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Biomedical subjects

A A Fauser

Publications and source records attributed to A A Fauser.

118 records · Page 7Linked to original sources
PubMed1980

Properties of human pluripotent hemopoietic progenitors.

Human pluripotent hemopoietic progenitors (CFU-GEMM) from mixed colonies when cultured in methylcellulose or agar in the presence of erythropoietin and PHA-LCM. The observed frequency is low and varies for different individuals between 0 and 4 mixed colonies/O5 mononuclear cells. CFU-GEMM do not adhere to glass or plastic surfaces; their density is less than 1.077 g/ml, and their sedimentation velocity profile peaks at 4.5 mm/h. They do not form rosettes with sheep red blood cells. These physical parameters can be used preparatively to enrich for CFU-GEMM to facilitate assessment of their biological properties such as cycle state analysis and measurement of self-renewal capacity. Preliminary information suggests that some CFU-GEMM are capable of self-replication. Cycle state data are available for a larger number of patients with various clinical conditions. CFU-GEMM were found to be quiescent under steady-state conditions. They proliferate actively during bone marrow regeneration and in stem cell disorders like Polycythemia rubra vera or CML. These changes in cycle state activity were not reflected in numerical alterations of CFU-GEMM. It was thus concluded that the assay may be used more meaningfully to assess biological properties of human pluripotent progenitors rather than their frequency.

Cell Adhesion↗
PubMed1979

Proliferative state of human pluripotent hemopoietic progenitors (CFU-GEMM) in normal individuals and under regenerative conditions after bone marrow transplantation.

The proliferative state of human pluripotent hemopoietic progenitors (CFU-GEMM) was assessed in normal bone marrow transplant donors and in recipients after engraftment using the tritiated thymidine suicide method. In contrast to BFU-E and CFU-C, CFU-GEMM were found to be quiescent. In samples obtained during early regeneration after transplantation, CFU-GEMM were significantly reduced after short-term exposure to 3H TdR when compared to controls. This observation suggests active participation of CFU-GEMM in bone marrow regeneration.

Bone Marrow Cells↗
PubMed1979

Identification of megakaryocytes, macrophages, and eosinophils in colonies of human bone marrow containing neurtophilic granulocytes and erythroblasts.

Pluripotent hemopoietic progenitors in human bone marrow can be identified by their ability to give rise in culture to colonies that contain more than one lineage of hemopoietic differentiation. Growth of these mixed colonies is supported by media conditioned by leukocytes in the presence of phytohemagglutinin (PHA-LCM) and erythropoietin. They can be readily recognized by direct microscopic observation because of their composition of colorless cells and cells with a red appearance typical for hemoglobin. Seventy-three individual mixed colonies from 6 individuals were prepared by cytocentrifugation for further cytological examination. In addition to neutrophilic granulocytes and erythroblasts, megakaryocytes were present in 16 of the 73 colonies, as identified by positive reaction for acid phosphatase. Macrophages were found in 24 and eosinophils in 6 of the 73 colonies.

Bone Marrow Cells↗
PubMed1978

Granuloerythropoietic colonies in human bone marrow, peripheral blood, and cord blood.

Colonies that contain granulopoietic and erythropoietic cells can be grown in specimens of human bone marrow, peripheral blood, and cord blood. Growth of these colonies is promoted by media conditioned by leukocytes in the presence of phytohemagglutinin (PHA-LCM) and the addition of erythropoietin on days 4 or 5 to the cultures. Sedimentation velocity profiles for these granuloerythrocytic colonies suggest their origin from single cells (CFU-G/E) rather than from doublets or clumps. This hypothesis is supported by cocultivation of male and female specimens. Cells in granuloerythrocytic colonies that developed in such mixing experiments were either uniformly female by Y-chromatin analysis or contained Y-chromatin bodies in both the granulocytic and erythroid cells.

Blood Cells↗
PubMedDate not supplied

Optimization of retroviral vector generation for clinical application.

BACKGROUND: For many inherited and acquired diseases of the blood system, gene transfer into hematopoietic cells is a promising strategy to alleviate disease-related symptoms or even correct genetic alterations. In clinical gene therapy applications, low transduction efficiencies have been a major limitation mainly because of insufficient effective titers of the retroviral supernatants used. Thus, optimization of clinical-grade vector production under current 'Good Manufacturing Practice' (GMP) conditions is a prerequisite for successful gene therapy trials. METHODS: We established stable retroviral producer clones with single integrations of a retroviral vector encoding for the multidrug-resistance gene 1 (MDR1). Optimization of vector production in multi-tray cell factories (MTCFs) was studied with particular regard to harvest medium, cell density and harvest time point. RESULTS: We demonstrated that high-titer vector stocks could be produced in serum-free medium. By reducing the volume of harvest medium, titers could be increased up to four-fold. Plating optimal cell densities of 1 x 10(4) cells/cm2, repetitive harvests of vector supernatant were feasible over four consecutive days. Combining the most advantageous culture and harvest parameters tested, we were able to produce large quantities of serum-free vector supernatant in 40-tray MTCFs. Highly efficient gene transfer into primary human CD34+ progenitor cells demonstrated the quality of these vector stocks. CONCLUSION: The large-scale vector-production protocol in MTCFs described here is easy to handle, is applicable to a wide range of adherent producer cell lines and, most importantly, complies with current GMP guidelines.

Antigens, CD34↗
PubMedDate not supplied

Treatment of severe sepsis in bone marrow transplant recipients with teicoplanin in combination with beta-lactams and aminoglycosides.

We evaluated teicoplanin for suspected gram-positive infections after inadequate response to initial empiric beta-lactam and aminoglycoside combination therapy. All 20 patients included in this study received either an allogeneic (8 patients) or an autologous (12 patients) bone marrow transplant for acute myeloid leucaemia (AML), non-Hodgkin's-lymphoma (NHL, high grade) or other malignant diseases. All patients developing primary septicaemia of unknown origin (18 patients) or catheter-related septicaemia (2 patients) were treated with 400 mg teicoplanin, administered i.v. once daily in combination with a cephalosporin and an aminoglycoside (ceftazidime 2 g i.v., t.i.d.; netilmicin 400 mg once daily). All patients responded to therapy, 19 patients were clinically cured and one patient improved under therapy. The therapeutic regimen was well tolerated; only one adverse drug reaction was observed. We did not observe any delayed take or prolonged neutropenia or thrombocytopenia with this therapeutic regimen when our patients were compared to other bone marrow transplant patients (who did not receive this antimicrobial therapy). Our results suggest that teicoplanin is a potentially effective and well tolerated antimicrobial agent in bone marrow transplant patients with infections not responding primarily to beta-lactams and aminoglycosides.

Adolescent↗
PubMedDate not supplied

A randomized clinical trial of ceftriaxone and teicoplanin versus ceftazidime and teicoplanin as antibiotic therapy in febrile neutropenic cancer patients and bone marrow transplant recipients.

A prospective, randomized clinical trial comparing combination therapy with ceftriaxone and teicoplanin versus ceftazidime and teicoplanin in the treatment of febrile episodes in neutropenic cancer patients and bone marrow transplant recipients was performed. One hundred and two patients were randomized, but two patients were considered unevaluable for efficacy, and three patients were withdrawn due to incorrect randomization. Of the remaining 97 patients, infection resolved without modification of therapy in 31/49 (63%) patients treated with ceftriaxone/teicoplanin versus 27/48 (56%) patients treated with ceftazidime/teicoplanin (P = 0.48). Of all 97 patients treated therapy was modified in 18/49 (36%) with ceftriaxone/teicoplanin and 21/48 (43%) with ceftazidime/teicoplanin. Nineteen patients treated with ceftriaxone/teicoplanin received netilmicin and 21 patients treated with ceftazidime/teicoplanin also received netilmicin according to the study design (escalation therapy). When netilmicin was added infection resolved in 78% of patients treated with ceftriaxone/teicoplanin versus 84% of those treated with ceftazidime/teicoplanin. It was concluded that combination therapy with ceftriaxone/teicoplanin is an alternative to combination therapy with ceftazidime/teicoplanin, and has the advantage of once daily administration.

Adolescent↗