Biomedical subjects
H W Kreth
Publications and source records attributed to H W Kreth.
Human immunodeficiency virus infection in microglia: correlation between cells infected in the brain and cells cultured from infectious brain tissue.
In acquired immunodeficiency syndrome, the lesions of the central nervous system in association with the human immunodeficiency virus are thought to be related to an infection of microglia, although no studies are available in which cultured and physiological characteristics of microglia cells infected in vivo have been examined. In this report, we used brain tissue from a child dying of human immunodeficiency virus infection and show that microglia cells were the main cell population being infected. Moreover, isolated macrophage-like cells from fresh brain material revealed a close resemblance to peripheral blood macrophages in their content of surface and intracellular antigens. No virus particles or viral antigens were produced by these cells during the first week of cultivation. Productive infection was readily apparent, however, by day 30. This finding illustrates the slow nature of the virus life cycle in these cells and the minimal cytopathology that accompanied the infection.
Epstein-Barr virus infection and associated diseases in children. II. Diagnostic and therapeutic strategies.
Epstein-Barr virus (EBV), an ubiquitous human B lymphotropic virus, is the cause of infectious mononucleosis. Moreover, EBV infection can be followed by lymphoproliferative diseases in patients with inherited and acquired immunodeficiencies. Primary EBV infection may be a threat to all children after marrow or organ transplantation or those receiving chronic immunosuppressive treatment for various other reasons. The virus has been also implicated in the pathogenesis of different malignant tumours such as Burkitt lymphoma, nasopharyngeal carcinoma, Hodgkin disease and also some T-cell lymphomas. This review focuses on various aspects of virus-host interactions, immune mechanisms of the host, and the still experimental therapeutic approaches in EBV-associated diseases.
Epstein-Barr virus infection and associated diseases in children. I. Pathogenesis, epidemiology and clinical aspects.
Epstein-Barr virus (EBV), an ubiquitous human B lymphotropic virus, is the cause of infectious mononucleosis. Moreover, EBV infection can be followed by lymphoproliferative diseases in patients with inherited and acquired immunodeficiencies. Primary EBV infection may be a threat to all children after marrow or organ transplantation or those receiving chronic immunosuppressive treatment for various other reasons. The virus has been also implicated in the pathogenesis of different malignant tumours such as Burkitt lymphoma, nasopharyngeal carcinoma, Hodgkin disease and some T-cell lymphomas. This review focuses on various aspects of virus-host interactions, immune mechanisms of the host, and the still experimental therapeutic approaches in EBV-associated diseases.
Clinical value of measuring the interferon-induced enzyme 2'-5'-oligoadenylate synthetase in children.
2'-5'-oligoadenylate synthetase, an interferon-induced enzyme and a sensitive indicator of the presence of interferon, was measured in peripheral blood mononuclear cells in children with inflammatory disorders of known and unknown origin in order to assess the value of such a test in patient management. Differences in median 2'-5'-oligoadenylate synthetase values in groups of children with viral or bacterial diseases or healthy children were observed. Considerable overlap of the 2'-5'-oligoadenylate synthetase range in the three groups was observed. All children with acute viral infections had increased levels early in their disease and a low value clearly argued against an acute viral infection. However, as more than one-third of children with bacterial diseases displayed elevated 2'-5'-oligoadenylate synthetase concentrations, distinction between a viral and bacterial cause of disease by measuring this enzyme was difficult. Estimation of 2'-5'-oligoadenylate synthetase concentrations in patients with inflammatory diseases of unknown origin, including juvenile rheumatoid arthritis, systemic lupus erythematosus, idiopathic uveitis and glomerulonephritis did not contribute to establishing a diagnosis or measuring disease activity.
Epstein-Barr virus-associated lymphoproliferative syndromes: studies in two European families.
The X-linked lymphoproliferative syndrome (XLP), also known as Duncan's disease, is an X-linked recessive disorder that is characterized by the inability of affected individuals to mount a sufficient immune response to Epstein-Barr virus (EBV). After EBV primary infection, male family members suffer from severe infectious mononucleosis (IM), aplastic anemia, hypogammaglobulinemia, and a spectrum of lymphoproliferative diseases. Autosomal mode of inheritance with similar symptoms as in XLP has been reported. We have studied two families with EBV-associated syndromes and an X-linked and an autosomal mode of inheritance, respectively. Affected family members presented with severe IM, hemophagocytosis, aplastic anemia, acquired hypogammaglobulinemia, and B-cell lymphoproliferative diseases.
[Epstein-Barr-virus-induced lymphoproliferative diseases].
Infections with EBV are of increasing importance in pediatrics. Molecular and immunological methods have led to important advances in our understanding of the biological properties of this virus and the immunological consequences to its host. EBV-associated lymphoproliferative disorders mainly arise in immunodeficient patients by the unchecked polyclonal outgrowth of EBV-infected B-cells. On the other hand, primary genetic changes in B-cells (chromosomal translocation and oncogene deregulation) may also lead to induction of monoclonal lymphoma.
[Tumor suppressor genes: occurrence, significance and function].
Tumor-suppressor-genes were detected by DNA-analysis of childhood tumors. A homozygous deletion or mutation of these genes is closely associated with different malignant tumors. Tumor-suppressor-genes seem to play an important role in cellular development and differentiation. The understanding of this pathomechanism in cancerogenesis is most important for calculating a genetic risk for tumor development.
Demonstration of HLA restricted killer cells in patients with acute measles.
The relationship between HLA determinants on effector and target cells and cell-mediated cytotoxicity was studied using the release of 51Cr from measles virus-infected PHA-blasts. HLA compatibility between effector and target cells was not required if effector lymphocytes were derived from measles seropositive adults, from a patient with SSPE, and from children after live measles vaccination. Cytotoxicity was always abolished after removal of Fc receptor-bearing lymphoid cells. In these donors, the effect is, therefore, probably due to K cells. In contrast, lymphocytes from children with acute measles preferentially killed those virus-infected target cells with which they shared HLA antigens. Selective lytic activity was still observed after elimination of Fc receptor-bearing lymphoid cells. It is suggested that HLA-dependent killer cells represent specific cytotoxic T lymphocytes. These cells seem to be limited to the acute phase of measles.
Cell-mediated cytotoxicity against measles virus in SSPE. I. Enhancement by antibody.
In patients with subacute sclerosing panencephalitis (SSPE) virus persistency has been explained by a blocking factor of specific cell-mediated immunity in SSPE serum and cerebrospinal fluid (CSF). In the present study the effect of SSPE serum and CSF on cell-mediated cytotoxicity against 51Cr-labeled allogenic measles virus-infected target cells was tested. Pretreatment of SSPE peripheral lymphoid cells by serum or CSF neither blocked nor increased measles-specific cytotoxicity when cells were subsequently tested in FCS containing tissue culture medium. However, killing activity was always enhanced after pretreatment of target cells or direct addition of serum or CSF to the cytotoxic assay. Enhancement was also observed with non-SSPE-derived measles antibodies. The effect was dependent on measles antibody concentrations. These results suggest that antibody-dependent killing by K cells is intact in patients with SSPE. It is possible that virus-infected brain cells are protected from an immune attack in vivo by antibody-induced antigenic modulation.
Cell-mediated cytotoxicity against measles virus in SSPE. II. Analysis of cytotoxic effector cells.
An analysis of subacute sclerosing panencephalitis (SSPE) lymphocytes was performed in order to find out whether T or K cells were involved in killing of 51Cr-labeled allogeneic measles virus-infected target cells. Lymphocyte donors were three patients with SSPE, 10 measles seropositive controls and 2 children with measles rash. It was found that about 75% of measles-specific cytotoxicity was lost after removal of Fc-receptor-bearing cells by adsorption onto immune complex monolayers. K cell activity (as measured by lysis of 51Cr-labeled-sensitized chicken red blood cells) was reduced to the same extent. After adsorption, the enhancing effect by specific antibody was no longer observed. Unfractionated peripheral lymphoid cells that had been treated with pronase and kept in culture 24 hr were inactive in the cytotoxicity test when compared to freshly isolated cells. However, cytotoxicity could be restored almost completely by the addition of measles antibodies. The results indicate that measles-specific cytotoxicity by peripheral lymphoid cells from all three groups of donors is mediated by K cells. It is probable that specificity is provided by a small amount of contaminating serum antibody or immune complexes.
[Immunologic studies in SSPE].
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Letter: HL-A and subacute sclerosing panencephalitis.
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