antibiotic regimen. After the evaluation of 67 controlled clinical trials a combination of antibiotics disintegrating aerobic and anaerobic bacteria was recognized as an effective antibiotic prophylaxis. Clinically proved combinations are neomycin/metronidazole and neomycin/bacitracin.

Adult↗
PubMed1980

Human intestinal diamine oxidase: substrate specificity and comparative inhibitor study.

For an 80-fold purified preparation of human intestinal diamine oxidase the optimum conditions of incubation, the substrate and the inhibitor specificity were tested. Putrescine was the most favoured substrate but N tau-methylhistamine and 2-methylhistamine were metabolized at optimum conditions with nearly the same velocity. Histamine reached about 50% of the reaction velocity of putrescine. Aminoguanidine and semicarbazide inhibited the human intestinal enzyme like a classical diamine oxidase. However, a distinct inhibition of human intestinal and pea seedling diamine oxidase was observed in presence of beta-aminopropionitrile (weak inhibition of the human enzyme, strong inhibition of pea seedling diamine oxidase) and burimamide (strong inhibition of human intestinal enzyme, nearly no influence on pea seedling diamine oxidase). It is proposed to differentiate on the basis of functional considerations diamine oxidases with more histamine detoxicating activities from those being more involved in regulating polyamine levels in growing tissues.

Amine Oxidase (Copper-Containing)↗
PubMed1980

The influence of carcinoma growth on diamine oxidase activity in human gastrointestinal tract.

The distribution of diamine oxidase (DAO) activity was studied in patients having no carcinoma disease. Besides in gut DAO occurred in high activity only in kidney and mesenteric lymph nodes. In patients with adenocarcinoma of the large bowel or of the stomach the enzymic activity was reduced in the tumour tissue itself as compared with the adjacent mucosa in which part the highest activities were observed. In stomach it seemed most important that the enzymic activity was enhanced in the whole mucosa, also in a 10 cm distance from tumour where no histological alterations were found. This fact should be checked for significance in early tumour diagnosis.

Adenocarcinoma↗