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Biomedical subjects

A Neubauer

Publications and source records attributed to A Neubauer.

At least 73 records · Page 4Linked to original sources
PubMed2000

Helicobacter heilmannii-associated primary gastric low-grade MALT lymphoma: complete remission after curing the infection.

BACKGROUND & AIMS: Cure of Helicobacter pylori infection may lead to complete remission of associated low-grade mucosa-associated lymphoid tissue (MALT) lymphoma in stage EI. This study investigated whether Helicobacter heilmannii infection-associated primary gastric MALT lymphoma will regress after cure of the infection. METHODS: H. heilmannii-induced gastritis was diagnosed histologically, by a new specific immunoglobulin G enzyme-linked immunosorbent assay, and with 16S ribosomal RNA amplification and sequencing in 5 consecutive patients with primary gastric MALT lymphoma clinical stage EI. Patients received 40 mg omeprazole and 750 mg amoxicillin 3 times per day for 14 days. Polymerase chain reaction (PCR) was used to detect rearrangement of immunoglobulin heavy-chain genes before treatment and during follow-up. RESULTS: Five patients (3 men, 2 women; mean age, 65 years; range, 42-79 years) were studied. H. pylori was not detected by culture, histology, serology, or PCR. Treatment resulted in the cure of H. heilmannii infection in each case and complete histological and endoscopic remission of the tumors. Three of 5 patients showed monoclonal B cells before treatment, 2 of whom remained PCR positive. Within a median follow-up period of 24 months, no relapse of the lymphoma or reinfection with H. heilmannii occurred. CONCLUSIONS: These data suggest that gastric MALT lymphoma may arise in patients with H. heilmannii infection. Cure of this infection may lead to complete remission of the MALT lymphoma.

Adult↗
PubMed2000

Malignant tumors of the stomach. Gastric mucosa-associated lymphoid tissue lymphoma and Helicobacter pylori.

With the help of many clinical studies, the diagnosis and therapy of gastric MALT lymphoma have evolved. Major progress has been seen in this area, including improvement of biopsy diagnosis, better histologic classification, new information concerning pathogenesis, and, especially, the start of a revolution in the treatment of low-grade gastric MALT lymphomas by eradicating H. pylori. About 12 clinical studies with almost 400 patients and case reports have shown that cure of H. pylori infection is associated with complete remission in approximately 80% of patients with low-grade MALT lymphoma in an early clinical stage. To establish H. pylori eradication as the primary choice in low-grade gastric MALT lymphoma further, it is necessary to select patients before therapy who are most likely to benefit from this single treatment modality. An excellent histologic workup of obtained biopsy specimens and comprehensive clinical staging are necessary. Because of the supposition that H. pylori-related growth support may play a role only in the early stages of low-grade gastric MALT lymphoma, the importance of determining the depth of lymphoma infiltration in the gastric wall is evident. Examinations by endosonographic ultrasonography have been shown to be the most reliable method to differentiate the layers of the gastric wall and to determine the infiltration depth of lymphomas. Eradication of H. pylori has to be considered as a first-line and single treatment modality in patients with low-grade gastric MALT lymphoma in clinical stage EI1. As a therapy with fewer side effects than radiation, surgery, or chemotherapy and as a stomach-conserving treatment, eradication of H. pylori in patients with low-grade gastric MALT lymphoma should be the treatment of the choice within clinical trials because there are no long-term results available thus far. Besides pretreatment patient selection, careful follow-up with endoscopy, biopsies, and clinical staging including endoscopic ultrasonography is necessary. A 5- to 10-year follow-up is necessary before the definitive value of H. pylori eradication can be established, but long-term results are excellent thus far. There are many questions to be addressed: What are the exact mechanisms that lead to the malignant transformation of a reactive infiltrate? Why do approximately 20% of low-grade MALT lymphomas not regress after H. pylori eradication? Is there a molecular-genetic or immunologic point of no return? What is the biologic significance of the immunoglobulin rearrangement detected with PCR? What will be the 5- and 10-year relapse-free survival rates of patients suffering from low-grade MALT lymphoma treated with H. pylori eradication alone as first and only treatment? The wave of new data each year about the role of H. pylori in gastric MALT lymphoma may help many of these questions to be answered.

Adult↗
PubMed2000

High speed immuno-affinity chromatography on supports with gigapores and porous glass.

Immuno-affinity chromatography exploiting the Ca2+ dependent interaction of the anti-Flag antibody and Flag-tagged proteins has been investigated. The antibody has been immobilized on porous glass beads (Prosep) containing gigapores and on a monolith, the polymethacrylate based Convective Interactive Media (CIM) column at a ligand density of 2 mg/g and 10 mg/ml respectively. The performance of the columns was assessed by applying clarified yeast culture supernatant containing overexpressed Flag-human serum albumin. Dynamic binding capacity and purity was checked at various flow rates ranging from 100 cm/h to 800 cm/h. 95% purity could be obtained. Anti Flag-CIM columns showed a higher unspecific adsorption, requiring a longer wash cycle to obtain the same purity compared to the Prosep column. Anti Flag-CIM columns showed a flow independent performance, which is explained by its monolithic structure. A decreasing dynamic binding capacity with flow was observed with anti-Flag-Prosep columns. Both columns are suited to purify milligrams of protein out of a yeast culture supernatant within a few minutes. We considered them as promising candidates for high throughput screening, where fast purification is a necessity.

Chromatography, Affinity↗
PubMed2000

Dose-reduced conditioning for allogeneic blood stem cell transplantation: durable engraftment without antithymocyte globulin.

Between February 1998 and October 1999, 24 patients with advanced leukemia, lymphoma or solid tumors received G-CSF mobilized peripheral blood stem cells (PBSC) from HLA-matched sibling donors after dose-reduced conditioning therapy. Only patients with reduced performance status or major infectious complications, not eligible for standard transplant procedures, were included. The 5-day conditioning therapy consisted of 3.3 mg/kg intravenous busulphan x 2 days and 30 mg/m2 fludarabine x 5 days. GVHD prophylaxis was performed with either CsA alone (n = 5), CsA combined with short course methotrexate (n = 5) or mycophenolate mofetil (n = 14). The day 100 survival was 95.2% for the whole group. All patients engrafted after a median of 15 days (range, 11-19) and 12.5 days (range, 10-19) for neutrophils and platelets, respectively. The median time to a neutrophil count of <0.5 x 109/l was 7 days (range, 2 to 12). Acute GVHD >I was observed in six patients, whereas eight patients have signs of chronic GVHD. The prospective 12 month overall survival with a median follow-up of 7 months is 63%. Relapse of disease and toxicity associated with chronic GVHD were the main causes of death. The treatment-related mortality was 12.5%. Dose-reduced conditioning using intravenous busulphan and fludarabine allows stable engraftment without ATG in related transplants and leads to a reduction of transplant-related mortality.

Adult↗
PubMed2000

Characteristics and analysis of normal and leukemic stem cells: current concepts and future directions.

Acute myeloid leukemias (AML) are considered to be clonal disorders involving early hematopoietic progenitor cells. The recent advances in characterization of early stem cells give rise to the question whether it is possible to distinguish healthy progenitors from cells of the leukemic clone in leukemia patients. Differences and similarities in phenotype, genotype and biology are described for leukemic cells and normal hematological progenitors. Recent new insights into human stem cell development offer the perspective that distinction between benign and malignant progenitors might be possible in the future at a very early stage of maturation.

Acute Disease↗
PubMed2000

[Frequency, pattern and differential diagnosis of echogenic splenic changes: sonographic follow-up study].

AIM: This study analyzes frequency, sonographic pattern and differential diagnosis of echogenic splenic foci and the value of ultrasound follow-up examinations. METHOD: Clinical data and ultrasound examinations of 137 patients with echogenic splenic foci were evaluated. Patients with uncertain diagnosis were identified and underwent a second examination (n = 31). RESULTS: Echogenic splenic foci are extremely rare. We found 137 cases in 12 1/2 years (12.2 of 10,000 ultrasound examinations). 5 sonographic patterns with differing but characteristic differential diagnosis were seen (round echogenic, round echogenic with halo and/or central liquefaction, round predominantly echogenic with hypoechoic parts, echogenic wedge-form, calcifications or gas). In patients with underlying malignant disorders the splenic foci were benign in 26 cases (34.7%), malignant in 36 cases (48.0%), and in 13 cases (17.3%) the diagnosis was uncertain. In patients with benign disorders the foci themselves were benign in 59 cases (95%), and in 3 cases (5%) the diagnosis was uncertain. CONCLUSION: Echogenic splenic foci are rare. Distinguishing between benign and malignant foci based upon sonographic patterns alone is only possible in exceptional cases. Short term follow-up ultrasound examinations taking into consideration the patients' underlying disease lead to the correct diagnosis in most cases.

Calcinosis↗
PubMed2000

[Focal echogenic splenic involvement in malignant lymphoma: a diagnostic problem].

AIM: The aim of our study was to describe clinical data, frequency of the findings, sonographic patterns, confirmation of diagnosis, and differential diagnosis of focal echorich splenic lymphoma involvement. PATIENTS: During the last 20 years a focal splenic lesion was found in 178 patients with malignant lymphoma. Echorich splenic lesions were seen in 11 out of 178 cases (6.2%). METHODS: Splenic size, echomorphology of lesions, size and number of lesions, and presentation during sonographic follow-up examination were presented. RESULTS: Echorich infiltrates of the spleen were predominantly seen in patients with low grade Non-Hodgkin-Lymphoma (9 out of 11), the size of lesions mostly was less than 3 cm in diameter (9 out of 11), the underlying splenic size was over 8 x 20 cm in 9 out of 11 patients. Diagnosis was confirmed by sonographic follow-up (n = 11) and autopsy (n = 1). CONCLUSION: Echorich splenic lymphoma involvement is a rare event and is characterised by a variable presentation during follow-up. Up to date the clinic significance of our observation is still unclear.

Aged↗
PubMed2000

Increased sensitivity of myeloid leukemia cell lines: potential of lovastatin as bone-marrow-purging agent.

Lovastatin reduces the isoprenylation of p21ras via suppression of mevalonic acid generation. Lovastatin has been shown to reduce tumor cell proliferation in a dose-dependent manner. Here, the potential of lovastatin for purging leukemia cells from bone marrow was investigated using the myeloblastic cell lines K562 and KG-1 as a model system, derived from an erythroleukemia and an acute myelogenous leukemia, respectively. Optimal purging conditions were determined using an MTT proliferation and a leukemia colony assay. Elimination of leukemia cells was time- and dose-dependent. Depletion of K562 was 2.5 logs for 100 microM of lovastatin at 72 h of incubation. Compared to another purging agent, 100 microg/ml mafosfamide had an activity comparable to 100 mM lovastatin. Interestingly, KG-1 acute myelogenous leukemia cells were even more sensitive to lovastatin than K562 cells. In clonogenic assays, 100 microM of lovastatin resulted in a 3- to 4-log reduction of K562 colonies. Lovastatin had a progressive effect on normal hematopoietic progenitor cells. At a concentration of 100 microM of lovastatin, CFU-GM colonies were reduced by 1-2 logs. In conclusion, a differential effect on leukemia and normal progenitor cells could be detected in a clonogenic assay. These results suggest that lovastatin deserves further study as an agent for ex vivo marrow purging.

Bone Marrow Cells↗
PubMed1999

Stable engraftment after megadose blood stem cell transplantation across the HLA barrier: the case for natural killer cells as graft-facilitating cells.

BACKGROUND: The case of a patient with chronic myelogenous leukemia who underwent transplantation with highly purified CD34+ peripheral blood stem cells from his two-antigen-mismatched mother is reported. No graft-versus-host disease has been observed so far and stable engraftment has been documented until day 100. METHODS: Weekly analysis of chimerism in different cellular subsets was performed using a quantitative polymerase chain reaction assay for nine short tandem repeat markers in leukocytes sorted by fluorescence-activated cell sorting. RESULTS: No donor CD4+ or CD8+ T cells have been detected up to 3 months after transplantation, whereas a rapid increase of donor CD56+ natural killer (NK) cells was observed in parallel with circulating donor CD34+ progenitors and myeloid cells. CONCLUSIONS: Because the graft contained virtually no T and NK cells, we believe the rapid in vivo generation of NK cells supported stable engraftment across the HLA barrier. The differentiation of CD34+ progenitors into NK cells might be a distinct feature of megadose stem cell transplants.

Adult↗
PubMed1999

Colonic mucosal proliferation is related to serum deoxycholic acid levels.

BACKGROUND: Hyperproliferation of the colorectal mucosa is regarded as an early step in colorectal carcinogenesis. Deoxycholic acid, a secondary bile acid, stimulates colorectal epithelial proliferation in animals and is considered a tumor promoter in human colorectal carcinogenesis. The aim of this study was to investigate the correlation between colorectal mucosal proliferation and the serum deoxycholic acid level. METHODS: From each of 19 patients (10 men and 9 women) with (n = 3) or without (n = 16) colorectal adenoma, 18 biopsy specimens were obtained by colonoscopy, 3 from each of the 6 colonic segments. A crude nuclei fraction was prepared, and DNA was stained by propidium iodide to determine the proliferative index (the percentage of cells in the S and G2/M phases of the cell cycle) by flow cytometry. Serum levels of deoxycholic acid were determined by gas-liquid chromatography. RESULTS: The colonic proliferation rates (median of the values obtained in all segments, 14.1%; range, 10.0-18.7%) and the fasting serum deoxycholic acid levels (median, 0.86 micromol/L; range, 0.28-1.58 micromol/L) showed a significant correlation (r = 0.51, P = 0.03). Serum lithocholic, cholic, chenodeoxycholic, and ursodeoxycholic acid levels were not correlated with the proliferation rates. CONCLUSIONS: Levels of deoxycholic acid in serum are correlated with the rates of the colorectal mucosa. These results are consistent with the concept that deoxycholic acid promotes colorectal carcinogenesis.

Adenoma↗
PubMed1999

A new PCR MIMIC strategy to quantify low mdr1 mRNA levels in drug resistant cell lines and AML blast samples.

Determination of the MDR-phenotype in patients suffering from AML is an important hallmark of treatment outcome but is often complicated by technical problems in P-gp assessment. A PCR-MIMIC strategy was employed to construct PCR-fragments for a competitive and quantitative mdr1 reverse transcription-PCR-assay. Using K562 cells, which had been selected for drug resistance to the epipodophyllotoxin VP16, a stepwise increase of mdr1 levels depending on the concentration of VP16 was shown with the MIMIC technique. Comparison of mdr1 levels in drug selected K562 cells with the corresponding levels for P-gp and functional data indicated a mRNA threshold that has to be exceeded for the full expression of the MDR-phenotype. Subsequently mdr1 levels of 34 samples of de novo acute myeloid leukemia were determined with the PCR-MIMIC strategy. Ten patient samples could be identified with elevated mdr1 levels which were substantially lower than the levels observed in the MDR-cell line K 562 0.7 microM VP16. Outcome analysis revealed that eight of the ten patients had an unfavourable prognosis and did not achieve CR after induction chemotherapy. Coexpression of mdr1 and CD 34 was not associated with CR in all examined cases. Moreover all these patients had unfavourable cytogenetic aberrations. These data indicate a sensitive technique with applicability in patient material.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Phase I clinical study applying autologous immunological effector cells transfected with the interleukin-2 gene in patients with metastatic renal cancer, colorectal cancer and lymphoma.

Natural killer-like T lymphocytes termed cytokine-induced killer (CIK) cells have been shown to eradicate established tumours in a severe combined immune deficient (SCID) mouse/human lymphoma model. Recently, we demonstrated that CIK cells transfected with cytokine genes possess an improved proliferation rate and a significantly higher cytotoxic activity as compared to non-transfected cells. Here, in a phase I clinical protocol, autologous CIK cells were generated from peripheral blood obtained by leukapheresis in patients with metastatic renal cell carcinoma, colorectal carcinoma and lymphoma. CIK cells were transfected with a plasmid containing the interleukin-2 (IL-2) gene via electroporation. Transfected cells generated IL-2 in the range of 330-1800 pg 10(-6) cells 24 h(-1) with a mean of 836 pg 10(-6) cells 24 h(-1). Ten patients received 1-5 intravenous infusions of IL-2-transfected CIK cells; five infusions with transfected CIK cells were given. In addition, the same patients received five infusions with untransfected CIK cells for control reasons. In three patients, WHO grade 2 fever was observed. Based on polymerase chain reaction of peripheral blood transfected cells could be detected for up to 2 weeks after infusion. There was a significant increase in serum levels of interferon gamma (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor beta (TGF-beta) during treatment. Interestingly, there was also an increase in CD3+ lymphocytes in the blood of patients during therapy. In accordance, a partial increase in cytotoxic activity in peripheral blood lymphocytes (PBLs) was documented when patient samples before and after therapy were compared. Concerning clinical outcome, six patients remained in progressive disease, three patients showed no change by treatment, and one patient with lymphoma developed a complete response. In conclusion, we were able to demonstrate that CIK cells transfected with the IL-2 gene can be administered without major side-effects and are promising for future therapeutic trials.

Adolescent↗
PubMed1999

Rapid quantification of mixed chimerism using multiplex amplification of short tandem repeat markers and fluorescence detection.

Monitoring the engraftment of donor cells after allogeneic blood stem cell transplantation (BSCT) may be important for the early diagnosis of graft failure or relapse of disease. Several techniques have been reported for this purpose. PCR-based assays analyzing polymorphic short tandem repeat (STR) markers are attractive because they are sensitive and can be performed rapidly. The intent of the present study was to test a novel approach for the quantification of mixed chimerism using a commercial multiplex STR assay with fluorescence-based detection for forensic purposes. The feasibility of this assay and the accuracy of quantitative results was tested using serial cell mixtures of unrelated individuals. Sample preparation was optimized to obtain information from minute amounts of starting material, eg from patients with aplasia or from sorted cell populations. Using the STR-PCR, discrimination between donor and recipient was possible in all patients analyzed (n = 25). Cell dilution experiments showed a linear correlation between the cell numbers added and the proportions found, with the limit of detection for a minor cell population being 5%. Comparison of values obtained with standard FISH analysis in patients transplanted from sex-mismatched donors showed an excellent correlation with the STR-PCR results. Taken together, this procedure allows the rapid, versatile and accurate quantification of mixed chimerism, even with minuscule numbers of cells.

Amelogenin↗
PubMed1999

Axl expression is associated with adverse prognosis and with expression of Bcl-2 and CD34 in de novo acute myeloid leukemia (AML): results from a multicenter trial of the Swiss Group for Clinical Cancer Research (SAKK).

Receptor tyrosine kinases (RTK) play a significant role in the signal transduction of normal, and malignant hematopoietic cells. We have previously shown that Axl, a novel RTK, is mainly expressed in leukemias of myeloid origin, and that its expression may be associated with cells of monocytic origin. Since expression of certain RTKs in cancer may be associated with different biology and survival, we investigated whether the expression of Axl is associated with clinical characteristics and survival in acute myeloid leukemia (AML). RNA from 54 patients with AML treated in a cooperative group trial was analyzed in a retrospective and blinded manner using a semi-quantitative reverse transcriptase polymerase chain reaction-based assay with primers specific for the Axl gene. Axl expression was found in 19 out of the 54 cases (35%). Axl expression was not detected more frequently in patients of older age, specific FAB categories, or cases with extramedullary disease. However, there existed a correlation between Axl and bcl-2 expression levels. AML cells with high bcl-2 expression showed higher Axl expression (r = 0.32; P = 0.02), and furthermore, Axl transcript numbers were also higher in AML with high CD34 expression (n = 38, r = 0.42; P = 0.008). No significant difference between leukemias expressing and not expressing Axl was found with regard to complete remission rate. However, quantitative Axl expression was associated with worse progression-free and overall survival. Higher Axl levels had worse prognosis for progression-free (beta: 0.68, s.e.: 0.28, P = 0.015) and overall survival (beta: 0.61, s.e.: 0.31, P = 0.05) using multivariate Cox models adjusted for age, Auer rods and leukocyte counts. In conclusion, in this retrospective analysis, no difference with regard to clinical characteristics at diagnosis was found between AML patients whose leukemia cells show Axl expression vs patients whose cells are Axl negative. The association between Axl and bcl-2 and Axl and CD34 expression in de novo AML needs further investigation. Similarly, the negative impact of Axl levels on outcome should be confirmed in a larger cohort.

Acute Disease↗
PubMed1999

Detection of cytogenetic aberrations both in CD90 (Thy-1)-positive and (Thy-1)-negative stem cell (CD34) subfractions of patients with acute and chronic myeloid leukemias.

Acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) are thought to arise from malignant hematopoietic progenitor cells representing early and undifferentiated stem cell clones. In CML there is evidence for a progenitor cell subset free of leukemic clones, depending on the course of the disease. Additionally, it has been suggested that in AML, the early stem cell compartment (CD34+/90+) does not harbor the malignant clone. We analyzed white blood cells from leukemia patients for the presence of aberrant cells in stem cell subfractions. Sixteen patients with CML, six patients with AML, two patients with acute lymphatic leukemia (ALL) and one with chronic myelomonocytic leukemia (CMMOL), all with known cytogenetic abnormalities, were evaluated according to their CD90 (Thy-1)-positive or -negative phenotype. Subsets were sorted on to slides and further characterized by FISH and/or standard cytogenetic testing. The bcr-abl translocation or gross chromosomal abnormalities could be detected in equally high amounts of 92.2% and 89.2% in both stem cell subsets. We conclude, that in progressed AML and CML cells characterized by specific genetic aberrations implicated in the malignant state can be found in the CD34+/CD90+ and CD90- population, thus making CD90 an inappropriate marker to distinguish benign from malignant cells in these leukemias.

Acute Disease↗
PubMed1999

Efficacy and toxicity of IFN-alpha2b combined with cytarabine in chronic myelogenous leukaemia.

Newly diagnosed chronic myelogenous leukaemia (CML) patients (n = 65) were treated with interferon (IFN)-alpha2b (5 x 106 IU/d s.c.) combined with monthly courses of cytarabine (20 mg/d s.c. for 14 d). Median age of patients enrolled was 45 years. The endpoints of the study were clinical efficacy and toxicity. The survival rates at 3 years and 5 years were 77% and 56%, respectively. The rate of complete haematological response was 60%. Evaluation of cytogenetic response was available in 29/65 patients. A complete cytogenetic response was seen in 3/29 patients (10%). W.H.O. toxicity grade 3-4 occurred in only 22/523 evaluable treatment cycles. Since the study protocol required intermittent or definitive discontinuation of cytarabine in case of moderate leucopenia (white blood cells (WBC) <5 x 109/l), combined cytopenia (WBC < 5 x 109/l, platelets <100 x 109/l), and isolated moderate thrombocytopenia (<100 x 109/l), the drug had to be discontinued temporarily or definitively in 200 cycles and the dose of cytarabine had to be reduced in 35 cycles. Thus, only 25% of the planned dose of cytarabine could be administered. At this dosage it would appear that cytarabine had no effect on survival and did not improve remission rates. We conclude that a clinical benefit for the addition of cytarabine to the treatment of CML with IFN might only be achieved by the administration of a higher cumulative dose of cytarabine, suggesting that lower leucocyte counts of 2-4 x 109/l have to be tolerated.

Adolescent↗