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Biomedical subjects

J Varga

Publications and source records attributed to J Varga.

At least 163 records · Page 9Linked to original sources
PubMed1994

Functional analysis of human alpha 1(I) procollagen gene promoter. Differential activity in collagen-producing and -nonproducing cells and response to transforming growth factor beta 1.

To gain a further understanding of the regulation of human type I collagen gene expression under physiologic and pathologic conditions, we characterized 5.3 kilobase pairs (kb) of the human alpha 1(I) procollagen gene promoter. A series of deletion constructs containing portions of the alpha 1(I) procollagen 5'-flanking region (with end points from -5.3 kb to -84 base pairs (bp)) ligated to the chloramphenicol acetyltransferase (CAT) reporter gene were transiently transfected into NIH/3T3 cells. Maximal CAT activity was observed with constructs having 5' end points from -804 to -174 bp. A further 5' deletion to -84 bp caused a marked reduction in CAT activity. Cells transfected with plasmids containing longer 5'-flanking fragments of the alpha 1(I) procollagen gene (-2.3 or -5.3 kb) showed reduced CAT activity compared with the -804 bp construct. The activity of the alpha 1(I) procollagen promoter was much lower in cells that do not normally express type I collagen (HeLa cells) compared with collagen-producing NIH/3T3 cells. The CAT activity of deletion constructs containing longer 5' regions than -84 bp was increased by approximately 2-fold in NIH/3T3 cells treated with transforming growth factor beta 1 (TGF beta 1). Electrophoretic mobility shift assays indicated that protein-DNA complex formation with a probe corresponding to the -170 to -80 bp fragment of the alpha 1(I) procollagen promoter was markedly enhanced in nuclear extracts prepared from TGF beta 1-treated fibroblasts as compared with untreated fibroblasts. The DNA binding activity stimulated by TGF beta 1 was specific for an Sp1-like sequence at positions -164 to -142 bp in the promoter. These results demonstrate that 1) there are both positive and negative cis-acting regulatory elements in the human alpha 1(I) procollagen promoter, 2) these regulatory regions function differently in collagen-producing and -nonproducing cells, 3) the alpha 1(I) procollagen promoter contains TGF beta 1-responsive sequences located between -174 and -84 bp from the transcription start site, and 4) TGF beta 1 caused marked stimulation of the DNA binding activity of a nuclear factor interacting with an Sp1-like binding site located within a region encompassing -164 to -142 bp of the alpha 1(I) procollagen promoter.

3T3 Cells↗
PubMed1994

Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind study.

OBJECTIVE: To evaluate the efficacy and safety of iloprost, a prostacyclin analog, administered intravenously in patients with Raynaud phenomenon secondary to systemic sclerosis. DESIGN: Multicenter, randomized, parallel placebo-controlled, double-blind study. SETTING: University medical centers. PATIENTS: 131 patients with systemic sclerosis (101 women, 30 men) ages 20 to 79 years. INTERVENTION: Patients were randomly assigned to receive one of two parallel treatments of five daily sequential, 6-hour intravenous infusions of iloprost (0.5 to 2.0 ng/kg per min) or to receive a similar volume of placebo. MEASUREMENTS: Frequency of Raynaud attacks, Raynaud severity score, physician's overall rating of treatment effect, and digital cutaneous lesion healing. RESULTS: Of the 131 patients enrolled, 126 completed the 5-day infusion and 114 (87%) completed at least 6 weeks of follow-up. Sixty-four patients were randomly assigned to receive iloprost and 67 patients, to receive placebo. The mean weekly number of Raynaud attacks decreased 39.1% with iloprost and 22.2% with placebo (P = 0.005). In addition, the mean percentage of improvement in a global Raynaud severity score during the entire 9-week follow-up was greater in patients given iloprost (34.8%) than in those receiving placebo (19.7%) (P = 0.011). The physician's overall rating of treatment effect showed greater improvement with iloprost than with placebo at week 6 (52.4% compared with 27.4%; P = 0.008) and week 9 (60.9% compared with 26.9%; P < 0.001). At week 3, 14.6% more patients receiving iloprost had 50% or more lesions heal compared with those given placebo (95% CI, 0.9% to 30%). During the infusion, 59 (92%) of the patients receiving iloprost had one or more side effects compared with 38 (57%) of the patients receiving placebo. CONCLUSION: Iloprost is effective for the short-term palliation of severe Raynaud phenomenon in patients with systemic sclerosis.

Adult↗
PubMed1994

Assignment of RFLP, RAPD and isoenzyme markers to Aspergillus nidulans chromosomes, using chromosome-substituted segregants of a hybrid of A. nidulans and A. quadrilineatus.

Chromosome-substituted haploid segregants were selected from among the benomyl-induced progeny of an interspecific hybrid produced by polyethylene-glycol-induced fusion of protoplasts of an Aspergillus nidulans 'master strain' and an A. quadrilineatus auxotrophic mutant. These segregants were examined by RFLP, RAPD, and isoenzyme analysis. The A. nidulans ribosomal repeat unit was assigned to chromosome V, while the benA and the pyrG genes were assigned to linkage groups VIII and I, respectively, of A. nidulans. None of the other cloned genes tested (gdhA, amdS and 25s rRNA) showed polymorphism between the two parents. The method was also used to assign RAPD markers and isoenzyme bands of beta-arylesterase, phosphatases, NAD-dependent malate dehydrogenase, and cellulase, to A. nidulans chromosomes and/or to their A. quadrilineatus equivalents. The isoenzyme and DNA sequences assigned to chromosomes could be used to saturate the genetic map of A. nidulans, or could serve as starting points for the construction of a genetic map of A. quadrilineatus. No method affording the same possibilities has been described so far in Aspergilli. This chromosome-assay method may be a useful alternative to pulsed-field-gel electrophoretic procedures for the assignment of molecular markers to chromosomes.

Aspergillus↗
PubMed1994

Technetium-99m sestamibi scintigraphy for the assessment of lower extremity ischaemia in peripheral arterial disease.

Technetium-99m sestamibi was used for functional investigation of the muscle perfusion of lower extremities in 35 patients with peripheral vascular disease. The aim was to test what useful information could be obtained by additional imaging of the legs in patients referred for risk stratification with dipyridamole myocardial scanning. Posterior images were acquired over the thighs and calves after postocclusive reactive hyperaemia and at rest. Inter- and intraextremity ratios and differences between the stress and rest data were used for the assessment of abnormal circulation. Arteriography was performed in every case, and surgical procedures or transluminal angioplasty in 31 patients. To estimate diagnostic accuracy, the results of 99mTc-sestamibi scintigraphy were compared with those of angiography and the functional consequences of revascularization procedures. The sensitivity and specificity of 99mTc-sestamibi scintigraphy were 55% and 25%, respectively, with an overall accuracy of 50%. Apparently methodological error was not responsible for these poor results. Instead, a paradoxically high uptake of the radiopharmaceutical in muscles supplied by significantly stenosed vessels was identified as the main source of both false-negative and false-positive results. The phenomenon resembles the findings of a previous study involving delayed administration of thallium-201 after exercise. In conclusion, 99mTc-sestamibi scintigraphy has not proved sufficiently reliable to help in the management strategy for patients with peripheral vascular disease.

Dipyridamole↗
PubMed1994

Double-stranded RNA mycoviruses in section Nigri of the Aspergillus genus.

Double-stranded RNA bands were detected electrophoretically in about 7% of natural isolates and in 13 of 51 collection strains belonging in section Nigri of the genus Aspergillus. The identity of these bands was proved by S1 nuclease and RNase treatment. Most of the virus-containing natural isolates came from Indonesia. Electron microscopic examination of the strains revealed the presence of virus-like particles in the mycelia of the strains examined. All of the virus-like particles were isometric and their size was around 30-35 nm, while some Indonesian isolates also contained virus-like particles in the size range 23-25 nm. It was possible to cure some of these strains of virus-like particles by mutagenic treatment. The four strains tested lost their virus-like particles and also their 'arginine-proline leaky' phenotype and became prototrophic. Virus transfer was possible among these four strains by protoplast fusion. It also proved possible to transfer mycoviruses into a more distantly related Aspergillus tubingensis strain by prolonged incubation of the polyethylene glycol treated protoplasts in osmotically stabilized medium. In spite of the finding that all Aspergillus foetidus and both Aspergillus heteromorphus strains examined contained double-stranded RNA segments and virus-like particles, no phenotypes related to the presence of these VLPs have been observed so far.

Aspergillus↗
PubMed1994

Mitochondrial DNA restriction fragment length polymorphisms in field isolates of the Aspergillus niger aggregate.

The mitochondrial DNAs (mtDNAs) and the ribosomal repeat unit (ribosomal DNA, rDNA) of black Aspergillus isolates collected in various parts of the world were examined. Wide-ranging mtDNA variation was observed in natural populations of the Aspergillus niger aggregate. Most isolates were classifiable as A. niger or Aspergillus tubingensis according to their rDNA and mtDNA patterns. The mtDNA variation was distributed unevenly in the populations studied. The mtDNAs of most of the isolates collected in Australia were of the A. tubingensis type, with an unexpectedly high degree of variation, while the rDNA of these isolates exhibited the same A. tubingensis pattern as that of isolates from other locations. Some other local populations displayed very little polymorphism in their mtDNA and rDNA. Hybridization experiments in which cloned A. niger and Aspergillus nidulans mtDNA fragments were used revealed that the two main mtDNA groups corresponding to A. niger and A. tubingensis are more distantly related than concluded earlier. Six of the 13 Brazilian isolates examined exhibited mtDNA and rDNA types different from those of all the other strains and could not be classified into the above species. Classical taxonomic examination of these strains is in progress.

Aspergillus↗
PubMed1994

Elevated expression of type VII collagen in the skin of patients with systemic sclerosis. Regulation by transforming growth factor-beta.

A hallmark of systemic sclerosis (SSc) is the development of tissue fibrosis. Excessive production of several connective tissue components normally present in the dermis, including type I, III, V, and VI collagens as well as fibronectin and proteoglycans, is a consistent finding in the skin of SSc patients. Type VII collagen is a major constituent of anchoring fibrils, present in the skin at the dermal-epidermal basement membrane zone. TGF-beta has been shown to upregulate the expression of the type VII collagen gene. In this study, we assessed the expression of type VII collagen and TGF-beta in the skin of patients with SSc. Indirect immunofluorescence showed an abundance of type VII collagen in the patients' skin, including the dermis. Ultrastructural analysis of SSc skin revealed an abundance of fibrillar material, possibly representing type VII collagen. The increased expression of type VII collagen epitopes was accompanied by the elevated expression of immunodetectable TGF-beta 1 and TGF-beta 2. Dermal fibroblasts cultured from the affected individuals showed a statistically significant (P < 0.02) increase in the expression of type VII collagen at the mRNA level, as detected by reverse transcription-PCR with a mutated cDNA as an internal standard, and increased deposition of the protein as assessed by indirect immunofluorescence. Thus, type VII collagen is abundantly present in SSc patients' dermis, a location not characteristic of its normal distribution, and its aberrant expression may relate to the presence of TGF-beta in the same topographic distribution. The presence of type VII collagen in the dermis may contribute to the tightly bound and indurated appearance of the affected skin in SSc patients.

Adult↗
PubMed1994

[Development and investigation of preparations containing kitasamycin and flumequine].

Swine dysentery and poultry cholera are very harmful animal diseases which cause great damage. Flumequine and kitasamycin are new and up-to-date preparations for the treatment of these diseases. ++ Imequyl ad us. vet. and ++ Trubin ad us. vet. are the registered medicines. The doses are 7 mg flumequine and 21 mg kitasamycin/body weight kg. The drug technological problem is that flumequine does not dissolve sufficiently in water. It dissolves well at pH = 10, but kitasamycin is unstable at this pH. It was hoped that these two components would together act as agonists, and that kitasamycin would promote the dissolution of flumequine. An injection preparation and a powder mixture for dissolution were developed. Chemical interaction between the components was conformed by IR and NMR measurements.

Animals↗
PubMed1994

L-Tryptophan in supraphysiologic concentrations stimulates collagenase gene expression in human skin fibroblasts.

BACKGROUND: Collagenase plays a critical role in regulating connective tissue breakdown in physiologic and pathologic processes. The expression of collagenase is modulated by a variety of biologic and pharmacologic agents. L-tryptophan is an essential amino acid with diverse biologic effects not shared by other amino acids. EXPERIMENTAL DESIGN: In this study, we examined the effects of L-tryptophan on collagenase gene expression in normal human skin fibroblasts using Northern hybridizations and transient transfection assays. RESULTS: The results indicate that L-tryptophan at supraphysiologic concentrations caused a marked increase in collagenase gene expression. The increase in collagenase mRNA levels was reversible, time- and dose-dependent, and was accompanied by enhancement of procollagenase synthesis and secretion. Parallel accumulation of mRNA for tissue inhibitor of metalloproteinase was also noted, whereas stromelysin mRNA levels remained undetectable. The enhancement of collagenase mRNA was specific for L-tryptophan, and was abrogated by alpha-amanitin or dexamethasone. The apparent half-life of collagenase mRNA transcripts was similar in cultures exposed to interleukin-1 beta or L-tryptophan. In contrast to interleukin-1 beta, L-tryptophan-induced increase in collagenase mRNA was not preceeded by expression of c-jun or c-fos. Transient transfection of human skin fibroblasts with a collagenase promoter, chloramphenicol acetyl transferase construct indicated marked dose-dependent increase in promoter activity with L-tryptophan. CONCLUSIONS: These results demonstrate that L-tryptophan in supraphysiologic concentrations is a potent inducer of collagenase gene expression in vitro at a transcriptional level by human skin fibroblasts.

Adult↗
PubMed1993

The effects of brain natriuretic peptide-32 on electroconvulsive shock-induced amenesia in rats. The role of neurotransmitters.

Partial amnesia was induced in rats by electroconvulsive shock (ECS) immediately after passive avoidance learning. This partial amnesia could be prevented by administering porcine brain natriuretic peptide-32 (pBNP-32) into the lateral brain ventricle. The effects of pretreatment with different receptor blockers (haloperidol, atropine, phenoxybenzamine, propranolol, naloxone, bicuculline and methysergide) on the pBNP-32-induced antiamnesia were investigated. In the doses selected, the blockers had no influence on the ECS-induced amnesia. Haloperidol, atropine, phenoxybenzamine and propranolol blocked the antiamnesic action of the peptide, while naloxone, bicuculline and methysergide were ineffective. These results suggest that pBNP-32 may influence learning processes and that the antiamnesic action of this peptide is mediated by dopaminergic, cholinergic alpha- and beta-adrenergic mediator systems.

Amnesia↗
PubMed1993

[Experience with routine use of combined inhalation-perfusion lung scintigraphy. The most reliable diagnosis of pulmonary embolism].

The authors performed combined inhalation/perfusion scintigraphy in 217 patients with suspected pulmonary embolism in order to improve the diagnostic accuracy. Before the conventional perfusion study they also visualized the distribution of ventilation with a Venticis-II inhalator equipment. Regarding pulmonary embolism 10 (5%), 96 (44%), 39 (18%) investigations were "very low", "low", and "high probability", respectively. The inhalation study was successful in 93 percent of patients. These results were necessary in 141 patients. However, it was uncertain in 26% of cases (57 patients) concerning the diagnosis of pulmonary embolism. As the inhalation scintigraphy was applied without preselection, this study was unnecessary in 30%. On the other hand, if the combined studies had been performed only in the cases of previously proved segmental perfusion defects, the number of perfusion scintigraphies would have increased by 65%. The authors recommend the routine use of the inhalation lung scintigraphy.

Bronchial Provocation Tests↗
PubMed1993

Myopathy with mitochondrial alterations in patients with primary biliary cirrhosis and antimitochondrial antibodies.

OBJECTIVE: To describe a syndrome of severe progressive myopathy, cardiomyopathy, and gastrointestinal dysmotility in 2 patients with asymptomatic primary biliary cirrhosis (PBC) and circulating antimitochondrial autoantibodies, and to review pertinent literature concerning this syndrome. METHODS: Clinical, electrophysiologic, serologic, and pathologic studies of the 2 affected patients were conducted. RESULTS: Skeletal muscle involvement was manifested by progressive weakness of the proximal muscles, marked diaphragmatic dysfunction with consequent hypoventilation and respiratory failure, and moderately elevated levels of muscle-associated enzymes. Serum from both patients contained antimitochondrial antibodies that reacted with components of the mitochondrial keto acid dehydrogenase enzyme complex. Results of electromyography were consistent with a myopathic process. The microscopic and ultrastructural changes in the skeletal muscles were distinct from those of typical myositis, and were notable for striking subsarcolemmal aggregation of abnormal mitochondria in the absence of significant inflammation. CONCLUSION: Severe skeletal muscle, cardiac, and gastrointestinal pathology with abnormalities of the muscle mitochondria develops in a subset of patients with mild PBC and antimitochondrial antibodies. The pathogenesis of this syndrome is unclear, but may be related to the presence of the antimitochondrial autoantibodies.

Adult↗
PubMed1993

Endoluminal ultrasonography of the distal esophagus in systemic sclerosis.

BACKGROUND: The aim of this study is to apply high-resolution endoluminal sonography (HRES) to the study of the esophageal disease in systemic sclerosis (SSc). METHODS: An HRES transducer was used to image the esophagus. Autopsy specimens of normal and SSc esophagi were imaged to define a hyperechoic abnormality in the normally hypoechoic muscularis propria. The presence or absence of this hyperechoic abnormality of the esophagus in SSc patients was compared with sonographic findings in normal volunteers. The degree of the hyperechoic abnormality was correlated with the results of functional esophageal studies including esophageal motility, lower esophageal sphincter pressure, and 24-hour pH monitoring in SSc patients. RESULTS: A hyperechoic abnormality in the normally hypoechoic muscularis propria on HRES seemed to correspond with the presence of fibrosis on histological sections from the distal esophagus in SSc autopsy specimens. A significant difference was found in the presence of this hyperechoic abnormality in patients with SSc when compared with normal controls (P < 0.001). Finally, there were strong positive correlations between the degree of this hyperechoic abnormality and esophageal manometric abnormalities (r = 0.89; P < 0.001) and supine (r = 0.74; P < 0.01) and total (r = 0.70; P < 0.02) acid reflux on 24-hour pH monitoring. CONCLUSIONS: HRES is a sensitive new method to determine the presence or absence of hyperechoic abnormalities in the muscularis propria and to predict functional abnormalities of the esophagus in patients with SSc.

Adult↗
PubMed1993

ANP(1-28), BNP(1-32) and CNP(1-22) increase the severity of picrotoxin-kindled seizure syndrome in rats.

The administration of rANP(1-28) in doses of 1.0 and 2.0 nmol (but not 0.2 nmol) into the lateral cerebral ventricle (i.c.v) of rats preliminarily kindled with picrotoxin resulted in an increase of the severity of picrotoxin-kindled convulsions 24 hrs after injection of the peptide. I.c.v. injection of pBNP(1-32) also resulted in a proepileptic effect when it was applied in the same doses with a similar time course; the increased seizure severity was observed 48 hrs after injection of pBNP in a dose of 2 nmol. I.c.v. administration of CNP(1-22) in a dose of 2 nmol induced an increase in the severity of picrotoxin-kindled convulsions 24 and 48 hrs after application of the peptide. None of the peptides influenced the seizure syndrome immediately after the injections. It is presumed that the delayed proepileptic properties of the three natriuretic peptides could be caused by some of their stable fragments which accumulate during their metabolism.

Animals↗
PubMed1993

L-tryptophan and the eosinophilia-myalgia syndrome: current understanding of the etiology and pathogenesis.

The eosinophilia-myalgia syndrome (EMS) is a newly recognized illness that occurred in an epidemic form during the summer of 1989. The illness was characterized in the acute phase by myalgia and eosinophilia, followed in many patients by chronic cutaneous lesions, progressive neuropathy, and myopathy. EMS was associated with ingestion of L-tryptophan, an essential amino acid marketed as a nutritional supplement but widely used as a therapeutic agent. Evidence of abnormal L-tryptophan metabolism has been described in patients with EMS, and most likely reflects increased activity of indoleamine 2,3-dioxygenase, the rate-limiting enzyme of tryptophan metabolism. A contaminant identified in EMS-associated L-tryptophan preparations has been isolated and characterized, but its biologic effects and role as the etiologic agent in EMS remain to be established. Pathologic observations and experimental studies indicate that eosinophils, mononuclear inflammatory cells, and fibroblasts are potential effector cells, and interleukin-5 and transforming growth factor-beta are important mediators in the pathogenesis of the syndrome. Although few new cases of EMS occurred following the withdrawal of L-tryptophan, affected patients continue to manifest late sequelae of the disease, including dermal fibrotic conditions. This tragic outbreak of a newly recognized illness has focused interest on the role of chemical and environmental agents in the pathogenesis of various idiopathic illness characterized by tissue inflammation and fibrosis.

Animals↗