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Biomedical subjects

W Hinterberger

Publications and source records attributed to W Hinterberger.

At least 127 records · Page 7Linked to original sources

Aplastic anemia: assessment of myeloid progenitor cells in the bone marrow and blood provides prognostic information.

15 patients with aplastic anemia were prospectively followed after having measurements of myeloid progenitor cells in bone marrow and blood. Treatment included androgens, low or high dose steroids and standardized supportive care. The median length of survival was 5.8 months. When patients were grouped according to the numbers of myeloid progenitor cells present in their blood and bone marrow, we found that the survival length of aplastic patients with higher progenitor cell numbers was prolonged when compared to that of patients with lower numbers of these cells. The prognostic information obtained from such in vitro cultures was particularly indicative when the patients were grouped according to 'growth' and 'no growth': the absence of colony-forming myeloid stem cells was associated with survival times significantly shorter than those of patients whose cells maintained their colony-forming capacity. Besides initial numbers of myeloid progenitor cells, only initial numbers of granulocytes were related to survival length. Thus, the measurement of myeloid progenitor cells in bone marrow and blood can be of prognostic value in patients with aplastic anemia.

Aged↗

Evidence of HLA-DR antigen biosynthesis by human keratinocytes in disease.

As opposed to normal human skin where HLA-DR expression is restricted to the Langerhans cell (LC) population, HLA-DR, but not HLA-DS antigens can be readily detected on keratinocytes (KC) in certain disease states, i.e., cutaneous T cell lymphoma (CTCL), graft-vs-host disease (GVHD), and lichen planus (LP). To clarify the cellular origin of KC-bound HLA-DR antigens, we used a monoclonal antibody directed against determinants solely expressed on the cytoplasmic HLA-DR gamma chain (VIC-Y1) and observed that, by immunofluorescence, KC displaying HLA-DR alpha/beta complexes on their surface uniformly displayed cytoplasmic VIC-Y1 reactivity. In view of the crucial role of the gamma chain for HLA-DR biosynthesis, we conclude that HLA-DR antigens on KC are actively synthesized by these cells.

Epidermis↗

Malignant histiocytosis with unusual features. Disseminated intravascular coagulation with severe hyperfibrinolysis, acute polyneuroradiculitis Guillain-Barré, and a unique chromosome abnormality.

The case of a 25-year-old man with the characteristic features of malignant histiocytosis (proliferation of abnormal histiocytic cells with erythrophagocytosis, hepatosplenomegaly, increased serum acid phosphatase, hypercalcemia, and bone pain) is reported. Chromosome studies revealed a near tetraploid karyotype with a pair of marker chromosomes. A few hours after initiation of chemotherapy with cyclophosphamide, Adriamycin (doxorubicin), vincristine, and prednisolone (CHOP regimen), the patient developed an acute ascending paralysis. Cerebrospinal fluid (CSF) findings were consistent with a diagnosis of Guillain-Barré Syndrome. On the next day, disseminated intravascular coagulation (DIC) with severe hyperfibrinolysis occurred. After intensive chemotherapy, complete remission could be achieved.

Adult↗

Efficacy of the M-2 protocol in previously untreated patients with advanced multiple myeloma.

37 consecutive, previously untreated patients with advanced multiple myeloma (16 patients Stage II, 21 patients Stage III) were treated with a five drug regimen consisting of carmustine, melphalan, vincristine, cyclophosphamide and prednisolone (M-2-protocol) in a prospective manner. Remission was achieved in 24 patients (65%). The median time to remission was 10 weeks, the median duration of remission 15,3 months. Median survival time from the onset of treatment was 24 months for all patients. Responding patients have a projected 65% three year survival. Median survival in non-responders was 10 months. 8 patients died during the first year of treatment. These results do not confirm the favourable results with this drug combination obtained in a previous trial. The discrepancy may be explained by a higher proportion of poor risk patients in the present study.

Aged↗

Range and clinical significance of the number of myeloid-committed stem cells in the blood of patients with acute leukaemia in remission.

Circulating granulocyte/macrophage progenitor cells (CFU-GM) were assayed serially during remission in 17 patients with acute leukaemia (9 ALL, 8 AML). In patients with ALL receiving cyclophosphamide, 6-mercaptopurine and methotrexate, CFU-GM numbers were significantly lower than in normal individuals; cycles of 'reinduction' chemotherapy (vincristine, prednisolone) caused a 10-fold increase in CFU-GM per ml of blood. In 2 ALL patients a substantial increase in CFU-GM numbers preceded the morphologically detectable relapse. In patients with AML receiving repeated courses of cytosine-arabinoside and 6-mercaptopurine, circulating CFU-GM were likewise reduced. In 6 patients who relapsed, a further reduction of CFU-GM was seen. A complete absence of circulating CFU-GM was observed in 10 of the 23 investigations performed within 6 weeks prior to the morphologically detectable relapse, while such a 'zero'-growth occurred in only 1 of 54 experiments performed during stable remission. In summary, in patients with ALL in remission, circulating CFU-GM are increased following treatment with vincristine and prednisolone. In patients with AML, declining numbers of circulating CFU-GM may predict an imminent relapse.

Acute Disease↗

T-cell alterations in hemophiliacs treated with commercial clotting factor concentrates.

Various immunological parameters were determined in 46 patients with severe hemophilia A and in 9 patients with severe hemophilia B. All patients were treated over many years with commercial factor VIII or IX concentrates. Patients with severe classic hemophilia had a significantly reduced relative and absolute number of T-helper cells and a significantly increased relative and absolute number of T-suppressor cells. About half of these patients had an inverse T-helper/suppressor cell ratio. Patients with moderate hemophilia A and severe hemophilia B did not show these abnormalities. Hemophiliacs with an inverse ratio had a significantly higher concentration of serum total protein, IgG and IgM. No relationship between the amount of factor VIII concentrate administered, the HLA-type of the patient, the presence or absence of CMV-antibodies, hepatitis markers, thrombocytopenia and abnormal liver function tests to the T-cell abnormalities could be established. Lymphadenopathy was frequently associated with an inverse ratio. Indirect evidence suggests that the alterations of the immune system began in 1979/80.

Acquired Immunodeficiency Syndrome↗

Methods for the preparation of purified granulopoiesis-inhibiting factor (chalone).

This paper describes in some detail methods which may be useful for the preparation of chalone-like granulopoietic inhibitor(s). Details are given for a) preparation of crude starting material from various sources, b) primary extraction and crude fractionation techniques, c) gel chromatography, d) anion exchange chromatography, and e) thiol-binding chromatography. Possibilities for the chromatographic use of marker substances are discussed and methods for obtaining the factor in radioactively labeled form are given. Some of the stability problems encountered during working and storage of granulopoiesis-inhibiting factor (GIF) are discussed. The purpose of this paper is to provide simple chemical techniques for the purification of GIF for investigators with mainly biological interests.

Animals↗

[Bone marrow transplantation for aplastic anemia--initial results in 8 patients].

8 young patients (aged 11 to 23 years) with severe aplastic anaemia received bone marrow grafts from their HLA-identical, MLC-non reactive siblings. All patients had received repeated transfusions previously and had been unsuccessfully treated with corticosteroids (7 out of the 8 patients) and/or anabolic drugs (4 out of the 8 patients). In order to prevent graft rejection 5 patients received donor buffy coat cells after the marrow infusion and 3 patients underwent total body irradiation with 400 rad prior to the marrow transplantation. 5 patients are alive, 3 patients died. Death occurred from Candida septicaemia (day 4 after transplantation), left ventricular failure (day 14) and graft versus host reaction of the gut (day 85). The 5 living patients are in a very good state of health 30 to 166 days after transplantation. 4 patients already have normal blood cell counts. 2 of the surviving patients developed a transient GVH-reaction of the liver. One patient had a mild GVH-reaction of the skin on day 130.

ABO Blood-Group System↗

Systemic candidiasis complicating bone marrow transplantation in aplastic anemia. Case report.

A 17-year-old male patient with aplastic anemia underwent bone marrow transplantation and succumbed 4 days after marrow infusion from sudden myocardial failure. Fever of unknown origin (FUO) had accompanied the patients course from admission until death. The cause of death was fungus myocarditis, which had escaped detection in vivo, in spite of a daily culture program for bacteria and fungi, and a close monitoring of the patients circulation and ventricular performance. Commonly applied diagnostic criteria for systemic mycosis, such as topical colonization, malfunction of invaded organs and positive fungus cultures failed to provide a timely diagnosis. With regard to the problems in diagnosing systemic mycosis, the potential stem cell toxicity of antifungal drugs and the need for immunosuppressive therapy prior to marrow infusion, we strongly recommend not to start the transplantation procedure unless FUO has been treated successfully.

Adolescent↗

[Causal therapeutic management of aplastic anaemia (author's transl)].

Aplastic anaemia is characterized by hypoplasia of haemopoietic tissue. The aetiology of aplastic anaemia is multifactorial, the majority of cases being termed "idiopathic" because of lack of discernible noxious agents. Treatment can include stimulation of haemopoietic stem cells or replacement of stem cells by bone marrow transplantation. Some cases show autoimmune-mediated marrow failure and these patients may respond to immunosuppressive therapy. Pathophysiological subclassification of individual cases is necessary to ensure the correct choice of therapy offering the best chance of success, at minimum risk, from amongst a multitude of therapeutic procedures.

Adrenal Cortex Hormones↗

[Prognosis of panmyelopathy: a retrospective study (author's transl)].

45 patients with pancytopenia were admitted and treated at the 1st Department of Medicine, University of Vienna, between 1972 and 1978. Retrospective analysis disclosed a significantly longer survival time in association with a hypercellular bone-marrow smear. These patients showed a higher incidence of remission with cortisone anabolic therapy, but more often developed acute leukaemia as well. The median survival time of patients with pancytopenia and a hypocellular or blank marrow was five months. This group of patients should, therefore, be considered for early bone-marrow transplantation.

Adolescent↗

Coexisting suppressor cells for myeloid colony formation in the bone marrow of patients with aplastic anaemia.

Suppressor cells for colony forming cells (CFUC) were found in the bone marrow of 1 of 6 patients with aplastic anaemia. The assay applied was based on the fact that coexisting suppressor cells are more sensitive to dilution than CFUC, as long as adequate stimulation is provided by a source of colony stimulating activity. In the patient with suppressor cells, a 4 d trial of 1000 mg methylprednisolone per d failed to improve the blood cell production and had to be discontinued due to gastric irritation.

Aged↗

[The determination of myeloid-committed stem cells in systemic disorders of myelopoiesis: implications for physiopathology, diagnosis and prognosis].

Myeloid committed stem cells belong to a subpopulation of small nucleated cells, which are defined by their capacity to form colonies of mature myeloid cells in agar-medium. They are termed "Colony forming Unit, CFUC", and such cells are detectable in bone marrow and peripheral blood. Bone marrow cells from 15 control patients with regular myelopoiesis contained 86 +/- 46 CFUC/10(5) bone marrow cells and 23 +/- 14 CFUC/ml blood. In 10 patients with aplastic anemia, only 0-10, 5 CFUC/10(5) BM-cells were found and no CFUC were detectable in the peripheral blood. 17 patients with chronic myeloid leukaemia showed a moderate elevation of bone marrow CFUC (X = 105), while the circulating CFUC were markedly elevated (105-42.000/ml). The circulating CFUC were closely correlated with the number of leukocytes (p less than 0,001). In 12 patients with primary osteomyelofibrosis, the number of circulating CFUC was also (raised (325-22.199/ml) and again, a correlation with the number of leukocytes was observed (p less than 0,05). As, on the other hand, there was no difference in the leukocyte count between the control group and patients with osteomyelosclerosis, the simultaneous assessment of circulating leukocytes and CFUC proves a diagnostic tool. Pancytopenia with a hypercellular bone marrow results from either neoplastic or metabolic alterations of haemopoiesis; in pancytopenia with neoplastic infiltration or transformation, the number of CFUC was lowered, whereas it was slightly elevated in pancytopenia due to metabolic alterations. In patients with acute leukaemia, only a minority of cells was capable of proliferation in vitro. The growth of leukaemic cells in culture, their prolonged survival along with the expression of functional properties may be clinically used for a more subtle classification of blast populations. The data on patients with acute leukaemia indicate, that basic mechanisms of normal blood cell regulation operate in leukaemic haemopoiesis as well.

Adolescent↗

[Ineffective granulopoiesis in pernicious anemia (author's transl)].

The mechanism of neutropenia was studied in 6 patients with pernicious anemia. While the peripheral blood of these patients disclosed neutropenia, the number of myeloid committed stem cells in the bone marrow was increased when compared with values obtained from 15 patients with undisturbed granulopoiesis. In 2 of 3 patients investigated, the number of circulating stem cells was also elevated. In 2 patients the number of stem cells was monitored during treatment with vitamin B12: A rapid decline of stem cells was observed, which was followed by an increase in mature granulocytes. These studies demonstrate an expanded stem cell pool, which is associated with ineffective granulopoiesis.

Agranulocytosis↗

[Control of leukaemic and normal myeloid haemopoietic cells (author's transl)].

The proliferation of myeloid haemopoietic stem cells is absolutely dependent on the presence of a heterogeneous group of proteins with colony stimulating activity (CSA). CSA is generated by monocytes and lymphocytes. The estimation of the molecular weight of colony stimulating factors from both cell lines demonstrates a non-identity. All monocyte derived molecular weight fractions induce differentiation of myeloid stem cells into granulocytes and macrophages. Lymphocyte derived factors have identical biologic activity, with the exeption of one factor which promotes differentiation into eosinophilic granulocytes. Granulocytes release factors which inhibit the growth of myeloid stem cells. Blasts from patients with acute leukaemia do not generate significant amounts of colony stimulating activity, however, in four of nine cases investigated the production of inhibitors for normal stem cell growth is found. Blasts from patients with chronic myeloid leukaemia in blast crisis may be capable of producing colony stimulating activity. Granulocytes from patients with chronic myeloid leukaemia in the chronic phase exhibit no measurable release of inhibitors of myeloid stem cells. In myeloid leukaemias the normal leukocyte population is entirely or partially replaced by leukaemic leukocytes; thus, the proliferation of leukaemic and normal haemopoietic cells is likely to occur under abnormal control.

Animals↗

Different types of endotoxin-induced release of colony stimulating factors by adherent leucocytes in the presence of fresh and heat-inactivated autologous serum.

Human adherent leucocytes stimulate in vitro granulopoiesis by releasing colony stimulating factors (CSF), which promote the growth of myeloid committed stem cells (CFUC). The effect of lipopolysaccharide (LPS) on CSF generation by adherent leucocytes was studied with fresh and heat-inactivated autologous serum. Adherent leucocyte conditioned media were fractionated on Sephadex G-75. LPS, in the presence of fresh serum, caused a significant increase of CSF release by adherent leucocytes within 1 h. Heat inactivation of autologous serum abolished this effect. Adherent leucocyte CSF had 3 activity peaks at greater than 75 000, 23 000 and less than 4 000 daltons. LPS-fresh serum initiated CSF, harvested after culture periods of 1 and 24 h, disclosed identical elution profiles.

Cell Adhesion↗