PubMed Health⌕ Search

Biomedical subjects

Wolfgang Fischbach

Publications and source records attributed to Wolfgang Fischbach.

14 recordsLinked to original sources
PubMed2006

Influence of polymorphisms in the NOD1/CARD4 and NOD2/CARD15 genes on the clinical outcome of Helicobacter pylori infection.

Host immune response influences the clinical outcome of Helicobacter pylori infection leading to ulcer disease, gastric carcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. A genetic risk profile for gastric cancer has been identified, but genetic susceptibility to develop MALT lymphoma is still unclear. We investigated the role of NOD1 and NOD2 as intracellular recognition molecules for pathogen-associated molecules in H. pylori infection in vitro and analysed the influence of single nucleotide polymorphisms on susceptibility to ulcer disease and MALT lymphoma. Expression of NOD1 and NOD2 significantly sensitized HEK293 cells to H. pylori-induced NF-kappaB activation in a cag pathogenicity island (cagPAI)-dependent manner. In cells carrying the Crohn-associated NOD2 variant R702W the NF-kappaB response was significantly diminished. NOD1/NOD2 expression levels were induced in the gastric epithelium in H. pylori-positive patients. No mutations were found to be associated with gastritis or gastric ulcer development. However, the R702W mutation in the NOD2/CARD15 gene was significantly associated with gastric lymphoma. Carrier of the rare allele T had a more than doubled risk to develop lymphoma than controls [odds ratio (OR): 2.4, 95% confidence interval (CI): 1.2-4.6; P < 0.044]. H. pylori-induced upregulation of NOD1 and NOD2 in vivo may play a critical role in the recognition of this common pathogen. A missense mutation in the leucine-rich region of CARD15 is associated with gastric lymphoma.

Adaptor Proteins, Signal Transducing↗
PubMed2005

[Acute liver failure and hemolysis in a 16-year-old woman. First manifestation of Wilson's disease].

HISTORY AND CLINICAL FINDINGS: A 16-year-old previously healthy female patient was admitted with progressive weakness and jaundice. There was no history of journeys to far-away countries. The patient was on oral contraceptives but no other medication, there were no signs of drug abuse. Apart from scleral and skin jaundice all physical findings were normal. INVESTIGATIONS AND DIAGNOSIS: Diagnostic ultrasound showed an enlarged and hyperdense liver. Laboratory tests revealed a markedly increased serum bilirubin, while aminotransferases were only slightly elevated and alkaline phosphatase was unexpectedly low. Prothrombin and antithrombin III levels were low. There was a Coombs-negative hemolytic anemia. Ceruloplasmin was lower than normal. Based on these findings, acute Wilson's disease was suspected. TREATMENT AND COURSE: The patient was immediately transferred to a hepatologic center with transplantation facilities. There, urinary copper excretion and copper concentration in the liver tissue were found to be elevated. Liver histology showed fibrosis but no cirrhosis. Under conservative therapy with trientine liver function recovered, and the patient is well 3 years after the onset of symptoms. CONCLUSION: Acute liver insufficiency should always suggest the possibility of Wilson's disease, particularly when hemolysis is also present.

Acute Disease↗
PubMed2005

Germline variations of the topoisomerase IIalpha gene as risk factors for primary gastric B-cell lymphoma.

We investigated if germline variations of the Topoisomerase II alpha gene could predispose patients with chronic Helicobacter pylori infection to develop gastric lymphoma and conducted a mutation detection of the entire promoter region. Single marker and haplotype analysis did not reveal any associations with development of gastric lymphoma in general, histological grade or stage of disease (P>0.05). No genetic variations in the promotor region were found in 92 chromosomes of lymphoma patients and controls and linkage disequilibrium indicated a highly conserved genomic region. The results of our work exclude genetic variations as predisposing factors of primary gastric B-cell lymphoma development.

Adult↗
PubMed2005

Association study of a functional Toll-like receptor 4 polymorphism with susceptibility to gastric mucosa-associated lymphoid tissue lymphoma.

Toll-like receptor 4, as part of innate immune response, is the main receptor for lipopolysaccharide on marginal zone B cells. The rare allele of TLR4 Asp299Gly attenuates receptor signaling and diminishes the inflammatory response. We genotyped 87 patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, 594 Helicobacter pylori positive controls and 358 healthy blood donors to investigate an association of TLR4 Asp299Gly in the development of gastric MALT lymphoma. Heterozygote genotype was significantly less frequent in patients with gastric MALT lymphoma compared to H. pylori-infected controls (4.6% vs. 11.6%, Fischer's exact P=0.019, odds ratio=0.37, 95% confidence interval 0.13-1.03). Because 10% of caucasians are carriers of the rare allele G TLR4 Asp299Gly appears to be only one factor in the genetic susceptibility to gastric lymphoma. Further studies in larger samples are needed to confirm our findings and fully elucidate the role of TLR4 and its genetic variants in the pathophysiology of H. pylori infection and gastric lymphoma.

Adolescent↗
PubMed2005

Helicobacter pylori and Gastric Malignancy.

Last year there were a few important clinical data on long-term prognosis of mucosa-associated lymphoid tissue (MALT) lymphoma after eradication of Helicobacter pylori. Similarly, there were clinical data to support the role of eradication of H. pylori in the primary prevention of gastric cancer. We understand more about the host susceptibility as well as the pathogenetic mechanisms of the bacteria in the gastric mucosa. This article summarizes the important breakthroughs in H. pylori and gastric malignancies last year.

Helicobacter Infections↗
PubMed2005

A functional promotor polymorphism of TNF-alpha is associated with primary gastric B-Cell lymphoma.

BACKGROUND AND AIMS: The host genetic background to develop primary gastric B-cell lymphoma in patients with chronic Helicobacter pylori infection is unknown. Tumor necrosis factor (TNF)-alpha plays a key role in H. pylori-associated inflammation and appears to be involved in the evolution of lymphoproliferative disorders. We investigated four functional promotor polymorphisms in the TNF-alpha gene for association with the development of primary gastric B-cell lymphoma. PATIENTS AND METHODS: A total of 144 lymphoma patients, 595 H. pylori-infected controls and 534 healthy blood donors were genotyped for TNF-alpha-238, -308, -857, and -1031 by Taqman technology and case-control analysis was conducted. RESULTS: There was no significant difference in allele and genotype frequencies in H. pylori-infected patients and healthy controls. TNF-857 T allele was found in 15.1% of patients with low-grade lymphoma and 9.1% of H. pylori-infected patients (Pearson's=5.7, p=0.017, OR=1.8, Wald 95% CI: 1.1< O.R.< 2.8). Carrier of the rare allele T had a 1.8-fold increased risk to develop low-grade lymphoma (Pearson's=5.4, p=0.021). Patients with high-grade lymphoma were significantly more frequent carriers of the TNF-857 T allele than healthy blood donors (30.9%vs 18.9%, Pearson's=4.5, p=0.033). Carriage of the T allele conferred a 1.9-fold increased risk (Wald 95% CI: 1.0<O.R.< 3.6). There were no associations found between any of the SNPs and disease progression. CONCLUSION: In conclusion, our data provide further evidence for host genetic factors in the susceptibility of Caucasians to gastric B-cell lymphoma. Further studies are needed to elucidate the mechanistic role of TNF-alpha in tumorigenesis.

Adult↗
PubMed2003

Decreased frequency of HLA-B35 in patients with gastric MALT lymphoma.

Persistent infection with Helicobacter pylori has been shown to be strongly associated with the development of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, the prevalence of H. pylori infection exceeds the incidence of MALT lymphoma by far. This discrepancy might at least partially be explained on a genomic basis of the host. To evaluate the association between HLA type and MALT lymphoma, we investigated 46 patients with MALT lymphoma recruited in a prospective multicenter study from October 1998 to March 2001. Over 13,000 voluntary stem cell donors from over 40 German blood banks represented the control group. Exploratory statistical analysis using Fisher's exact test showed significantly decreased frequency of HLA-B35 in the MALT lymphoma group compared to the control group. Our data suggest a negative association between HLA-B35 and MALT lymphoma; however, larger studies are necessary to confirm a protective role of this HLA antigen.

Adult↗
PubMed2003

Helicobacter pylori and carcinogenesis of gastric B-cell lymphomas.

Primary non-Hodgkin's lymphomas of the stomach are associated with Helicobacter pylori infection. We analyzed gastric lymphoma onset data with respect to prior H. pylori infections based on the multistage theory of carcinogenesis. This theory provides a link between epidemiological data and biological processes. The study involved 133 patients, aged 29-75 years, diagnosed with marginal zone B-cell lymphoma (MZBL) and diffuse large cell B-cell lymphoma (DLBL). A 2-parametric Weibull model was applied to MZBL and DLBL onset data. Median age of diagnosis of MZBL (DLBL) was 59 years (55 years) in males and 65.5 years (64 years) in females. Infection with H. pylori was found in 81.3% (59.5%) of the patients diagnosed with MZBL (DLBL). Lymphoma latency data were fitted to Weibull distributions with a shape parameter of 5.7 for MZBL cases and 4.2 for DLBL. The shape parameter that indicates the number of steps in carcinogenesis was approximately independent of the status of infection with H. pylori in DLBL in contrast to MZBL. It was shown that gastric lymphoma onset data can be described by Weibull distribution functions. The findings support the hypothesis that MZBL and DLBL have different lines of development. There is indication of stronger antigen dependency in the carcinogenesis of MZBL in comparison to DLBL.

Adult↗
PubMed2002

Minimal residual low-grade gastric MALT-type lymphoma after eradication of Helicobacter pylori.

Helicobacter pylori eradication is the initial treatment of choice in localised low-grade gastric MALT (mucosa-associated lymphoid-tissue)-type lymphoma. We describe the natural course of seven patients who refused further oncological treatment for persistent lymphoma after successful eradication of H pylori. Despite persistent clonality, neither lymphoma progression nor high-grade transformation arose during a mean observation period of 34 (range 22-44) months. In view of the favourable course of these patients, a watch-and-wait strategy could be a valid approach to management of this disease.

Adult↗
PubMed2002

Diagnostic accuracy of EUS in the local staging of primary gastric lymphoma: results of a prospective, multicenter study comparing EUS with histopathologic stage.

BACKGROUND: Grade of malignancy and stage of disease are the decisive prognostic factors and therapeutic determinants in primary gastric lymphoma. It is supposed that EUS allows determination of depth of tumor infiltration and perigastric lymph node involvement, thus defining stages I1, I2, and II1. This multicenter study evaluated the accuracy of EUS in the staging of gastric lymphoma. METHODS: Data from preoperative EUS procedures performed at 34 centers were compared with the histopathologic stage of resection specimens in 80 patients with newly diagnosed primary gastric lymphoma. Ten patients with stage II2 were excluded from analysis because EUS is inappropriate for the evaluation of nonregional lymph node involvement. RESULTS: EUS correctly classified the lymphoma in 37 of 70 patients (53%). Sensitivity of EUS was as follows: stage I1, 67% (95% CI [38%, 88%]; p = 0.01); stage I2, 83% (95% CI [52%, 98%]; p = 0.01); and stage II1, 71% (95% CI [49%, 87%]; p = 0.02). CONCLUSION: The accuracy of EUS in the local staging of gastric lymphoma has to be improved if nonsurgical treatment strategies based on the grade of malignancy and stage of the disease are to be used. Because most of the participating centers performed EUS in relatively few patients, no conclusion could be drawn with respect to accuracy in relation to EUS experience available at each center or technical considerations with respect to the types of instruments used.

Adult↗