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L Lakatos

Publications and source records attributed to L Lakatos.

At least 19 recordsLinked to original sources

Is the incidence and prevalence of inflammatory bowel diseases increasing in Eastern Europe?

Limited data are available on the frequency of inflammatory bowel diseases in East European countries. A recent study from Hungary reported an increasing incidence rate for ulcerative colitis (from 1.6 to 11.0) and for Crohn's disease (from 0.4 to 4.7) from 1977 to 2001. A similar trend was seen in Croatia. In contrast, other countries (for example, Czech Republic, Poland, Romania, Slovakia, and Baltic countries) reported low incidence and prevalence rates. This review will discuss the available data on the epidemiology of inflammatory bowel diseases in Eastern Europe, as well as consider the possible factors responsible for the differences seen between countries and epidemiological trends.

Adolescent↗

Management of inflammatory bowel diseases in Eastern Europe.

Limited data are available on the management of inflammatory bowel diseases (IBD) in East European countries. The diagnostic tools and most treatment options are also available in Eastern Europe. The diagnostic procedures commonly used became more sophisticated in the past few years, with a greater use of computed tomography/magnetic resonance imaging and serology testing; however, double contrast barium enema, enteroclysis, and endoscopy remained standard. The medical therapy and surgical strategies are also somewhat different from those applied in Western countries. In ulcerative colitis, besides mesalazine, the use of sulphasalazine is still frequent, while azathioprine is only used in a minority of patients. The use of conventional corticosteroids is common and the rate of non-colorectal cancer associated colectomies is low. In contrast, 5-aminosalicylates are still used for maintenance in Crohn's disease and azathioprine is generally less frequently given compared with Western Europe. Biological agents have also become available about five years ago, yet their use is restricted mainly to specialised centres.

Europe, Eastern↗

[Molecular genetics and gene therapy in diseases of the esophagus, stomach, colon and pancreas].

There has been a major improvement in our knowledge in the area of molecular genetics in the past 20 years. It has become evident that genetic factors are important in the initiation, progression and prognosis of most diseases. Many studies addressed the issue of tumorigenesis, which provided insight into the molecular basis of the sequencional development of cancer, driven by the accumulation of genomic defects. Most of the neoplasms are genetically heterogeneous, independent pathways and simultaneous tumorigenesis may exist within the same organ. As some mutations exist in benignant and also in malignant conditions, it is an important challenge to define the molecular characteristics of significant versus non-significant lesions. A new form of therapeutic intervention is gene therapy. During the next decade it will likely play an increasing role in clinical practice and particularly in the treatment of cancer.

Animals↗

[Epstein-Barr virus genome positive lymphoepithelioma-like carcinoma of the stomach].

EBV is associated with a high number of tumours and non-tumourous conditions. The rare lymphoepithelioma like carcinoma of the stomach,--just as similar tumours of foregut origin (thymus, lung, salivary gland)--are frequently EBV genom positive with the expression of only a few genes (EBV nuclear antigen 1, EBV encoded ribonucleoproteins/EBER/, latency I). On the basis of the clinicopathological analysis of two cases and literature data the authors point out the male predominance and the relatively favourable prognosis of the patients, furthermore the frequent cardial-subcardial localization of these tumours. Since the frequent non-lymphoepithelioma like stomach tumours,--adenocarcinomas,--show EBV genom positivity in about 1% of the cases, it is concluded that the characteristic lymphoepithelioma like histological pattern is not a sine qua non condition of EBV genom positivity. It may also be assumed, that the CD8 and TIA 1 cytotoxic lymphocytes are not virus but tumour cell specific, however not efficient, perhaps not activated. The low level of apoptotic tumour cells supports this assumption. In one of the cases a double tumour, a genom positive lymphoepithelioma like carcinoma and a genom negative adenocarcinoma, adjacent to each other was seen which speaks in favour of common carcinogenetic factors and shows that microscopic neighbourhood is not a necessary condition in viral association. The origin of the possible oncogenic effect of EBV in the absence of the transforming gene products latent membrane protein 1 and EBNA 2 in genom positive stomach carcinomas is uncertain. The significance of the presence in both cases of CD 5+ tumour cells is not clear, the study of further cases is indicated.

Adult↗

TBP is not universally required for zygotic RNA polymerase II transcription in zebrafish.

General transcription factors TFIIA, B, D, E, F, H, and RNA polymerase II (Pol II) are required for accurate initiation of Pol II transcription. The TATA binding protein (TBP), a subunit of TFIID, is responsible for recognition of the TATA box, a core element shared by a category of class II promoters [1]. Recently, novel TBP-like factors (TLFs) have been described in metazoan organisms [2]. In spite of the numerous in vitro studies describing the general role of TBP in RNA polymerase II (Pol lI) transcription initiation, the precise function of TBP and the newly described TLF is poorly understood in vivo. We inhibited TBP and TLF function in zebrafish embryos to study the role of these factors during zygotic transcription. A dominant-negative variant of TLF mRNA and a TBP morpholino antisense oligo was used to block either TLF or TBP function. Both TBP- or TLF-blocked embryos developed normally until the midblastula stage; however, they then failed to gastrulate. Several zygotic regulatory genes were downregulated by a block in either TBP or TLF function, while others were differentially affected. These results suggest that TBP is not universally required for Pol II transcription in vertebrates and that there is a differential requirement for TBP and TLF during early embryogenesis.

Animals↗

Tissue-specific signal(s) activate the promoter of a metallocarboxypeptidase inhibitor gene family in potato tuber and berry.

The molecular basis of the differential expression of the GM7-type metallocarboxypeptidase inhibitor (MCPI) genes in tuberizing (StMCPI) and non-tuberizing Solanum species (SbMCPI) was investigated. It was shown that the StMCPI is encoded by a gene family in Solanum tuberosum (potato), but SbMCPI might be a single-copy gene in the non-tuberizing species Solanum brevidens. The StMCPI promoter shows evolutionary relatedness to the S. brevidens-derived SbMCPI and to the fruit-specific tomato promoter 2A11. Both StMCPI and SbMCPI promoter regions were able to confer tuber- and berry-specific expression for the beta-glucuronidase reporter gene in potato suggesting that the difference in MCPI gene expression is in trans regulatory factors between the tuberizing and the non-tuberizing Solanum species. The MCPI promoters did not respond to metabolic, environmental or hormonal signals in leaves. Thus, the MCPI genes are regulated in a different way than the other known tuber-specific genes and potentially are suitable for biotechnological application in potato to provide specific transgene expression in tuber and berry.

Amino Acid Sequence↗

D-Penicillamine for preventing retinopathy of prematurity in preterm infants.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To answer the question: Among very low birth weight infants, what is the effect of prophylactic administration of d-penicillamine on the incidence of acute ROP or severe ROP, and side effects including death? SEARCH STRATEGY: Searches were made of multiple electronic databases, previous reviews including cross references, abstracts, conference/symposia proceedings, and expert informants. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials that administered d-penicillamine to infants less than 2000g birth weight within the day following birth were considered relevant to this review. Additional case series were examined for potential side effects. DATA COLLECTION AND ANALYSIS: Data on clinical outcomes were excerpted by 3 reviewers independently, and consensus reached. Data analysis was conducted according to the standards of the Neonatal Cochrane Review Group. MAIN RESULTS: Two randomized trials on the effects on ROP were identified. When combined, they showed a significantly lower incidence of acute ROP in the treated infants, relative risk of 0.09, 95% CI [0.01,0.71]. Severe stages of ROP could not be analyzed. There was no effect on death rates, relative risk 0.99 95% CI [0.70,1.39]. No side effects were reported, and follow up at one year revealed no significant differences in spasticity or developmental delay, although there were more rehospitalizations among the controls. In other reports of using d-penicillamine in over 140 infants for hyperbilirubinemia, skin rashes were reported in 2 infants and one had vomiting that may have been related. REVIEWER'S CONCLUSIONS: D-penicillamine is unlikely to affect survival, and may reduce the incidence of acute ROP among survivors. Studies to date justify further investigation of this drug in a broader population; careful attention to possible side effects is needed.

Chelating Agents↗

TBP-like factor is required for embryonic RNA polymerase II transcription in C. elegans.

Recently, a novel family of TATA binding protein (TBP)-like factors (TLFs) have been described in metazoan organisms; however, their function has not yet been elucidated. Using Caenorhabditis elegans (Ce) as a model, we demonstrate that CeTLF is required in vivo for zygotic transcription during embryogenesis. Elimination of CeTLF expression by RNA interference caused embryonic lethality either due to the lack of expression of early patterning genes or to their ectopic expression. Moreover, the absence of CeTLF in vivo prevented the correct soma-specific phosphorylation of RNA polymerase II (Pol II). Thus, CeTLF may positively or negatively regulate Pol II transcription, depending on the developmental stage of the embryo.

Amino Acid Sequence↗

Immunology of inflammatory bowel diseases.

The pathogenesis of inflammatory diseases involves complex interactions among genetic, environmental and immunologic factors, where the immune system plays a crucial role. The initiating factor may be a commonly present environmental antigen, but the defective mucosal immune response can't downregulate the inflammatory process, the resulting in chronic inflammation and tissue damage. The abnormal amplification of the immune system seems more likely to be a secondary and not a primary factor in the disease. IBD patients exhibit abnormalities in epithelial antigen presentation, and in the cellular and humoral immune system. The role of autoimmunity is unclear in IBD. The inflammatory mediator production and balance is also altered in IBD. Crohn's disease is characterised by a Th1 cytokine profile, while ulcerative colitis is characterised rather by a Th2 cytokine profile. Recent advances in the understanding of the pathogenesis of IBD led to major changes in the treatment of the disease. The newer agents target the key mediators involved in the inflammatory process.

Animals↗

[Helicobacter pylori infection and cancer of the stomach].

Although the incidence of gastric cancer has declined in the past few decades in developed countries, it has remained one of the most frequent malignomas with high mortality. Epidemiological, clinical and basic research studies confirm the role of Helicobacter pylori in the pathogenesis of the tumors of the distal stomach and low-grade MALT lymphomas. On the contrary more and more data suggest a possible protective role of the infection in the gastro-oesophageal reflux disease, tumors of the cardia and adenocarcinoma of the distal oesophagus. The intensive research being done in the past few years prove our previous concept, that the pathogenesis of gastric cancer is a multifactorial process, which is affected by Helicobacter pylori ("a major environmental factor") together with distinct environmental, social and genetic factors. The interaction of these factors and the importance of them urge further investigations, which may differ in different populations.

Helicobacter Infections↗

[Pathophysiology of Helicobacter pylori infection].

The (re)discovery of the gastric pathogen Helicobacter pylori almost one and a half decade ago completely changed our conception on gastroduodenal ulcer disease and gastric cancer. The most important issue is that Helicobacter pylori induces a mild, antrum dominant chronic pangastritis without increased risk of severe diseases in most of the cases. A smaller part of the infected develops antrum dominant gastritis with increased risk of duodenal ulcer. In a few cases the corpus is also affected, pangastritis occurs with increased risk to develop gastric ulcer and gastric cancer. Until now it is not quite obvious why some of the infected patients get ill while others not, and why different diseases develop in different patients. 1. From the bacterial point of view it is ascertained that toxin-producing strains (VacA, CagA positive) are more likely to induce ulcer formation and gastric carcinoma. 2. Genetic phenotype of the infected patients (blood-group and HLA antigens) may also be of importance. 3. Environmental factors may affect (promote or inhibit) disease development. All of these factors determine the complex immunological, functional and morphological changes characteristic for the developing disease.

Gastric Acid↗

Potato StubSNF1 interacts with StubGAL83: a plant protein kinase complex with yeast and mammalian counterparts.

StubSNF1 is a potato cDNA that encodes a protein kinase similar to the yeast SNF1 gene involved in transcriptional regulation of glucose-repressible genes. The yeast SNF1 functions in a complex with GAL83/SIP1/SIP2 and SNF4 proteins. We have used StubSNF1 as bait in a yeast two-hybrid system to screen for potato cDNAs encoding proteins that bind to StubSNF1. Three overlapping cDNAs, two different in size, were isolated. DNA sequence analysis revealed that they were orthologues of the yeast GAL83/SIP1/SIP2 genes and their mammalian counterparts, AMPK beta-subunits. The direct interaction between the potato proteins StubGAL83 and StubSNF1 was shown by an in vitro binding assay. Southern and Northern hybridisations revealed that StubGAL83 exists in a low copy number in the potato genome and is highly (but organ-specifically) expressed in potato. In contrast, StubSNF1 possesses low transcript levels in each organ, except in flowers where high amounts of StubSNF1 mRNA could be detected. We demonstrate here that StubGAL83 can also interact with yeast SNF4 in a yeast two-hybrid system suggesting that plant SNF1 kinases may function in complexes similar to those detected in yeast and mammals.

Amino Acid Sequence↗