Biomedical subjects

Béla Molnár

Publications and source records attributed to Béla Molnár.

At least 19 recordsLinked to original sources

PubMed2006

Use of routinely collected amniotic fluid for whole-genome expression analysis of polygenic disorders.

BACKGROUND: Neural tube defects related to polygenic disorders are the second most common birth defects in the world, but no molecular biologic tests are available to analyze the genes involved in the pathomechanism of these disorders. We explored the use of routinely collected amniotic fluid to characterize the differential gene expression profiles of polygenic disorders. METHODS: We used oligonucleotide microarrays to analyze amniotic fluid samples obtained from pregnant women carrying fetuses with neural tube defects diagnosed during ultrasound examination. The control samples were obtained from pregnant women who underwent routine genetic amniocentesis because of advanced maternal age (>35 years). We also investigated specific folate-related genes because maternal periconceptional folic acid supplementation has been found to have a protective effect with respect to neural tube defects. RESULTS: Fetal mRNA from amniocytes was successfully isolated, amplified, labeled, and hybridized to whole-genome transcript arrays. We detected differential gene expression profiles between cases and controls. Highlighted genes such as SLA, LST1, and BENE might be important in the development of neural tube defects. None of the specific folate-related genes were in the top 100 associated transcripts. CONCLUSIONS: This pilot study demonstrated that a routinely collected amount of amniotic fluid (as small as 6 mL) can provide sufficient RNA to successfully hybridize to expression arrays. Analysis of the differences in fetal gene expressions might help us decipher the complex genetic background of polygenic disorders.

Amniotic Fluid↗

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

[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↗

PubMed2005

[The p53 gene and protein in 2005: new results, promising opportunities].

The p53 gene and protein in 2005: new results, promising opportunities. The p53 gene is one of the most important genes which is involved in the regulation of cell division and tumor formation. The normal function of the p53 protein is to arrest the cell division and to turn the cell towards apoptosis in the case of cell stress and DNA damage, thereby to protect the integrity of the genome. Several p53 gene mutations that have function in carcinogenesis have been found in various tumors, including gastrointestinal carcinomas. The loss of p53 response plays an important role in the malignantly transformed cell proliferation. Promising experiments try to substitute the lost functions of the p53 gene. With their help new anti-tumor therapeutic methods should be developed.

Animals↗

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

Prevalence of sexual dysfunction in patients with schizophrenia: international variation and underestimation.

The prevalence of sexual dysfunction in schizophrenia patients was investigated as part of this large (n = 7655), prospective, international (27 countries) study. Based on patient reports, sexual dysfunction affected approx. 50% of patients and the prevalence of complaints varied significantly between regions (p < 0.0001). The prevalence of sexual dysfunction, as perceived by psychiatrists, also varied significantly across regions (p < 0.0001). Psychiatrists significantly underestimated the presence of impotence/sexual dysfunction (p < 0.0001) and loss of libido (p < 0.0001), compared to reports from patients. The frequency of sexual dysfunction was significantly higher in patients who had been using prolactin-elevating antipsychotics prior to study entry, compared to those who had been treated with prolactin-sparing antipsychotics (patient reports, p = 0.002; psychiatrist perception, p = 0.0004). This study has shown that the prevalence of sexual dysfunction is high in both male and female patients with schizophrenia and frequently underestimated by psychiatrists. Regional variation is evident in both psychiatrist perceptions and patient reports of sexual dysfunction. Given the importance of sexual function to quality of life and treatment compliance, proactive assessment of sexual function is required to optimize schizophrenia management.

Adult↗

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↗

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

[Experiences in surgical management of acute arterial occlusions of the lower limb in the course of 20 years].

INTRODUCTION: In Hungary surgeons perform every year more then 2000 operations for treatment of acute arterial occlusion. Because of the advanced age and poor general condition of these patients, the postoperative mortality and complication rate is considerable. AIM: Authors analyzed changes in the etiology and therapy of acute arterial occlusions of lower limb in the last 20 years in a retrospective study. PATIENTS AND METHODS: 563 patients were operated on with acute arterial occlusion of lower extremities from 1983 to 2002 by the authors. Patients with vascular surgery in their history were excluded from this study. Student's two-samples "t"-test, chi2- and Fisher's exact test were used in Statistica 6.0 for statistics. RESULTS: Period of 1983-1992 compared to period of 1993-2002 they found increased rate of occlusions caused by thrombosis (35 vs. 46%, p < 0.01) and increased number of acute vascular reconstructions performed with indication of acute thrombosis (17.6 vs. 47.0%, p < 0.001). Mortality was higher in patients operated with embolism than in patients with thrombosis (17.7 vs. 11.6%, p < 0.01), but the ratio of postoperative amputation following embolectomy was lower than following thrombectomy (5.0 vs. 16.0%, p < 0.01). Thrombectomy itself could solve the occlusion caused by thrombosis only in 50% of cases. Results of reoperations following unsuccessful thrombectomies are very poor. Amputation was necessary in 6.8% (in 5 cases of 74 patients) after primary reconstructions, but in 28.6% (in 14 cases of 49 patients) after reoperations. There was no significant difference in postoperative mortality among primary reconstructed, reoperated and conservatively treated groups. CONCLUSIONS: By author's experience, in cases of acute occlusion caused by thrombosis as a complication of chronic obliterative arterial disease, basic cause of occlusion should be searched for and--if conditions are suitable--procedure should be extend to vascular reconstruction.

Acute Disease↗

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↗

PubMed2004

[Use of DNA-chips technology in colorectal cancer].

The examination of gene expression in colorectal cancer may develop the bases of early diagnosis and of individual therapeutic strategies. With the few cDNA microarray examinations in colorectal cancer the expression of hundreds and thousands of genes were studied, although both the sample collection and the final results showed differences. Beside the exposition of the practical advantages of the chip technology our aims are the standardization of the currently available data in the international scientific literature and the description of the results in a comprehensible way. To summarize one can say that gene expression examinations in colorectal cancer show the accentuated role in carcinogenesis of not only the tumor suppressor, apoptosis- or cell-cycle regulation related genes, but of some mitochondrial, metabolic and cell-cell or cell-extracellular matrix conjunction gene families.

Colorectal Neoplasms↗

PubMed2004

[Necessity of chip technology in stomach cancer].

Gastric cancer is one of the most frequent cancer type in the world today. This fact emphasises the importance of identification of useful diagnostic and prognostic markers for gastric cancers in their earliest stages. Aim of this review is to summarize the genetic knowledge related to gastric carcinogenesis and progression and to offer a survey of the gene expression pattern changes and their functional classification. Microarray results show that the gene expression pattern detected in gastric cancers highly depends on the histological type and heterogeneity of the sample, array type and data analyzing softwares. Recent experiments point out the changes of not just the alterations of tumor suppression, apoptosis, cell cycle regulation and signal transduction, but tumor cell metabolism and cell-microenvironment interactions, too. All results show connection to and complete the already known molecular background of gastric cancer.

Adenocarcinoma↗

PubMed2004

[Past, present and future of digital pathology].

The four main aspects of applied medical information technology, which change the traditional systems of the entire health service are signal and data processing, digital modelling and interface optimisation. The information technology serving individual clinical specialties including clinical histopathology is changing at each of the four levels resulting in transformation of the communication paradigms. The object of investigation in histopathology is the digital slide, which is accessible throughout the world with no time or geographical limits. It permits the digital modelling of routine histological and/or cytological slide and it also allows measurements by using image analysis or stereology software packages. The electronic slide can be viewed, examined and diagnosed on a computer connected to a microscope, a new interface in diagnostic histopathology. This study describes the main theoretical and practical aspects, including challenges, of digital pathology and it also discusses the conditions required for successful information management. It reviews the experiences of the last one and half decades gained in the field of pathological information technology in Hungary including its main episodes and milestones of development. Introducing its present state, this paper describes the concept and the mode of investigation of the digital slide. It shows the development and use of a virtual microscope in Hungary. Based on know-how including the British experience this review describes the possible uses of digital slides, which by improving communication could have a positive effect on the entire health care system. It summarises the possible and necessary components of a digital pathology laboratory, which may include the new Slide Archive and Communication System (SACS). Using experimental data it mentions the possibility of generating primary digital pathological sample and producing the so called optical biopsy with no need for removing tissue from the patient.

Analog-Digital Conversion↗

PubMed2004

Scanning fluorescent microscopy is an alternative for quantitative fluorescent cell analysis.

BACKGROUND: Fluorescent measurements on cells are performed today with FCM and laser scanning cytometry. The scientific community dealing with quantitative cell analysis would benefit from the development of a new digital multichannel and virtual microscopy based scanning fluorescent microscopy technology and from its evaluation on routine standardized fluorescent beads and clinical specimens. METHODS: We applied a commercial motorized fluorescent microscope system. The scanning was done at 20 x (0.5 NA) magnification, on three channels (Rhodamine, FITC, Hoechst). The SFM (scanning fluorescent microscopy) software included the following features: scanning area, exposure time, and channel definition, autofocused scanning, densitometric and morphometric cellular feature determination, gating on scatterplots and frequency histograms, and preparation of galleries of the gated cells. For the calibration and standardization Immuno-Brite beads were used. RESULTS: With application of shading compensation, the CV of fluorescence of the beads decreased from 24.3% to 3.9%. Standard JPEG image compression until 1:150 resulted in no significant change. The change of focus influenced the CV significantly only after +/-5 microm error. CONCLUSIONS: SFM is a valuable method for the evaluation of fluorescently labeled cells.

Fluorescent Dyes↗

PubMed2004

Scanning fluorescent microscopy analysis is applicable for absolute and relative cell frequency determinations.

BACKGROUND: Flow cytometry (FCM) and laser scanning cytometry (LSC) are the routine techniques for fluorescent cell analysis. Recently, we developed a scanning fluorescent microscopy (SFM) technique. This study compares SFM to LSC (two slide-based cytometry, SBC, techniques) and FCM, in experimental and clinical settings. METHODS: For the relative cell-frequency determinations, HT29 colorectal cancer cells and Ficoll separated blood mononuclear cells (FSBMCs) were serially diluted (from 1:1 to 1:1,000) and measured by each of the three techniques. For the absolute cell number determinations (only for SBC) FSBMCs were smeared on slides, then HT29 cells were placed on the slide with a micromanipulator (5-50 cells). Tumor cells circulating in the peripheral blood were isolated by magnetic separation from clinical blood samples of colorectal cancer patients. All samples were double-stained by CD45 ECD and CAM5.2 FITC antibodies. For slides, TOTO-3 and Hoechst 33258 DNA dyes were applied as nuclear counter staining. RESULTS: In the relative cell frequency determinations, the correlations between the calculated value and measured values by SFM, LSC, and FCM were r(2) = 0.79, 0.62, and 0.84, respectively (for all P < 0.01). In the absolute cell frequency determinations, SFM and LSC correlated to a high degree (r(2) = 0.97; P < 0.01). CONCLUSIONS: SFM proved to be a reliable alternative method, providing results comparable to LSC and FCM. SBC proved to be more suitable for rare-cell detection than FCM. SFM with digital slides may prove an acceptable adaptation of conventional fluorescent microscopes in order to perform rare-cell detection.

Antiporters↗

PubMed2003

[Possibilities of investigation and clinical application of adult human stem cells].

Multipotent adult tissue stem cells have high plasticity and transdifferentiation ability. The stem cell therapy can be the solution of curing many severe diseases such as osteogenesis imperfecta, hepatic failure, heart muscle damage after myocardial infarction, I-type diabetes, variety of central nervous system disorders such as brain injury, stroke, Parkinson's disease and other neurodegenerative disorders. Isolation of certain types of stem cells is solved nowadays, but low frequency of these cells and lack of special identification markers make their isolation and search more difficult. The more and more developed in vitro cell culture technologies, the widespread macromolecule amplification and examination techniques of molecular biology and the gene technology tools for genetic modification of stem (and other) cells contribute to research and therapeutic applications of stem cells. Transfer of new genetic material to stem cells and expression of the gene product in daughter cells--because missing or damaged genes can be replaced--is an exiting approach of the treatment of congenital (enzyme deficiencies) and acquired human diseases (cancers).

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↗