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Biomedical subjects

I Nagy

Publications and source records attributed to I Nagy.

At least 55 records · Page 3Linked to original sources
PubMed1998

The 20S proteasome of Streptomyces coelicolor.

20S proteasomes were purified from Streptomyces coelicolor A3(2) and shown to be built from one alpha-type subunit (PrcA) and one beta-type subunit (PrcB). The enzyme displayed chymotrypsin-like activity on synthetic substrates and was sensitive to peptide aldehyde and peptide vinyl sulfone inhibitors and to the Streptomyces metabolite lactacystin. Characterization of the structural genes revealed an operon-like gene organization (prcBA) similar to Rhodococcus and Mycobacterium spp. and showed that the beta subunit is encoded with a 53-amino-acid propeptide which is removed during proteasome assembly. The upstream DNA region contains the conserved orf7 and an AAA ATPase gene (arc).

Acetylcysteine↗
PubMed1998

Histological evaluation of the response to interferon-alpha therapy in chronic hepatitis C.

BACKGROUND AND AIMS: The response rate of interferon-alpha (IFN-alpha), recently introduced in the treatment of chronic hepatitis C, is merely 25-50%. The aims of this follow-up study were to compare the efficacy of 6 and 12-month IFN-alpha treatment via liver biopsy scores and to evaluate the correlation with the biochemical response. PATIENTS AND METHODS: Twenty chronic hepatitis C patients were studied; 10 received IFN-alpha therapy for 6 months and 10 for 12 months. Liver biopsy material was taken before and after therapy. RESULTS: There was a significant serum alanine aminotransferase (ALT) level improvement in both groups, but a significant histological improvement in necroinflammatory activity (grade) only in the 12-month group. The Chevallier stage scores demonstrated a significant progression in both groups. CONCLUSIONS: Twelve-month IFN-alpha treatment affords a better response in the liver histology grade and serum ALT level, but does not influence the staging; a normal ALT does not guarantee hepatitis inactivity. Liver biopsies appear indispensable for monitoring.

Adult↗
PubMed1997

[The favorable effect of humic acid based complex micro-element preparations in cadmium exposure].

The authors have studied the effect of consumption of a humic acid based complex microelement preparation (potassium, magnesium, iron, zinc, manganese, copper, vanadium, cobalt, molibden, selenium bound to humic acids) for six weeks (10 ml daily) on the biological exposure indices (blood and urine cadmium levels) and clinical laboratory parameters (liver and kidney tests, blood picture) of men (n = 18; 39.7 +/- 10.4 years of age;) working in cadmium exposure for 8.3 +/- 5.0 years. The initial mean blood and urine cadmium levels of the non-smoking subjects was twice higher than that of the non-smoking male controls living in the same urban area (n = 35), and significantly correlated with the length of exposure. Their mean serum alanin-aminotransferase, gamma-glutamyl-transferase, creatinine, uric acid and urinary N-acetyl-beta-D-glucosaminidase levels were significantly higher than that of the controls. After the six-week treatment blood cadmium level, activity of serum alanin-aminotransferase, serum uric acid and urinary protein concentrations decreased significantly, the abnormal serum iron levels normalized. According to this results, the absorption of cadmium decreased on the effect of the complex microelement supplementation and the adverse laboratory changes attributable partly to cadmium exposure improved. Therefore humic acid based complex microelement supplementation is recommended as an effective tool for prevention and health protection in occupational cadmium exposure as well as for smokers known to be considerably burdened by cadmium.

Cadmium↗
PubMed1997

[Successful management of malum perforans resulting from spina bifida].

Authors observed a boy presented a protrusion positioned lumbosacral, existing since his birth. Later, on inner side of both heels ulcers began to take shape, being not curable by local treatment. Neurologic examination verified severe radicular lesion, magnetic resonance investigation showed lumbosacral lipo-meningocele. After its surgical treatment, ulcers on soles healed up. Neurotropic ulcer develops on sites exposed to pressure, being generally painless. Several sickness may lead to its development. In childhood occurrence is relatively rare. At this age mostly various closure troubles of medullary tube may stand in the background. To successful treatment of malum perforans--besides local therapy--that of underlying illness is essential as well.

Abnormalities, Multiple↗
PubMed1997

Subunit topology of the Rhodococcus proteasome.

The 20S proteasome, isolated from the nocardioform actinomycete Rhodococcus erythropolis strain NI86/21, is built from two alpha-type and two beta-type subunits. In order to probe the subunit topology, we have set up an expression system which allows coexpression of the genes encoding the alpha- and beta-subunits in all possible combinations. The four respective constructs obtained yielded fully assembled and proteolytically active proteasomes. Biochemical, kinetic and electron microscopy analysis allow us to rule out several of the models which were originally envisaged for the subunit topology of the Rhodococcus proteasome. The experiments further indicate that the assembly pathways of the Rhodococcus and of the Thermoplasma proteasome differ in some important details.

Cloning, Molecular↗
PubMed1997

Delayed cardiac protection against harmful consequences of stress can be induced in experimental atherosclerosis in rabbits.

Multiple brief periods of rapid ventricular pacing confer both short- and long-term protection on the ischaemic heart. The duration of the short-term protection does not exceed 2 h, whereas the long-term protective effect appears several hours after the inducing insults, with maximal protection 24-48 h later. Up to now, delayed cardiac protection by preceding ischaemic insults against harmful consequences of stress has been produced in the normal, healthy animal only. The purpose of this study was, therefore, to test whether delayed cardiac protection can be induced in experimental atherosclerosis in rabbits produced by feeding cholesterol-rich diet over 2 months. Repeated brief periods of rapid ventricular pacing were used to induce delayed protection of the heart. Moderation of post-pacing right intracavitary ST segment elevation and that of the left ventricular end-diastolic pressure (both produced by ventricular overpacing: 500 beats/min for 15 min) were found in normal animals as well as in those fed cholesterol-enriched diet. The short-lived protection induced by a single 'preconditioning' pacing was reproducible only in normal animals. As measured by means of radioimmunoassay, the protective effect of either short- or long-term protection appeared in parallel with an attenuation of ischaemia-induced increase in cardiac cyclic AMP content, in both normal and atherosclerotic rabbits. An increase in cardiac cyclic GMP content was characteristic of the short- but not long-term protection. These results suggest that the delayed cardiac protection by preceding multiple brief rapid pacings operates even in experimental atherosclerosis, but the short-term protection induced by a single preconditioning stimulus is lost.

Animals↗
PubMed1997

Loss of pacing-induced preconditioning in rat hearts: role of nitric oxide and cholesterol-enriched diet.

We examined whether the inhibition of nitric oxide (NO) synthesis by NG-nitro-L-arginine (lNNA) abolished pacing-induced preconditioning, and if prolonged exposure to cholesterol-enriched diet led to the loss of preconditioning due to decreased cardiac NO formation. Therefore, Wistar rats fed 2% cholesterol-enriched diet or standard diet for 24 weeks were treated with a single dose of 1 mg/kg lNNA or its solvent at the end of the week 24, respectively. Isolated hearts from all groups were subjected to either preconditioning induced by three consecutive periods of pacing at 600 beats/min for 5 min, with 5-min interpacing periods, or time-matched non-preconditioning perfusion, followed by a 10-min coronary occlusion, respectively. In the control group, coronary occlusion after a non-preconditioning protocol decreased aortic flow (AF) from 45.4+/-2.4 to 15.6+/-1.5 ml/min, and resulted in a lactate dehydrogenase (LDH) release of 219+/-55 mU/min/g, however, preconditioning attenuated the consequences of coronary occlusion [AF: 27.3+/-1.7 ml/min (P<0.05); LDH: 44+/-14 mU/min/g (P<0.05)]. Preconditioning did not confer protection in the lNNA-treated (AF: 17.4+/-1.5 ml/min; LDH: 151+/-21 mU/min/g), and/or in the high-cholesterol-fed groups (AF: 15.7+/-1.2 ml/min; LDH: 168+/-22 mU/min/g). Preconditioning was preserved however, when hearts were treated with lNNA after the preconditioning protocol [AF: 29.6+/-2.2 ml/min (P<0.05); LDH: 48+/-17 mU/min/g (P<0.05)]. Both lNNA treatment and cholesterol-enriched diet markedly decreased cardiac NO content assayed by electron spin resonance spectroscopy. We conclude that NO may be involved in the triggering mechanism of pacing-induced preconditioning, the protective effect of which is blocked by sustained exposure to dietary cholesterol, possibly by influencing cardiac metabolism of NO.

Animals↗
PubMed1997

One-year treatment with cholecystokinin-octapeptide and secretin: effects on pancreatic trophism in the rat.

The effects of long-term administration of cholecystokinin octapeptide (CCK-8) with or without secretin on the pancreas were examined in groups of rats treated with: (1) CCK-8 (1 microgram kg-1); (2) secretin + CCK-8 (1 microgram kg-1 of each); or (3) saline, administered subcutaneously twice daily for 5 out of 7 days for 6 or 12 months. A number of rats from all groups were studied for: (1) pancreatic size and biochemical composition (n = 6 for each group); (2) pancreatic secretion in the anesthetized state (n = 5 for each group); and (3) pancreatic histology (n = 6 for each group) after a 6-month treatment period. The rest of the animals treated for an additional 6-month period (n = 13 for each group) were examined for pancreatic size and histology. CCK-8 increased the weight of the pancreas and its contents of DNA, protein, trypsinogen, chymotrypsinogen, proelastase, secretory trypsin inhibitor and amylase, but not that of lipase when given for 6 months, whereas administration of secretin + CCK-8 doubled the pancreatic content of lipase and increased all trophic parameters (except the amylase content) over those of CCK-8-treated rats. Maximum pancreatic volume and protein outputs in response to CCK-8 were higher in both of the hormone-treated groups than in the control; the sensitivity to the secretory action of CCK-8 was not altered. Pancreatic mass increased in response to either treatment after 12 months as well. Histological examination did not reveal pancreatic neoplasia in either group. The results indicate that long-term administration of CCK-8 or secretin + CCK-8 in rats results in sustained pancreatic hypertrophy and hyperplasia with secretory hyperfunction with no evidence of neoplastic alterations.

Animals↗
PubMed1997

Glibenclamide sensitivity of neural relaxation of the rabbit sphincter of oddi.

In this article we studied whether the nitrergic relaxation of the rabbit sphincter was sensitive to glibenclamide. Field stimulation relaxed the sphincter of Oddi rings after incubation with atropine (1 microM) and guanethidine (4 microM) with threefold and fourfold increases in tissue guanosine 3':5'-cyclic monophosphate and adenosine 3':5'-cyclic monophosphate contents, respectively. These changes were blocked by 30 microM NG-nitro-L-arginine methyl ester. Glibenclamide (0.1-10 microM) attenuated the field stimulation-induced relaxation and completely abolished the relaxation produced by 0.1 microM cromakalim. We conclude that nitrergic relaxation of the rabbit sphincter of Oddi comprises a mechanism sensitive to glibenclamide.

Animals↗
PubMed1997

Spontaneous and cholecystokinin-octapeptide-promoted regeneration of the pancreas following L-arginine-induced pancreatitis in rat.

CONCLUSION: In L-arginine (Arg)-induced pancreatitis, evidence of acute inflammation was observed on d 1-3. Continuous tissue atrophy became visible at the sites of previous pancreatic necrosis, with simultaneous regeneration of the pancreas, mainly around the Langerhans islets. Administration of low doses of cholecystokinin-octapeptide (CCK-8) increased the inflammatory signs of pancreatitis in the early phase, but subsequently diminished the level of atrophy and accelerated the processes of regeneration in this model of pancreatitis. BACKGROUND: The aim of this work was to study the regenerative processes following Arg-induced pancreatitis in rats. Besides the spontaneous regeneration, the effects of low doses of CCK-8 on the laboratory and morphologic parameters in this type of experimental pancreatitis were investigated. METHODS: Male Wistar rats were divided into three groups. In group I, the rats received 200 mg/100 g body weight of Arg i.p. twice, at an interval of 1 h, and 0.5 mL saline was administered s.c. twice daily. In group II, besides the same amount of Arg, the rats received 1 microgram/kg of CCK-8 s.c. in 0.5-mL saline twice daily (7 AM and 7 PM). In the control animals (group III), an identical amount of glycine was administered i.p. instead of Arg at the same times. The rats were examined on d 1, 3, 7, 14, and 28 after pancreatitis induction. The pancreatic weight/body weight ratio (pw/bw) was calculated in each case. The serum levels of amylase, and glucose and the pancreatic contents of soluble protein, trypsin, amylase and DNA were determined, and histologic examinations were performed. RESULTS: In groups I and II, both pw/bw (3.5 +/- 0.2 mg/g and 4.1 +/- 0.28 mg/g, respectively) and the serum amylase level (8900 +/- 560 IU/L and 11100 +/- 1390 IU/L, respectively) were significantly elevated on d 1 vs group III (2.1 +/- 0.06 mg/g and 5562 +/- 373 IU/L, respectively). Pw/bw was significantly decreased in groups I (0.96 +/- 0.12 mg/g, 0.8 +/- 0.1 mg/g, and 1.8 +/- 0.1 mg/g, respectively) and II (1.4 +/- 0.15 mg/g, 1.7 +/- 0.2 mg/g, and 1.95 +/- 0.1 mg/g, respectively) on d 7, 14, and 28 vs group III (2.6 +/- 0.3 mg/g, 3.1 +/- 0.15 mg/g, and 2.7 +/- 0.1 mg/g, respectively), whereas in group II it was significantly elevated vs. group I on d 7 and 14. The pancreatic contents of soluble protein, DNA, trypsin and amylase were significantly decreased on d 3-14 in groups I and II vs group III. The pancreatic DNA level was significantly elevated in group II (1.23 +/- 0.2 mg/pancreas) vs group I (0.7 +/- 0.1 mg/pancreas) on d 7. In group II, the soluble protein (73.1 +/- 15.5 mg/pancreas) and amylase (1104 +/- 160 IU/pancreas) levels were significantly elevated on d 14 as was that of trypsin (27.2 +/- 3.1 IU/pancreas) on d 28, vs group I (26.4 +/- 5.3 mg/p, 525 +/- 111 IU/pancreas, and 16.3 +/- 1.1 IU/pancreas, respectively). On histologic sections, the signs of acute inflammation of the pancreas were more pronounced in group II than in group I on d 1-3. After that time, in spite of the progressive atrophy of the pancreas, the signs of tissue repair were more expressed in group II.

Amylases↗
PubMed1997

Eubacterial proteasomes.

Proteasomes are large, multisubunit proteases with highly conserved structures. The 26S proteasome of eukaryotes is an ATP-dependent enzyme of about 2 MDa, which acts as the central protease of the ubiquitin-dependent pathway of protein degradation. The core of the 26S complex is formed by the 20S proteasome, an ATP-independent, barrel-shaped protease of about 700 kDa, which has also been detected in archaebacteria and, more recently, in eubacteria. Currently, the distribution of 20S proteasomes in eubacteria appears limited to the actinomycetes, while most other eubacteria contain a related complex of simpler structure.

Amino Acid Sequence↗
PubMed1997

The effect of continuous versus intermittent treatment with transdermal nitroglycerin on pacing-induced preconditioning in conscious rabbits.

1. Tolerance to the hypotensive effect of nitroglycerin (NG) blocks preconditioning induced by rapid ventricular pacing (RVP) in rabbits. In the present work the effect of continuous versus intermittent treatment with transdermal nitroglycerin on the pacing-induced preconditioning phenomenon was studied in conscious rabbits. 2. RVP (500 beats min-1 over 5 min) increased left ventricular end-diastolic pressure (LVEDP) from baseline 4.1 +/- 0.9 to postpacing 13.8 +/- 2.9 mmHg (P < 0.001) with a right intraventricular ST-segment elevation of 1.25 +/- 0.13 mV, two indicators of myocardial ischaemia. These changes were significantly attenuated when the RVP period was preceded by a preconditioning pacing of the same rate and duration with an interpacing interval of 5 min. 3. Protection by preconditioning was abolished when the animals had been made tolerant to the vasodilator effect of 30 micrograms kg-1 NG by the application of transdermal NG (approx. 0.07 mg kg-1 h-1) over 7 days. Furthermore, transdermal NG per se attenuated both RVP-induced ST-segment elevation and LVEDP-increase over the 7 day period. 4. With intermittent transdermal NG treatment (12 h 'patch on' vs 'patch off'), neither development of vascular tolerance nor attenuation of the NG- or preconditioning-induced anti-ischaemic effects were observed. However, the severity of pacing-induced myocardial ischaemia was significantly increased during the 'patch off' periods. 5. In a second set of experiments, postpacing changes in cardiac cyclic GMP and cyclic AMP levels were determined by means of radioimmunoassay in chronically instrumented anaesthetized open-chest rabbits with the same NG-treatment protocols. Preconditioning reduced postpacing increase in cyclic AMP with an increase in cyclic GMP concentrations in hearts of the untreated animals and in those given patches intermittently during both 'patch on' and 'patch off' periods. However, the preconditioning effect on either cyclic nucleotide was blocked in the tolerant animals. 6. Transdermal NG increased resting levels of both cardiac cyclic nucleotides in the non-tolerant but not in the tolerant state. The postpacing increase in cyclic AMP content was inhibited by transdermal NG, independent of vascular tolerance development, whereas an cyclic GMP content was exclusively seen in the non-tolerant animals. 7. We conclude that the anti-ischaemic effect of NG is independent of the cyclic GMP mechanism in the tolerant state. While intermittent NG therapy prevents development of vascular tolerance and preserves preconditioning, the nitrate-free periods yield an increased susceptibility of the heart to ischaemic challenges.

Administration, Cutaneous↗
PubMed1997

Changes in left ventricular mass during treatment with minoxidil and cilazapril in hypertensive patients with left ventricular hypertrophy.

Attainment of the regression of hypertension-associated left ventricular hypertrophy (LVH) seems to be a desirable goal of blood pressure (BP)-reducing therapy. Since antihypertensive drugs of differing types may exhibit markedly different abilities to modulate LVH, we examined the effects of the angiotensin-converting enzyme inhibitor cilazapril, and the potassium channel activator minoxidil, alone or in combination with each other, on the left ventricular mass (LVM) in patients with severe essential hypertension who had LVH detected by echocardiography. All patients received the same base therapy of bopindolol and guanfacine. After a run-in period, they were treated with: (1) cilazapril (n = 10); (2) minoxidil, combined with a diuretic (n = 10); or (3) both cilazapril and monoxidil (n = 6) for 12 months. The LVM index (LVMI; LVM per body surface area) was estimated every 3 months by means of echocardiography. Each kind of therapy decreased the arterial pressures to a similar degree. The 1-year treatment with the cilazapril-based regimen resulted in a significantly diminished LVMI (from a mean +/- s.d. of 173 +/- 38 to 152 +/- 22 g/m2; P < 0.05). On the other hand, the minoxidil-based therapy led to a significant increase in LVMI (from 148 +/- 19 to 170 +/- 35 g/m2; P < 0.05). There were no significant LVMI changes in patients receiving the combined, cilazapril + minoxidil-based treatment (172 +/- 34 vs the pretreatment 183 +/- 54 g/m2). The results confirm that long-term treatment with cilazapril is effective both in reducing BP and in reducing LVM. In spite of yielding a satisfactory reduction of BP, minoxidil therapy, even in combination with a diuretic and a beta-blocker, may lead to an aggravation of pre-existing LVH; this effect of minoxidil could be prevented by the simultaneous administration of cilazapril.

Adult↗
PubMed1997

New method for RNA isolation from actinomycetes: application to the transcriptional analysis of the alcohol oxidoreductase gene thcE in Rhodococcus and Mycobacterium.

A new protocol for the isolation of RNA from Rhodococcus and other actinomycetes such as Mycobacterium and Amycolatopsis was developed. The method is based on rapid lysis of cells in a high-speed reciprocal shaker using small abrasive particles followed by spin column purification of the lysate. This quick procedure yields RNA preparations suitable for functional studies. This was shown for the thcE gene of R. erythropolis NI86/21, which encodes a N,N'-dimethyl-4-nitrosoaniline-dependent alcohol oxidoreductase. The thcE transcript was detected by Northern hybridization in R. erythropolis, R. fascians, Mycobacterium chlorophenolicum and Mycobacterium smegmatis. The transcriptional start point of the gene was determined by primer extension of the R. erythropolis mRNA.

Alcohol Oxidoreductases↗
PubMed1997

Effect of smoking on the results of esophageal pH measurement in clinical routine.

Because data on the effects of smoking on gastroesophageal reflux are controversial, we evaluated the effect of smoking on the results of esophageal 24-hour pH-metry in clinical routine. Participants were 280 consecutive patients with symptoms suggestive of reflux disease, 78 smokers, and 202 nonsmokers. Of the smokers, 45 actually smoked during the pH measurement and 33 abstained from smoking. The frequency of reflux episodes, the fraction of time pH was < 4, and the percentage of abnormal 24-hour pH-metry results were compared among actual smokers, abstaining smokers, and nonsmokers. In actual smokers, the effect of smoking on gastroesophageal reflux was further analyzed by comparing the reflux frequency and the fraction of time that pH was < 4 for a 10-minute period before, during, and after smoking. We found no difference in reflux frequency and fraction of time that pH was < 4 among actual smokers, abstaining smokers, and nonsmokers, regardless of a normal or an abnormal pH-metry result. The percentage of patients with a pH-metry result indicating disease was similar in the three groups, at 53%, 52%, and 50%, respectively. Gastroesophageal reflux was not increased during smoking a cigarette or in the postsmoking period compared with the presmoking period. Neither being a smoker nor actually smoking a cigarette had a negative influence on gastroesophageal reflux. Thus smoking or abstaining from smoking does not modify the results of pH-metry in clinical routine.

Diagnostic Tests, Routine↗
PubMed1997

Thiocarbamate herbicide-inducible nonheme haloperoxidase of Rhodococcus erythropolis NI86/21.

During biodegradation of thiocarbamate herbicides by Rhodococcus erythropolis NI86/21, a protein with an M(r) of 30,000 is induced (I. Nagy, G. Schoofs, F. Compernolle, P. Proost, J. Vanderleyden, and R.De Mot, J. Bacteriol. 177:676-687, 1995). Based on N-terminal sequence data for the protein purified by two-dimensional electrophoresis, the corresponding structural gene, thcF, was cloned and sequenced. The deduced protein sequence of ThcF is homologous to those of nonheme haloperoxidases. A particularly high level of sequence identity (72.6%) was observed for the chloroperoxidase from Pseudomonas pyrrocinia. A polyclonal antibody against the latter enzyme cross-reacted with ThcF either produced by the original Rhodococcus cells or overexpressed heterologously in Escherichia coli. In both thiocarbamate-grown Rhodococcus cells and E. coli cells expressing thcF, the haloperoxidase activity of ThcF was demonstrated. The thiocarbamate-inducible R. erythropolis ThcF protein represents the first (nonheme) haloperoxidase to be identified in a nocardioform actinomycete.

Amino Acid Sequence↗
PubMed1997

Transposition of the IS21-related element IS1415 in Rhodococcus erythropolis.

Three copies of the IS21-related transposable element IS1415 were identified in Rhodococcus erythropolis NI86/21. Adjacent to one of the IS1415 copies, a 47-bp sequence nearly identical to the conserved 5' end of integrons was found. Accurate transposition of IS1415 carrying a chloramphenicol resistance gene (Tn5561) was demonstrated following delivery from a suicide vector to R. erythropolis SQ1.

Amino Acid Sequence↗