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Biomedical subjects

D Geissler

Publications and source records attributed to D Geissler.

At least 37 records · Page 2Linked to original sources
PubMed1990

"Intravascular lymphomatosis" (angioendotheliomatosis): evidence for a T-cell origin in two cases.

Intravascular lymphomatosis (IL) is a rare and potentially fatal multifocal intravascular proliferative disorder, most often involving the skin and the central nervous system. Originally considered an endothelial disorder, IL has recently been reclassified as an angiotropic lymphoma, most often of B-cell origin. We report immunocytochemical and ultrastructural findings in two patients with IL, both representing angiotropic T-cell lymphomas. In one patient, lesional tissue was examined by Southern blot analysis and monoclonal T-cell receptor rearrangement was found. As an additional feature in one patient, a myelosuppressive serum factor was demonstrated in peripheral blood progenitor cell cultures as the cause of underlying chronic anemia and leukopenia; this factor is thought to be a cytokine product of the lymphoma cells.

Aged↗
PubMed1990

Recombinant interferon-alpha-2C in chronic myelogenous leukaemia: relationship of sensitivity of committed haematopoietic precursor cells in vitro (BFU-E, CFU-GM, CFU-Meg) and clinical response.

In an ongoing phase-II trial we aimed to predict clinical responsiveness of Philadelphia chromosome positive (Ph1+) chronic myelogenous leukaemia (CML) to recombinant IFN-alpha-2C (rIFN-alpha-2C) by pretesting in vitro. From five normal controls and 14 CML patients in chronic phase, bone marrow samples were taken before treatment and tested for antiproliferative activity by rIFN-alpha-2C, using a microagar culture system for BFU-E, CFU-GM, and CFU-Meg. Light-density nucleated bone marrow cells were stimulated for BFU-E and CFU-Meg colony formation with Alpha medium containing 20% serum obtained from a patient with severe aplastic anaemia. CFU-GM growth was induced with conditioned medium from the cell line GCT. In normal controls BFU-E, CFU-GM and CFU-Meg colony formation was inhibited by rIFN-alpha-2C in a dose-dependent manner. BFU-E proved to be the most sensitive cell lineage (IC50: 65; range: 53-116 U/ml) whereas CFU-GM was about 20 times less sensitive (IC50: 643; range: 480-897 U/ml). The sensitivity of CFU-Meg ranged between these two colony types with 50% growth inhibition at an IFN concentration of 160 (range: 68-246 U/ml). A heterogeneous response to rIFN-alpha-2C in vitro was seen in CML patients. Three of the 14 patients were 'resistant' to rIFN-alpha-2C in vitro with IC50 values for BFU-E, CFU-GM and/or CFU-Meg colony formation greater than 10(4) U/ml. Patients were subsequently treated with a daily dose of rIFN-alpha-2C of 5 x 10(6) U. Four patients achieved a complete and six achieved a partial haematological response. Of the four non-responders three rapidly progressed into blastic crisis. Thus it was seen that treatment failure to interferon was accompanied by IFN-resistance in vitro of BFU-E, CFU-GM and/or CFU-Meg colony formation by bone marrow precursors (p less than 0.01). These results suggest a predictive value of IFN-sensitivity testing in vitro in Ph1 + CML.

Adult↗
PubMed1990

[Computer-assisted identification and comparative studies of the human skull].

The comparison of reconstructed skull profiles with photographic or other patterns for identification up to the reply to questions for sex, age, and race by the help of image analysis represents a relatively new development in forensic medicine. Using a Robotron image analyzing system 20 human skulls of different races were analysed morphometrically. Standardized profile functions, which were put through a morphometric analysis, showed characteristic individual features. By the help of the computerbased identification method mathematic differences between skulls of varions races became veritable.

Cephalometry↗
PubMed1989

Abnormal megakaryopoiesis in patients with myelodysplastic syndromes: analysis of cellular and humoral defects.

In 13 patients with myelodysplastic syndrome (MDS) mature and immature erythropoietic (CFU-E, BFU-E), granulopoietic (CFU-GM) and megakaryopoietic (CFU-Meg) colony formation from human bone marrow mononuclear cells was evaluated in a microagar culture system. All but three patients exhibited abnormal CFU-Meg. The defect of CFU-Meg paralleled the reduction of BFU-E, whereas CFU-GM number declined to a lesser extent. Not only the CFU-Meg number, but also the number of megakaryocytes (Mk) per colony was reduced suggesting an additional functional CFU-Meg defect. Megakaryocytic growth factor (Meg-CSF) abnormalities in MDS patients were detected using normal nonadherent T-lymphocyte depleted bone marrow cells as target cells for serum testing. Even for sera from patients with a reduction of platelets and bone marrow megakaryocytes Meg-CSF levels were not increased. No cellular or humoral inhibition could be detected in an MDS patient with a 5q- karyotype, who had an isolated defect of the megakaryocytic cell lineage at presentation. Some patients revealed a spontaneous formation of mixed erythrocytic, granulocytic and megakaryocytic clusters in the presence of fetal calf serum or autologous patient serum, probably representing autonomous proliferation of the malignant clone. In conclusion, both cellular and humoral factors can cause abnormalities of the megakaryocytic cell lineage in MDS patients.

Adult↗
PubMed1988

Stimulation of human early and late erythropoietic progenitor cells by insulin: evidence for different mechanisms.

In order to investigate cellular mechanisms involved in insulin stimulation of erythropoiesis, we have studied the response of early (BFU-e) and late (CFU-e) erythroid progenitor cells in a serum-free agar culture system. In this assay system, CFU-e proliferation occurred in media containing low-density lipoproteins, bovine serum albumin, transferrin and recombinant erythropoietin (rEPO). Insulin in physiological concentrations as low as 10(-12)M, added directly to cultures, augmented CFU-e colony formation. This stimulatory effect was also seen when monocyte- and T lymphocyte-depleted cells from normal donors were cultured. In contrast, BFU-e was not stimulated by media devoid of insulin. Occurrence of BFU-e colonies required the presence of insulin in concentrations higher than 10(-8)M. This insulin effect was not dependent on the presence of monocytes and T lymphocytes. Delayed addition studies of rEPO to insulin containing cultures revealed a slight but significant survival rate of CFU-e. A similar survival rate was found for BFU-e. From this, we conclude that insulin stimulates CFU-e by an EPO-like activity. For BFU-e, however, the decline in the number of bursts caused by EPO deprivation implies that insulin does not act directly as a burst-promoting activity but that it probably induces the release of this activity from non-adherent and T lymphocyte-depleted bone marrow cells.

Animals↗
PubMed1988

Serum colony stimulating factors in patients undergoing bone marrow transplantation: enhancing effect of recombinant human GM-CSF.

Sera from 11 patients undergoing autologous or allogeneic BMT were tested for their content of megakaryocytic, granulocytic and erythrocytic colony stimulating factors. During the first week after BMT, all patients sera revealed a low/inadequate production of granulocytic, erythrocytic and megakaryocytic colony-stimulating activity (defined as the number of colonies per plate induced by 30% test serum from monocyte and T-lymphocyte depleted bone marrow cells). Thereafter an increase of colony-stimulating activity for all cell lineages tested was observed with peak levels between days 8 to 14 after BMT. The peak level was followed by a decline of colony stimulating activity, which shows an inverse correlation to basal blood leukocyte counts suggesting an adequate counter-regulation during this period. The GM colonies grown in the presence of patient serum were found to consist largely of neutrophilic granulocytes with only single monocytic colony, but without eosinophilic colony formation, suggesting that granulopoietic colony formation during this period is mediated predominantly by G-CSF and not by GM-CSF. All patients undergoing autologous BMT revealed a low/inadequate endogenous CSF production. rh GM-CSF addition in vitro was able to compensate from the impaired endogenous granulopoietic CSA in all patients and resulted in a constant augmentation of granulopoietic colony formation. The percentage of eosinophilic colony formation showed an inverse correlation to endogenous CSF production also suggesting that G-CSF is secreted during this period. In contrast to the granulopoietic colony formation, erythropoietic and megakaryopoietic colony formation was not enhanced by GM-CSF addition in vitro and even showed a slight reduction in some experiments. Our results suggest the treatment with recombinant GM-CSF might be beneficial for a faster reconstitution of granulo-monocytopoiesis after BMT, that rh GM-CSF therapy should be started immediately after bone marrow transplantation and that G-CSF is the main factor secreted in allogeneic bone marrow transplantations in the regeneration period.

Bone Marrow Transplantation↗
PubMed1988

Proliferation and differentiation of human erythropoiesis in vitro: effect of different human lipoprotein species.

In order to permit erythroid proliferation in agar, a serum-free system was developed based on McCoy's 5A medium at pH 8.0, containing deionized and delipidated bovine serum albumin, iron-saturated transferrin, and crude erythropoietin (step III). Addition of the entire complement of serum lipoproteins, termed lipoprotein fraction I (density, less than 1.21 g/ml), increased the number of erythroid colony-forming units and erythroid burst-forming units to numbers indistinguishable from those observed with media containing serum. Moreover, terminal differentiation occurred to fully hemoglobinized normoblasts and even mature erythrocytes. Under these conditions, the erythropoietin dose-response curve obtained when not using serum was comparable to that with serum. Colony formation also displayed a linear relationship to seeding densities down to limiting dilutions. For differential analysis of the main density lipoprotein fractions, sequential ultracentrifugation was performed to isolate very low-density lipoproteins, low-density lipoproteins (LDL), high-density lipoproteins2 (HDL2), and HDL3, which were then added individually to serum-free cultures. Of the main lipoprotein classes, LDL exhibited the most proliferative capacity, followed by HDL2 and HDL3. Our findings indicate that when serum is substituted by well defined compounds including highly purified lipoprotein fractions, a serum-like proliferation and differentiation of human erythropoietic progenitor cells in agar can be obtained.

Bone Marrow↗
PubMed1987

[Plasmapheresis treatment in 3 simultaneously occurring autoimmune diseases: Hashimoto thyroiditis with hyperthyroidism, autoimmune thrombopenia and autoimmune hemolytic anemia].

A 49 year-old women with a 2-year history of a Coombs-positive autoimmune haemolytic anaemia was hospitalized with Hashimoto's thyroiditis and thyrotoxic crisis. The clinical course was further complicated by an autoimmune thrombocytopenia. Primary resection of the thyroid thus seemed to be too risky, so we decided to perform therapeutic plasma exchange. This led to clinical improvement, enabling us to perform a thyroidectomy. The present investigation reveals the high efficiency of plasmapheresis in the treatment of combined autoimmune diseases. Therapeutic plasma exchange resulted in a reduction of both the relevant autoantibodies and the level of circulating thyroid hormones.

Anemia, Hemolytic, Autoimmune↗
PubMed1987

Improved management of congestive heart failure. Use of continuous ambulatory peritoneal dialysis.

Four patients suffering from end-stage congestive heart failure (CHF) refractory to conventional medical treatment were treated with continuous ambulatory peritoneal dialysis (CAPD) for one to 21 months. All four patients improved from class IV CHF to class II, as defined by the New York Heart Association, and experienced a definite improvement in their sense of well-being. Three patients, women between 42 and 59 years of age with contraindications for heart transplantation, were all professionally rehabilitated. One 21-year-old patient received CAPD until he underwent a successful orthotopic heart transplantation. We thus propose CAPD as an effective treatment for end-stage CHF refractory to conventional medical treatment.

Adult↗
PubMed1987

Progressive preleukemia presenting amegakaryocytic thrombocytopenic purpura: association of the 5q- syndrome with a decreased megakaryocytic colony formation and a defective production of Meg-CSF.

The authors present a patient with the typical clinical picture of an acquired amegakaryocytic thrombocytopenic purpura. After 16 months of observation, the patient developed acute myelomonocytic leukemia. During the preleukemic phase and after progression to overt leukemia, serial in-vitro analyses of megakaryocytic, granulocytic, erythrocytic and T-lymphocytic colony growth were carried out in a microagar culture system. At presentation, a marked diminution of CFU-M was observed, whereas CFU-E, BFU-E, CFU-C and CFU-TL were in the normal range. The CFU-M number remained at its low level during the whole observation period. The CFU-C number declined steadily during the preleukemic period, while BFU-E, CFU-E and CFU-TL remained constant until January 1985 when the patient developed AML. After progression to overt leukemia, a distinct reduction became evident in all colony-forming cells. Cytogenetic studies performed during the preleukemic phase indicated the presence of a 5q- chromosome. The authors submit evidence here that the patient was not only characterized by defective megakaryocytic colony formation but also by a deficiency of functional megakaryocyte colony-stimulating activity. No humoral or cellular inhibitors of CFU-M colony formation were found. It is concluded that in preleukemia with a 5q- chromosome the megakaryocytic cell lineage may be involved in the process that precedes overt leukemia at an earlier time than cells of granulocytic and erythrocytic lineages. In addition, it is shown here that megakaryocytopoiesis during the preleukemic period can be characterized by two different defects: first, an intrinsic megakaryocytic stem cell defect and, second, a deficiency of functional megakaryocytic colony-stimulating activity.

Adult↗
PubMed1987

Changes of the phenotype of erythroid progenitor cells (BFU-E, CFU-E) and their progenies during early steps of differentiation.

Early differentiation processes of human erythroid progenitor cells (BFU-e, CFU-e) have been studied during in vitro proliferation using a panel of monoclonal antibodies with known reactivity on different levels of the erythroid cell line. Two antibodies recognizing structures on BFU-e (VIP-2b, BMA 021), two antibodies reactive with CFU-e and nucleated red cells (5F1, CLB-Ery-3) and one antibody directed against glycophorin A (VIE-G4) were used for this study. Normal human bone marrow cells were induced to proliferation in an erythroid progenitor cell assay and, after different periods of incubation, agar cultures were treated with these antibodies and complement. Thereafter, the remaining erythroid cells were incubated again to continue their proliferation with the same stimulators as before. The changes of the phenotype of BFU-e and CFU-e progenies during in vitro proliferation were determined by the reduction of colony formation in comparison with untreated control cultures. Our results indicate that the loss of HLA-DR antigens and the p45 structure is accompanied by the acquisition of structures recognized by the antibodies 5F1 and CLB-Ery-3. After 5-7 d of incubation BFU-e derived progenies exhibit the same antigenic structure as has been found for CFU-e. Glycophorin A expression could only be demonstrated at a late differentiation stage of the erythroid cell lineage.

Antibodies, Monoclonal↗
PubMed1987

The role of erythropoietin, megakaryocyte colony-stimulating factor, and T-cell-derived factors on human megakaryocyte colony formation: evidence for T-cell-mediated and T-cell-independent stem cell proliferation.

Recent studies suggest that megakaryocytopoiesis is governed by a dual-level regulatory process, with megakaryocyte colony-stimulating factor (Meg-CSF) primarily influencing proliferation of the committed precursors and thrombopoietin required for megakaryocyte ploidy amplification and for maturation. The authors have examined different sources of Meg-CSF in a microagar culture system with a view to their capacity to enhance megakaryocyte colony formation directly or via an indirect T-lymphocyte- or monocyte-mediated effect. The comparative influences of phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM), erythropoietin (Epo), sera of patients with severe aplastic anemia, and direct PHA addition to the culture were evaluated for their capacity to enhance megakaryocytic colony formation as well as for the maturation rate of megakaryocytes (Mk) grown in our microagar culture system. Each treatment by itself enhanced colony formation from unseparated low-density cells. Removal of T-lymphocytes and monocytes from the bone marrow sample caused a cessation of the enhancing effect of direct PHA addition to cultures stimulated with Epo, but did not influence the enhancing activities of severe aplastic anemia serum (SAA), PHA-LCM, and Epo. The results show that SAA serum, Epo, and PHA-LCM induced Mk colony formation directly and therefore may act via a common mechanism. Differences, however, were observed concerning their colony-stimulating potency and their influence on the Mk maturation rate.

Anemia, Aplastic↗
PubMed1986

The influence of T lymphocyte subsets and humoral factors on colony formation by human bone marrow and blood megakaryocyte progenitor cells in vitro.

Cellular and humoral influences of T lymphocytes on human megakaryocyte colony formation in vitro were assessed by using a microagar system. Megakaryocyte colony formation from nonadherent low density T lymphocyte-depleted (NALDT-) bone marrow cells was increased significantly after the addition of aplastic anemia serum (AAS) or purified megakaryocyte colony-stimulating factor (Meg-CSF). The addition of conditioned medium obtained from phytohemagglutinin-stimulated T lymphocytes replaced, at least partially, the requirement for AAS or purified Meg-CSF for the growth of megakaryocyte colonies. The cellular influence of T lymphocytes and T lymphocyte subsets on megakaryocyte colony formation was assessed by removing either T cells from nonadherent peripheral blood mononuclear cells with monoclonal OKT4, OKT8, or OKT3 antibodies plus complement, or by adding back populations of bone marrow or blood T4+ or T8+ lymphocytes, isolated by means of fluorescence-activated cell sorting, respectively, to NALDT--bone marrow or -blood cells. When sorted T cell subpopulations were added to a fixed number of NALDT--bone marrow or -peripheral blood cells in the presence of AAS or Meg-CSF, T4+ cells enhanced megakaryocyte colony formation and T8+ cells decreased it. These studies demonstrate that although the stimulation of megakaryocytic progenitor cells by Meg-CSF may not require the presence of monocytes or T lymphocytes, T4+ lymphocytes enhance and T8+ lymphocytes down-regulate megakaryocyte colony formation induced by Meg-CSF. These observations suggest that the immune system is capable of modulating the proliferative response of human megakaryocytic progenitor cells to Meg-CSF.

Antibody Formation↗
PubMed1986

[Interferon-alpha in the treatment of hematologic neoplasms].

This report aims to review briefly the current status of treatment of haematological malignancies with interferon-alpha (IFN-alpha). Overall hairy cell leukemia and chronic myelogenous leukemia appear to be most sensitive to IFN-alpha. We started to investigate, how interferon exerts its antileukemic activity and in which way interferon therapy can be optimized. Our preliminary results fail to support the view of interferon mediated enhancement of host responses. They rather indicate direct effects of IFN on leukemic cells in vitro. By means of IFN-dependent biological markers (e.g. beta-2-microglobulin, neopterin) clinically effective but atoxic doses of IFN-alpha could be defined for HCL and CML. In final conclusion, the recent studies on the clinical efficacy of IFN-alpha revealed its potent antitumoral effect in hematological malignancies. However, the further proof of the potential benefit of IFN treatment versus conventional therapeutic strategies remains to be elucidated.

Cell Division↗
PubMed1986

In vitro growth of erythropoietic progenitor cells in long-term remission of acute leukemia.

In vitro growth of CFU-e and BFU-e in bone marrow and of circulating BFU-e in a group of adult long-term survivors of acute leukemia has been evaluated. Six patients with acute nonlymphoblastic and three patients with acute lymphoblastic leukemia in first continuous remission for more than four years (range 4-12 years) and without maintenance therapy for at least one year were studied. BFU-e and CFU-e growth in patients' bone marrow was not statistically different from a control group of 12 healthy adult volunteers. However, proliferation of BFU-e in peripheral blood of patients was significantly reduced (p less than 0.001). This growth pattern was found in both lymphoblastic and myeloblastic leukemia.

Acute Disease↗
PubMed1986

Effect of human plasmalipoproteins on erythropoietic progenitor cells in serum-free cultures.

The purpose of the present study was to investigate the influence of human lipoproteins on CFU-e and BFU-e proliferation from human bone marrow in a serum-free system. In our previously described miniaturized agar system the main lipoprotein-density-classes from human plasma, namely very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), low density lipoproteins (LDL), high density lipoproteins2 (HDL2) and HDL3 and a mixture of all the five lipoproteins were added in rising concentrations (from 1/10 to normal human plasma concentration) to serum-free medium containing delipidated and deionized bovine serum albumin (BSA), iron saturated transferrin and erythropoietin. The results demonstrate that all lipoproteins markedly increased the CFU-e and BFU-e proliferation after 7 and 14 days of incubation, respectively. Moreover, the lipoproteins induced a shift towards a lower threshold concentration of erythropoietin. Serumlike conditions were obtained if LDL and the mixture of lipoproteins were added to serum-free medium. Furthermore, in the serum-free cultures a maturation to the mature erythrocyte could be found.

Agar↗
PubMed1986

Human erythropoiesis in vitro and the source of burst-promoting activity in a serum-free system.

Bovine serum albumin (BSA) can markedly increase the number of size of erythropoietic bursts produced by mononuclear cells from human bone marrow and peripheral blood, and reduce the threshold amount of erythropoietin (Epo) required for initial burst formation. The purpose of this study was to determine a possible burst-promoting activity (BPA) of BSA. The experiments were performed in a miniaturized agar system, in which the addition of sheep Epo to cultures with or without BSA was delayed for five days. The results obtained have shown that, with or without BSA, Epo deprivation of up to five days (an epoprival state) did not markedly decrease the number of bursts produced by unfractionated peripheral mononuclear cells compared to the number produced in the presence of Epo from the beginning of culture. Similar results were found whether the fetal calf serum (FCS) concentration was 15% or 2%. The preservation of potential BFU-e formation during the epoprival state has therefore been attributed to the ability of T-lymphocytes and/or monocytes to supply BPA. In order to reduce the endogenous amount of BPA, a nonadherent, E-rosette-negative cell fraction was cultured in the presence of Epo, with or without BSA, in serum-free medium containing transferrin (TF). Under these conditions, an equal number of bursts was obtained in FCS and in serum-free medium containing Epo, BSA and TF, whereas no BFU-e growth was found in the presence of Epo and TF, but without BSA. If Epo was withheld for up to five days, the capacity to form erythroid colonies was still retained by the monocyte- and T-lymphocyte-depleted cell fraction in the continuous presence of BSA. However, BPA could not be detected in the BSA. This observation was further supported by experiments in serum-free medium using human recombinant Epo, in which no BFU-e colony formation could be detected in the presence of BSA. From our investigations carried out at limited cell density and in serum-free medium, it could be concluded that the crude Epo preparation was the source of BPA.

Animals↗