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Biomedical subjects

B Kubanek

Publications and source records attributed to B Kubanek.

At least 109 records · Page 6Linked to original sources
PubMed1986

Conversion of acute undifferentiated leukemia phenotypes: analysis of clonal development.

The cellular origin of acute undifferentiated leukemia (AUL) is still a matter of controversy. We report on two cases in which the diagnosis of AUL was established according to restricted criteria. Blast cells of both patients showed phenotypic conversion during the course of disease. In one case, within 24 days from starting treatment, the leukemic phenotype changed from AUL to acute myelomonocytic leukemia (FAB L1, TdT+ to FAB M4, TdT-). The initial phenotype of this acute leukemia was characterized by the co-expression of both B-lymphoid and myeloid markers on the same cell. Moreover, analysis of esterase isoenzyme pattern showed the whole spectrum of isoenzymes typically seen in myelomonocytic leukemias already at diagnosis, yet blast cells additionally contained all three isoenzymes of beta-hexosaminidase typically seen in AUL. However, examination of immunoglobulin (Ig) heavy chain gene rearrangement initially and after conversion revealed an identical monoclonal configuration of Ig heavy chain sequences in both samples. The second AUL patient relapsed after allogeneic bone marrow transplantation with common ALL-antigen (CALLA) positive acute leukemia. Subsequent Southern blot analysis showed a novel rearranged Ig fragment compared to the analysis before transplantation indicating that the leukemic clones prior to and after transplantation were not identical. No chromosomal abnormalities were observed in both cases. These data support the view that AUL cells originate from a pluripotent stem cell that is capable to differentiate in the myelomonocytic lineage (patient 1), and confirm the value of Ig gene analysis as marker for cellular clonality.

Adult↗
PubMed1986

Hemopoietic reconstitution after bone marrow transplantation.

Forty-one patients underwent bone marrow transplantation (BMT) for treatment of severe aplastic anemia or hematologic malignancies. Hemopoietic reconstitution after BMT was monitored by peripheral blood counts, counts of bone marrow cellularity, and clonal assays for hemopoietic progenitors (CFUc, CFUe, and BFUe), along with bone marrow morphology. The number of transplanted nucleated cells and the number of transplanted progenitors (CFUc, CFUe, and BFUe) correlated significantly with the time of reticulocyte recovery. The number of transplanted CFUc correlated significantly with the time of granulocyte recovery. Platelet recovery occurred late and showed large variations. No correlation between the transplanted cells and the recovery of nucleated cells or hemopoietic progenitors (CFUc, CFUe, and BFUe) in the bone marrow was found. Bone marrow cellularity and hemopoietic progenitors showed a rapid, but incomplete, recovery during the first 56 days after BMT. Hematologic studies on seven long-term survivors with an uncomplicated posttransplantation course revealed subnormal bone marrow cellularity and hemopoietic progenitor incidence up to three years after BMT, despite normal peripheral blood counts. The low progenitor incidence could be explained by a proliferative defect of the stem cells, compensated for by an amplification in the more differentiated compartment of hemopoiesis.

Anemia, Aplastic↗
PubMed1986

Acute undifferentiated leukemia: implications for cellular origin and clonality suggested by analysis of surface markers and immunoglobulin gene rearrangement.

Although B cell leukemias and, recently, T cell leukemias can be identified both by surface marker and molecular analysis, there remains a population of acute undifferentiated leukemias (AUL) that cannot be allocated definitively to a single cell lineage. AUL was diagnosed in nine patients according to stringent criteria. We combined both immunologic and molecular approaches to analyze further the ambiguous origin of AUL cells. Southern blot analysis revealed rearranged Ig heavy-chain genes in seven patients and indicated a biclonal or oligoclonal leukemic cell population in three of them, including one case of AUL with translocation (4;11). Analysis of cell surface markers showed expression of at least one early B cell-associated antigen (BA-1, BA-2, B4, UL-38) in six of these seven patients, with coexpression of a myeloid antigen (VIM-2) in three patients. Leukemic cells of two other patients neither exhibited Ig chain gene rearrangements nor expressed B cell-associated antigens. T cell receptor beta-chain genes showed germline configuration in all nine cases. Our results demonstrate heterogeneity among AUL patients based on molecular and surface marker analyses and suggest that most AUL blast cells are derived from a precursor cell that shares phenotypic and genotypic characteristics of early B cells with certain surface antigens of myeloid cells, in some cases of AUL more than one abnormal cell clone or subclone may exist, and the cellular origin, at least of some AULs exhibiting t(4;11), may be truly B cell lineage committed.

Antibodies, Monoclonal↗
PubMed1986

[Therapy using blood components. Prerequisites, indications and clinical use].

The therapeutic benefit of blood components for specific substitution and volume replacement has been recognized for more than ten years. The increasing demand for blood and blood products, especially for albumin in connection with an only moderate growth of the base of blood donors has promoted the idea of a more efficient utilization of blood by specific replacement with blood components. The component therapy has reduced the side effects and improved the efficacy of blood transfusion and last but not least has led to a positive cost-effectiveness. Our clinical management of blood transfusion with a nearly complete use of components in surgical patients is presented. Particularly, the therapeutic strategy for massive transfusions by component therapy is discussed. In face of the technical and logistic problems, a transfusion schedule was developed which outlines the nearly exclusive therapeutic use of components. It applies with modifications and adjustment to the critical parameters to all cases of rapid and massive blood loss. In addition, diagnostic and therapeutic strategies are considered to preserve hemostasis or correct occurring hemostatic defects and to prevent thrombo-embolic events.

Blood Coagulation Factors↗
PubMed1985

Platelet-adjusted IFN dosage in the treatment of advanced hairy cell leukemia.

It has been demonstrated that hairy cell leukemia (HCL) can be efficiently treated by various preparations of alpha interferons (IFN). Nevertheless, there are several open questions, such as the route, mode and dosage of IFN application. These variables of IFN treatment may be critical since a myelosuppressive effect of IFN, which is commonly seen in the initial phase of treatment, can result in further deterioration of the already impaired platelet production in advanced HCL. The present study shows that serious side effects can be avoided and the flu-like syndromes described by others almost completely reduced by s.c. application of IFN via a portable pump during a daily 8 h period. IFN is initially given five times a week and the daily dose is adjusted according to the actual platelet count. The efficiency controls show that the increase of platelets in the peripheral blood, which is most critical in advanced HCL, may be seen earlier by this than by other protocols, which usually recommend higher daily doses of IFN and only three instead of five weekly applications.

Adult↗
PubMed1985

Severe combined immunodeficiency: treatment by bone marrow transplantation in 15 infants using HLA-haploidentical donors.

In 15 infants with severe combined immunodeficiency (SCID), immunological reconstitution was attempted by bone marrow transplantation (BMT) from HLA-haplo-identical parents. To prevent graft versus host disease (GvHD), marrow grafts were depleted of contaminating T-lymphocytes using lectin agglutination and rosette formation with sheep red blood cells. Thirteen patients received transplants without undergoing prior cytoreductive conditioning. Eleven of these developed donor-dependent T-cell functions, two failed to do this. One of these two as well as two further patients received cytoreductive treatment prior to repeat and to first transplants and in two, complete lymphohemopoietic reconstitution was observed. Of the 15 patients who received transplants, 11 are currently alive. Two recently treated patients remain in the hospital, nine are at home with stable T-cell functions. Normal humoral immune functions have developed upto now in three patients. In the others, gamma globulins are regularly substituted. Complications of acute or chronic GvHD were not observed with the exception of one case who developed transient GvHD of the skin. These results suggest that in a majority of patients with SCID, T-cell functions can develop without GvHD following haploidentical, T-cell-depleted BMT. Exceptional patients require preconditioning to allow donor cell engraftment, an approach that also appears to facilitate reconstitution of humoral immune functions.

Bone Marrow Transplantation↗
PubMed1985

Extramedullary haemopoiesis after bone marrow transplantation.

44 patients underwent bone marrow transplantation (BMT) for treatment of severe aplastic anaemia or haematological malignancies. During their post-transplant phase all patients had erythroblasts and granulocytic precursors in their peripheral blood. 15 patients died between day +6 and +346 after BMT and autopsies were performed. The sections of all 15 patients revealed extramedullary haemopoiesis in the spleen. Extramedullary haemopoiesis in the liver was found only in those patients who died early (between d +6 and d +21 after BMT). Medullary haemopoiesis, normally only occurring in the vertebral body, was also observed in the shaft of the femur. The present data show that after BMT all tissues with a haemopoietic matrix in ontogenesis can be repopulated with haemopoiesis in the early phase of reconstitution, possibly to compensate for the haemopoietic insufficiency after conditioning therapy. The expansion of haemopoiesis in the later period of up to 1 year after BMT, remains to be explained.

Acute Disease↗
PubMed1985

The central role of the macrophage in hemopoietic microenvironmental regulation.

Based on the macrophage-specific release using crystalline silica, and the production and secretion of at least three hemopoietic regulatory factors (erythropoietin, colony stimulating factor and a multipotential stem cell enhancing and maintaining factor) into the extracellular fluid of bone marrow-derived macrophages grown on hydrophobic teflon foils, a hypothesis for the regulation of hemopoiesis is proposed. The macrophage is viewed as that component in the hemopoietic microenvironment responsible for hemopoietic regulation, by acting as an "intermediary" between extracellular signals and the controlled release of regulatory factors acting on responsive cells at different levels in the hemopoietic hierarchy.

Animals↗
PubMed1985

Growth and cytogenetic characteristics of bone marrow colonies from patients with 5q-syndrome.

Early erythroid precursor cells and myeloid progenitor cells (CFU-GM) from four patients with 5q-syndrome were cultured in order to study the in vitro growth patterns and to determine the clonal origin of this hematologic disorder. Cultures of CFU-GM exhibited normal colony growth, while erythroid progenitor cells demonstrated a marked decrease or absence of colony growth. Chromosomal studies indicate the 5q-chromosome is present in both hematopoietic progenitor cells, suggesting that the syndrome is an acquired clonal disease arising from a pluripotent hematopoietic stem cell. Follow-up cytogenetic studies reveal a decrease in the number of normal metaphases. This finding is consistent with reports that emphasize the slowly progressive nature of this malignant stem cell defect.

Aged↗
PubMed1983

Acute iron overload in mice: pathogenesis of Salmonella typhimurium infection.

The bacterial growth in the tissues of C3D2F1 male mice was measured during an experimental infection with two Salmonella typhimurium strains (high virulence, strain 2386/74; low virulence, strain L15403). This experimental model was used for evaluation of the pathogenesis in normal and iron-overloaded animals. Acute iron overload was accomplished by intramuscular injections of chelated iron (with 2,3-dihydroxybenzoic acid and citrate) with a single dose of 100 micrograms of iron per mouse. Bacteria were given intraperitoneally 1 h after the iron injection. Serum iron levels, transferrin levels, and the bacteria counts in blood and liver were measured simultaneously in all animals. There was a significant increase of bacterial growth in all tissues in the iron-treated animals. Iron abolished the normal clearance of the bacteria with low virulence from the blood. This study demonstrates that a general iron overload, as determined by an increased serum iron level, resulting from preinjection of iron, enhances bacterial growth.

Animals↗
PubMed1983

The fate of cells with chromosome aberrations after total-body irradiation and bone marrow transplantation.

Cytogenetic studies were done on bone marrow cells and peripheral lymphocytes of four patients (three with acute nonlymphocytic leukemia, one with aplastic anemia) at various intervals up to 861 days after total-body X irradiation (TBI) at doses between 4.5 and 10 Gy (450-1000 rad) followed by syngeneic or allogeneic bone marrow transplantation. Whereas no radiation-induced aberrations could be found in the bone marrow, apart from a transient finding in the patient with the lowest radiation dose, aberrant metaphases were seen in the peripheral lymphocytes of three patients in the range from 2.5 to 46% even at 861 days after the exposure. There were no demonstrable aberrations related to TBI in the only patient developing graft-versus-host disease. The dicentric yield as determined in the aberrant metaphases with 46 centromeres ranged between 3.4 +/- 1.3 and 4.9 +/- 0.4. In one patient it was demonstrated by BUdR-labeling that after 10 Gy (1000 rad) TBI the surviving and heavily damaged lymphocytes can go into cell cycle and reach at least the third mitosis. The percentage of aberrant cells diminished by about 25% at each mitotic division.

Acute Disease↗
PubMed1982

The effect of reduced oxygen tension on colony formation of erythropoietic cells in vitro.

The effect of reduced oxygen tension and the role of cellular components known to protect the cell against oxygen toxicity has been studied with respect to erythropoietic colony formation in vitro. Alphathioglycerol can be partially replaced by vitamin E and completely replaced by reduced glutathione (GSH) at physiological concentrations. Incubation of bone marrow and fetal liver early (BFU-E) and late (CFU-E) erythropoietic progenitor cells, in the presence of GSH, in an atmosphere containing 5% oxygen, 5% carbon dioxide and 90% nitrogen, as opposed to air supplemented with 5% carbon dioxide, resulted in an increase in colony numbers and response to erythropoietin (Epo). The number of colonies derived from bone marrow and fetal liver CFU-E increased by 1.2--2.8-fold with a relative Epo sensitivity increase of 3.5--4-fold. Bursts obtained from bone marrow and fetal liver BFU-E increased from 2.6- to 3.8-fold with an increased response to Epo of 2--3-fold. The effects of GSH and low oxygen tension are interpreted as causing a reduction in oxygen toxicity of the cells, thereby increasing the life span in vitro and so increasing the number of cells capable of forming colonies. The heightened response of BFU-E to Epo, analogous to the effect seen for CFU-E, implies that BFU-E may be responsive to physiological Epo concentrations at physiological oxygen tensions.

Animals↗
PubMed1982

Infection prophylaxis in acute leukaemia patients: comparison of selective and total antimicrobial decontamination of the gastrointestinal tract.

In a retrospective study, total antimicrobial decontamination with strict reverse isolation (ITD) and selective decontamination without isolation (SD) were compared as means of preventing infection in patients with acute leukaemia. Thirty patients were treated with ITD and 34 patients with SD. The surveillance cultures indicated that aerobic gram-negative bacilli and yeast could be equally eliminated effectively in both the groups. The anaerobic flora was only minimally influenced by SD. The incidence of acquired infections was 1.17 per patient in group ITD as compared to 0.85 in group SD. In group ITD, acquired bacterial infections were mostly caused by gram-negative bacilli (63%) whereas in the group SD these microorganisms accounted only for 25% of the infections. In group SD the total number of fever days was significantly lower and the mean duration of pyrexial episodes was substantially shorter. The results indicate that SD is an effective and inexpensive method for preventing gram-negative infections and might be at least as effective as ITD.

Acute Disease↗
PubMed1982

Release of erythropoietin from macrophages mediated by phagocytosis of crystalline silica.

The hormone erythropoietin (Ep), which regulates erythropoiesis, can be shown to be released extrarenally from macrophages of the spleen, bone marrow, peritoneal exudate, lung, liver, and fetal liver when suspensions of these cells are preincubated with crystalline silica. The cell supernatants are assayed for Ep activity in the erythroid colony-forming technique using 12- 13-day fresh or cryopreserved fetal liver cell suspensions as a source of Ep-sensitive CFU-E target cells. This report describes the optimal conditions required for release of Ep from silica-treated spleen macrophages. The requirement for phagocytosis of silica in mediating Ep release is shown by four different methods, namely, temperature dependency, inhibition of phagocytosis by Cytochalasin B, the presence of calcium in the medium, and the fact that silica particles coated with serum or poly-2-vinylpyridine-N-oxide can decrease Ep release to control levels. In addition, the reduction to background Ep levels when reduced glutathione, alpha tocopherol (vitamin E), and alpha-thioglycerol are added either separately or in combination with silica-treated macrophages is discussed in terms of a possible mechanism of silica action.

Animals↗