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Biomedical subjects

H Braunsteiner

Publications and source records attributed to H Braunsteiner.

At least 109 records · Page 6Linked to original sources

Studies of myelopoiesis in vitro on blood and bone marrow cells of patients with acute leukemia in long-term remission.

In vitro myelopoiesis in a group of ten patients with acute leukemia (6 AML, 1 APML, 3 ALL) in long-term remission has been studied. The patients remained in first stable remission for at least 4 years and maintenance therapy had been completed in all patients except one. In the patients, colony formation of bone marrow cells after 7 days of incubation was significantly increased compared to a representative control group. The proliferation of microclusters after 3 incubation days was also markedly enhanced, and accelerated proliferation of all aggregates (microclusters, macroclusters and colonies) could be demonstrated in culture with the patients' bone marrow cells. The use of autologous feeder layers and autologous serum showed no inhibitory effect on colony formation. The proportion of eosinophil colonies formed with the patients' bone marrow cells was in the normal range. In contrast to the high proliferation capacity of bone marrow precursor cells the CFU-c number of peripheral blood was significantly decreased in the patients' group. No significant correlation between CFU-c number of bone marrow and blood cells could be found. The colony stimulating activity of the patients' peripheral mononuclear cells was normal compared to healthy controls. We conclude from this study that even in long-term remission of acute leukemia certain in vitro abnormalities exist in myelopoietic proliferation and regulation.

Bone Marrow↗

A case of acquired pure red cell anemia studied by cloning of erythroid progenitor cells in vitro.

A 70-year-old woman developed typical clinical symptoms of pure red cell anemia (PRCA) following a history of rheumatoid arthritis (RA). The patient's bone marrow erythropoietic progenitors cells were cloned in a micro agar culture system several times over a period of 11 months, revealing a diminished frequency of bone marrow erythroblasts paralleled by a markedly reduced number of CFU-e and BFU-e in vitro. No inhibitory activity in the patient's IgG fraction could be detected either by preincubation with IgG and/or rabbit complement, or in the continuous presence of IgG. Depletion of T lymphocytes from the patient's bone marrow cells led to an improved in vitro erythroid proliferation. Cytostatic therapy with cyclophosphamide clinically induced a marked increase in the bone marrow erythroblast and reticulocyte number, correlated in vitro by normalization of CFU-e levels and increase in the number of BFU-e. Nevertheless, BFU-e values never attained normal levels, which could be attributed to a reduced stem cell pool resulting from previous therapy with cyclophosphamide and/or antirheumatic drugs. Two independent factors, a reduced pool of committed stem cells as well as an autoimmune cell-mediated suppression, may both contribute to the pathomechanism of the disease in this patient.

Aged↗

Human autologous mixed lymphocyte reactivity is primarily specific for xenoprotein determinants adsorbed to antigen-presenting cells during rosette formation with sheep erythrocytes.

We present evidence that most T cells proliferating in response to autologous sheep erythrocyte (SRBC)-separated non-T cells (NT) cells are not specific for autoantigens but for antigens derived from xenogeneic sources. The conclusion was based on the following three observations. First, we found that NT cells isolated in the absence of xenoproteins by means of density gradient centrifugation on Percoll only weakly stimulated autologous T cells. Because this weak proliferation could not be expanded in restimulation experiments, its significance as an immune recognitive event remains questionable. NT cells isolated by the above method in the absence of xenogeneic determinants readily acquired stimulatory capacity after brief exposure to either SRBC or fetal calf serum. Second, restimulation of T memory cells generated in 1 degree autologous mixed lymphocyte reaction (AMLR) against SRBC-separated autologous NT cells was exclusively seen when NT cells exposed to or separated with xenoproteins were used for restimulation. Third, T memory cells generated against SRBC-separated autologous NT cells were specifically restimulated by autologous Percoll-separated NT cells that had been pulsed with a variety of xenogeneic mammalian sera. These xenogeneic determinants were preferentially recognized in context with autologous HLA-DR+ cells. From these findings and from our previous results that indicated an absolute requirement of HLA-DR+-adherent NT cells (8), we conclude that human AMLR primarily does not represent an autoantigen but a xenoantigen response that is genetically restricted by the HLA-DR type of the antigen-presenting cell.

Animals↗

[Density distribution of human lymphocytes. I. Results of research on normal lymphoid tissue].

The aim of this study was to analyze the density distribution patterns of subsets of normal human lymphocytes. Density distribution was assessed by equilibrium centrifugation on linear polysucrose-metrizoat gradients. Results of the analyses of various subsets of lymphoid cells differing in their degree of cellular maturation and functional activation suggested that their distribution patterns are determined by three independent factors: the derivation, the stage of differenciation and the functional activity.

B-Lymphocytes↗

[Density distribution of human lymphocytes. II. Distribution patterns of malignant lymphocytes and their prognostic significance in patients with non-Hodgkin's lymphoma].

The aim of this study was to investigate the prognostic significance of density distribution profiles in non-Hodgkin lymphomas. Density profiles were evaluated by equilibrium centrifugation on linear polysucrose-metrizoat gradients. Biopsy cells from 44 untreated non-Hodgkin lymphomas in advanced stages according to their density patterns could be classified into one of two distinct groups: Group A lymphomas exhibited high to intermediate densities and resembled normal resting B or T lymphocytes; they showed low spontaneous proliferation and favourable histologies. Group B lymphomas exhibited light densities, resembling activated lymphocytes and frequently revealed high spontaneous proliferation and unfavourable histology. Within a minimal time of observation of 40 months only 28% of the group A but 75% of the Group B lymphomas died. Simultaneously performed surface marker studies excluded the possibility that variable proportions of normal lymphocytes contaminating the lymphoma suspensions are responsible for the two density groups. They rather suggested that these patterns reflect the individual capacity of a lymphoma to differentiate into denser tumour clones with low spontaneous proliferation. We therefore conclude that analyses of density profiles from non-Hodgkin lymphomas represenmts a promising method for the prognostic classification of this disease.

Animals↗

Normal suppressor-cell activity in systemic lupus erythematosus. A study on 26 cases.

Suppressor-cell activity of 26 SLE patients suffering from active disease was compared to that of 15 healthy controls. ConA-induced and spontaneous suppression was evaluated. The mitogen-driven proliferation of normal allogeneic cells was significantly impaired by ConA-induced as well as spontaneous suppressor cells. However, no difference in suppressor-cell activity could be demonstrated between SLE patients and controls.

Concanavalin A↗

[Bone marrow culture, cytochemistry and electron microscopy in agar in patients with preleukemic syndrome and aplastic anemia].

Thirty-seven patients with chronic cytopenia were studied using a CFU-c assay in agar. On the basis of the growth pattern three types of preleukaemic syndrome (PL) and two types of aplastic anaemia were distinguished. Further evaluation of the bone marrow dysfunction was attempted with a combined application of cytochemistry and electron microscopy for the morphologic study of cells proliferating in vitro. Well-defined maturation defects in the growing cells from the bone marrow of patients with PL were demonstrated with cytochemical stainings performed in agar. These results were supported by electron microscopic findings of Auer-body-like inclusions in "statu nascendi" in the vacuoles of preleukaemic cells. On the basis of our results a high risk group of PL for development of overt leukaemia and a group of patients with a grave prognosis in aplastic anaemia were distinguished. The data obtained are relevant for the clinical diagnosis and prognosis of patients with cytopenias.

Adult↗

[A microagar culture system for clonal growth of human T-lymphocytes].

A simple and reproducible micro-agar culture system for cloning human T lymphocytes has been described. The system consists of an agar layer and a liquid phase, which enables the easy addition of test substances and a prolonged proliferation. Further advantages of this system are a low incubation volume and a better morphological, cytochemical, immunological and electron-microscopical study of colonies obtained from the liquid phase.

Culture Media↗

[Quantitative-cytochemical evaluation of acid phosphatase activity in skin window macrophages (author's transl)].

The acid phosphatase activity (acP) of developing skin window macrophages topically treated with 6-methyl-prednisolone (6-MP) has been evaluated by a quantitative-cytochemical technique (SMP 05/PDP 12-20). The following conclusions can be drawn: 1. The degranulation of migrated monocytes can be inhibited by local application of 0.1 to 10.0 micrograms of 6-MP per skin window lesion. 2. The increase of acP-activity associated with the physiologic transformation of monocytes into macrophages and the concomitant activation of the lysosomal system was clearly inhibited by 0.05 to 10.0 micrograms per skin window lesion. 3. 6-MP alters the morphology of the developing macrophages and alters the intracellular distribution of acP. 4. It can be concluded that 6-MP inhibits the development of monocytogenic macrophages. This effect is observed with amounts of 6-MP which correspond to those obtained by systemic application of 6-MP in usual dosages. The antiphlogistic effect of 6-MP probably is due to a considerable proportion by the direct influence on the inflammatory cells.

Acid Phosphatase↗

A micro agar culture system for cloning human erythropoietic progenitors in vitro.

A simple and reproducible micro agar culture method for cloning erythropoietic progenitor cells from human bone marrow is described. Mononuclear cells (MNC) were immobilized in an agar layer and stimulated by erythropoietin (Ep), which was added to a liquid overlayer. The cultures were routinely incubated, fixed, transferred to microscopic slides, dried, and stained, and erythroid colonies were morphologically examined. The dynamics of growth observed from days 2 to 26 of incubation in the presence of 2.4 U Ep/ml showed basically three kinds of aggregates, which reached maximum growth on different days of incubation. A close Ep dose-response relationship was found for CFUE and BFUE at a concentration of 7.5 x 10(4) seeded cells. By varying the plated cell concentration between 2.5 and 10 x 10(4) cells a linear increase in the aggregates formed was found. On the basis of their growth dynamics and morphologic composition, the existence of three populations of erythropoietic progenitor cells in human bone marrow is tentatively proposed.

Agar↗

Prognostic significance of lymphocyte density distribution profiles in adult non-Hodgkin lymphomas.

Biopsy material from 24 adults with advanced stages of non-Hodgkin lymphomas (NHL) were examined for the distribution profiles of infiltrating cells following centrifugation to equilibrium on linear density gradients. Seven of these biopsies were predominantly composed of cells with high buoyant densities and 9 further biopsies predominantly of cells with intermediate buoyant densities. Both patterns were associated with favorable histologic features and with low proliferation of lymphoma cells. Intensive polychemotherapy was rarely required to achieve long-lasting disease control; in both groups, only 28% of patients died within a minimal observation period of 40 mo. In 8 biopsies, a predominance of light lymphoma cells was observed. This pattern was frequently associated with unfavorable histology and with high spontaneous tumor cell proliferation. Despite intensive polychemotherapy, rapid disease progression occurred in all cases, leading to death in 75% of the patients within a minimal observation period of 40 mo. Surface marker studies excluded the hypothesis that only the variable proportions of normal lymphocytes contaminating the lymphoma suspensions were responsible for the differences in the density distribution patterns described above; they rather suggested that these patterns reflect the individual capacity of a lymphoma to differentiate into dense tumor clones with low spontaneous proliferation.

Adult↗

[Proliferation of myeloid precursor cells in a microagar culture system].

A microagar-culture system for the in vitro study of myelopoiesis committed stem cells has been reported. Stimulation was induced by a commercially available conditioned medium obtained from culture of histiocytoma cells. The effect of different concentrations of conditioned medium and a linear relation between the seeded cells and the formed colonies has been established. The granulocytic-monocytic character of cell aggregates has been shown by morphologic studies. Further possibilities for the use of the described method have been briefly discussed.

Agar↗

[Therapeutic strategies in the treatment of breast cancer (author's transl)].

Breast cancer is the most common cause of cancer death in women. The probability of being cured of this disease is below 50%. However, for certain stages of disease prognosis can be improved by the application of modern therapeutic strategies. The present paper deals firstly with the relationship between prognosis, staging, and tumour cell characteristics (receptor status and cell kinetic findings). Thereafter, selection and efficacy of cytotoxic chemotherapy and endocrine treatment is discussed and related to the prognostic different entities. The current therapeutic regimen of our group is outlined.

Adult↗

A micro-culture system for cloning human T lymphocytes in agar.

A simple and reproducible single-layer micro-agar culture system for cloning of human T lymphocytes has been described. The system consists of an agar layer, in which mononuclear cells from peripheral blood were suspended, and a liquid overlayer containing the mitogenic substance. The advantages of the described method are a low incubation volume (0.5 ml) and the liquid overlayer. The addition of different test substances to the liquid overlayer is simple and easily controllable. Depending on the agar concentration a different number of formed colonies can be found floating in the liquid phase. The morphological, cytochemical and immunological characteristics of the cells from those aggregates could be easily studied. The T-cell characteristics of formed clusters and colonies was confirmed by immunofluorescence and E rosette formation. The effects of agar, serum and cell concentrations, as well as the mitogenic activation caused by three lectins on the development and number of colonies were studied on day 7, 10 and 14 of incubation.

Clone Cells↗

Spontaneous and conA-induced suppressor lymphocytes: a comparative study.

Suppressor monocytes, Concanavalin A(ConA)-induced suppressor T cells, and short-lived suppressor lymphocytes have been describe in humans. The present study was performed to evaluate spontaneous suppression in a test system similar to that employed for the demonstration of ConA-induced suppressor cells: Lymphocytes were either stimulated by ConA (= induced suppressor cells) or immediately mitomycin-treated (= spontaneous suppressor cells). Both preparations were tested for their capacity to suppress mitogen-induced proliferation of autologous cells. Depletion of monocytes or B lymphocytes did not affect spontaneous suppression. The active cells were short-lived in vitro. Therefore the net increase in suppressor activity generated by preculture with ConA is in part related to a loss of spontaneous inhibitory activity in the control cultures kept without mitogen. Spontaneous suppressor cell activity was comparable to that of ConA-induced suppressor cells.

Carrageenan↗

The role of adherent HLA-DR+ mononuclear cells in autologous and allogeneic MLR.

The aim of this study was to define the significance of HLA-DR+ cells for the in vitro induction of human autoreactive T cell proliferation. Proliferation was induced by autologous or allogeneic non-T cells or EB virus-transformed LCL. Pretreatment of stimulator cells with low concentrations of RAHLA-DR and C and with high amounts of RAHLA-DR alone abolished the capacity to stimulate autologous or allogeneic T cells. This suggested that antigens associated with HLA-DR+ stimulator cells or HLA-DR itself are involved in the induction of this proliferation. At the responder cell level the cytotoxic elimination of HLA-DR+ cells as well as depletion of adherent cells by passage through Sephadex G-10 columns reduced both autoreactive and alloreactive responsiveness. Responses of serologically and physically depleted populations were both restored by reconstitution with mitomycin-C treated autologous adherent cells. These cells were resistant to lysis with T cell specific antibodies and preferentially cooperated with T cells of autologous deprivation. Co-cultivation experiments further revealed that such accessory cells were capable of amplifying T cell proliferation in the presence of suboptimal numbers of autologous LCL. We concluded, therefore, that an HLA-DR+-adherent cell, presumably of monocytic origin, is required for optimal proliferative responsiveness of both autoreactive and alloreactive T cells.

Animals↗