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Biomedical subjects

A Neubauer

Publications and source records attributed to A Neubauer.

At least 55 records · Page 3Linked to original sources
PubMed2001

Long-term follow-up of gastric MALT lymphoma after H. pylori eradication.

For almost 10 years, we have been familiar with the concept of mucosa-associated lymphoid tissue (MALT)-type lymphoma of the stomach caused by chronic Helicobacter pylori infection. Many epidemiologic, biologic, and molecular genetic studies have implicated H. pylori for its role in lymphoma genesis. Since the first reports on complete remission of gastric MALT lymphomas after cure of bacterial infection, many clinical studies have investigated the effect of eradicating H. pylori on the course of MALT lymphoma, and indeed were able to confirm remission of the lymphoma. To date, more than 650 patients worldwide have been treated for gastric MALT lymphoma with antibiotics, and we have gained many new insights concerning the biologic behavior of this disease, especially from the deepened knowledge of cytogenetics. Furthermore, factors relevant for the prediction of treatment outcome have been identified, which has helped to stratify patients into risk groups.

Follow-Up Studies↗
PubMed2001

Sequential monitoring of chimerism and detection of minimal residual disease after allogeneic blood stem cell transplantation (BSCT) using multiplex PCR amplification of short tandem repeat-markers.

Sequential analysis of chimerism after allogeneic blood stem cell transplantation (BSCT) has been shown to be predictive for graft failure and relapse. We have explored the impact of a novel approach for the quantitative determination of chimerism using a commercial PCR assay with multiplex amplification of nine STR-loci and fluorescence detection. The feasibility was studied in 121 patients transplanted from related or unrelated donors. Follow-up investigation was performed in 88 patients. Twenty-eight of these patients had received a transplantation after dose-reduced conditioning therapy. Results were compared to data obtained by FISH analysis in a subgroup of patients receiving grafts from sex-mismatched donors. The analysis was possible in all patients, the median number of informative alleles was 4 (range 1-8) compared to 7 (range 1-9) in the related and unrelated situation, respectively. A good correlation was seen in 84 samples from 14 patients analyzed in parallel with STR-PCR and FISH. Decreasing values of donor chimerism were detected prior to or concomitantly with the occurrence of graft failure and relapse of disease in all patients investigated prospectively. Using FACS-sorted material, eg peripheral blood CD34+ cells, the assay permitted the detection of residual recipient cells with high sensitivity (down to one CD34+ Kasumi cell in 40,000 normal WBC). Evaluation of the inter-laboratory reproducibility revealed that in 20 samples analyzed in three different centers, the median coefficient of variation was 2.1% (range 0.7-9.6%). Taken together, the results support the use of the test as a valuable tool in the follow-up of patients undergoing allogeneic BSCT. In cases lacking PCR-detectable disease-specific gene products, this assay may represent an alternative to recently established real-time PCR methods.

Adolescent↗
PubMed2001

Mutations in ras proto-oncogenes are associated with lower mdr1 gene expression in adult acute myeloid leukaemia.

Mutations in ras genes have been found to be the most frequent genetic aberrations in adult myeloid leukaemia (AML). Some reports have shown an improved outcome of ras-mutated AML. In order to understand the biology of ras mutation in AML, we studied a cohort of patients treated in a prospective multicentre trial for ras mutational status and resistance gene expression. Blast samples from 162 adult patients with de novo or secondary AML were examined for resistance gene expression (mdr1, mrp1 and lrp) and ras mutations using reverse transcription-polymerase chain reaction and protein nucleic acid-competitive polymerase chain reaction strategies respectively. Ras mutations were confirmed using DNA sequencing. Ras mutations leading to an exchange of amino acids were found in 40 (25%) patients. Thirty AML patients had N-ras mutations and nine patients had K-ras mutations. One patient showed both N-ras and K-ras mutations. Resistance gene expression was positive for mdr1 in 30%, for mrp1 in 43% and for lrp in 62% of patients. There was a strong inverse correlation between the presence of ras mutation and mdr1 expression (P = 0.005). However, no significant difference was seen between patients with or without ras mutations and mrp1 or lrp expression. Whereas mdr1 expression was associated with a lower complete remission rate (P < 0.04), ras mutations had no significant influence on remission status. Neither ras mutation nor mdr1 expression had a significant impact on overall or disease-free survival to date. For the first time, there is evidence that activated ras genes are associated with lower mdr1 expression in AML.

ATP-Binding Cassette Transporters↗
PubMed2001

[Sonographic patterns of littoral cell angioma: case report and review of the literature].

AIM: Littoral cell angioma is a rare benign tumour of vascular proliferation unique to the spleen. Definitive sonographic patterns are yet unknown and are described in this paper. METHOD: We report about 2 patients with histologically confirmed Littoral cell angioma. The sonographic features of these and 5 additional cases in the literature are presented. RESULTS: Littoral cell angioma is characterized by splenomegaly (6 out of 7 cases) with small nodular hyperechoic focal lesions (6 out of 7 cases). A solitary hyperechoic tumour (1 out of 7 cases) is a rare event. CONCLUSION: Littoral cell angioma is a recently discovered tumour and should be included in the differential diagnosis of a hyperechoic splenic tumour.

Diagnosis, Differential↗
PubMed2001

[Functional hyposplenia after allogenic bone marrow transplantation: a case report].

Functional hyposplenia/asplenia is a severe longterm complication after allogeneic stemcell transplantation predominantly seen in patients who suffer from extensive chronic graft versus host disease (cGvHD). The risk of acquiring an overwhelming infection with encapsulated bacteria is ca. four fold increased in patients with functional hyposplenia/asplenia. Therefore follow up of patients who have received allogeneic blood stem cells (bone marrow or peripheral blood stem cells) should embrace screening for functional hyposplenia. When functional hyposplenia is diagnosed triple vaccination against streptococcus pneumonia, Haemophilus influenza type B and Meningococcus neisseria should be considered. Goldstandard in diagnosing functional hyposplenia is hepatosplenic scintigraphy. We present the case of 37 year old female in whom sonography was indicative of functional hyposplenia. The diagnosis was confirmed by scintigraphy. Sonography including color coded duplex sonography is a safe and cost saving procedure. Sensitivity, Specificity and predictive value of the following sonographic finding: a) decreasing splenic size and b) diminished or absent parenchymal blood flow are currently evaluated in a prospective study.

Adult↗
PubMed2001

Naturally occurring Clostridium perfringens nontoxic alpha-toxin variant as a potential vaccine candidate against alpha-toxin-associated diseases.

Clostridium perfringens mutant strain 121A/91 shows neither enzymatic (phospholipase C) nor hemolytic activity. Nevertheless, the cpa gene and the corresponding alpha-toxin variant are detectable. Vaccination with this genetically constructed alpha-toxin variant, rAT121/91, induces antibodies capable of significantly reducing activities induced by wild-type toxin. Thus, rAT121/91 could be a useful vaccine candidate.

Amino Acid Substitution↗
PubMed2001

Helicobacter pylori and gastric cancer:current status of the Austrain Czech German gastric cancer prevention trial (PRISMA Study).

AIM: To test the hypothesis that Helicobacter pylori eradication alone can reduce the incidence of gastric cancer in a subgroup of individuals with an increased risk for this fatal disease. METHODS: It is a prospective, randomized, double blind, placebo controlled multinational multicenter trial. Men between 55 and 65 years of age with a gastric cancer phenotype of Helicobacter pylori gastritis are randomized to receive a 7 day course of omeprazole 2 X 20mg, clarithromycin 2 X 500mg, and amoxicillin 2 X 1g for 7 days, or omeprazole 2 X 20mg plus placebo. Follow-up endoscopy is scheduled 3 months after therapy, and thereafter in one-year intervals. Predefined study endpoints are gastric cancer, precancerous lesions (dysplasia, adenoma), other cancers, and death. RESULTS: Since March 1998, 1524 target patients have been screened, 279 patients (18.3%) had a corpus dominant type of H. pylori gastritis, and 167 of those were randomized (58.8%). In the active treatment group (r = 86), H. pylori infection infection was cured in 88.9% of patients. Currently, the cumulative follow-up time is 3046 months (253.38 patient years, median follow up 16 months). So far, none of the patients developed gastric cancer or any precancerous lesion. Three (1.8%) patients reached study endpoints other than gastric cancer. CONCLUSION: Among men between 55 and 65 years of age, the gastric cancer phenotype of H. pylori gastritis appears to be more common than expected. Further follow up and continuing recruitment are necessary to fulfil the main aim of the study.

Amoxicillin↗
PubMed2001

Development of early gastric cancer 4 and 5 years after complete remission of Helicobacter pylori associated gastric low grade marginal zone B cell lymphoma of MALT type.

AIM: To report 3 of 120 patients on the German MALT lymphoma trial with H. pylori associated gastric MALT lymphoma who developed early gastric cancer 4 and 5 years, after complete lymphoma remission following cure of H. pylori infection. PATIENTS AND RESULTS: Three patients (two men, 74 and 70 years; one women, 77 years) with H. pylori-associated low-grade MALT lymphoma achieved complete lymphoma remission after being cured. Surveillance endoscopies were performed twice a year in accordance to the protocol. Four years after complete lymphoma remission in two patients, and after 5 years in the other, early gastric adenocarcinoma of the mucosa-type, type IIa and type IIc, respectively, was detected, which were completely removed by endoscopic mucosa resection. In one patient, the gastric cancer was diagnosed at the same location as the previous MALT lymphoma, in the other patients it was detected at different sites of the stomach distant from location of the previous MALT lymphoma. The patients were H. pylori negative during the whole follow-up time. CONCLUSION: These findings strengthen the importance of regular Long-term follow-up endoscopies in patients with complete remission of gastric MALT lymphoma after cure of H. pylori infection. Furthermore, gastric adenocarcinoma may develop despite eradication of H. pylori.

Adenocarcinoma↗
PubMed2001

Molecular diagnostics in low-grade gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type after Helicobacter pylori eradication therapy.

The primary gastric lymphomas are extranodal non-Hodgkin's lymphomas that likely originate from the mucosa-associated lymphoid tissue (MALT). Data suggest that chronic infection with Helicobacter pylori (H pylori) is significantly associated with the pathogenesis of low-grade gastric MALT lymphomas. This is in keeping with the observation that many patients with early low-grade MALT lymphomas have complete remissions after H pylori eradication therapy. However, the stability of these remissions remains unclear and relapses have been reported. It can be difficult to distinguish between early malignant and benign disorders of the gastric mucosa. A polymerase chain reaction (PCR) assay can detect rearrangements of the variable region of immunoglobulin heavy chains. This assay can be used to distinguish the clonality of B lymphocytes and has been investigated as a test for differential diagnosis of MALT lymphomas. Monoclonality is observed in the majority of MALT-lymphoma samples at diagnosis but has been found in gastritis samples as well. Whether the presence of monoclonal B cells is associated with the risk of lymphoma progression remains unclear. As many as 50% of patients who have complete histologic remissions of MALT lymphoma after H pylori eradication therapy have persisting monoclonal bands in follow-up PCR monitoring. Although it is unclear as to whether monoclonality indicates the presence of minimal residual disease, patients who have persistent monoclonal bands during follow-up should be considered at risk for relapse. The PCR assay for rearrangements of the variable region of the immunoglobulin heavy-chain gene appears to be of low value in the diagnosis of B-cell malignancies but could provide a useful tool in the follow-up of patients who achieve remissions after H pylori eradication.

Anti-Bacterial Agents↗
PubMed2000

Cloning of an interferon regulatory factor 2 isoform with different regulatory ability.

Interferons (IFNs) are a family of multifunctional proteins involved in immune activation, regulation of cell growth and antiviral response. They exert their functions by induction of several IFN-stimulated genes, including IFN regulatory factors (IRFs), a family of transcriptional regulators. One of these factors, IRF-2, was initially cloned as an antagonistic counterpart to IRF-1 with oncogenic potential. Here we describe a second isoform of IRF-2, termed IRF-2s, cloned from human and murine cells. This isoform lacks two amino acids located C-terminal of the DNA-binding domain, which is conserved in all IRF family members, leading to a change in the predicted secondary structure. Both isoforms have similar binding affinities to known target sequences in electrophoretic mobility shift assays. Using reporter gene constructs with the type IV promoter region of the MHC class II transactivator (CIITA), which is the essential factor for IFN-gamma-induced MHC class II expression, we show that the short isoform IRF-2s exhibits a weaker activation ability compared to IRF-2. Thus, our data present the first evidence of two IRF-2 isoforms with different regulatory ability.

Amino Acid Sequence↗
PubMed2000

Expression of interferon regulatory factor 4 in chronic myeloid leukemia: correlation with response to interferon alfa therapy.

PURPOSE: Mice experiments have established an important role for interferon regulatory factor (IRF) family members in hematopoiesis. We wanted to study the expression of interferon regulatory factor 4 (IRF4) in various hematologic disorders, especially chronic myeloid leukemia (CML), and its association with response to interferon alfa (IFN-alpha) treatment in CML. MATERIALS AND METHODS: Blood samples from various hematopoietic cell lines, different leukemia patients (70 CML, 29 acute myeloid leukemia [AML], 10 chronic myelomonocytic leukemia [CMMoL], 10 acute lymphoblastic leukemia, and 10 chronic lymphoid leukemia patients), and 33 healthy volunteers were monitored for IRF4 expression by reverse transcriptase polymerase chain reaction. Then, with a focus on CML, the IRF4 level was determined in sorted cell subpopulations from CML patients and healthy volunteers and in in vitro-stimulated CML cells. Furthermore, IRF4 expression was compared in the CML samples taken before IFN-alpha therapy and in 47 additional CML samples taken during IFN-alpha therapy. IRF4 expression was then correlated with cytogenetic response to IFN-alpha. RESULTS: IRF4 expression was significantly impaired in CML, AML, and CMMoL samples. The downregulation of IRF4 in CML samples was predominantly found in T cells. In CML patients during IFN-alpha therapy, a significant increase in IRF4 levels was detected, and this was also observed in sorted T cells from CML patients. The increase seen during IFN-alpha therapy was not due to different blood counts. In regard to the cytogenetic response with IFN-alpha, a good response was associated with high IRF4 expression. CONCLUSION: IRF4 expression is downregulated in T cells of CML patients, and its increase is associated with a good response to IFN-alpha therapy. These data suggest IRF4 expression as a useful marker to monitor, if not predict, response to IFN-alpha in CML.

Acute Disease↗
PubMed2000

Gastric MALT lymphoma and its relationship to Helicobacter pylori infection: management and pathogenesis of the disease.

Chronic Helicobacter pylori infection is strongly associated with the development of primary gastric B cell lymphoma of MALT-type. Therapeutic decisions in primary gastric MALT lymphomas, e.g., the choice for gastric surgery or stomach-conserving treatments in the form of radio-, chemo-, or eradication therapy, should be based on an accurate histopathological diagnosis, grading and clinical staging. Primary gastric low-grade MALT-NHLs in an early clinical stage associated with H. pylori infection were shown to respond with complete remission in approximately 77% of cases upon successful cure of the infection as only treatment modality. The effect of curing H. pylori infection on the course of a high-grade gastric MALT lymphoma is largely uncertain but preliminary results indicate a possible benefit for patients with high-grade MALT lymphoma upon eradication therapy. Concerning the pathogenetic mechanisms of lymphomagenesis, there are many questions to be addressed in the near future. In general, it is still unclear what the exact mechanisms are which lead to the malignant transformation of a reactive infiltrate. Is there a molecular-genetic or immunological point of no return? What is the biological significance of the immunoglobulin rearrangement detected with PCR? The wave of new data each year about the role of H. pylori in gastric MALT lymphoma might help that many of these questions addressed above might be answered within the next years.

Gastric Mucosa↗
PubMed2000

Facilitated detection of oncogene mutations from exfoliated tissue material by a PNA-mediated 'enriched PCR' protocol.

An 'enriched polymerase chain reaction (PCR)' protocol has been established for the sensitive detection of oncogene mutations in body fluid samples from cancer patients. This two-step protocol combines an allele-specific PCR clamping step followed by a PCR-RFLP (restriction fragment length polymorphism) confirmatory step. The method thus resembles a nested PCR technique starting directly from genomic DNA material and, in no more than 54 PCR cycles, allows the sensitive detection of one mutant allele in 10(3) normal alleles. This protocol was tested on bronchial cytology samples and sputum taken from lung cancer patients and point mutations could be detected both in codon 12 of K-ras and in three codons (248, 249, and 273) of the p53 gene. Comparing this protocol with a different 'enriched PCR' method based on repetitive PCR-RFLP steps, a high concordance was noted between the two methods. Although the present protocol seems to be less sensitive by approximately one order of magnitude, it is much easier to perform and thus could be applied to the rapid but sensitive detection of allelic subfractions in a population of cells derived from exfoliative material.

Bronchoalveolar Lavage Fluid↗
PubMed2000

Eradication of Helicobacter pylori and stability of remissions in low-grade gastric B-cell lymphomas of the mucosa-associated lymphoid tissue: results of an ongoing multicenter trial.

The normal human stomach is devoid of any organized lymphatic tissue. Acquisition of mucosa-associated lymphatoid tissue (MALT) in the stomach is considered to be a direct consequence of chronic infection with Helicobacter pylori. Thus, MALT appears to be part of the host defense against the pathogen H. pylori. Consequently, lymphomas arising from gastric MALT may be seen as an end point of a clonal evolution starting from the infection. Cumulative data from several studies show that eradication of H. pylori induces complete histologic remissions in about 70%-80% of the patients. Here we present data of an extended analysis of an ongoing multicenter trial. Eighty-four patients with low-grade gastric MALT lymphoma in stage EI were treated using a dual regimen to eradicate H. pylori. Complete remission was observed in 68 (81%) patients; a partial remission was found in seven (8%) patients. In contrast, nine (11%) patients revealed "no change" and were referred for alternative treatment strategies. The majority of these cases were found to harbor high-grade lymphomas in deeper mucosal areas. Polymerase chain reaction (PCR) performed on the VDJ rearrangements of the immunoglobulin heavy chain yielded monoclonal bands in 50 of 65 analyzed patients (77%) at diagnosis. Interestingly, in patients analyzed during follow up after achieving complete histologic remission, ongoing PCR monoclonality was found in 19 of 39 eligible patients (49%). Several patients who developed local relapse of the lymphoma were found in the group with ongoing PCR monoclonality. Together with data from the literature, these results suggest that the majority of low-grade gastric MALT lymphomas in stage EI respond to eradication of H. pylori. Longer follow-up investigations are necessary to determine whether remissions really indicate a cure from the disease and to elucidate whether PCR monoclonality after complete histological remission is predictive of increased relapse rate.

Anti-Bacterial Agents↗