MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18.

Signaling through the adaptor protein myeloid differentiation factor 88 (MyD88) promotes carcinogenesis in several cancer models. In contrast, MyD88 signaling has a protective role in the development of azoxymethane (AOM)/dextran sodium sulfate (DSS) colitis-associated cancer (CAC). The inability of Myd88(-/-) mice to heal ulcers generated upon injury creates an altered inflammatory environment that induces early alterations in expression of genes encoding proinflammatory factors, as well as pathways regulating cell proliferation, apoptosis, and DNA repair, resulting in a dramatic increase in adenoma formation and progression to infiltrating adenocarcinomas with frequent clonal mutations in the beta-catenin gene.

RAGE gene polymorphisms in patients with multiple sclerosis.

The pathogenesis of multiple sclerosis (MS), a devastating neuroinflammatory disorder of the central nervous system, has been presumed to involve the possible importance of the receptor for advanced glycation end products (RAGE). The aim of this study was to investigate the relevance of the genetic polymorphisms of RAGE in MS patients. A total of 168 patients with MS were enrolled; 136 healthy blood donors served as controls.

Polymorphisms of the ApoE, HSD3B1, IL-1beta and p53 genes are associated with the development of early uremic complications in diabetic patients: results of a DNA resequencing array study.

Genetic polymorphisms of the genes involved in angiogenesis, the inflammatory cascade or apoptosis control can influence the chronic complications of diabetic patients. Parallel evaluation of multiple genetic polymorphisms became available with the development of DNA resequencing arrays. We aimed to develop a 16-gene, 18,859-nucleotide resequencing array to analyze the genetic background of uremic and gastrointestinal complications.

T-251A polymorphism of IL-8 relating to the development of histological gastritis and G-308A polymorphism of TNF-alpha relating to the development of macroscopic erosion.

Objectives: Genetic variations of the inflammatory IL-8 and TNF-alpha genes can influence the outcome of gastric alterations. Our aims were to determine the prevalence and effect of the T-251A functional polymorphism of IL-8 and the G-308A polymorphism of TNF-alpha in histological and macroscopic gastric diseases related to Helicobacter pylori infection.

Methods: Genomic DNA was extracted from biopsy samples from patients with gastritis (n=86, H.

High mobility group box 1 protein induction by Mycobacterium bovis BCG.

Unlabelled: High mobility group box 1 protein (HMGB1), a nuclear protein, is a critical cytokine that mediates the response to infection, injury, and inflammation. The aim of our study was to elaborate a reliable in vitro model to investigate whether Mycobacterium bovis BCG is able to induce HMGB1 secretion from the monocytic U-937 cells. Western blot technique was applied for the detection of HMGB1 from supernatants of cells, following induction with Mycobacterium bovis BCG.

Chronic infections and genetic factors in the development of ischemic stroke.

The aim of this study was to examine whether chronic infections and genetic factors of the host play roles in the pathophysiology of acute noncardioembolic ischemic stroke. Blood samples from 59 subjects with ischemic stroke and 52 control patients were investigated by nested PCR for the presence of C. pneumoniae DNA, HCMV DNA and enterovirus RNA, by ELISA for the levels of antibodies to C.

The risk of early and late lung sequelae after conformal radiotherapy in breast cancer patients.

Purpose: To study the risks of early and late radiogenic lung damage in breast cancer patients after conformal radiotherapy.

Methods And Materials: Radiogenic lung sequelae were assessed prospectively in 119 patients by means of clinical signs, radiologic abnormalities, and the mean density change (MDC) of the irradiated lung on CT.

Results: Significant positive associations were detected between the development of lung abnormalities 3 months or 1 year after the radiotherapy and the age of the patient, the ipsilateral mean lung dose (MLD), the radiation dose to 25% of the ipsilateral lung (D(25%)) and the volume of the ipsilateral lung receiving 20 Gy (V(20 Gy)).

Genetic polymorphisms of NOD1 and IL-8, but not polymorphisms of TLR4 genes, are associated with Helicobacter pylori-induced duodenal ulcer and gastritis.

Background: Intracellular pathogen receptor NOD1 is involved in the epithelial cell sensing Helicobacter pylori, which results in a considerable interleukin (IL)-8 production. The aim of this study was to evaluate the relationship between NOD1 and IL-8 genetic polymorphisms and the development of H. pylori-induced gastritis and duodenal ulcer (DU), as compared with TLR4 polymorphisms.

Genetic polymorphisms in patients with myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is a family of clonal disorders characterized by dyshematopoiesis and susceptibility to acute myelogenous leukemia. Tumor necrosis factor-a (TNF-alpha) and transforming growth factor-beta (TGF-beta) are cytokines that play key roles in the pathogenesis of MDS. There have been several reports on the presence of genetic polymorphisms in the DNA sequence encoding the leader sequence of the TGF-beta protein, and in the -308 promoter region of TNF-alpha.

Polymorphism of the heat-shock protein gene Hsp70-2, but not polymorphisms of the IL-10 and CD14 genes, is associated with the outcome of Crohn's disease.

Objective: In Crohn's disease (CD) a Th-1 dominant immune reaction is induced, which could be associated with genetic predisposition. Several previous studies have investigated the roles of CD14, heat-shock protein (Hsp)70 and IL-10 gene polymorphisms in the development of the disease. The results are contradictory and inter-racial differences are implicated.

Clinical importance of transforming growth factor-beta but not of tumor necrosis factor-alpha gene polymorphisms in patients with the myelodysplastic syndrome belonging to the refractory anemia subtype.

Objectives: Tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) are cytokines that play key roles in the myelodysplastic syndrome (MDS). There have been several reports on the presence of genetic polymorphisms in the DNA sequence encoding the leader sequence of the TGF-beta1 protein, located in codon 10 in exon 1 and in the -308 promoter region of TNF-alpha. The objective of this study was to investigate the association between TNF-alpha and TGF-beta1 gene polymorphisms and the susceptibility to MDS and the progression of the disease among patients with MDS belonging to the refractory anemia (RA) subtype.

Genetic polymorphism of interleukin-8 (IL-8) is associated with Helicobacter pylori-induced duodenal ulcer.

Background And Aims: Helicobacter pylori infection almost invariably causes chronic gastritis, but only a proportion of the infected subjects develop peptic ulcers. The local inflammation associated with H. pylori infection is characterized by an increased production of the proinflammatory cytokines IL-1-B, IL-6, IL-8 and TNF-alpha.

Helicobacter pylori-induced immunological responses in patients with duodenal ulcer and in patients with cardiomyopathies.

The interaction between the bacteria and the host is a key factor determining the clinical consequences of H. pylori infection. The immune system plays an important role in either promoting or preventing the disease.

Tumour necrosis factor-alpha and heat-shock protein 70-2 gene polymorphisms in a family with rheumatoid arthritis.

Objectives: The aim of this work was to investigate the prevalence of TNF-alpha-308 polymorphism among the 29 members of a family with RA and the association between the MHC-linked biallelic HSP70-2 gene and the TNF-alpha polymorphism. Five of the members with RA were diagnosed by using the revised 1987 ACR criteria, and 1 member suffered from SLE.

Methods: The variations in the TNF-alpha and the HSP70-2 genotypes were analyzed by PCR-RFLP, using NcoI and PstI restriction enzymes.

Investigation of the prognostic value of TNF-alpha gene polymorphism among patients treated with infliximab, and the effects of infliximab therapy on TNF-alpha production and apoptosis.

Objectives: Infliximab, a chimeric anti-tumor necrosis factor (TNF) antibody, is highly effective for the treatment of Crohn's disease (CD) and rheumatoid arthritis (RA). Our experiments focused on RA and CD patients receiving infliximab. Since cytokine production is largely determined by genetic factors, the promoter polymorphisms of TNF-alpha were examined among these patients.

Effects of Helicobacter pylori infection on gastric inflammation and local cytokine production in histamine-deficient (histidine decarboxylase knock-out) mice.

Unlabelled: Helicobacter pylori infection in humans causes gastritis. The infection elicits a complex immune response in which the activation of mast cells and histamine release is of particular importance. Histamine further promotes the immune response and stimulates gastric acid secretion.

Local and peripheral cytokine response and CagA status of Helicobacter pylori-positive patients with duodenal ulcer.

The mucosal production of TNF-alpha, IL-6, IL-8, IL-10 and nitrotyrosine was investigated in H. pylori-positive patients with duodenal ulcer (DU). The concentrations of these cytokines in gastric antrum mucosal specimens from patients infected with H.