Biomedical subjects

Zsolt Tulassay

Publications and source records attributed to Zsolt Tulassay.

At least 19 recordsLinked to original sources

PubMed2007

[Chemotherapy agents, response rates and mechanisms of resistance in the therapy of the colorectal carcinoma].

Colorectal carcinoma is one of the most common cancers in Hungary, responsible for about 5000 deaths each year. In the first line treatment the most commonly used drugs are 5-fluorouracil, oxaliplatin and irinotecan. The most frequently used drug is 5-fluorouracil, which has no effect in 90% of the cases. In combination with leukovorin or with 5-ethyl-2'-deoxyuridin fluorouracil has an increased effect. The main mechanisms of the resistance against 5-fluorouracil are due to the overexpression of dihydropyrimidine dehydrogenase, MRP8, thymidylate synthase, and NFkB p65. Oxaliplatin forms reactive platinum complexes, which are believed to inhibit DNA synthesis by forming interstrand and intrastrand cross-linking of DNA molecules. The oxaliplatin-5-fluorouracil-leucovorin combination was the first to reach more than 20 months median survival. The main mechanisms of resistance are decreased accumulation, increased detoxification and increased DNA repair. Irinotecan inhibits the topoisomerase I enzyme, resulting in the inhibition of the repair of DNA breaks occurring during DNA synthesis. With sequential 5-fluorouracil, oxaliplatin, irinotecan combination 26 months median survival was reached. Mechanisms resulting in resistance are decreased accumulation, increased enzymatic detoxification, alterations of ABC transporters, DNA repair system, apoptotic pathways and topoisomerase I. Survival can be elongated using biological therapy (cetuximab, bevacizumab). In the near future biological therapy is expected to spread.

Antibodies, Monoclonal↗

PubMed2006

mRNA expression, functional profiling and multivariate classification of colon biopsy specimen by cDNA overall glass microarray.

AIM: To understand the local pathophysiological alterations and gene ontology-based functional classification of colonic biopsies into inflammatory and neoplastic diseases. METHODS: Total RNA was extracted from frozen biopsies and amplified by T7-method. Expression profile was evaluated by Atlas Glass 1K microarrays. After microarray quality control, applicable data were available from 10 adenomas, 6 colorectal adenocarcinomas (CRCs), and 6 inflammatory bowel diseases (IBDs). Multivariate statistical and cell functional analyses were performed. Real-time RT-PCR and immunohistochemistry were used for validation. RESULTS: Discriminant analysis of selected genes, could correctly reclassify all 22 samples using 4 parameters (heat shock transcription factor-1, bystin-like, calgranulin-A, TRAIL receptor 3). IBD samples were characterized by overregulated chemokine (C-X-C motif) ligand 13, replication protein A1, E74-like factor 2 and downregulated TNF receptor-associated factor 6, BCL2-interacting killer genes. In adenomas upregulation of TNF receptor-associated factor 6, replication protein A1, E74-like factor 2 and underexpression of BCL2-associated X protein, calgranulin-A genes were found. CRC cases had significantly increased epidermal growth factor receptor, topoisomerase-1, v-jun, TNF receptor-associated factor 6 and TRAIL receptor 3, and decreased RAD51 and RAD52 DNA repair gene, protein phosphatase-2A and BCL2-interacting killer mRNA levels. Epidermal growth factor receptor RT-PCR and immunohistochemistry, topoisomerase-1 RT-PCR confirmed the chip results. CONCLUSION: Different histological alterations can be reclassified by functional, multivariate analysis using cDNA microarrays. Further studies with expanded sample number are needed for subclassification of pathological alterations.

Adenocarcinoma↗

PubMed2006

Automated virtual microscopy of gastric biopsies.

BACKGROUND: Automated virtual microscopy of specimens from gastrointestinal biopsies is based on cytometric parameters of digitized histological sections. To our knowledge, cytometric parameters of gastritis and of adenocarcinoma have yet to be fully characterized. Our objective was to classify gastritis and adenocarcinoma based on cytometric parameters. We hypothesized that automated virtual microscopy using this novel classification can reliably diagnose gastritis and adenocarcinoma. METHODS: Routinely processed hematoxylin-and-eosin-stained histological sections from specimens that showed normal mucosa (14 cases), gastritis (35 cases), and adenocarcinoma (30 cases) diagnosed by conventional optical microscopy were scanned and digitized at high resolution. Thirty-eight cytometric parameters based on density and morphometry were applied to glands and superficial epithelium. Twelve cytometric parameters based on cytologic detail were applied to individual cells. RESULTS: Statistically significant differences in cytometric parameters for normal mucosa, gastritis, and adenocarcinoma were found. The most discriminatory parameter was the ratio of the total number of cells to the number of interstitial cells. These differences correctly classified adenocarcinoma at 100% accuracy and overall correctness was 86%. CONCLUSIONS: We describe a novel method of analyzing gastric mucosal histology based on cytometric parameters. Automated virtual microscopy can be used to classify gastric mucosa as normal, gastritis, or adenocarcinoma with reasonable accuracy. Further research is necessary to determine whether automated virtual microscopy can subclassify gastric mucosal histology in greater detail.

Adenocarcinoma↗

PubMed2006

[Nucleotide sequence variants of the glucocorticoid receptor gene and their significance in determining glucocorticoid sensitivity].

Nucleotide sequence variants of the glucocorticoid receptor gene and their significance in determining glucocorticoid sensitivity. The physiologic response and sensitivity to glucocorticoids may significantly differ among species, individuals, tissues and cell types. The variability of the effect of endogenous and exogenous glucocorticoids is largely determined by genetic components, of which the authors review the knowledge on the glucocorticoid receptor gene. The authors describe the genomic and non-genomic pathways of receptor function, the significance of isoforms produced during receptor protein formation, the pathomechanism of glucocorticoid resistance syndrome and the results of clinical investigations related to receptor gene polymorphisms. Through subtle alteration of receptor function, the gene polymorphisms may increase or diminish sensitivity to glucocorticoids and may play a role in the pathogenesis of metabolic disorders. In their own studies the authors found, that the N363S polymorphism, which increases glucocorticoid sensitivity, may play a role in the pathogenesis of bilateral adrenal adenomas, it may modify the clinical phenotype of patients with congenital adrenal hyperplasia, and may have an impact on steroid-induced ocular hypertension. It is presumed that further research in other diseases will continue to complete our knowledge on the pathophysiology of glucocorticoid receptor gene polymorphisms.

Adenoma↗

PubMed2006

[Inflammatory bowel disease and colorectal cancer].

The colorectal cancer is one of the most serious complication of inflammatory bowel disease. Longer duration of the disease, extensive colitis, primary sclerosing cholangitis, family history of colorectal cancer are the main risk factors. The relative risk of colorectal cancer in ulcerative colitis is increased, however, there're marked geographically differences. Relative risk of colorectal cancer is 2.5 and small bowel cancer risk is 31.2 in Crohn's disease. There aren't prospective, randomized, controlled trials that definitively prove the benefit of surveillance of colorectal cancer in IBD. Colonoscopy improve the 5-year survival rate, however, there is no evidence for the reduction of mortality. Meta-analysis showed efficacy of mesalamine in the reduction of risk of colorectal cancer, but prospective trials have been missed. Chemoprotective role of other immunomodulators has not been proven yet.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2006

[Insulin-like growth factor receptor, hepatocyte-derived growth factor receptor and telomerase expression in ulcerative colitis].

BACKGROUND: The risk of colorectal carcinoma development is elevated in chronic, longstanding ulcerative colitis. The changes of such regenerative and immortalizing pathways caused by the inflammatory process that are proved to be carcinogenic in other human tissues have not been fully and uniformly described. Aim of the study was to describe the expression alterations of regenerative signal receptors and cell aging inhibitory systems within colonic crypts considering the histological activity of the disease. MATERIALS AND METHODS: I-type insulin-like growth factor receptor (IGF1R), hepatocyte derived growth factor receptor (HGFR), telomerase reverse transcriptase (TERT) and telomerase associated protein (TP-1) expression were evaluated immunohistochemically on formalin fixed paraffin embedded biopsy specimen from 10 mild, 10 moderate, and 10 severe active inflammation of ulcerative colitis and from 10 normal colonic tissue. RESULTS: In mild inflammation all observed parameter showed significantly elevated protein expression in protein level compared to normal (p <0.005). In moderately active inflammation only IGF1R expression was significantly higher compared to normal and to mild inflammation (p <0.005). There were no regenerative signal expression alteration in severe inflammation compared to normal, and epithelial telomerase expression was not detectable in these cases. CONCLUSION: The expression of regenerative signal receptors and immortalizing factors is elevated in mildly (and moderately) inflamed ulcerative colitis. This phenomenon let the genetically defected epithelial cells to pathologically survive and proliferate, so thus favours the development of tumors.

Adult↗

PubMed2006

[Microelectrodes and their application in diagnostic medicine].

Microelectrodes are in common use in medical detection systems. The binding of two complementary nucleic acid sequences is called hybridization. Today the major obstacle of large-scale hybridization approaches is the large time-dependency of a single reaction, which is up to 16 hours. As the DNA molecules can be electronically charged, the binding could be facilitated and confirmed using an electronic control system. The authors' team aimed to develop a microelectrode system capable for the detection and control of hybridization. A microelectrode head is immersed in small liquid drop. Here, the platinum counterelectrode is surrounded by a non-conducting quartz capillary. The reference electrode is chloridized silver immersed in saturated Ag/Cl dilution. The Ag/AgCl/1 M KCl +AgCl microelectrode in stabilized against the calomel electrode in the first hours, and remains stable between 7th and 30th hours. This can be verified by the minimal drop in the potential difference. Thus the AgCl saturated KCl electrode is usable for several days for actual measurements. The detector is controlled by an attached computer. The system can be used to detect hybridization in a micro-cell located on a gold-plate. The electrode can be dismounted and reused after repeated chloridization of the Ag wire. The microelectrode is simple, cheap; thus is best suited for application in future automated diagnostic detection systems.

Diagnostic Techniques and Procedures↗

PubMed2006

Laser microdissection in translational and clinical research.

Laser microdissection (LMD) is now a well established method for isolating individual cells or subcellular structures from a heterogeneous cell population. In recent years, cell, DNA, RNA, and protein based techniques has been successfully coupled to LMD and important information has been gathered through the analysis of the genome, transcriptome, and more recently the proteome of individual microdissected cells. The aims of this review are to summarize and compare the principles of different laser microdissection instruments and techniques, to discuss sample preparation procedures for microdissection, and to provide wide variety of examples of translational/clinical research applications of LMD. Novel techniques specifically developed for the improved isolation of stained cells, living cells, or rare cells are also discussed.LMD has become an indispensable tool in the preparation of homogenous samples for sophisticated cell or molecular assays. Despite major technological advances, the labor requirements of LMD are still relatively high. However, understanding the advantages and disadvantages of LMD technology and associated sample preparation procedures may aid in the earlier introduction of this method into the routine clinical diagnostics.

Animals↗

PubMed2006

Functional genomics approaches for the study of sporadic adrenal tumor pathogenesis: clinical implications.

Although sporadic adrenal tumors are frequently encountered in the general population their pathogenesis is not well elucidated. The advent of functional genomics/bioinformatics tools enabling large scale comprehensive genome expression profiling should contribute to significant progress in this field. Some studies have already been published describing gene expression profiles of benign and malignant adrenocortical tumors and phaeochromocytomas. Several genes coding for growth factors and their receptors, enzymes involved in steroid hormone biosynthesis, genes related to the regulation of cell cycle, cell proliferation, adhesion and intracellular metabolism have been found to be up- or downregulated in various tumors. Some alterations in gene expression appear so specific for certain tumor types that their application in diagnosis, determination of prognosis and the choice of therapy can be envisaged. In this short review, the authors will present a synopsis of these recent findings that seem to open new perspectives in adrenal tumor pathogenesis, with emphasis on changes in steroidogenic enzyme expression profiles and highlighting possible clinical implications.

Adrenal Gland Neoplasms↗

PubMed2006

[Molecular biology background of inflammatory bowel disease].

The exact pathological background of inflammatory bowel disease has not been clarified yet. Many aspects of genetical and environmental factors, as well as certain alterations of the functions of epithelial cells and immunoregulation which may attenuate chronic inflammation in the gastrointestinal tract are known. These three components have many connecting points. Among the inflammatory bowel disease genes we know only the function of the NOD2/CARD gene, and we have some idea about the OCTN and DRG genes. The function of the intestinal epithelial cells is changed in inflammatory bowel disease. The latter two genes may have a role in the increased permeability, so as the tumor necrosis factor alpha, interferon gamma may play affect it. The interleukin-10 helps the mucosal integrity. The interleukin-6 production is elevated in these diseases, and the interleukin-8 level can be elevated in case of mutation of toll like receptor 5. The tumor necrosis factor alpha, interferon gamma and lymphotoxin-3-alpha increased the chemokine secretion and adhesion molecule expression also. The amount of certain cytokines are changed in inflammatory bowel disease. There were no association between the incidence and phenotype of Crohn's disease and cytokine gene polymorphisms, except the interleukin 6 gene. It seems that these alterations are secondary, and don't play a major role in the pathogenesis of inflammatory bowel disease.

Crohn Disease↗

PubMed2006

[Possible applications of functional genomics in the study of the pathogenesis of adrenal and pituitary tumors].

Functional genomics represents one of the most rapidly evolving fields of contemporary medical research. It is being more and more exploited in endocrinological research, as well, including studies on endocrine tumours. By comparing gene expression profiles of different tumour tissues or to their healthy counterparts, large amounts of information can be obtained that was unfeasible even until recently. There are only few data available on the pathogenesis of sporadic adrenal and pituitary tumours. Owing to recent studies applying functional genomics tools, novel genes were identified that could have pathogenetic relevance. Some of these genes may even be applicable in clinical practice, e.g. for the study of malignancy, determination of prognosis or the choice of therapy. In this short review, the authors attempt to present a synopsis of the possible applications of functional genomics in the field of endocrine tumours by summarizing recent studies on adrenal and pituitary tumours.

Adrenal Gland Neoplasms↗

PubMed2006

[Genetic background of irritable bowel syndrome].

Irritable bowel syndrome (IBS) is a functional disorder which affects the 20% of the population. The exact origin is unknown. IBS is the result of interaction of genes and environmental factors. Familial aggregation and higher concordance rate of monozygotic twins compared to dizygotic twins provide evidence for the importance of genetic factors in the pathogenesis of IBS. Interest has focused on genetic variants of serotonin transporter and receptors, because of their role in gut motility, visceral sensitivity, immune processes and mood. Firm conclusions about the role of serotonin system, as well as other neuroreceptors, G-proteins, cytokine polymorphisms in the pathogenesis of IBS cannot be made.

Cytokines↗

PubMed2006

[Antioxidant therapy in chronic liver diseases].

In chronic liver diseases with inflammatory reactions (chronic viral hepatitis, alcoholic liver disease, non-alcoholic steatohepatitis, autoimmune hepatitis, chemicals and drug induced hepatitis, Wilson disease, haemochromatosis) the oxidative stress, the cell alteration induced by free radicals is an important part of the pathogeneis beside the aetiological factors. In this paper the development of free radicals and their physiological role are demonstrated. The factors, which are influenced by the free radicals and antioxidants, as well as the pathological effects caused by oxidative stress in biological systems are discussed in details. The authors demonstrate the free radical processes as key factors in alcoholic liver diseases and non-acoholic steatohepatitis, furthermore the possible treatment modalities in the inhibition of these alterations. Also the free radical processes in chronic viral hepatitis and autoimmune hepatitis are discussed as well. The oxidative stress is able to enhance the progression of chronic inflammatory liver disease independently from the aetiological factor or with it together. That is why the antioxidant drugs could be applied also in the treatment of chronic liver diseases beside the therapy based on the aetiological factors.

Antioxidants↗

PubMed2006

[Association of coeliac disease and myasthenia gravis].

Coeliac disease is a malabsorption syndrome induced by the gluten-containing cereals leading to the damage of small intestinal mucosa. A case of a young woman is presented whose coeliac disease became overt in the puerperium. Despite strict adherence to gluten-free diet, her muscle weakness affecting several muscle regions persisted. Following a diagnostic work-up covering numerous co-disciplines, the diagnosis of myasthenia gravis was set up underlying her muscle symptoms. After the thorough review of the corresponding literature, the authors could not find any case report on the association of coeliac disease with myasthenia gravis.

Adult↗

PubMed2006

[New trend in treatment in patients with chronic hepatitis C].

The combination of pegilált interferon plus ribavirin is significantly more effective than conventional interferon plus ribavirin, and is thus the current therapy of choice for patients with chronic hepatitis C. Forty-eight weeks of treatment with combination of pegilált interferon plus ribavirin has produced overall sustained virologic response 54-56% in patients with chronic hepatitis C. This article summarize the new therapy of chronic hepatitis C, the antiviral therapy of hepatitis C virus patients with normal aminotransferase levels, the therapy in patients with compensated cirrhosis and who were nonresponders to previous combination therapy, the effect of antiviral therapy on necroinflammation and fibrosis, and the favourable effect of haemopoetic growth factors on results of antiviral therapy. A substantial proportion of patients with chronic hepatitis C have persistently normal alanin-aminotransferase levels. Many studies have indeed provided evidence that although the majority of hepatitis C virus patients with normal alanin-aminotransferase may have active and progressive liver disease. Initiation of antiviral therapy might be decided mainly on the basis of histological findings. Extending the treatment duration from 48 to 72 weeks in patients with hepatitis C virus genotype 1 significantly reduces relapse rates and increases sustained virological rates. Induction phase with a higher dose of pegilált interferon may be of value in improving outcomes in patients with genotype 1 who were nonresponders to previous combination therapy. The combination of pegilált interferon and ribavirin was effective and well tolerated in patients with compensated cirrhosis. Interferon-based therapy may reduce hepatic inflammation in the absence of a sustained virologic response. This results suggest that interferon maintenance therapy may slow disease progression. The virologic response rates could be improved by utilizing haemopoetic growth factors, as opposed to reducing the ribavirin and interferon dose.

Alanine Transaminase↗

PubMed2006

Vertebral fracture risk reduction with strontium ranelate in women with postmenopausal osteoporosis is independent of baseline risk factors.

UNLABELLED: Strontium ranelate (2 g/day) was studied in 5082 postmenopausal women. A reduction in incident vertebral fracture risk by 40% was shown after 3 years. This effect was independent of age, initial BMD, and prevalent vertebral fractures. INTRODUCTION: Strontium ranelate is an orally active treatment able to decrease the risk of vertebral and hip fractures in osteoporotic postmenopausal women. The aim of this study was to assess the efficacy of strontium ranelate according to the main determinants of vertebral fracture risk: age, baseline BMD, prevalent fractures, family history of osteoporosis, baseline BMI, and addiction to smoking. MATERIALS AND METHODS: We pooled data of two large multinational randomized double-blind studies with a population of 5082 (2536 receiving strontium ranelate 2 g/day and 2546 receiving a placebo), 74 years of age on average, and a 3-year follow-up. An intention-to-treat principle was used, as well as a Cox model for comparison and relative risks. RESULTS: The treatment decreased the risk of both vertebral (relative risk [RR] = 0.60 [0.53-0.69] p < 0.001) and nonvertebral (RR = 0.85 [0.74-0.99] p = 0.03) fractures. The decrease in risk of vertebral fractures was 37% (p = 0.003) in women <70 years, 42% (p < 0.001) for those 70-80 years of age, and 32% (p = 0.013) for those > or = 80 years. The RR of vertebral fracture was 0.28 (0.07-0.99) in osteopenic and 0.61 (0.53-0.70) in osteoporotic women, and baseline BMD was not a determinant of efficacy. The incidence of vertebral fractures in the placebo group increased with the number of prevalent vertebral fractures, but this was not a determinant of the effect of strontium ranelate. In 2605 patients, the risk of experiencing a first vertebral fracture was reduced by 48% (p < 0.001). The risk of experiencing a second vertebral fracture was reduced by 45% (p < 0.001; 1100 patients). Moreover, the risk of experiencing more than two vertebral fractures was reduced by 33% (p < 0.001; 1365 patients). Family history of osteoporosis, baseline BMI, and addiction to smoking were not determinants of efficacy. CONCLUSIONS: This study shows that a 3-year treatment with strontium ranelate leads to antivertebral fracture efficacy in postmenopausal women independently of baseline osteoporotic risk factors.

Bone Density↗

PubMed2006

[Clinical features and pathogenesis of Carney complex, a rare form of multiple endocrine neoplasia syndromes].

Carney-complex is the rarest and most recently described form of multiple endocrine neoplasia syndromes that is unique both from clinical and pathogenetic aspects. Clinical features include spotty skin pigmentation, cutaneous and cardiac myxomas, multiple endocrine abnormalities and schwannomas. The most characteristic endocrine abnormality is primary pigmented nodular adrenal hyperplasia that may result in clinically apparent Cushing's syndrome. Acromegaly, hyperprolactinaemia, tumours of the testis and ovaries have also been described. Approximately fifty percent of Carney-complex cases are familial, with an autosomal dominant inheritance pattern. About 45-65% of Carney-complex cases are related to mutations of the PRKAR1A gene encoding a regulatory subunit of protein kinase A, but other genetic mechanisms seem to be involved, as well. Here, the authors present a brief synopsis of its clinical and pathogenetical features.

Cyclic AMP-Dependent Protein Kinase RIalpha Subuni↗

PubMed2006

[Is the successful eradication of Helicobacter pylori sufficient for the healing of peptic ulcer?].

Helicobacter pylori has a major role in the pathogenesis of peptic ulcer disease. Cure of the infection is essential in ulcer healing, but an additional PPI therapy after completing eradication treatment is widespread in clinical practice. In the present work clinical studies evaluating peptic ulcer healing followed or not by PPI treatment after eradication therapy were analyzed. The results of these trials are concordant that only a minority of patients with duodenal ulcer would benefit from prolonged acid suppressive treatment, a successful eradication therapy (that counts for a large proportion) is sufficient. There are less data available concerning gastric ulcer: successful eradication is also essential to ulcer healing and to avoid relapse, however it seems that post-eradication PPI therapy might be beneficial.

Antacids↗