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Biomedical subjects

R G Geissler

Publications and source records attributed to R G Geissler.

26 records · Page 2Linked to original sources
PubMed1991

Effect of recombinant human transforming growth factor beta and tumor necrosis factor alpha on bone marrow progenitor cells of HIV-infected persons.

With progressive disease, the majority of patients with human immunodeficiency virus (HIV) infection develop bone marrow failure with anemia, leukopenia, and thrombocytopenia, the cause of which has not yet been clarified. Besides direct infection of bone marrow progenitor cells and immune-mediated cytolysis, the action of inhibitory cytokines, like transforming growth factor beta (TGF-beta) and tumor necrosis factor alpha (TNF-alpha), has to be discussed with regard to their pathophysiological role in HIV-induced bone marrow failure. Therefore, the influence of recombinant human TGF-beta and TNF-alpha on colony growth of pluripotent (CFU-GEMM), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells from the bone marrow of HIV-1-infected persons and normal controls was assessed in methylcellulose cultures. Both cytokines inhibited the colony formation of hematopoietic progenitor cells from HIV-positive persons. When added to unseparated bone marrow cells from HIV-infected persons and normal controls, the 50% inhibition (ID50) of BFU-E by TGF-beta occurred at 1.3 ng/ml and 3.7 ng/ml, respectively, while the ID50 of CFU-GM occurred at 15.5 ng/ml and 142.7 ng/ml. Concentrations of TNF-alpha, causing 50% inhibition of colony formation by bone marrow cells from HIV-infected or noninfected individuals were 6.3 U/ml and 17.0 U/ml for BFU-E, and 24.4 U/ml and greater than 3,000 U/ml for CFU-GM, respectively. The ID50 of the CFU-GEMM growth was below the lowest concentration of both cytokines tested. The suppressive effects were specifically abolished by antibodies against TGF-beta and TNF-alpha, thus confirming that the inhibitory activities were due to the cytokine preparation used.

Adult↗
PubMed1991

TIBO R82913, a new HIV-1 inhibiting agent, does not inhibit hematopoietic progenitor cells.

In progressive stages of infection with human immunodeficiency virus type 1 (HIV-1), the majority of patients develop a pathophysiologically not yet completely explainable bone marrow failure with anemia, leukopenia, and thrombocytopenia. The clinically most widely used HIV-inhibiting antiviral drugs azidothymidine (AZT) and dideoxyinosine (ddI) frequently are hematotoxic to the host, resulting in dose reduction or discontinuation of antiviral therapy. In recent studies, a novel series of benzodiazepine derivatives highly active against HIV-1 was synthesized. These antiviral compounds have a much more favorable therapeutical index than the well-known 2'3'-dideoxyribosides, like AZT. In the experiments presented here, the authors investigated the most promising derivative R82913 [(+)-S-4,5,6,7-tetrahydro-9-chloro-5-methyl- 6-(3-methyl-2-butenyl)-imidazo[4,5,1-jk] [1,4]-benzodiazepin-2(1H)-thione] (TIBO) with regard to its toxicity on bone marrow-derived hematopoietic progenitor cells from six HIV-1+ and HIV- persons, respectively. In methylcellulose assays for hematopoietic colony growth any hematotoxic effects of R82913 in vitro were excluded, as both groups showed no difference of progenitor cell growth with or without the TIBO derivative, even at concentrations 6.7 x 10(4) times higher than the 50% inhibitory concentration for cytopathicity by HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed1988

[Cold agglutinin disease].

Cold agglutinin disease is a normo- or macrocytic anemia due to antibodies, active under body temperature, mostly belonging to the immunoglobulin class M. Initially the agglutination of erythrocytes with acrocyanosis is reversible at body temperature. High antibody activity or long lasting period of coldness lead to intravascular or intrahepatic hemolysis, but high risk anemia is rare. Beside the idiopathic form, infection induced (especially infectious mononucleosis, cytomegalovirus, Mycoplasma pneumoniae, Klebsiella), and drug induced (especially quinidine, alpha methyldopa, penicillin, para-aminosalicylic acid, various analgetics, sulfonylurea), tumor associated (especially malignant lymphomas), and autoimmune disease associated (especially systemic lupus erythematosus) cold agglutinin anemias are discribed. "Cross reacting antigenity" to the hemolysing agent and the membrane of erythrocyte, exogenous induced changing of erythrocytic antigenity, and diversification concerning the production of antibodies are discussed as pathophysiological explanations.

Agglutinins↗
PubMed1988

[Cold agglutinin disease--initial description in erythroblastosis and polycythemia vera].

The cold agglutinin disease is a hemolytic anemia induced by antibodies. Beside other etiological factors the disease is associated with tumors. In this paper cold agglutinin disease combined with erythroblastosis and combined with polycythemia vera is presented at the first time. In one case malignant proliferation followed the appearance of cold agglutinin antibodies. Blood transfusion, plasmapheresis, corticosteroids and chlorambucil were not successful. In the other case antibodies were temporarily expressed after a long time of malignant proliferation. Blood transfusion and corticoids were sufficient. Production of antibodies as a kind of tumor defence is discussed as reason for hemolysis. "Cross reacting antigenity" between normal and malignant erythrocytes is postulated.

Aged↗
PubMedDate not supplied

Early detection of chronic disseminated Candida infection in leukemia patients with febrile neutropenia: value of computer-assisted serial ultrasound documentation.

Computer tomography (CT) is known to be as sensitive as magnetic resonance imaging (MRI) in detecting fungal microabscesses in chronic disseminated candidiasis. However, all imaging techniques have to be repeated in cases of suspected fungal infection. Therefore, use of the CT or MRI scan is limited. Only ultrasound (US) examinations can be repeated as often as needed. The disadvantage of US is a lack of sufficient documentation. We analyzed the value of computer-assisted documentation in serial ultrasonography of leukemia patients with suspected chronic disseminated candidiasis. From November 1996 until October 1997, a total of 220 ultrasound examinations (Kranzbühler Logiq 500, 3.5 MHz convex array) were performed in 58 patients undergoing intensive chemotherapy. Initial US pictures were stored on a personal computer and compared with the live US at the time of reevaluation in cases of persistent fever. Ultrasound detected microabscesses in liver and/or spleen in eight of the 58 patients. Diagnosis was confirmed by autopsy/biopsy (n = 6), blood culture (n = 1), and a significant Candida antibody titer (n = 1). Focal lesions occurred only after neutrophil recovery. However, a newly evolving nonhomogeneous, micronodular pattern of liver and spleen occurred during febrile neutropenia in three patients, and two of these developed focal lesions subsequently. Follow-up was easy, since US pictures could be compared directly with stored examinations on screen. We conclude that serial US is sensitive in detecting microabscesses in the liver or the spleen. Computer-assisted US documentation proved to be a helpful tool for detection as well as in the follow-up of patients with chronic disseminated candidiasis.

Adolescent↗
PubMedDate not supplied

Decreased haematopoietic colony growth in long-term bone marrow cultures of HIV-positive patients.

Deficiencies in bone marrow stromal cells, i.e. fibroblasts, macrophages, endothelial cells and adipocytes, are considered to play a pathophysiological role in HIV-associated haematopoietic failure. Long-term bone marrow cultures (LTBMC) enable the longitudinal investigation of haematopoietic progenitor cell and bone marrow stromal growth. Therefore, in this study, the haematopoietic colony growth of bone marrow from patients with severe HIV infection was compared to that from healthy controls in LTBMC. The total cumulated number of colony-forming units/granulocyte-macrophage (CFU-GM) was 6.7-fold higher (293.6% vs. 44.0%, p < 0.01), that of colony-forming units/granulocyte-erythrocyte-macrophage-megakaryocyte (CFU-GEMM) was 3.5-fold higher (28.7% vs 8.3%), and that of burst-forming units/erythrocyte (BFU-E) was 31.1-fold higher (68.4% vs 2.2%) than that from HIV-positive patients, respectively (colony number before LTBMC = 100%). In contrast, the cumulated cell number at the end of LTBMC from HIV-positive patients was not reduced (cell numbers in percent of initially seeded cells: HIV-positive 418.4%, HIV-negative 397.1%). The significantly reduced colony-forming capacity over a significantly shorter time span, without reduction in the absolute cell number, in LTBMC from patients with severe HIV-infection as compared to healthy controls, suggests that uncoupling between cell proliferation and differentiation is a pathophysiological mechanism in HIV-dependent haematopoietic failure.

Adult↗