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Biomedical subjects

I Nagy

Publications and source records attributed to I Nagy.

At least 73 records · Page 4Linked to original sources

Further sequence analysis of the DNA regions with the Rhodococcus 20S proteasome structural genes reveals extensive homology with Mycobacterium leprae.

The sequence of the respective DNA regions downstream of the 20S proteasome structural genes prcB1A1 (6 kb) and prcB2A2 (3.3 kb) of Rhodococcus erythropolis NI86/21 were determined. A highly conserved gene organization was observed between the two clusters which differed significantly in G + C content (68.8% versus 62.6%). Several ORFs were homologues of putative genes previously identified by genomic sequencing of the equivalent DNA in the related nocardioform actinomycete, Mycobacterium leprae, and thought to be specific for this pathogen. Three ORFs (ORF8(1), ORF8(2), ORF12[1]) without a counterpart in M. leprae were found. No significant homology to known sequences including proteasome-related gene products was detected, except for ORF9(1) and ORF9(2) which display a high level of sequence identity with a partially sequenced ORF in Streptomyces chrysomallus. These downstream ORFs also show a significant level of sequence homology with the ORF6(1) and ORF6(2) which are located upstream of the proteasome structural genes in the respective clusters.

Amino Acid Sequence↗

Beneficial effect of lovastatin on sphincter of Oddi dyskinesia in hypercholesterolemia and hypertriglyceridemia.

This report describes an impaired sphincter of Oddi relaxation function in relation to hypercholesterolemia and hypertriglyceridemia. As indicated by repetitive amyl nitrite-augmented quantitative hepatobiliary scintgraphy, normalization of serum lipids by means of diet and a 3-month treatment period with 20 mg of lovastatin per day resulted in an improvement of sphincter of Oddi relaxation.

Aged↗

Thoracic and lumbar sympathectomy with the application of ROMICRO mini laparotomy set.

The authors present the use of ROMICRO set (originally developed for mini laparotomy) for thoracic and lumbar sympathectomy. They review 3 thoracic and 2 lumbar sympathectomy operations that had good effects and uneventful recoveries. The advantage of the method is that no special instruments are needed and it can be done as a conventional operation.

Cholecystectomy, Laparoscopic↗

Impaired nitrergic relaxation of the sphincter of Oddi of hyperlipidaemic rabbits.

Field stimulation relaxed the sphincter of Oddi muscle rings of the rabbit after incubation with phentolamine, oxprenolol and atropine (all 1 microM). The relaxation was blocked by NG-nitro-L-arginine methyl ester (30 microM) and was reversed by 3 mM L-arginine but not D-arginine. Sphincter of Oddi preparations from hypercholesterolaemic rabbits exhibited contractions under the same conditions. We conclude that nitrergic relaxation is impaired in the sphincter of Oddi from hypercholesterolaemic rabbits.

Animals↗

Identification of a Rhodococcus gene cluster encoding a homolog of the 17-kDa antigen of Brucella and a putative regulatory protein of the AsnC-Lrp family.

By sequence analysis, a gene encoding a homolog of the 17-kDa protein antigen of the Gram-negative pathogen Brucella abortus (Hemmen et al., Clin Diagn Lab Immunol 2: 263, 1995) was identified in the nocardioform actinomycete Rhodococcus sp. NI86/21. Database searching also revealed a partial human cDNA sequence for a putative eukaryotic homolog of this presumptive Brucella-specific protein. These proteins display a low but significant level of similarity with lumazine synthases involved in bacterial riboflavin biosynthesis. In the upstream region, a Rhodococcus gene for a putative regulatory protein of the AsnC family is located.

Amino Acid Sequence↗

Serum and ascitic levels of soluble intercellular adhesion molecule-1 in patients with alcoholic liver cirrhosis: relation to biochemical markers of disease activity and alcohol intake.

The overexpression of intercellular adhesion molecule-1 (ICAM-1) has been shown to be involved in the pathogenesis of various necroinflammatory diseases, including alcoholic hepatitis. Shedding of this molecule from cell surfaces results in a circulating form, soluble ICAM-1 (sICAM-1). In this work, the serum and ascitic concentrations of sICAM-1 were studied in relation to clinical and laboratory data in patients with alcoholic liver cirrhosis of different disease activities. Elevated circulating concentrations of this adhesion molecule were found in all cirrhotic patients, the highest in those with superimposed severe alcoholic hepatitis, and the levels in regularly drinking cirrhotics without severe alcoholic hepatitis were likewise significantly higher than in those who had stopped drinking. The serum sICAM-1 concentration was best related to the serum AST activity, and also exhibited significant correlations with the prothrombin activity, serum bilirubin, albumin, peripheral leukocyte count. Maddrey's discriminant function value, Child grading, and antecedent alcohol consumption. Multivariate regression analysis revealed that the serum AST and prothrombin activities were independent predictors of the circulating sICAM-1 concentration. The concentration of sICAM-1 in the uninfected ascitic fluid of cirrthotics was about seven times lower than that in the serum; the ratio of its ascitic and serum levels was lower than that of the ascitic and serum total protein concentrations. These data contradict a significant intraperitoneal production of the molecule. It is concluded that the serum sICAM-1 level may be useful as a marker for the current disease activity (the severity of underlying acute necroinflammatory reactions) in alcoholic liver cirrhosis.

Adult↗

Relevance of ICAM-1 to alcoholic liver cirrhosis.

An elevated serum concentration of soluble intercellular adhesion molecule-1 (sICAM-1) was observed in patients with alcoholic liver cirrhosis in strong correlation with the current activity of the liver disease and the history of alcohol consumption. Circulating ICAM-1 levels were significantly elevated in the sera of all of 25 patients (1,400 +/- 850 ng/ml) compared with normal healthy subjects. The highest levels of sICAM-1 (2,650 +/- 560 ng/ml) were measured in those patients who suffered from superimposed acute alcoholic hepatitis (SAH). Regularly drinking cirrhotic patients without SAH also exhibited significantly higher results than those who had stopped drinking. The serum ICAM-1 concentration showed a negative correlation with the duration of abstinence. No elevated sICAM-1 was found in ascitic fluid of cirrhotic patients, which tends to discount a significant intraperitoneal production of this molecule. flow cytometric analysis revealed an increased expression of ICAM-1 molecules on peripheral blood monocytes of cirrhotic patients. Proliferating bile ducts and parenchymal cells of cirrhotic livers displayed a positive ICAM-1 immunohistochemical reaction in 3 autopsy cases. It is concluded that the elevated levels of sICAM-1 in the serum of patients with alcoholic liver diseases may provide useful diagnostic or prognostic information. However, determination of the exact source of circulating ICAM-1 in patients with alcoholic cirrhosis still demands further investigations.

Adult↗

Sub-population of capsaicin sensitive primary afferent neurons in thoracic, lumbar and sacral dorsal root ganglion in young rats revealed by stimulated cobalt uptake.

The number of dorsal root ganglion (DRG) neurons, the relative number of capsaicin sensitive DRG cells and the diameter distribution of these neurons were investigated in the thoracic 11, lumbar 5 and sacral 1 DRG ganglia in young rats. The capsaicin sensitivity of DRG cells was shown by the stimulated cobalt uptake technique in in vitro conditions. Cobalt labelled and non-labelled neurons were counted using the dissector method. Our results show that the total number of DRG cells in the Th11, L5 and S1 segments (4200-6500 per ganglion) were not significantly different from each other and about 8% of these cells were capsaicin sensitive in the segments studied. These findings also show that the capsaicin sensitive DRG cells belong to the small diameter DRG cell population. Control experiments on neonatally capsaicin injected animals indicate that the capsaicin stimulated cobalt uptake provides selective and specific staining of capsaicin sensitive DRG neurons.

Animals↗

Possible branching of myelinated primary afferent fibres in the dorsal root of the rat.

A combined physiological and morphological examination of rat dorsal root ganglion cells revealed branching of the central process of neurones with myelinated fibres (conduction velocity > 2 m/s; n = 24). Single shock electrical stimulation of spinal dorsal roots triggered double action potentials (early and late spike) in two dorsal root ganglion cells recorded by intracellular electrodes in the in vitro spinal cord-dorsal root ganglion preparation from 12-20 day-old rats. The action potentials had different stimulus thresholds (lower for the late spike). In one dorsal root ganglion cell the differences in delay between the two spikes inhibited the soma invasion of the second spike, when both action potentials were evoked at resting membrane potential. Depolarization of the soma membrane by DC current, injected through the electrode, recovered the blocked action potential. Membrane depolarization by GABA reduced the threshold for the early spike and changed the pattern of activation. After electrophysiological characterisation, intracellular biotin/avidin staining of the neurone revealed branching of the central axon in the dorsal root. None of the other cells, which responded with single action potentials after dorsal root stimulation showed secondary branching (n = 5). This rare observation shows that differences between the conduction velocities and activation thresholds in branches of individual dorsal root ganglion cell axons may produce block of spike invasion into the soma and perhaps the spinal terminal field of large primary afferents.

Action Potentials↗

[Screening of newborn infants for medium-chain acyl-CoA dehydrogenase deficiency in Hungary].

The authors publish for the first time the Hungarian frequency of the medium chain acyl-CoA dehydrogenase (MCAD) deficiency. The determination was carried out with molecular biological methods in 1121 newborns. The disease is inherited as an autosomal recessive trait, caused by mutation in the enzyme gene. The deficiency is extremely frequent in the Anglo-Saxon populations. Here it is as common as phenylketonuria. The first episode presents usually in the first 2 years of life, and the mortality may approach 60 percent. Early and prompt diagnosis can lead to an effective management of the disorder. The severity of the disease and its frequency in foreign countries made the screening necessary.

Acyl-CoA Dehydrogenases↗

The first characterization of a eubacterial proteasome: the 20S complex of Rhodococcus.

BACKGROUND: The 26S proteasome is the central protease of the ubiquitin-dependent pathway of protein degradation. The proteolytic core of the complex is formed by the 20S proteasome, a cylinder-shaped particle that in archaebacteria contains two different subunits (alpha and beta) and in eukaryotes contains fourteen different subunits (seven of the alpha-type and seven of the beta-type). RESULTS: We have purified a 20S proteasome complex from the nocardioform actinomycete Rhodococcus sp. strain NI86/21. The complex has an apparent relative molecular mass of 690 kD, and efficiently degrades the chymotryptic substrate Suc-Leu-Leu-Val-Tyr-AMC in the presence or absence of 0.05% SDS. Purified preparations reveal the existence of four subunits, two of the alpha-type and two of the beta-type, the genes for which we have cloned and sequenced. Electron micrographs show that the complex has the four-ringed, cylinder-shaped appearance typical of proteasomes. CONCLUSIONS: The recent description of the first eubacterial ubiquitin, and our discovery of a eubacterial proteasome show that the ubiquitin pathway of protein degradation is ancestral and common to all forms of life.

Amino Acid Sequence↗

[Non-ketotic hyperglycinemia].

Three children with non-ketotic hyperglycinaemia (NKH) is reported. Two patients had typical neonatal form of NKH, one patients had atypical form of NKH. The clinical symptoms laboratory findings and therapeutical approach are discussed. One of the patients with typical neonatal form of NKH is died, neuropatological examination revealed corpus callosal agenesis and diffuse hypomyelinisation. The two children treated with N-methyl-D-aspartate-antagonist drugs reached a significantly better clinical condition. The authors reviewed the data of the literature, especially focused on the therapeutical possibilities.

Amino Acid Metabolism, Inborn Errors↗

The loss of pacing-induced preconditioning in atherosclerotic rabbits: role of hypercholesterolaemia.

A brief rapid pacing has been shown to protect rabbit heart against global myocardial ischaemia induced by subsequent longer pacing. We studied whether pacing-induced preconditioning was reproducible in experimental hypercholesterolaemia. In conscious rabbits with an implanted right ventricular electrode and left ventricular polyethylene catheters, pacing of 500 bpm over 20 min induced an intracavitary ST-segment elevation of 3.2 +/- 0.41 mV, shortened ventricular effective refractory period and increased left ventricular end-diastolic pressure from prepacing 105 +/- 3.9 ms and 4.0 +/- 0.93 mmHg to post-pacing 62 +/- 6.4 ms and 27.9 +/- 7.2 mmHg, respectively. A 10-min preconditioning pacing followed by a 5-min interval markedly attenuated these test pacing-induced ischaemic changes. Rabbits were fed a cholesterol-enriched diet over 4, 8 and 12 weeks, responded to a 5- or 10-min pacing with ischaemic changes of the same degree as did controls to a 10- or 20-min pacing, respectively. A 4-week diet elevated total serum cholesterol from 1.7 +/- 0.4 to 24.1 +/- 2.9 mmol/l without apparent atherosclerotic lesions in the thoracic aorta assessed by Oil-Red O staining and planimetry, but it abolished protection induced by a 5-min preconditioning pacing. A 12-week diet increased serum cholesterol and lesion surface area to 26.9 +/- 3.2 mmol/l and 89.6 +/- 6.4%, respectively, and continued to block preconditioning. When these animals were refed normal chow over additional 6 weeks, serum cholesterol level dropped to 2.6 +/- 0.80 mmol/l with no change in atherosclerotic lesions, the preconditioning effect, however, recovered. We conclude that hypercholesterolaemia blocks preconditioning irrespective of the development of atherosclerosis.

Animals↗

Characterization of the Rhodococcus sp. NI86/21 gene encoding alcohol: N,N'-dimethyl-4-nitrosoaniline oxidoreductase inducible by atrazine and thiocarbamate herbicides.

A protein with a mol.mass of 51,000 (ThcE) that was induced in Rhodococcus sp. NI86/21 during assimilation of thiocarbamate herbicides, atrazine, ethanol, propanol, glycerol, propionaldehyde or ethanolamine was identified by two-dimensional electrophoresis. The thcE gene was cloned and sequenced. The deduced amino acid sequence revealed ThcE as a member of group III alcohol dehydrogenases. ThcE displayed strong homology with sequenced subunit fragments of the homodecameric N,N'-dimethyl-4-nitrosoaniline-dependent alcohol oxidoreductases (MNO) of Amycolatopsis methanolica and Mycobacterium gastri. N-Terminal sequence analysis of purified MNO from Rhodococcus sp. NI86/21 confirmed the identity with ThcE. When overproduced in Escherichia coli, ThcE was insoluble and no MNO activity was detected.

Alcohol Oxidoreductases↗

Involvement of Fenton reaction products in differentiation induction of K562 human leukemia cells.

ADP-Fe2+ (or ATP-Fe2+) complex and H2O2, components of the Fenton reaction, were added to K562 cells, then cultured for 96 h. Ara-C-induced differentiation served as a basis for comparison. Cell numbers, viability, benzidine staining, thymidine incorporation, and cell-cycle distribution by means of flow cytometry were determined. The Fenton reagents reduced the growth rate and thymidine incorporation of leukemic cells in a dose-dependent manner as regards the added H2O2 (from 0.01 to 1.0 mM), accompanied by an accumulation of hemoglobin in them. Differentiation of the cells was accompanied by considerable changes in total SOD and catalase activities. Ara-C caused an increase of SOD to 366%, and of catalase to 235%, while the complete Fenton reaction resulted in SOD increase to 705% and catalase decrease to 38% of the untreated control cultures. These shifts in enzyme inductions suggest the existence of a higher H2O2 flux in the differentiating cells. The results are consistent with the assumption that products of the Fenton reaction, among them OH. radicals deriving from H2O2 by heterolysis, may play a causal role in cell differentiation, whereas an overproduction of these radicals causes aging or death of the cells.

Adenosine Diphosphate↗