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Biomedical subjects

G Lengyel

Publications and source records attributed to G Lengyel.

At least 37 records · Page 2Linked to original sources

Role of free-radical reactions in liver diseases.

Role of free-radical reactions is most significant in toxic liver injuries. Two traditional groups of liver injuries induced by drugs and chemicals are distinguished, 1. direct toxic type and 2. idiosyncratic type. Liver injury of direct toxic type is generally developed following toxin exposure, it is dose dependent, incubation period is short, and the injury often affects other organs (e.g. kidney). Direct toxins frequently cause typical zonal necrosis usually without concomitant signs of hypersensitivity. It is typical of idiosyncratic reaction that it appears only in a shorter period of exposure, it cannot be predicted, it is not dose-dependent, its incubation period varies and sometimes (in one-fourth of cases) it is accompanied by extrahepatic symptoms of hypersensitivity (fever, leukocytosis, eosinophilia, rashes), its morphologic picture shows great variety. A part of direct toxins is toxic itself, in the other part the basic compound is not toxic but it changes into toxic metabolites in the liver. Liver is well-protected against free-radicals developing in the organism: it is one of our best antioxidant supplied organs. It is probably due to the one of the important tasks of liver, namely detoxication of drugs, chemicals and toxic materials, with subsequent release of free-radicals. It is proved by the fact that in normal bile peroxidized lipids produced by free-radical chain reactions can also be detected. The pathologic free-radical reactions and one of their sequelae, peroxidation of lipids (LPO) do not necessarily cause cell and tissue damage. Antioxidant protection of cells and tissues is able to prevent free-radical injury and it enables, that the already developed damages become reversible. According to recent investigations, the lipid peroxidation, caused by free-radical reactions, or covalent binding of radical products to biomolecules does not lead directly to cellular destruction, only via further reactions. Such intermediary steps can be the phospholipase A2 activation, accumulation of lysophosphatides, poly-ADP-ribose polymerase repair enzyme activation, following oxidative damage of DNA, with subsequent NAD and ATP depletion. Its significance may be that the irreversible cellular and tissue damage can be prevented perhaps not only by administration of antioxidants, but also by compounds (e.g. phospholipase A2 inhibitors) affecting the above-mentioned biochemical mechanisms.

Animals↗

[Chronic gastritis and the presence of Helicobacter pylori in patients with non-ulcerative dyspepsia].

After definition in the group of the non ulcer dyspepsia (NUD) can be counted all those patients at whom beside the dyspeptical complaints, the radiological and endoscopical examinations didn't show ulcerative changes. The authors made biopsy 550 times on the occasion of 1390 gastroscopical examination (39.5% of the cases). The histological examination showed chronic gastritis in 372 cases (26.7% of all the examinations, 67.6% of the histological examinations). At this group of patients the dyspeptical complaints gave the principal indication of gastroscopical examination. Also it was examined the presence of dysplasia and intestinal metaplasia beside the different severity grade of chronic gastritis. The presence of Helicobacter pylori (Hp) was examined by histological methods. Hp positivity was noticed in 16.4% in the upper group. The authors made Hydrogen-breath examinations in 34 cases between patients with NUD. The results of Hydrogen-breath examinations also raise the multifactorial nature of the NUD. On the basis of examinations chronic gastritis and CP infection can form subdivisions in the heterogenic group of patients with NUD. For exacter judgement of Hp pathogenicity are needed further and wide-spread examinations. The authors would like to call the attention to the indispensability of the biopsy during the gastroscopical examination.

Chronic Disease↗

Human fetal hepatocytes respond to inflammatory mediators and excrete bile.

Under strict observation of the ethical guidelines of the 1975 Declaration of Helsinki Human Research Committee, primary hepatocyte cultures were prepared from second-trimester fetal liver specimens. We have shown for the first time that fetal hepatocytes have the capacity to produce an acute-phase response on treatment with inflammatory mediators. Addition of interleukin-6 to the cultures resulted in strong induction of C-reactive protein and alpha-1-antichymotrypsin expression, whereas albumin expression was repressed. In contrast to interleukin-6, transforming growth factor-beta did not induce C-reactive protein expression. However, as in adult hepatocytes, fetal cells responded to transforming growth factor-beta by reduced albumin synthesis. We were able to show by virtue of fluorescein excretion into sealed clefts that fetal hepatocytes have the functional capacity to form bile. Our findings indicate that second-trimester hepatocytes can be regarded as fairly mature liver cells.

Acetylcholine↗

[The role of interleukin-1 beta in the regulation of liver-specific gene expression in human hepatoblastoma cells].

The authors studied the function of liver cells--on level of DNA and gene regulation--by methods of molecular biology. They found that treating human hepatoma (Hep G2) cells with interleukin-1 (IL-1) leads to the induction of alpha-1-acidglycoprotein (AGP) and complement 3 (C3) mRNA synthesis, and to a concomitant downregulation of albumin (alb), alpha-fetoprotein (AFP) and alpha-2-macroglobulin (alpha 2M) mRNA synthesis. Levels of specific mRNA were measured by Northern-blot analysis. They conclude that Hep G2 cells may serve as a suitable in vitro model for study of the liver specific gene expression, and IL-1 is one of the mediators of these gene control. The regulation is pretranslational as the direction of change in specific mRNA corresponds to the changes in synthesis of the respective proteins.

Blotting, Northern↗

Regulation of interleukin 6 receptor expression in human monocytes and monocyte-derived macrophages. Comparison with the expression in human hepatocytes.

IL-6 is a cytokine with pleiotropic biological functions, including induction of the hepatic acute phase response and differentiation of activated B cells into Ig-secreting plasma cells. We found that human peripheral blood monocytes express the IL-6-R, which is undetectable on the large majority of lymphocytes of healthy individuals. Stimulation of monocytes by endotoxin or IL-1 causes a rapid downregulation of IL-6-R mRNA levels and a concomitant enhancement of IL-6 mRNA expression. IL-6 itself was found to suppress the IL-6-R at high concentrations. A gradual decrease of IL-6-R mRNA levels was observed along in vitro maturation of monocytes into macrophages. We show that downregulation of IL-6-R mRNA levels by IL-1 and IL-6 is monocyte specific, since IL-6-R expression is stimulated by both IL-1 and IL-6 in cultured human primary hepatocytes. Our data indicate that under noninflammatory conditions, monocytes may play a role in binding of trace amounts of circulating IL-6. Repression of monocytic IL-6-R and stimulation of hepatocytic IL-6-R synthesis may represent a shift of the IL-6 tissue targets under inflammatory conditions.

Blotting, Northern↗

Regulation of interleukin-6 receptor expression in human monocytes and hepatocytes.

Human blood monocytes normally express the interleukin-6 receptor. Treatment of cultured monocytes with endotoxin, interleukin-1 beta, or interleukin-6 results in a decrease in interleukin-6 receptor mRNA levels. Glucocorticoids aso cause a drop in monocytic interleukin-6 receptor mRNA levels. We also found interleukin-6 receptor expression in cultured human hepatocytes, but in contrast to monocytes, where interleukin-6 receptor mRNA is presented by the ligand and by interleukin-1, treatment of hepatocytes with interleukin-6 or interleukin-1 resulted in increased interleukin-6 receptor mRNA levels. Induction of interleukin-6 receptor mRNA in hepatocytes was less pronounced when glucocorticoids were omitted from the culture medium. We conclude that during noninflammatory homeostasis, blood monocytes are involved in binding of trace amounts of circulating interleukin-6. During inflammatory events, the main target of interleukin-6 may be changed from the monocytic population not only to activated B-cells, but also to the hepatocytes.

Acute-Phase Reaction↗

[Familial occurrence of carcinoid of the small intestine].

The case of a 41 year old woman has been reported, whose "flush" syndrome was caused by a carcinoid tumor originated from the jejunum. The patient's father had to be operated for intestinal carcinoid tumor several times. The occurrence of different forms of carcinoid tumors, especially in the gastrointestinal tract, has been discussed in connection with the diagnostic approaches and therapeutical possibilities. The authors considered the case interesting for publications, because carcinoid is a rather rare tumor, and one cannot find its familiar occurrence in the available literature.

Adult↗

Tumor necrosis factor-alpha induces a kappa B sequence-specific DNA-binding protein in human hepatoblastoma HepG2 cells.

Tumor necrosis factor-alpha is an inducer of acute-phase protein synthesis in liver cells. The mechanism by which tumor necrosis factor-alpha alters gene expression in these cells is largely unknown. In this study, we demonstrate that tumor necrosis factor-alpha stimulates human immunodeficiency virus-1 long terminal repeat-promoted gene expression in the human hepatoblastoma HepG2 cell line and increased binding of trans-activating factors to kappa B (kappa B) DNA sequences. In contrast to lymphocytic cells where the nuclear factors recognizing the kappa B sequences are activated by both tumor necrosis factor-alpha and phorbol-12-myristate-13-acetate through a posttranslational mechanism, in HepG2 cells phorbol-12-myristate-13-acetate does not activate these factor(s), and de novo protein synthesis seems to be required in HepG2 cells for gene activation by tumor necrosis factor-alpha.

Base Sequence↗

Inhibition of lipid peroxidation by dihydroquinoline-type antioxidant (CH 402).

The in vitro effect of a non-toxic, water soluble, low molecular weight, stable dihydroquinoline-type antioxidant, CH 402 (Na (2,2-dimethyl-1,2-dihydroquinoline-4-yl)-methane sulphonic acid) was studied on free radical reactions in brain subcellular fractions. Experiments were performed using rat and mouse brain homogenate and microsomal fractions. Non-enzymatically induced lipid peroxidation by ascorbic acid was studied in correlation with ascorbic acid and CH 402 concentrations and incubation time. Malondialdehyde production during lipid peroxidation was measured by the thiobarbituric acid test. In a concentration range of 10(-2)-10(-5) M CH 402 dose-dependently inhibited the ascorbic acid induced in vitro lipid peroxidation in mouse and rat brain subcellular fractions.

Animals↗

[Seasonal disposition of gastroduodenal ulcer--legend or reality?].

The seasonal activity of peptic gastroduodenal ulcers was studied on the basis of 17,106 gastroduodenoscopies which were done during a 10 years period. The activity of gastric and duodenal ulcer was increased only in autumn; their number in spring did not deviate from the average. The frequency of bleeding in duodenal ulcers was increased in autumn, whereas the gastric ulcer-bleeding was detected in more patients during winter. According to this examination the regular spring-autumn periodicity is not typical for the peptic ulcer.

Cross-Sectional Studies↗

[Endoscopy of the bile ducts and pancreas in children].

ERCP was carried out in 8 children under 14 years age. The indications of examinations were in 7 cases obstructive jaundice caused in 3 patients by congenital anomalies of the biliary tract. In one case the ERCP was performed because of acute relapsing pancreatitis. The examinations were carried out under general anesthesia in 5 children and after sedative premedication in 3 cases. No complications of the procedures were recorded. ERCP is a useful method also in children for diagnosing bilio-pancreatic anomalies.

Acute Disease↗

[Rennet as a source of Salmonella occurrence in various dairy products].

During a microbiological examination of foodstuffs, frequent occurrence of salmonellas of S. agona serotype was found in milk products, namely in ewe's milk cloddy cheese, ewe's milk curd and hard cheeses. The rennet produced by one enterprise was a source of salmonella spreading. To solve this problem, 1268 different samples were examined in which salmonellas were isolated in 69 cases. The Veterinary Service worked out and in cooperation with other bodies took steps to liquidate the occurrence of salmonellas in a short time; the level of that serotype in the population was not increased.

Animals↗