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Biomedical subjects

I Kiss

Publications and source records attributed to I Kiss.

At least 19 recordsLinked to original sources

Prevalence and genetic pattern of feline coronaviruses in urban cat populations.

The prevalence and phylogeny of feline coronaviruses were studied in urban cat populations by sampling of 113 clinically healthy cats. Rectal swab samples were subjected to a nested reverse-transcription polymerase chain reaction, specific for the conservative nucleocapsid region of the virus genome. More than 30% of the sampled animals proved positive for the presence of feline coronaviruses. The nucleotide sequences of amplified 440 bp products were determined, aligned and the phylogenetic analysis revealed noticeable genetic clusters among the prevalent feline coronaviruses in the surveyed geographic area. These findings will hopefully contribute to the elucidation of the epidemiology of feline infectious peritonitis.

Animals↗

[Prognostic value of the presence of the mutation of the codons 12, 13 and 61 in K-ras oncogene in colorectal cancer].

Despite of extensive and intensive investigations, the predictive and prognostic value of c-K-ras mutation is not unequivocal. There has been reported about investigation the occurrence of mutations in the 88 colorectal cancer patient's specimen using polymerase chain reaction. Age: 61.9 years (27-80), gender 8 male, 42 female. Dukes' stages: 43 at the B, 35 at C, 10 at D. Primary of tumour: 52 colon, 36 rectal adenocarcinoma. Mutation out of one of the three ras-codons was detectable in the 54 cases, more frequently at the stage Dukes' C (p < 0.05). The ras-mutation concerned to more elevated death-rate in the stages Dukes' B and C (p < 0.01). Mean survival time to progression was significantly longer at the stage Dukes' B if mutation had not been detected (p < 0.01). The occurrence of the rate of genetic alteration was significantly more frequent at tumours of right-side colon, than left side (p < 0.02) or rectum (p < 0.05) one's. However, at the age of 41-50 years it was significantly more presented at the cases of rectal cancer (p < 0.01). At the age of 51-60 years mutations were detected among men at higher rate (p < 0.05). The cases of local recurrences concerned by mutation at the codon of 13 (p < 0.05). Occurrence of ras-oncogene is the sign of extremely malignant potential of tumour. This fact manifested itself in the time to progression and mean survival time of patients at same clinical or pathological stage. The higher frequency of genetic alterations at the proximal colon may be the reason of more unfavourable prognosis of the disease localised to this site. Reconstructing the molecular events, the presence of ras mutation can serve as a basis for prognosis of the disease and permit of potentially individualised therapeutic intervention.

Adult↗

Matrilin-2, a large, oligomeric matrix protein, is expressed by a great variety of cells and forms fibrillar networks.

Matrilin-2 is a member of the protein superfamily with von Willebrand factor type A-like modules. Mouse matrilin-2 cDNA fragments were expressed in 293-EBNA cells, and the protein was purified, characterized, and used to immunize rabbits. The affinity-purified antiserum detects matrilin-2 in dense and loose connective tissue structures, subepithelial connective tissue of the skin and digestive tract, specialized cartilages, and blood vessel walls. In situ hybridization of 35S-labeled riboprobes localizes the matrilin-2 mRNA to fibroblasts of dermis, tendon, ligaments, perichondrium, and periosteum; connective tissue elements in the heart; smooth muscle cells; and epithelia and loose connective tissue cells of the alimentary canal and respiratory tract. RNA blot hybridization and immunoblotting revealed both matrilin-2 mRNA and protein in cultures of a variety of cell types, confirming the tissue distribution. Alternative splicing affects a module unique for matrilin-2 in all of the above RNA sources. SDS-polyacrylamide gel electrophoresis and electron microscopy reveals matrilin-2 from tissue extracts and cell line cultures as a mixture of mono-, di-, tri-, and tetramers. Matrilin-2 is substituted with N-linked oligosaccharides but not with glycosaminoglycans. Because of other, yet unidentified, cell-type dependent posttranslational modifications, the monomer is heterogeneous in size. Immunofluorescence showed that matrilin-2 functions by forming an extracellular, filamentous network.

Animals↗

Structural and functional characterization of the Drosophila glycogen phosphorylase gene.

We identified a P element insertional mutant of the Drosophila glycogen phosphorylase (DGPH) gene. Glycogen phosphorylase protein concentration and enzyme activity are decreased while glycogen content is increased in flies homozygous for the mutant allele. The DGPH gene has been cloned and sequenced; its open reading frame codes for a protein of 844 amino acids with a predicted molecular mass of 97 kDa. Comparison of the conceptual amino acid sequence of the Drosophila glycogen phosphorylase with glycogen phosphorylase sequences from other organisms shows a high degree of homology to mammalian enzymes. All the residues of the allosteric effector binding sites, the active site, and the site of phosphorylation are exactly conserved, but some of the residues of the glycogen storage site are not.

Amino Acid Sequence↗

[Epidemiologic study of regional inequalities].

The technological achievements of the recent years and the need for more advanced control of the processes within the health sector have supported the geographical epidemiology to become a distinct branch of epidemiology. The combined application of the simple standardized rates, statistical tests and different corrected risk parameters is able to describe the health status for geographically defined, small populations. Several statistical processes have been elaborated to estimate the number of the false positive results and to evaluate the role of chance in predicting the observed geographical pattern. These data completed with the usual risk measures quantify the risk difference within a broader region and determine the actual risk levels for the investigated small areas. The routine data processing system operating as a part of the public health surveillance identifies the high risk areas (the clusters) and without leaving the framework of routine data handling investigates the association between basic exposure data and health risks producing additional data about the nature of the aggregation of health related events. All the spetially varying etiological factors (environmental effects, social status, traditions, regional features of the health sector etc.) are ready to elicit regional alterations in the health status. The aim of the geographical information system is to cover the consequences of the uneven distribution of these factors. Since these kind of etiological factors play significant role in the generation of the most important public health problems in Hungary, and it is known that the small area inequalities are profound for these health impairments, the more extensive application of geographical information systems is expected to improve the efficiency of the control for public health problems and the performance of preventive medicine.

Data Interpretation, Statistical↗

The matrilins: a novel family of oligomeric extracellular matrix proteins.

The matrilin family at present has four members that all share a structure made up of von Willebrand factor A domains, epidermal growth factor-like domains and a coiled coil alpha-helical module. The first member of the family, matrilin-1 (previously called cartilage matrix protein or CMP), is expressed mainly in cartilage. Matrilin-3 has a similar tissue distribution, while matrilin-2 and -4 occur in a wide variety of extracellular matrices. Matrilin-1 is associated with cartilage proteoglycans as well as being a component of both collagen-dependent and collagen-independent fibrils and on the basis of the related structures other matrilins may play similar roles. The matrilin genes are strictly and differently regulated and their expression may serve as markers for cellular differentiation.

Animals↗

Identification of genes controlling malpighian tubule and other epithelial morphogenesis in Drosophila melanogaster.

The Drosophila Malpighian tubule is a model system for studying genetic mechanisms that control epithelial morphogenesis. From a screen of 1800 second chromosome lethal lines, by observing uric acid deposits in unfixed inviable embryos, we identified five previously described genes (barr, fas, flb, raw, and thr) and one novel gene, walrus (wal), that affect Malpighian tubule morphogenesis. Phenotypic analysis of these mutant embryos allows us to place these genes, along with other previously described genes, into a genetic pathway that controls Malpighian tubule development. Specifically, wal affects evagination of the Malpighian tubule buds, fas and thr affect bud extension, and barr, flb, raw, and thr affect tubule elongation. In addition, these genes were found to have different effects on development of other epithelial structures, such as foregut and hindgut morphogenesis. Finally, from the same screen, we identified a second novel gene, drumstick, that affects only foregut and hindgut morphogenesis.

Animals↗

The usefulness of in vivo gene expression investigations from peripheral white blood cells: a preliminary study.

Alterations of onco/tumour suppressor genes are involved in the formation of human hematological malignancies. Previously, in animal models, we demonstrated the applicability of in vivo gene expression investigations to monitor the effects of certain carcinogenic chemicals. In our present study we determined the expression of onco/suppressor genes from isolated peripheral white blood cells of patients with chronic myeloid leukaemia (CLL) and non-Hodgkin lymphoma (NHL). Gene expressions were determined by isolation of total RNA and slot blot hybridization with chemiluminescently labeled gene probes (Ha-ras, c-myc and p53) Expression levels were compared before and after treatment with a combined cytostatic protocol, containing cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP). Both the CLL and NHL group of patients exhibited significantly higher expression of the investigated genes than healthy controls. One month after the cytostatic treatment, we found considerably fewer individuals with overexpressed oncogenes than before the treatment. Our study proved that onco/tumour suppressor gene expressions could be used as biomarkers of certain hematological malignancies, and to monitor the therapeutical effect of cytostatic drugs.

Antineoplastic Combined Chemotherapy Protocols↗

Down-regulation of RpS21, a putative translation initiation factor interacting with P40, produces viable minute imagos and larval lethality with overgrown hematopoietic organs and imaginal discs.

Down-regulation of the Drosophila ribosomal protein S21 gene (rpS21) causes a dominant weak Minute phenotype and recessively produces massive hyperplasia of the hematopoietic organs and moderate overgrowth of the imaginal discs during larval development. Here, we show that the S21 protein (RpS21) is bound to native 40S ribosomal subunits in a salt-labile association and is absent from polysomes, indicating that it acts as a translation initiation factor rather than as a core ribosomal protein. RpS21 can interact strongly with P40, a ribosomal peripheral protein encoded by the stubarista (sta) gene. Genetic studies reveal that P40 underexpression drastically enhances imaginal disc overgrowth in rpS21-deficient larvae, whereas viable combinations between rpS21 and sta affect the morphology of bristles, antennae, and aristae. These data demonstrate a strong interaction between components of the translation machinery and showed that their underexpression impairs the control of cell proliferation in both hematopoietic organs and imaginal discs.

Amino Acid Sequence↗

Characterization and chromosome location of the mouse link protein gene (Crtl1).

Link protein (LP) plays an essential role in endochondral bone formation by stabilizing the supramolecular assemblies of aggrecan and hyaluronan. We have isolated and characterized the mouse link protein gene (Crtl1). It is longer than 40 kb and transcribed from two alternative promoters, leading to heterogenous mRNAs between 5.3 and 1.3 kb in size. Apart from the coding sequence, the 5' flanking region is also highly conserved in mammals. Immunostaining revealed high levels of LP expression in the cartilaginous primordia of skeletal elements and low levels in other tissues. Using single-strand conformation polymorphism analysis, Crtl1 was assigned to mouse chromosome 13, tightly linked to Dhfr.

Amino Acid Sequence↗

Observations on the quasispecies composition of three animal pathogenic RNA viruses.

The quasispecies nature of three animal pathogenic RNA viruses of field origin was examined by testing variants of classical swine fever virus (CSFV) originating from geographically different areas, feline coronavirus (FCoV) detected from the same animal by successive sampling, and rabbit haemorrhagic disease virus (RHDV) originating from successive outbreaks in the same geographic area. Clinical samples were investigated using reverse transcriptase polymerase chain reaction (RT-PCR) and ensuing single strand conformational polymorphism (SSCP) assay. By the combination of these methods even subtle differences could be detected among the amplified fragments of the same virus species of different origin. FCoV proved to comprise the most and CSFV the less heterogeneous virus quasispecies. The results show that the combination of RT-PCR and SSCP provides novel and highly sensitive means for the characterisation of RNA viruses, with special regard to genome composition, evolution, features of pathogenicity and molecular epizootiology.

Animals↗

The contribution of a pyrethroid insecticide to the massive eel (Anguilla anguilla) devastation, in Lake Balaton, in 1995.

In the summer of 1995, 30 tonnes of eel (Anguilla anguilla) died in Lake Balaton, Hungary. An investigation was carried out to find the causes of this ecocatastrophe. During this investigation, certain biochemical parameters, i.e. the blood sugar level, the acetylcholinesterase (AChE, EC 3.1.1.7), lactate dehydrogenase (LDH, EC 1.1.2.3), glutamic-oxaloacetic transaminase (GOT, EC 2.6.1.1), and glutamic-pyruvic transaminase (GPT, EC 2.6.1.2) activities in the blood serum of the collected surviving and dying eels were examined. Deltamethrin, the active ingredient of the insecticide K-OTHRIN 1 ULV, used against mosquitoes was detected in different animal species, i.e. eel, bream (Abramis brama), pike perch (Stizostedion lucioperca), and the common gull (Larus canus) and in sediment samples from the lake. Additionally, laboratory experiments were carried out to study the effects of deltamethrin on eels. During the investigation in the field it appeared that the AChE activity was significantly lower in the blood serum of the dying eels as compared to that in living animals (P<0.05, Student's t-test). The blood glucose content exhibited a difference, too: it was 2.5 times higher in the dying eels than in the surviving ones. A huge increase in the LDH level was measured in the dying eels. The GOT activities of the serum were twice as high in the dying eels as in the living fish, while the GPT was not significantly changed. Deltamethrin was detected in different tissue samples of the dying eels: 2.70-18.1 microg/kg in the liver, 9.0-31.1 microg/kg in the gill and 3.0 microg/kg wet tissue in the muscle. Deltamethrin residues were found in tissue samples from other animals, in the following concentrations: 0.44 microg/kg in bream, 2.14 microg/kg in pike perch and 1.06 microg/kg wet tissue in dead gulls. The sediment samples collected from the sites of the devastation contained deltamethrin in a concentration of 5.50-30.00 microg/kg wet sediment at the time of the eel deaths, and in a concentration 7.00-8.75 microg/kg wet sediment a month later. Laboratory experiments with the insecticide K-OTHRIN 1 ULV revealed that 1.00 microg/l of its active ingredient, deltamethrin, caused the death of 50% of the eels after an exposure time of 96 h. During this experiments similar trends could be observed in changes of enzyme activities of the treated eels to those that were detected in filed study during the eel devastation in Lake Balaton. At the end of a one-week treatment with the insecticide at the concentration of 0.5 microg/l of its active ingredient the gills of the treated eels contained deltamethrin at 12.6-44.8 microg/kg wet tissue concentration, while at the 24th hour after the treatment (11.2-42.7 microg/kg wet tissue) deltamethrin concentration in the liver of treated eels could be detected. All the above-mentioned changes and the detected deltamethrin residue in the eels appear to demonstrate the contribution of deltamethrin to the severe eel devastation. This information on the ecological risk of pyrethroid insecticides might be useful in their further application.

Animals↗

[Drug therapy of gastroesophageal reflux (a prospective controlled clinical trial)].

One year follow up(1.5, 3, 6, 12 months) study was established to examine the role of several classes of drugs in the treatment of reflux disease in 40 patients on the basis of objective control parameters (pH-metry, endoscopy, histology). The therapy was initiated, respectively, the different stage of severity (Savary-Miller): in stage 0 sucralfate + domperidone, in stage I and II: ranitidine + domperidone and in stage III-IV omeprazole was introduced. Our results proved that sucralfate + domperidone is curative on reflux oesophagitis in stage 0 cases. In stage I sucralfate and domperidone were effective in 3 of 9 cases, ranitidine + domperidone was optimal in 5 of 9, and omeprazole was required in 1 of 9 patients. In stage II, ranitidine + domperidone was effective only in 4 of 11 patients, and the initial therapy was modified to omeprazole in 7 of 11 patients to find the optimal drug in this stage. In stage III and IV only omeprazole showed curative effect and the doses required were 20 mg in 8 of 13 and 40 mg in 5 of 13 patients. The complaints improved in 34 of 40 patients after 6 weeks treatment, while histological healing of reflux oesophagitis was observed in 12 of 40 cases. After 3 months the endoscopic healing rate was 28/40, but histological healing could be reached after 6 months of optimal treatment in 30 of 40 cases. We can conclude, that the optimal drug selection may result a rapid improvement of complaints, but endoscopic and histological regeneration of the oesophageal mucosa is more graduated with time. The healing process of the reflux oesophagitis requires 3 months. Proton pump inhibitor drugs have an enhanced role in the treatment of gastrooesophageal reflux disease, and our results proved that the efficient and safety treatment of mild form (stage II) of disease requires the administration of proton pump inhibitors.

Adult↗

Central executive function in working memory: event-related brain potential studies.

Visual event-related brain potentials (ERPs) were recorded during a running memory task, in which subjects dynamically revised (updated) memory stores, and a control task not requiring maintenance of a changing memory set but utilising identical stimulus sequences and response patterns. In three experiments, ERPs associated with cognitive processes were isolated through subtraction of control potentials from ERPs acquired during updating. We provide evidence that resultant difference ERPs primarily reflected processing or processing control, as opposed to storage. These findings are consistent both with Baddeley's working memory model, which postulates separate storage and control modules, and Morris and Jones' behavioral evidence for specific involvement of Baddeley's central executive in memory updating. In addition, our ERP data indicate that updating requires processes not suggested by Morris and Jones' behavioural studies; possibly control processes engaged to reduce the effects of proactive interference. Overall the data are consistent with the discovery of an ERP correlate of central executive activity.

Adult↗

Terminal differentiation of chondrocytes is arrested at distinct stages identified by their expression repertoire of marker genes.

During endochondral bone formation, cells in the emerging cartilaginous model transit through a cascade of several chondrocyte differentiation stages, each characterized by a specific expression repertoire of matrix macromolecules, until, as a final step, the hypertrophic cartilage is replaced by bone. In many permanent cartilage tissues, however, late differentiation of chondrocytes does not occur, due to negative regulation by the environment of the cells. Here, addressing the reason for the difference between chondrocyte fates in the chicken embryo sternum, cells from the caudal and cranial part were cultured separately in serum-free agarose gels with complements defined earlier that either permit or prevent hypertrophic development. Total RNA was extracted using a novel protocol adapted to agarose cultures, and the temporal changes in developmental stage-specific mRNA expression were monitored by Northern hybridization and phosphor image analysis. Kinetic studies of the mRNA accumulation not only showed significant differences between the expression patterns of cranial and caudal cultures after recovery, but also revealed two checkpoints of chondrocyte differentiation in keeping with cartilage development in vivo. Terminal differentiation of caudal chondrocytes is blocked at the late proliferative stage (stage Ib), while the cranial cells can undergo hypertrophic development spontaneously. The differentiation of cranial chondrocytes is reversible, since they can re-assume an early proliferative (stage Ia) phenotype under the influence of insulin, fibroblast growth factor-2 and transforming growth factor-beta in combination. Thus, the expression pattern in the latter culture resembles that of articular chondrocytes. We also provide evidence that the capacities of caudal and sternal chondrocytes to progress from the late proliferative (stage Ib) to hypertrophic stage (stage II) correlate with their differing abilities to express the Indian hedgehog gene.

Animals↗

Oncogene and suppressor gene expression as a biomarker for ethylene oxide exposure.

Ethylene oxide is a proven genotoxic chemical, and there is lots of evidence suggesting its carcinogenic effects in humans. The unexpected massive appearance of a certain tumorous cluster in personnel exposed to ethylene oxide in a Hungarian county hospital focused attention on the effects of this toxic gas. Since we had developed an animal model for the investigation of alterations in onco/suppressor gene expression due to external carcinogenic agents, and this model had already been used to evaluate the carcinogenic effects of cytostatic drugs in humans, an analysis of the effects of ethylene oxide exposure seemed to offer further information on the usefulness of gene expression as a biomarker. The main purpose of our study was to determine whether or not ethylene oxide exposure causes an elevated expression of onco/suppressor genes in the white blood cells of exposed people. Two different exposed groups and one control group were included in the study. The N-ras and p53 genes were chosen for the investigations of gene expression. N-ras is known to be activated in several tumor types, and p53 is also involved in carcinogenesis and plays an important role in the cellular answer mechanism to exogenous toxic effects. RNA was isolated from the white blood cells, slot blotted onto nitrocellulose membranes, and hybridized with chemoluminescently labeled gene probes. The results were detected on X-ray films and scanned into a computer, and relative risk for elevated gene expression was calculated in each group. Elevated N-ras and detectable p53 expressions were observed more frequently in both exposed groups compared with the control group (relative risks--N-ras: 1.57 [0.77-3.22] and 2.34 [1.21-4.52]; p53: 6.67 [2.35-18.92] and 6.06 [2.10-17.49]).

Biomarkers, Tumor↗

Treatment of end-stage renal disease in central and eastern Europe: overview of current status and future needs.

The situation of end-stage renal disease (ESRD) patients in central and eastern Europe was very poor for many years during the so called socialistic era. Economical and political liberation resulted in the significant growth of renal replacement facilities in this region. The number of hemodialysis units increased significantly (56%) during the period 1990-1996, and the number of patients treated with this modality has risen by 75%. More dramatic progress was achieved in peritoneal dialysis. The number of units performing this method of renal replacement therapy (RRT) increased by 277% and the number of patients by more than 300%. Not only quantitative but also qualitative changes were observed. More modern hemodialysis machines installed in the vast majority of units allow for the performance of bicarbonate dialysis, controlled ultrafiltration, and sodium profile modeling. Also, a wider choice of biocompatible dialyzers has become available during the last few years. The number of centers performing renal transplantation has increased significantly, but the number of renal transplants has not followed this progress. Despite all the progress, further development of all RRT methods is necessary to achieve acceptance rates comparable to those observed in developed countries.

Europe↗