Biomedical subjects

Zsolt Tulassay

Publications and source records attributed to Zsolt Tulassay.

At least 55 records · Page 3Linked to original sources

PubMed2005

[Autoimmune polyendocrine syndromes and related diseases: pathogenesis and clinical features].

Autoimmune processes are involved in the pathogenesis of diseases of several endocrine organs. There are also syndromes, where autoimmune diseases of multiple endocrine and other organs occur simultaneously. The pathogenesis of certain syndromes belonging to this group has been clarified recently and this made possible the discovery of previously unknown aspects of autoimmunity. In this review the authors present a brief synopsis of the pathogenesis and clinical features of autoimmune polyendocrine syndrome type 1 and the IPEX syndrome that are inherited as monogenic traits. Although the etiology of type 2 autoimmune polyendocrine syndrome and POEMS syndrome are not as well characterized as that of the aforementioned monogenic diseases, considering their clinical importance, the authors summarize the main features of these syndromes, as well.

Humans↗

PubMed2005

[Improvement of bone metabolism after infliximab therapy in Crohn's disease].

BACKGROUND: Osteoporosis has received increasing attention as a potential complication of Crohn's disease. Among cytokines tumor necrosis factor-alpha plays a pivotal role in the pathogenesis of inflammatory bowel diseases by inducing a wide variety of inflammatory responses, including bone resorption. Only few data are present about the effect of infliximab on bone metabolism. AIMS: The authors evaluated the effect of infliximab on bone metabolism in patients with Crohn's disease. PATIENTS AND METHODS: Twenty seven patients (17 females, 10 males, mean age 32.58 yrs) with refractory fistulizing Crohn's disease were treated with a series of three infusions of 5 mg infliximab per kg at weeks 0, 2, and 6. Biochemical markers of bone formation (osteocalcin) and bone resorption (beta-CrossLaps) were measured before administration of each infliximab infusion. 54 patients were studied with inactive Crohn's disease (Crohn's disease activity index < 150) as a control. RESULTS: There were significant differences in beta-CrossLaps concentrations (ng/ml) between the day 0 and 14 (0.57 +/- 0.32 vs. 0.46 +/- 0.29, p < 0.01) and the day 0 and 42 (0.57 +/- 0.32 vs. 0.45 +/- 0.26, p < 0.05). The osteocalcin levels significantly increased from day 0 to day 42 (21.31 +/- 12.14 vs. 25.64 +/- 16.97, p < 0.05). The serum beta-CrossLaps and osteocalcin levels were 0.47 +/- 0.24, 27.2 +/- 8.44 in the control group respectively. These results differed from the serum levels of active patients before the treatment, but there were no notable differences at the day 42. CONCLUSION: Infliximab therapy in Crohn's disease patients displayed a rapid influence on bone metabolism by enhancing bone formation and decreasing bone resorption. In addition to its mucosal effect affecting the bone homeostasis, indicate a further rationale usage of tumor necrosis factor-alpha blockade in the therapy of inflammatory bowel diseases.

Adult↗

PubMed2005

[Hybridization and their application in the DNA array technology].

Hybridization and their application in the DNA array technology. DNA hybridization arrays measure simultaneously the expression of several genes. First, a known DNA sequence (probe) is fixed on a firm basis. Then the complementer sequence (target sequence) is linked to it during the hybridization process. The target sequence extracted from biological samples is fluorescently, enzimatically or radioactively labeled before detection. Higher expression results in higher signal in the detection system. Unlabeled DNA strands can also be detected, as the electronic and optical characteristics of the DNA is altered after complementer hybridization. In this review we summarize the basics of hybridisation and its newest application area in the DNA array systems.

Animals↗

PubMed2005

[Isolation and therapeutic use of human stem cells].

Nowadays, adult stem cells are the main target of biological research. Stem cell specific markers allow the extraction in enough quantity and high purity of multipotent cells from organic tissues, and their usage instead of the ethically reprehensible embryonal stem cells in experimental therapeutic purposes is also possible. The key point in the development of a new, stem-cell based therapeutic methodology is the determination of stem cell specific cell surface or cytoplasmatic antigens that makes reliable stem cell identification possible. Bone marrow derived multipotent stem cells can already be suitably identified, and other, more or less organic tissue-derived stem cell specific markers are also available. The first therapeutic interventions have been already done in diseases such as myocardial infarction or diabetes mellitus, and led to promising results.

Adult↗

PubMed2005

[Possibilities in the treatment of primary biliary cirrhosis].

The primary biliary cirrhosis (PBC) is a chronic, progressive disease of unknown origin with immune pathomechanism. The disease is accompanied with the chronic inflammation of the small and middle intra-hepatic bile ducts. It occurs in 90 per cent of women. The authors summarizes the possibilities ot its therapy after the review of the pathogenesis and clinical findings. They discuss the pathomechanism and the effects on the biochemical and histological findings of ursodeoxycholic acid (UDCA), which is the basis therapy of this disease, The place and indication of immunosuppressive drugs as well as possibilities of immune modulation are also reviewed on the basis of literary data. The therapy in the complication PBC and concomitant diseases are also discussed. The authors mention the opportunities of the therapy which will be applied in the future as a fruitful therapy.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2005

[Pharmacogenetics of inflammatory bowel disease].

There are interindividual variations with regard to efficacy and toxicity of many commonly employed drugs. Major causes of interindividual differences of drug effects include genetic variations of drug-metabolizing enzymes, transporters and targets. Pharmacogenetics studies the genetic background of the interindividual variations of drug response. By means of preliminary genetic screening personalized treatment can be achieved, drugs with low efficacy and many side-effects can be avoided. The pharmacogenetically best studied medications of inflammatory bowel disease are azathioprine/6-mercaptopurine. It is obvious that there is a genetic background of the efficacy and toxicity of corticosteroids, 5-ASA drugs, infliximab and other immunosuppressors as well, but further studies now require to confirm the functional significance of it. Therefore, at present, the application and clinical usefulness of pharmacogenetics in the management of inflammatory bowel disease is limited. The aims of future investigations are understanding of the mechanism of drug action, identification of new drug targets and acquainting with genetic factors that determine drug response.

Aminosalicylic Acids↗

PubMed2005

[The problem of multiple testing and solutions for genome-wide studies].

The problem of multiple testing and its solutions for genome-wide studies. Even if there is no real change, the traditional p = 0.05 can cause 5% of the investigated tests being reported significant. Multiple testing corrections have been developed to solve this problem. Here the authors describe the one-step (Bonferroni), multi-step (step-down and step-up) and graphical methods. However, sometimes a correction for multiple testing creates more problems, than it solves: the universal null hypothesis is of little interest, the exact number of investigations to be adjusted for can not determined and the probability of type II error increases. For these reasons the authors suggest not to perform multiple testing corrections routinely. The calculation of the false discovery rate is a new method for genome-wide studies. Here the p value is substituted by the q value, which also shows the level of significance. The q value belonging to a measurement is the proportion of false positive measurements when we accept it as significant. The authors propose using the q value instead of the p value in genome-wide studies.

Confidence Intervals↗

PubMed2005

Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn's disease: phenotype-genotype correlations.

AIM: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD. METHODS: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 healthy subjects were included. DNA was screened for possible NOD2/CARD15 mutations by denaturing high-performance liquid chromatography (confirmed by direct sequencing). TLR4 D299G was tested by PCR-RFLP. RESULTS: NOD2/CARD15 mutations were found in 185 patients (35.1%) and in 33 controls (16.5%, P<0.0001). SNP8/R702W (10.8% vs 6%, P = 0.02), SNP13/3020insC (19.4% vs 5%, P<0.0001) and exon4 R703C (2.1% vs 0%, P = 0.02) mutations were more frequent in CD, while the frequency of SNP12/G908R was not increased. The frequency of TLR4 D299G was not different (CD: 9.9% vs controls: 12.0%). Variant NOD2/CARD15 allele was associated with an increased risk for CD (OR(het) = 1.71, 95%CI = 1.12-2.6, P = 0.0001, OR(two-risk alleles) = 25.2, 95%CI = 4.37-8, P<0.0001), early disease onset (carrier: 26.4 years vs non-carrier: 29.8 years, P = 0.0006), ileal disease (81.9% vs 69.5%, OR = 1.99, 95%CI = 1.29-3.08, P = 0.02, presence of NOD2/CARD15 and TLR4: 86.7% vs 64.8%), stricturing behavior (OR = 1.69, 95%CI = 1.13-2.55, P = 0.026) and increased need for resection (OR=1.71, 95%CI: 1.13-2.62, P = 0.01), but not with duration, extra-intestinal manifestations, familial disease or smoking. TLR4 exhibited a modifier effect: age of onset in wt/TLR4 D299G carriers: 27.4 years vs NOD2mut/TLR D299G: 23 years (P = 0.06), in NOD2mut/wt: 26.7 years. CONCLUSION: These results confirm that variant NOD2/CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease, stricturing disease behavior in Hungarian CD patients. In contrast, although the frequency of TLR4 D299G polymorphism was not different from controls, NOD2/TLR4 mutation carriers tended to present at earlier age.

Adult↗

PubMed2005

Effect of inhibitors of myeloperoxidase on the development of aortic atherosclerosis in an animal model.

Our earlier studies have shown that some steroids increase myeloperoxidase enzyme (MPO) release from human granulocytes, and that MPO plasma levels are significantly lower in postclimacteric people. Moreover, we have proven that MPO inhibits production of atherogenic free radical superoxide anion and MPO-inhibitors increase superoxide release. The aim of the present study was to investigate the effect of MPO-inhibitors on the early phase of aortic atherosclerosis, namely the extent of intimal plaques and the thickening of the medial layer. Adult male rabbits were fed with lipid rich food (cholesterol: 1.3%, peanut oil: 8%) for 8 weeks. During this period MPO-inhibitors were also given (4-aminobenzoicacid-hydrazide/ABAH/-13.3 mg/kg/day or indometacin-5 mg/kg/day). All animals developed intimal lipid plaques (raised fatty streaks). The relative plaque-covered areas of the aortas were compared and the media thickness of the aorta was measured on plaque-free as well as plaque-containing areas. The medial smooth muscle density and peroxidase activity of the aortic media were also determined. The media thickness increased (p<0.05) in the cholesterol+ABAH as well as in the cholesterol+indometacin groups up to 375.7 (+/-60.5) and 442.5 (+/-123.4) microm, respectively, compared to the control group (cholesterol feeding alone) where it measured only 308.4 (+/-51.67) microm. The medial peroxidase activity decreased significantly in the indometacin treated group and showed a decreasing tendency using ABAH. In parallel to this there was a tendency of increase in the relative plaque covered areas. The smooth muscle density showed no significant modifications, while inhibitors of the MPO seemed to enhance aortic medial thickness, i.e. the grade of a pre-atherosclerotic lesion, in our animal model. Collectively, the anti-atherogenic effect of certain steroid hormones might be realized through the impact on MPO activity.

Aniline Compounds↗

PubMed2005

The results of the expression array studies correlate and enhance the known genetic basis of gastric and colorectal cancer.

Gastric and colorectal cancers belong to the most frequent cancer types in the world today. This fact emphasizes the importance of identification of useful diagnostic and prognostic markers, in the earliest stage of the disease. The examination of gene expression profile in gastric and colorectal cancer may develop the bases of early diagnosis and of individual therapeutic strategies. In the microarray examinations done so far for these types of cancers, the expression of hundreds and thousands of genes were studied, however, both the sample collection and the results showed wide variations. The diversity of expression array methods and data analysis makes the comparison of microarray results difficult. Beside the exposition of the practical aspects of the chip technology, our aims are the systematization of data that are currently available in the international scientific literature and the description of the results in a comprehensive way. Microarray results show that the gene expression pattern, detected in gastric and colon cancers, highly depends on the histological type and heterogeneity of the sample, array type, and softwares, used for data analysis. Recent experiments point out not just the changes of the alterations of tumor suppression, apoptosis, cell-cycle regulation, and signal transduction, but tumor cell metabolism and cell-microenvironment interactions also. Results show connection to and make more complete the already known molecular background of gastric and colorectal cancers. Based on the accumulation of recent and further data, such kind of multifunctional diagnostic microarrays that can be suited for completing the conventional histological diagnostics and subtypization will certainly become available in the near future.

Colorectal Neoplasms↗

PubMed2005

Growth in epithelial cell proliferation and apoptosis correlates specifically to the inflammation activity of inflammatory bowel diseases: ulcerative colitis shows specific p53- and EGFR expression alterations.

PURPOSE: Epithelial cell turnover related differences between ulcerative colitis, Crohn's colitis, and aspecific colitis are not known yet. METHODS: Totally 345 formalin-fixed, paraffin-embedded biopsy specimens from 33 ulcerative colitis, 26 Crohn's colitis, 30 aspecific colitis, and 10 healthy patients were observed with the TdT-mediated dUTP nick end labeling method and proliferating cell nuclear antigen-, p53-, and epithelial growth factor receptor immunohistochemistry. Because of epithelial growth factor receptor positivity of subepithelial cells epithelial growth factor receptor and CD45, CD68, or CD83 double fluorescence immunohistochemistry were performed on 16 freshly frozen samples from 8 severely active ulcerative colitis and 8 severely active Crohn's colitis patients to describe lamina propria's mononuclear cells, respectively. RESULTS: The epithelial growth factor receptor expression was significantly lower in each inflammatory group compared with normal (P < 0.005) and decreased significantly in mild ulcerative colitis compared with mild Crohn's colitis or aspecific colitis (P < 0.005). Numerous epithelial growth factor receptor and CD45 double-positive submucosal mononuclear cells were observed in moderate-severe inflammations. The p53-expression was significantly higher in each inflammatory group compared with normal (P < 0.05). Significant differences were found between mildly, moderately, and severely inflamed samples in ulcerative colitis (P < 0.05) compared with Crohn's colitis or aspecific colitis. Apoptotic/proliferative rates increased significantly in line with the inflammatory process (P < 0.0001/0.05), but the TdT-mediated dUTP nick end labeling and proliferating cell nuclear antigen-labeling characteristics did not show disease type specificity. CONCLUSIONS: Based on our results, the alterations of epithelial growth factor receptor and p53 expression show ulcerative colitis specificity, whereas the rate of epithelial apoptosis and proliferation are determined by the histologic activity of the inflammation. The increased epithelial growth factor receptor expression by the lamina propria's mononuclear cells in inflammation may suggest its role as an autoantigen.

Apoptosis↗

PubMed2005

Three-dimensional virtual microscopy of colorectal biopsies.

Conventional optical microscopy of specimens from colorectal biopsies commonly produces diagnostic errors due to incomplete sampling or poor orientation. Obtaining additional sections or re-embedding may help avoid these errors, but can prolong turnaround time. We describe new technology, which incorporates exhaustive sectioning, 3-dimensional reconstruction, and virtual microscopy, that may eliminate these problems by enabling pathologists to rapidly examine entire specimens and convert poorly oriented mucosa to well-oriented mucosa.

Aged↗

PubMed2004

[Ghrelin: a new peptide regulating the neurohormonal system and energy homeostasis].

Ghrelin: a new peptide regulating the neurohormonal system and energy homeostasis. Research leading to the identification of ghrelin started with the discovery of growth hormone secretagogues, continued with the description of ghrelin receptors and ended with description of the chemical structure of ghrelin. However, several aspects concerning the role of ghrelin in physiology and pathophysiology are still under investigation. The majority of ghrelin is produced in the stomach, but it is also expressed in the hypothalamus, pituitary, intestine, kidney, heart, pancreas and gonads. Ghrelin stimulates growth hormone secretion via growth hormone secretagogue receptors, and it increases appetite. Ghrelin secretion in the stomach depends on both acute and chronic changes in energy balance. Presently available data support the hypothesis that the stomach, in addition to its important role in digestion, not only influences pituitary hormone secretion via ghrelin production but it also sends orexigenic (appetite increasing) signals to hypothalamic nuclei involved in the regulation of energy homeostasis. In addition to these main effects, ghrelin influences the cardiovascular, gastrointestinal, reproductive and endocrine functions. It can be anticipated that further research on the physiological and pathophysiological role of ghrelin will lead to a better understanding of neurohormonal processes and the central regulation of energy homeostasis.

Animals↗

PubMed2004

[Single cell DNA analysis: possibilities, methods, implications in relation to stem cell therapy].

In the analysis of circulating tumor cells or in the preimplantation genetic diagnosis it is frequently necessary to examine one single cell. Some methods are appropriate to isolate single cells: Laser Assisted Microdissection, magnetic cell separation or FACS. The use of the whole genome amplification methods are needful, because the amount of the DNA extracted from the isolated cells is very low and inappropriate for additional examinations. With different molecular biological methods (e.g. sequencing, chip-technology) it is possible to determine genetic alterations in the analysed cells, and to return the modified cells with in vitro gene technological methods (viral vectors, non viral methods). Our aim is to summarize the methods and the possible technical problems developing during the process of the single cell molecular biological analysis.

DNA Mutational Analysis↗

PubMed2004

[The role of caveolin-1 gene in carcinogenesis].

Caveolin-1 is responsible for the development of caveolae, which are vesicular invaginations of the plasma membrane, and plays a key role in membrane traffic and signal transduction. The role of caveolin-1 in carcinogenesis has been a subject to numerous investigations, however, the expression pattern and the function of caveolin-1 are rather controversial both in gastrointestinal and extraintestinal cancers. The vast majority of results based on cancer cell line experiments indicate that caveolin-1 might act as a tumor suppressor gene. In tumor tissues, however, caveolin-1 seem to fulfill a tumor promoting role, since the expression of caveolin-1 is increased when compared to normal tissue counterparts. In this review, the authors summarize the results of caveolin-1 expression in gastrointestinal and extraintestinal cancer emphasizing possible future therapeutic implications.

Animals↗

PubMed2004

[Gaucher's disease: pathogenesis, diagnosis and therapy].

Gaucher's disease is the most common lysosomal storage disorder. Gene defect leads to deficiency or decreased activity of glucocerebrosidase followed by the accumulation of glucosylceramide. Most frequently hepatosplenomegaly, anemia, skeletal and hematological abnormalities are present. Different types are known based on the clinical findings. Recently used enzyme replacement therapy seems to eliminate bone marrow transplantation and has favourable effects on symptoms and outcome. Development of gene therapy (reintroduction of missing DNA sequence) hints the possibility of real causal therapy of the disease.

Anemia↗

PubMed2004

[NOD2/CARD15 mutations and genotype-phenotype correlations in patients with Crohn's disease. Hungarian multicenter study].

UNLABELLED: Recently mutations of the NOD2/CARD15 gene were identified as genetic markers for Crohn's disease (CD). It has also been suggested that the presence of mutation may influence the phenotype of the disease. The aim of this study was to determine the frequency of common NOD2/CARD15 mutations in Hungarian Crohn's patients. PATIENTS AND METHODS: DNA was obtained from 142 pts with Crohn's disease (70 male and 72 female, mean age: 36.2 yrs) and of 115 healthy subjects. Clinical data were obtained by filling in a questionnaire by the physician. DNA was screened for possible mutations by denaturing HPLC (WAVE Nucleic acid fragment analysis systems, Cheshire, UK) using published primers (Lesage et al, Am J Hum Gen 2002) for SNP's 8, 12, and 13. Mutations were then confirmed by direct sequencing on a ABI Prism 310 Genetic Analyzer (Perkin Elmer; Norwalk, USA). RESULTS: Mutations of NOD2/CARD15 were significantly more frequent in patients (n = 42, 29.6%) than in controls (11.3%, p = 0.0007, OR = 3.3, 95% CI = 1.7-6.5). R702W and 3020insC mutations were significantly more common in IBD compared to controls (4.3% and 2.6%); 18 patients had the R702W mutation (12.7%, p = 0.001, 13 homozygous, one homozygous for R703C) and 22 the 3020insC (15.9%, p = 0.001, 4 homozygous). 7 patients (4.9%) were heterozygous for the G908R, which was not different from the controls (4.3%). 5 patients were compound heterozygous. The allele frequency of R702W (11.6% vs. 4.3%, p = 0.0026, OR = 5.9, 95% CI: 2.3-14.9) and 3020insC (9.1% vs. 2.6% p = 0.004, OR = 7.6, 95% CI = 2.4-24.0) was significantly higher in Crohn's disease compared to the controls. Age at presentation was not different between carriers and non-carriers (26.7 +/- [SD] 10.3 yrs vs. 27.7 +/- 11.8 yrs). There was a tendency of ileal location to be more common in carriers of the mutation (40.5% vs. 29.0%), while colonic location was less frequent (16.7% vs. 44%). The presence of the mutation did not affect disease behaviour (carrier: inflammatory: 30.9%, stenosing: 26.2%, penetrating: 42.9%, non-carrier: inflammatory: 36%, stenosing: 27%, penetrating: 37%). Among the extraintestinal manifestations arthritis (30.1% vs. 47%, p = 0.05) and primary sclerosing cholangitis (0% vs. 9%, p = 0.047%) was significantly less frequent in carriers of the mutation. CONCLUSIONS: In concordance with European data we found a high number of NOD2/CARD15 R702W and 3020insC mutations in Hungarian patients with Crohn's disease. The G908R mutation was uncommon in Hungarian Crohn's patients. The presence of the mutation was associated with ileal but not with fibrostenosing disease and extraintestinal manifestations were less common in carriers of the mutation.

Adult↗

PubMed2004

[The importance and use of laser microdissection in clinical research and diagnostic method development].

The molecular biological analysis of rare cell samples has become increasingly important in medical research and applications. Using laser microdissection and special macromolecule isolation techniques allows us to understand the biological information even in a single cell and to examine the genetical and proteomical features of biologically homogenous cell populations. There are several type of laser microdissectors which have a very user-friendly actuation. In practice the most difficult parts are the sample preparation and the macromolecule extraction from rare cell samples. The aims of this study are to summarize current practical experiences and to foreshow the application possibilities of this quite new technique in clinical practice.

Animals↗