Biomedical subjects

Zsolt Tulassay

Publications and source records attributed to Zsolt Tulassay.

At least 91 records · Page 5Linked to original sources

PubMed2003

[Familial hypocalciuric hypercalcemia].

INTRODUCTION: Familial hypocalciuric hypercalcemia is often considered but rarely proved during evaluation for hypercalcemia. The disorder is characterized by lifelong persisting hypercalcemia and hypocalciuria. CASE REPORT: In this study, the authors analyzed a 25-yr-old Hungarian woman with mild hypercalcemia detected by routine laboratory testing. Evaluation revealed hypercalcemia, relative hypocalciuria and non-suppressed serum intact parathormone level. The diagnosis of hypocalciuric hypercalcemia was confirmed by the low ratio of calcium clearance/creatinine clearance. Genetic studies for calcium-sensing receptor gene mutations were performed in blood DNA samples. After polymerase chain reaction amplification, DNA sequencing of exons 2-7 were performed. The proband and her father had the same mutation (CCG-->CTG) at codon 55 of exon 2, leading to a conversion of the proline to a leucine. DISCUSSION: This case report presents the first case of familial hypocalciuric hypercalcemia, published in a Hungarian patient.

Adult↗

PubMed2003

[Immunobiology of dendritic cells and their application in clinical practice].

INTRODUCTION: Dendritic cells play a central role in the regulation of the immune responses towards cellular or humoral immunity. Several types of dendritic cells can be distinguished, which originate from different hematopoietic lineages, and differ from each other in function, morphology and localization within the organism. Immature dendritic cell-precursors originate from bone marrow haemopoietic stem cells, circulate in blood system and reach peripheral tissues, where they differentiate into active antigen capturing and processing cells. They have further maturation by the effect of adequate signals (antigen stimuli and inflammatory cytokines) and migrate into secondary lymphoid organs, presented cell surface MHC molecules-linked peptides from antigens which they have captured and processed, to T lymphocytes, induce immune reaction by T cell activation. Apart from the fact that dendritic cells as professional antigen presenting cells are essential to induction T cell-mediated immune responses, they influence activation and function of B lymphocytes and effector cells of natural immune system by cytokines and cell-cell interactions. CONCLUSIONS: Complex regulatory function of dendritic cells make a possibility for artificial alteration of immune processes by modification of dendritic cells: direct against definitive antigens, increase or decrease their intensity, hereby we can accomplish the immunotherapy of different diseases such as tumors, infection, autoimmune diseases, transplants' rejection.

Antigen Presentation↗

PubMed2003

Expression of caveolin-1 in gastrointestinal and extraintestinal cancers.

Caveolae are uniform vesicular invaginations of the cell membrane. Caveolin-1 is responsible for the formation of caveolae and plays a key role in membrane traffic and signal transduction. The contribution of caveolin-1 to carcinogenesis has been widely investigated; however, the expression pattern of caveolin-1 is controversial both in gastrointestinal and extraintestinal cancers. Most of the results based on cancer cell line experiments suggest that caveolin-1 might act as a tumor-suppressor gene. On the contrary, several studies on the expression of caveolin-1 in tumor tissues indicate a possible tumor-promoting effect of caveolin-1. In this article we summarize the divergent results of caveolin-1 expression in gastrointestinal and extraintestinal cancer regarding possible future therapeutic implications.

Animals↗

PubMed2003

[Failure of Helicobacter pylori eradication--suggestions for further therapy].

Success of first H. pylori eradication attempts in the literature is around 80-90% and based on urea breath test of 1027 patients in Hungary is 75%. Repeated eradication attempts are needed in 10-25% of cases. In the clinical practice in Hungary second and third eradication attempts were successful only in 36% and 20% of cases. To improve efficacy the following suggestions has to be kept in mind: 1. Do not repeat the same combination if the first attempt is failed. 2. After failure of the first PPI + amoxicillin + clarithromycin triple therapy, either the quadriple therapy (PPI + tetracycline + metronidazole + bismuth) or the replacement of PPI with ranitidine bismuth citrate in the triple therapy is suggested. 3. If PPI + amoxicillin + metronidazole/tinidazole therapy fails, the metronidazole/tinidazole can be replaced by clarythromycin. 4. Do not start with clarithromycin + metronidazole/tinidazole therapy. 5. In case of uncertain previous therapies and for third eradication treatment send the patient to specialist. Rifabutin-based combinations seem to be effective, but the use of them in general practice is not advised due to the possible development of mycobacterium tuberculosis resistance.

Age Distribution↗

PubMed2003

Loss of FHIT protein expression correlates with disease progression and poor differentiation in gastric cancer.

PURPOSE: The fragile histidine triad (FHIT) gene has recently been proposed as being a tumor suppressor gene. FHIT gene deletions or aberrant transcripts have been identified in a variety of human malignancies, including gastric carcinomas, suggesting that FHIT may play a key role in tumor development. However, the clinical impact of FHIT mutations in gastric carcinogenesis is still debated. Our purpose was to investigate whether FHIT expression in human primary gastric carcinoma is associated with the histological type, grade or stage of the tumor. METHODS: We analyzed a well-characterized set of 137 primary gastric cancers. FHIT protein expression was evaluated in gastric mucosal samples, both from the tumor and tumor-free areas by immunohistochemistry. Furthermore, in a subgroup of 30 patients, FHIT mRNA expression was assessed by nested RT-PCR. RESULTS: Absent or reduced expression of FHIT protein correlated significantly with diffuse type ( P<0.0001), poor differentiation ( P<0.0001), and advanced stage ( P<0.0001) of gastric cancer. In contrast, FHIT protein was strongly expressed and uniformly distributed in tumor-free areas. The FHIT mRNA expression was absent or altered in diffuse and poorly differentiated carcinomas. CONCLUSION: These results show that the expression of FHIT in gastric carcinoma is related to the type, grade, and stage of the tumor. We suggest that FHIT expression may be considered a potential prognostic factor in gastric cancer.

Acid Anhydride Hydrolases↗

PubMed2003

[DNA chips for gene expression analysis and their application in diagnostics].

Due to large genome projects more and more genetic information and more and more data about genetic background of various diseases can be obtained. By means of microarrays thousands to hundreds of thousands of molecular analysis can be performed at a time, rapidly, under identical conditions, hereby microarrays provide a solution to continuously increasing throughput demands from large genomic, pharmacogenetic and proteomic programmes. Microarrays offer unprecedented opportunities for qualitative and quantitative analysis of gene expression, understanding gene function and detection gene alterations, polimorphisms. Microarray expression profiles will define stages of different tumor types and new prognostic subgroups in cancer and other diseases. For individual patients, more precise diagnosis and risk assessment based on expression profiles are already achievable, leading to more accurate determination of prognosis and more individually tailored treatment. Microarrays will play an important role in diagnostics of infectious diseases and identification of novel diagnostic and therapeutic targets. Wide-spread application of microarrays in clinical practice is not typical today, but their production on an industrial scale and the increased information provided by microarrays should assure their entry into clinical practice as very powerful, sensitive, specific and rapid tools of diagnostics of various diseases.

Communicable Diseases↗

PubMed2003

Mutant p53 expression and apoptotic activity of Helicobacter pylori positive and negative gastritis in correlation with the presence of intestinal metaplasia.

BACKGROUND: Mutation of the p53 gene is detectable in most cases of gastric cancer, as it is the most common genetic alteration in human malignancies. It is also well documented that Helicobacter pylori infection plays an important role in gastric carcinogenesis. There is still no clarification, however, concerning how genetic instability influences the homeostasis of gastric epithelium. We have studied the effect of H. pylori infection on apoptosis of the antral epithelium in the presence/absence of intestinal metaplasia and the expression of the p53 oncoprotein. The relationship between these two processes is analysed. METHODS: Antral biopsies were taken from 36 patients who underwent routine upper endoscopy (17 men, 19 women, mean age 61.0 years). The biopsies were fixed in formalin and embedded in paraffin. Patients were classified into two histological groups: (1) as chronic gastritis without intestinal metaplasia (n = 19), and (2) chronic gastritis with intestinal metaplasia (n = 17). An immunohistochemical method was used to detect the expression of p53 oncoprotein, and the terminal transferase mediated dUTP nick end-labelling (TUNEL) method was used to detect apoptotic cells. RESULTS: In the absence of intestinal metaplasia, both the apoptotic index (0.0272 +/- 0.011 vs 0.0128 +/- 0.006) and expresssion of p53 (35.55 +/- 31.16 vs 18.33 +/- 19.65) were significantly higher in H. pylori positive cases compared to H. pylori negative cases. In the presence of intestinal metaplasia, p53 expression was further increased (P < 0.05), but apoptosis was similar to that observed in H. pylori negative gastritis without intestinal metaplasia. In the presence of intestinal metaplasia, H. pylori infection did not influence apoptosis (0.013 +/- 0.004 vs 0.011 +/- 0.004), or p53 ratio (70.16 +/- 22.54 vs 68.50 +/- 28.96). In the sequence of gastritis-intestinal metaplasia the two indices show a close negative correlation (P < 0.05). CONCLUSION: In the absence of intestinal metaplasia H. pylori infection increases both apoptotic activity and expression of p53 oncoprotein in the gastric mucosa. The lack of increased apoptosis with a higher p53 expression in the presence of intestinal metaplasia suggests an increased genetic instability and also may suggest that mutation of the p53 gene is an early step in the multistep process of gastric carcinogenesis.

Aged↗

PubMed2003

Quality of life assessment after pancreatic enzyme replacement therapy in chronic pancreatitis.

GOALS: To evaluate the quality of life (QoL) of patients with chronic pancreatitis before and after pancreatic enzyme replacement therapy in a prospective, multicentre, follow-up study. STUDY: Two groups of patients were evaluated. Group 1 consisted of 31 patients with newly diagnosed chronic pancreatitis who had never been treated with pancreatic enzyme preparations. Group 2 consisted of 39 patients whose disease was diagnosed on average 3.4 years before the start of the study. The latter group of patients had undergone pancreatic enzyme replacement therapy, but during follow-up this treatment proved to be insufficient. The dose of pancreatic enzyme replacement therapy was tailored in accordance with the degree of pancreatic exocrine insufficiency measured by means of exocrine pancreatic function tests. A modified European Organizaton for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) was used to assess QoL. RESULTS: The social functioning and financial strain were significantly better, while the levels of hope and confidence were significantly reduced in group 1 compared with group 2. A significant gain in body weight and a significantly reduced defecation rate were found in both groups one month after the beginning of the pancreatic enzyme replacement therapy when compared with the pretreatment values. The prevalence of general and disease-specific symptoms and the intensity of pain were reduced in both groups after one month of enzyme substitution therapy. The working ability, the financial strain and the overall QoL scores were improved significantly in both groups, while the cognitive functioning score was found to be significantly improved during the follow-up only in group 1. The overall increase in the QoL score correlated significantly with the increase in body weight and the decrease in defecation number in both groups. CONCLUSIONS: Pancreatic enzyme replacement therapy in patients with chronic pancreatitis not only reduced the extent of steatorrhea and pain, but also significantly improved a variety of other symptoms and the patient's QoL. Individually tailored enzyme replacement therapy improved the QoL not only in the untreated chronic pancreatitis patients, but also in the inadequately treated group. This study demonstrated that the EORTC QLQ-C30 questionnaire, with the addition of two further questions about steatorrhea, is a useful tool for the evaluation of QoL in patients with chronic pancreatitis.

Abdominal Pain↗

PubMed2003

Molecular detection of circulating cancer cells. Role in diagnosis, prognosis and follow-up of colon cancer patients.

BACKGROUND: The circulating tumor cells of solid tumors, especially in colorectal cancer has been of great interest in medical research in the last and new century. METHODS: A literature review of recent data for the preparation of a proposal for clinical applications. RESULTS: Starting with the detection of circulating cancer cells in histological sections, lymph nodes, bone marrow and peripheral blood have recently become the primary samples for these investigations. Following microscopic morphology, new methods were and are being developed continuously including rare cell enrichment and detection techniques like fluorescence microscopy, flow cytometry, RT-PCR and methylated DNA PCR. The sensitivity of these assays reaches down to the concentration of 1 tumor cell/ml blood. A lot of different epithelial markers were targeted with these techniques e.g. cytokeratins, EGFR, CEA, and EMA. Clinically, circulating tumor cells were found as independent prognostic factors in lymph nodes and bone marrow. In blood, their presence appears to be an early marker for recurrence and relapse. The change in their quantitative number is supposed to reflect the chemotherapeutic sensitivity and metastatic growth activity of the tumor. CONCLUSIONS: The detection of circulating tumor cells in bone marrow and lymph nodes is of clinical significance. Their presence in peripheral blood and therapeutic applications need further clarification.

Biomarkers, Tumor↗

PubMed2002

[Changes in the proliferation and apoptosis of colonic epithelial cells in correlation with histologic activity of ulcerative colitis].

BACKGROUND: The imbalance of epithelial cell kinetics in ulcerative colitis can lead to several gastrointestinal disorders such as ulcers or neoplasias. The changes of epithelial cell kinetics caused by the inflammatory process have not been fully and uniformly described. Aim of the study was to compare the rate of epithelial cell apoptosis and proliferation within colonic crypts considering the histological activity of ulcerative colitis. MATERIALS AND METHODS: Formalin fixed paraffin embedded biopsy specimens from mild, moderate, and severe active inflammation of ulcerative colitis and from normal colonic tissue were observed. Number of cases (apoptosis/proliferation): normal: 8/10; mild UC: 8/10; moderate: 8/8; severe: 12/8. For detecting apoptosis the TUNEL-POD-DAB method, and for proliferation the PCNA (PC-10)-Biotin-Streptavidin-AEC method were used, constrained with haematoxylin. Using light microscope, at least 500 crypt epithelial cells were encountered axially in whole, well-orientated colonic crypts per each specimen. RESULTS: The number of TUNEL positive epithelial cells were significantly higher in moderate and severe active inflammation compared to each other and to normal (p < 0.0001). Between mild inflammation and normal significant alteration was not found. The number of PCNA positive cells were significantly higher in each groups of inflammation compared to normal or each other. CONCLUSION: These results demonstrate that there is a strong correlation between the histological activity of ulcerative colitis and elevated crypt epithelial cell turnover, although the alterations in proliferation develop in the earlier stages of inflammation.

Adult↗

PubMed2002

[Quality of life in the course of enzyme replacement therapy for chronic pancreatitis].

AIM: The ultimate goal of any treatment in chronic pancreatitis is to maximize the patient's quality of life. The authors evaluated the QoL of patients with chronic pancreatitis prior to and after pancreatic enzyme replacement therapy in a prospective, multicenter, follow-up study. PATIENTS AND METHODS: Two groups of patients were evaluated. Group 1: 31 patients with newly diagnosed chronic pancreatitis who had never been treated with pancreatic enzyme preparations; Group 2: 39 patients whose disease was diagnosed on average 3.4 years before the start of the study. The latter group of patients had undergone pancreatic enzyme replacement therapy, but during the follow-up this proved to be insufficient. The dose of pancreatic enzyme replacement therapy was tailored in accordance with the degree of pancreatic exocrine insufficiency measured by means of exocrine pancreatic function tests. RESULTS: A significant gain in body weight and a significantly reduced defecation rate were found in both groups 1 month after the beginning of the pancreatic enzyme replacement therapy as compared to the pretreatment values. The prevalence of general and disease-specific symptoms, and the intensity of pain were reduced in both groups after 1 month of enzyme substitution therapy. The working ability, the emotional functioning, the financial strain and the overall QoL score were improved significantly in both groups, while the cognitive functioning was found to be significantly improved during the follow-up only in Group 1. The overall increase in the QoL score correlated significantly with the increase in body weight and the decrease in defecation number in both groups. CONCLUSIONS: Individually-tailored enzyme replacement therapy improved the QoL, reduced the extents of steatorrhea and pain, increased the body weight, not only in the untreated chronic pancreatitis patients, but even in the inadequately treated group.

Adult↗

PubMed2002

[Changes in cell kinetics and clinical course in inflammatory bowel diseases].

INTRODUCTION: The pathogenesis of inflammatory bowel diseases is still unknown, but is accessible from several ways. One possibility is the immunohistochemical analysis of cellular changes in the intestinal mucosa. The increased epithelial cell turnover is connected with false immunological pathways in the subepithelial layer. Behind these disturbances which can lead to chronic remitting inflammatory processes the imbalance of apoptosis and proliferation plays a key role. AIM: Of this study is to summarize our current knowledge of the cell kinetical alterations considering histological activity of disease. CONCLUSIONS: On the basis of current understanding it is known that the apoptosis and proliferation of epithelial cells increase in active inflammation compare to normal, although an uniform standpoint of evaluating is still missing. Some alterations of apoptosis and antigen presentation are described in the mononuclear cells of the subepithelial layer. Getting acquainted with and describing the changes of cell kinetics provide facilities to develop new and effective diagnostical methods and therapies.

Apoptosis↗

PubMed2002

[Neuroendocrine tumors of the digestive system].

Despite their rare occurrence, gastroenteropancreatic neuroendocrine tumors have been in the centre of interest because of the wide scale and variability of clinical signs and symptoms associated with oversecretion of different hormones. In the present review the authors summarize epidemiological data, pathologic findings, clinical symptoms, as well as diagnostic and therapeutic methods presently available for the management of patients with gastroenteropancreatic neuroendocrine tumors. In addition to surgical treatment and receptor-specific radionuclide therapy used in cases with surgically noncurable tumors, the therapeutic use of somatostatin analogues in recent years has resulted an important advance in the management of patients with these tumors. Somatostatin analogues alone or in combination with other pharmacological therapies may be used effectively for elimination of symptoms of hormonal oversection and, in a number of cases, for diminishing tumor progression.

Biomarkers, Tumor↗

PubMed2002

[Carcinoid tumors].

Carcinoids are characteristically indolent, but heterogeneous tumors with respect to their site of origin, endocrine features, clinical manifestations and biologic behaviour. The authors summarize the current laboratory, endoscopic and radiologic methods used for the diagnosis of carcinoid tumors. Treatment modalities should be directed against the tumor and the hormonal excess state. The authors review the outcome of most frequently used therapies, including somatostatin-analogue and interferon treatment, chemotherapy, embolization, receptor-targeted radiotherapy and surgical intervention). Patients with carcinoid tumors, with or without carcinoid syndrome, are best managed by a multidisciplinary approach.

Antineoplastic Agents↗

PubMed2002

Association of dehydroepiandrosterone sulfate and testosterone deficiency with bone turnover in men with inflammatory bowel disease.

BACKGROUND AND AIMS: We investigated the coexistence of dehydroepiandrosterone sulfate (DHEAS) and testosterone deficiency in men with inflammatory bowel disease (IBD) and their relationship with bone homeostasis. PATIENT AND METHODS: In 45 men with IBD (25 with ulcerative colitis, 20 with Crohn's disease) the testosterone and DHEAS levels were examined in relationship to bone mineral density, osteocalcin levels, and urinary deoxypyridinoline excretions. RESULTS: We detected osteoporosis in 10 and osteopenia in 22 patients at the lumbar spine and/or femoral neck. Lower testosterone levels were measured in 20. Lower DHEAS levels were present in 23 patients; these had higher deoxypyridinoline excretion and lower lumbar spine and femoral neck BMD T scores than patients with normal DHEAS. DHEAS and BMD were correlated at the lumbar spine and the femoral neck. Associations remained significant after adjustment for age, weight, steroid use, and inflammatory activity. No independent effect of testosterone deficiency was detected on bone parameters. CONCLUSION: DHEAS deficiency may contribute to the bone loss of men with IBD. This putative action of DHEAS on bone turnover is contrary to the common effect of testosterone deficiency and steroid therapy.

Adult↗

PubMed2002

Genomics of steroid hormones: in silico analysis of nucleotide sequence variants (polymorphisms) of the enzymes involved in the biosynthesis and metabolism of steroid hormones.

Alterations of steroid hormone biosynthesis and metabolism are suspected to be involved in the pathogenesis of several diseases. Several polymorphisms of the enzymes involved in these processes have already been described and some could be associated with certain diseases. We attempted to examine the sequence variants of these genes in order to find novel variants by an in silico analysis. We analyzed the known human nucleotide sequences of the enzymes p450 side-chain cleavage enzyme, steroid 17-alpha-hydroxylase/17,20-lyase, 3-beta-hydroxysteroid dehydrogenase types 1 and 2, 21-hydroxylase, 11-beta-hydroxylase, aldosterone synthase, aromatase, 11-beta-hydroxysteroid dehydrogenase types 1 and 2, steroid 5-alpha-reductase types 1 and 2, steroid 5-beta-reductase, dehydroepiandrosterone sulfotransferase, 17-beta-hydroxysteroid dehydrogenase types 1-3. The analysis was performed using the National Center for Biotechnology Information Database by the search tool blastn. We found numerous sequence variants in both coding and non-coding sequences. The majority of these sequence variants have already been described, nevertheless, some appear as novel variants. Some of these may also have functional significance. We hypothesize over the possible significance of these findings and briefly review the available literature.

Base Sequence↗

PubMed2002

Effect of Helicobacter pylori infection on epidermal growth factor receptor (EGFR) expression and cell proliferation of gastric epithelial mucosa: correlation to macroscopic and microscopic diagnosis.

Our aim was to compare the expression of EGFR and proliferative cell nuclear antigen (PCNA) in different histological and endoscopic diagnostic groups, in cases of Helicobacter pylori infection, in vivo. Paraffin embedded human gastric biopsy samples (86) were analysed by EGFR and PCNA immunohistochemistry and classified both on the basis of histology and endoscopic findings. In normal epithelia (NE), a positive correlation was found between PCNA and EGFR and in H. pylori-negative gastritis with and without intestinal metaplasia (P < 0.01). On the other hand, a negative correlation was detected between the two immunohistochemical findings in H. pylori-associated gastritis with intestinal metaplasia (HPGIM) and in the atrophic gastritis (AG) group. In HPGIM the percentage of EGFR-positive cells was significantly lower (32.4 +/- 30.4) when compared to either the NE (50.3 +/- 23.7) or H. pylori-negative gastritis with intestinal metaplasia (HNGIM) (48.3 +/- 23.7). In AG, EGFR was significantly lower when compared to the NE (P < 0.05). Based on the endoscopic findings, a significant decrease of EGFR expression was found in gastric ulcer cases as compared to NE, gastritis or erosion cases (P < 0.01). PCNA showed no significant alterations between the NE and gastritis, AG groups. The presence of H. pylori has an inverse effect on PCNA and EGFR expression in HPGIM.

Biomarkers↗

PubMedDate not supplied

Immediate DNA ploidy analysis of gastrointestinal biopsies taken by endoscopy using a mechanical dissociation device.

BACKGROUND: Quantitative DNA analysis of fresh biopsy material can contribute to a more accurate diagnosis and prognosis. The authors aimed to develop and test a mechanical, nuclear preparation protocol for quantitative DNA analysis. PATIENTS AND METHODS: Altogether 32 gastric (10 healthy, 17 gastritis, 7 adenocarcinoma) and 48 colon (21 healthy, 20 colitis ulcerosa, 7 adenocarcinoma) biopsy specimens were evaluated. The mechanical disruption was performed by Medimachine (DAKO, Denmark). The flow cytometry analysis was performed on a BD FACSStar flow cytometer. RESULTS: DNA Aneuploidy was found in gastric samples only in tumours. The S-phase fraction of the normal cases was 5.9 +/- 2.1%, 5.1% +/- 1.2% in gastritis and 10.7 +/- 1.6% in carcinomas. Seven out of 20 colitis ulcerosa and 4 out of 7 colon cancer samples were aneuploid. The S-phase fraction of normal colon cases was 5.7 +/- 3.4%, in colitis 8.1 +/- 4.2% and 15.1 +/- 5.7% in carcinomas, respectively. CONCLUSION: Mechanical nuclear isolation is a useful method for flow cytometric DNA ploidy analysis of fresh biopsy samples.

Adenocarcinoma↗