Search PubMed⌕ Search

Biomedical subjects

S Schreiber

Publications and source records attributed to S Schreiber.

At least 37 records · Page 2Linked to original sources
PubMed2005

Haplotype analysis of the CD11 gene cluster in patients with chronic Helicobacter pylori infection and gastric ulcer disease.

Helicobacter pylori infection leads to a broad spectrum of disease manifestations such as gastritis, ulcer disease, and even gastric carcinoma. The genetically determined immune response and subsequent inflammation influence the degree of mucosal damage. Adhesion molecules of the CD11 cluster play an important role in adherence of neutrophils to endothelial cells in inflammation. We conducted a haplotype-based analysis of the CD11 cluster in a sample of 315 patients with H. pylori infection and investigated associations with gastric erosions and ulcer disease. Twelve single nucleotide polymorphisms (SNPs) covering the genes CD11a, CD11b, and CD11c were genotyped by Taqman technology. Linkage disequilibrium (LD) was assessed within the CD11 cluster and haplotype case-control analysis was conducted. Sliding window haplotype analysis identified a haplotype consisting of the markers CD11c exon 15 and intron 31 associated with gastric ulcer disease. Patients carrying the haplotype GA bear a 2.4-fold increased risk. No significant associations of single markers with disease outcome were found. High-density LD mapping and mutation detection of CD11c in larger samples will be necessary to confirm our findings and identify the causative variant. Thus, we conclude that genetic variants in the CD11 cluster may play a role in the development of gastric ulcer in chronic H. pylori infection presumably by influencing leukocyte adhesion. The biological effect of genetic variants of CD11c in gastric inflammation needs further clarification.

Adult↗
PubMed2004

[Chronic inflammatory bowel diseases competence network ].

Inflammatory bowel diseases (IBD) are intermittently appearing, often chronic diseases mostly affecting young people between 20-30 years of age influencing their quality of life and socioeconomic efficiency. The triggering factors for the development of IBD are not completely understood: besides environmental factors there is clear evidence for additional genetic factors influencing the risk of disease and the pattern of gut inflammation in Crohn's disease. Pathopysiological discoveries are leading to new therapeutic opportunities which are conducted in large clinical studies with main participation of the competence network IBD. The disseminated structure of the network comprising universitary and nonuniversitary hospitals and labs, the self-help-organization DCCV and its vertical cooperation with general practitioners nationwide gives opportunity to describe the diseases from the point of view of the scientist and the physician simultaneously. Therefore the competence network IBD yields the basis for the standardized integration of patient information, for the development of guidelines and the establishment of a quality management system thus leading to an improvement of scientific and clinical research.

Biomedical Research↗
PubMed2004

Definition of polymorphisms and haplotypes in the interleukin-12B gene: association with IL-12 production but not with Crohn's disease.

Interleukin-12 (IL-12) is a key cytokine for the induction of Th1 immune responses. Recently, functional polymorphisms in IL-12p40 (IL12B) were found to be associated with susceptibility to several autoimmune diseases. Similarly, variation in IL12B might be involved in susceptibility to Crohn's disease (CD), a chronic inflammatory bowel disorder associated with high IL-12 expression. We searched for additional polymorphism in IL12B and genotyped a large cohort of CD patients. Differential in vitro secretors of IL-12 were tested for polymorphism. Polymorphisms were analyzed using the intrafamilial transmission disequilibrium test (TDT) and by case-control analysis. A novel polymorphism was strongly associated with differential expression of IL-12. However, no association with susceptibility to CD was seen for this and other polymorphisms. The high level of conservation is consistent with the key regulatory role of IL-12. The lack of association with IL12B makes it unlikely that this gene is directly involved in the susceptibility to CD.

Base Sequence↗
PubMed2004

Endoscopic injection of mitomycin adsorbed on carbon particles for advanced esophageal cancer: a pilot study.

BACKGROUND AND STUDY AIMS: Patients with advanced, unresectable esophageal carcinoma have an extremely poor prognosis, with dysphagia being the major problem. The aim of this prospective pilot study was to evaluate the efficacy of local injections of mitomycin adsorbed onto activated carbon particles (MMC-CH) in advanced unresectable esophageal squamous-cell carcinoma. The primary outcome parameter was survival time; secondary parameters were dysphagia and quality of life. PATIENTS AND METHODS: Ten consecutive patients with stage IV esophageal carcinoma (age: median 58, range 32 - 78), median tumor length 11 cm (range 5 - 15) received four weekly injections of 15 mg (10 ml) MMC-CH into the endoscopically visualized tumor, via a 5-mm sclerotherapy needle. The tumor stage, symptom score, and quality of life (measured using the Karnofsky index) were assessed before and after therapy and every 2 months thereafter. RESULTS: The median survival time after MMC-CH therapy was 16 weeks (95 % CI, 11.7 to 20.4). Dysphagia was reduced ( P < 0.001) in parallel with the reduction in the tumor mass ( r = 0.82, P = 0.01). The Karnofsky index ( P < 0.01) also improved after MMC-CH treatment. MMC-CH was well tolerated, and no side effects were observed. CONCLUSIONS: Endoluminal MMC-CH therapy appears to be an effective, inexpensive, and well-tolerated treatment for unresectable advanced squamous-cell esophageal carcinoma.

Adsorption↗
PubMed2004

Review article: exploration of the genetic aetiology of inflammatory bowel disease--implications for diagnosis and therapy.

Genomic technologies offer new approaches to the investigation of the aetiology and pathophysiology of inflammatory bowel disease. An important field relevant to inflammatory bowel disease therapy is the pharmacogenetic investigation of gene variations that may predict responses to certain medications in order to target these therapeutic interventions more precisely. To date, only about 12,000 of the estimated 30,000-50,000 human genes have been characterized. Therefore, the use of techniques for a global analysis of gene expression may allow the identification of new pathways or molecules in the therapeutic mechanisms of drugs. Recently, NOD2 has been identified as the first disease gene in inflammatory bowel disease. DLGS and OCTN-1 have been named as further disease genes. Although the detection of disease-associated variants has greatly advanced our understanding of the primary events that lead to the development of inflammatory bowel disease in a subgroup of patients with Crohn's disease, the implications of the findings for diagnostic and therapeutic algorithms are less clear. However, it appears that there is a clear association between certain subphenotypes of Crohn's disease and the disease-associated variants in the NOD2 gene. It can be anticipated that genomic findings will profoundly influence the future therapy of inflammatory bowel disease.

Gastrointestinal Agents↗
PubMed2004

Genetic variants in the CCR gene cluster and spontaneous viral elimination in hepatitis C-infected patients.

Hepatitis C virus (HCV) infection results in chronic hepatitis in more than 80% of infected patients while 10-20% of patients recover spontaneously. Host genetic factors may influence the ability to clear the virus after infection. Six single nucleotide polymorphisms and a 32 bp deletion in the genes coding for CCR3, CCR2 and CCR5 (which are all located in a cluster on chromosome 3) were investigated in 465 consecutively recruited patients infected with HCV and 370 matched controls. Genetic variants were tested for association with spontaneous viral elimination and, in the chronically infected patients, stage of fibrosis and response to antiviral therapy. The G190A polymorphism (variant allele Ile64) in the first transmembrane domain of CCR2 was under-represented in the 29 patients who had cleared the hepatitis C virus spontaneously (P = 0.018). None of the other variants in the CCR gene cluster showed association with the natural course of the infection, stage of fibrosis or response to therapy.

Adolescent↗
PubMed2004

Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease.

BACKGROUND AND AIMS: The intestinal bacterial microflora plays an important role in the aetiology of inflammatory bowel disease (IBD). As most of the colonic bacteria cannot be identified by culture techniques, genomic technology can be used for analysis of the composition of the microflora. PATIENTS AND METHODS: The mucosa associated colonic microflora of 57 patients with active inflammatory bowel disease and 46 controls was investigated using 16S rDNA based single strand conformation polymorphism (SSCP) fingerprint, cloning experiments, and real time polymerase chain reaction (PCR). RESULTS: Full length sequencing of 1019 clones from 16S rDNA libraries (n = 3) revealed an overall bacterial diversity of 83 non-redundant sequences-among them, only 49 known bacterial species. Molecular epidemiology of the composition of the colonic microflora was investigated by SSCP. Diversity of the microflora in Crohn's disease was reduced to 50% compared with controls (21.7 v 50.4; p<0.0001) and to 30% in ulcerative colitis (17.2 v 50.4; p<0.0001). The reduction in diversity in inflammatory bowel disease was due to loss of normal anaerobic bacteria such as Bacteroides species, Eubacterium species, and Lactobacillus species, as revealed by direct sequencing of variable bands and confirmed by real time PCR. Bacterial diversity in the Crohn's group showed no association with CARD15/NOD2 status. CONCLUSIONS: Mucosal inflammation in inflammatory bowel disease is associated with loss of normal anaerobic bacteria. This effect is independent of NOD2/CARD15 status of patients.

Adolescent↗
PubMed2004

Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis.

BACKGROUND: Ten to 15% of patients with pouchitis experience refractory or recurrent disease. The aim of this study was to evaluate the effectiveness of a single daily high dose probiotic preparation (VSL#3) in maintaining antibiotic induced remission, and quality of life (QOL), for one year in such patients. METHODS: Patients with pouchitis at least twice in the previous year or requiring continuous antibiotics, associated with a pouchitis disease activity index (PDAI) > or =7 (0 = perfect; 18 = worst), in whom remission was induced by four weeks of combined metronidazole and ciprofloxacin, were randomised to receive VSL#3 6 g or placebo once daily for one year or until relapse. Symptomatic, endoscopic, and histological evaluations were made before, and two and 12 months after randomisation or at the time of relapse. Remission was defined as a clinical PDAI < or =2 and endoscopic PDAI < or =1. Relapse was defined as an increased clinical PDAI score > or =2 and increased endoscopic PDAI score > or =3. QOL was assessed using the inflammatory bowel disease questionnaire (IBDQ). RESULTS: Thirty six patients were randomised: 20 to VSL#3 and 16 to placebo. Remission was maintained at one year in 17 patients (85%) on VSL#3 and in one patient (6%) on placebo (p<0.0001). The IBDQ score remained high in the VSL#3 group (p = 0.3) but deteriorated in the placebo group (p = 0.0005). CONCLUSION: The once daily high dose probiotic VSL#3 is effective in maintaining antibiotic introduced remission for at least a year in patients with recurrent or refractory pouchitis. This is associated with a high level of quality of life.

Adult↗