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Biomedical subjects

G Riethmüller

Publications and source records attributed to G Riethmüller.

At least 217 records · Page 12Linked to original sources

[Immunology].

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Allergy and Immunology↗

Opioid peptide-like immunoreactivity localized in GABAErgic neurons of rat neostriatum and central amygdaloid nucleus.

Opioid peptide-like (OPL)-immunoreactivity and (the GABA-biosynthetic enzyme) glutamic acid decarboxylase-like (GAD)-immunoreactivity were localized in rat neostriatum and central amygdaloid nucleus (ACE) using a polyclonal sheep antiserum to rat brain GAD and a monoclonal mouse antibody to the N-terminus of beta-endorphin (3-E7) as primary antisera. PAP-immunohistochemistry revealed GAD-immunoreactivity in the majority of neurons in neostriatum and ACE. OPL-immunoreactivity was observed in numerous neurons in ACE, but only in few neostriatal nerve cells. In double immunofluorescence in the same section OPL- and GAD-immunoreactivity colocalized in few medium size cells in the neostriatum, but in numerous neurons in ACE. The existence of opioid peptide containing GABAergic neurons in ACE and neostriatum is demonstrated.

Amygdala↗

Genetic influence on natural cytotoxicity and interferon production in multiple sclerosis studies in monozygotic discordant twins.

A dysfunction in natural killer (NK) cell activity has been assumed to play a substantial role in the pathogenesis of multiple sclerosis (MS). To investigate whether such a defect is genetically determined and thus in combination with a certain HLA status may represent an additional risk factor for contracting MS, spontaneous and interferon (IFN) induced NK cells activity against the K562 target cell were analyzed in nine pairs of monozygotic twins discordant for MS. In addition, IFN production was tested in nonadherent lymphocytes stimulated with PHA, influenza virus or leukemia cells. When compared to healthy controls, NK function appeared to be normal in healthy twins, whereas some MS patient displayed decreased activity. No difference in IFN induced NK cell activity and IFN production could be detected between normal controls, healthy twins, and MS patients. These data argue against a genetically determined dysfunction within the NK-IFN system in patients with MS.

Adult↗

Treatment of fresh human leukaemia cells with actinomycin D enhances their lysability by natural killer cells.

Human leukaemia cells isolated from peripheral blood were employed as targets for natural killer (NK) cells obtained from healthy donors and the effect of pretreatment of leukaemia cells with Actinomycin D on lysability was analysed in a chromium release assay. In 8/14 leukaemia cell samples a substantial enhancement of specific release could be repeatedly obtained by exposure of leukaemia targets to Actinomycin D for 4 h. The phenomenon was seen both with interferon-treated and untreated NK cells and could be demonstrated with fresh, as well as, liquid nitrogen stored leukaemia cells. In contrast, lysis of two leukaemia cell lines could not be further enhanced and no release was seen from normal lymphocyte targets or mitogen-induced blasts. Cold target inhibition studies indicate that enhanced killing is mediated by the same kind of natural killer cell, which is active against the Molt4 and K562 leukaemia cell lines.

Adult↗

Monoclonal antibody to the message sequence Tyr-Gly-Gly-Phe of opioid peptides exhibits the specificity requirements of mammalian opioid receptors.

Six myeloma cell hybrids producing antibodies to human beta-endorphin were isolated from a single mouse spleen. The monoclonal antibodies displayed different binding patterns with the antigen. We report the characterization of one antibody which recognizes the tetrapeptide Tyr-Gly-Gly-Phe representing the message sequence found at the NH2 terminus of all naturally occurring mammalian opioid peptides. Competition experiments in radioimmunoassay and immunohistochemistry show that the antibody fails to bind the beta-endorphin precursor beta-lipotrophin, does not discriminate among opioid peptides that share the same message sequence but have different COOH-terminal extensions, and does not react with pharmacologically inactive derivatives of beta-endorphin. The antibody recognition of the message sequence of natural opioid peptides is sensitive to those molecular changes that affect their receptor binding competence.

Amino Acid Sequence↗

Binding characteristics of a monoclonal beta-endorphin antibody recognizing the N-terminus of opioid peptides.

The present paper describes the isolation and characterization of a clone of hybrid myelomas (3-E7) secreting a mouse monoclonal antibody to beta-endorphin. An examination of its specificity against a series of human beta-lipotropin fragments and other opioid peptides revealed that the N-terminus portion of beta-endorphin is the determinant. Complete or almost complete cross-reactivity was obtained to methionine- and leucine-enkephalin, beta-lipotropin 60-65, and BAM 22; partial cross-reactivity was seen to dynorphin1-13 and alpha-neo-endorphin, whereas beta-lipotropin, alpha-N-acetyl-beta-endorphin, Des-Tyr1-beta-endorphin, in addition to a series of synthetic enkephalin derivatives, completely lacked cross-reactivity. The use of the monoclonal antibody in radioimmunoassay (RIA) for beta-endorphin resulted in a lower sensitivity related to respective polyclonal antibodies. An increase of 100% in tracer binding could, however, be obtained by use of beta-endorphin iodinated with its N-terminal tyrosine protected by coupling to an antibody. A solid-phase RIA was developed involving the internally 3H-labeled monoclonal antibody, which resulted in a 10-fold increase in sensitivity as compared with the homogenous RIA. These data indicate that for the binding to this antibody a tyrosine residue in position 61 is essential, and it thus recognizes a site that is of functional significance for many naturally occurring opioid peptides.

Amino Acid Sequence↗

Involvement of the cytotoxic/suppressor T-cell subset in liver tissue injury of patients with acute and chronic liver diseases.

So far, phenotypic and functional analyses of cytotoxic lymphocytes in viral hepatitis, as well as in primary biliary cirrhosis, have focused on circulating lymphocyte subpopulations, whereas their occurrence and distribution at the involved site, namely the liver, remain largely unknown. In the present study, monoclonal antibodies were used to characterize both circulating and liver-tissue-infiltrating lymphocyte subsets in acute cytomegalovirus hepatitis, in chronic B-virus hepatitis, and in primary biliary cirrhosis. Special emphasis was laid on the cytotoxic/suppressor T-cell subset. Total T cells were identified by the monoclonal antibody T411. The monoclonal antibody T811 was used to identify the cytotoxic/suppressor T-cell subset, which comprises virus-specific, altered self, and alloreactive cytolytic T lymphocytes and their precursors, a fraction of killer and natural killer cells. Furthermore, killer and natural killer cells were identified more specifically by the monoclonal antibody. HNK1. Irrespective of the number of cytotoxic/suppressor T cells in peripheral blood, these cells (T811 phenotype) were accumulated in the liver at the site of tissue injury. The preponderance of this lymphocyte subset at the site of tissue injury suggests an important role for these cells in the mechanism leading to tissue injury.

Adult↗

Serological and immunological investigations in patients with gross splenomegaly from the Gabon.

Serological investigations (immunoglobulin, haptoglobin, cryoglobulin, and antibody determination against Plasmodium falciparum and P. malariae antigens) were performed in 64 adults of the Albert-Schweitzer-Hospital, Lambarene, Gabon. The patients were referred consecutively for ultrasound examination of the upper abdominal tract. 31 patients had clinically and sonographically an enlarged spleen, whereas 34 had a normal-sized spleen. 18 patients were regarded as having a gross splenomegaly without an obvious underlying cause (tropical splenomegaly (TSS]. No significant differences were seen between the patient groups with regard to immunoglobulin M or antiplasmodial antibody concentration. Thus, a causal association of splenomegaly with chronic malaria infections could not be established. The haptoglobin levels were significantly (P less than 0.01) reduced in patients with splenomegaly. Peripheral T-lymphocyte subsets as defined by monoclonal antibodies showed in all 4 cases with gross splenomegaly examined distinct abnormalities. Tropical splenomegaly is thought to encompass a variety of diseases, most of them presenting an intermediate stage of reactive to autonome disorders of the lymphatic system.

Adolescent↗

Direct demonstration of an HLA-DR allotypic determinant on the low molecular weight (beta) subunit using a mouse monoclonal antibody specific for DR3.

A murine monoclonal antibody directed against a human B cell surface antigen with the characteristics of HLA-DR is described. The antigen detected is tightly linked to HLA and is correlated with the alloantigen HLA-Dw/DR3. Reactivity with a fraction of Dw/DRw6 cells is also observed. The determinant recognized by this antibody has been shown to be present on the smaller molecular weight beta subunit of the HLA-DR antigen.

Animals↗

Proliferation of T gamma-lymphocytes in two patients: clinical features and functional properties of the proliferating cells.

Two patients suffering form proliferation of T gamma cells exhibited uncommon clinical features, such as activation of intravascular coagulation after low dose irradiation of the enlarged spleen in one patient and isolated neutropenia in the other patients. While the malignant nature of the disease was doubtless in one patient, cell proliferation in the other patient was more likely reactive. In addition to T cell determinants the proliferating cells expressed a monocytic antigen. They did not suppress B-lymphocyte differentiation into plasma cells. In contrast the proliferating cell, especially in one patient, acted as potent effectors in NK and ADCC using melanoma and MOLT 4 target cells. Erythrophagocytosis by T gamma cells was seen in one patient. The data suggest that subsets of T gamma cells are related to the monocytic lineage and that these cells cen mediate both NKA and ADCC and partly can develop phagocytic activity.

Aged↗

Tissue specificity of anti melanoma monoclonal antibodies analyzed on cell lines.

Twenty-eight monoclonal antibodies (MoAbs) from the NIH melanoma exchange program were analyzed in a binding assay for reactivity with a panel of 22 cell lines which included melanomas, carcinomas, fibroblasts, and lymphomyeloid cells. In this test, most MoAbs showed reactivity with a wide range of cell lines. The MoAbs were also tested for binding with freshly removed tumor cells and normal peripheral lymphocytes.

Antibodies, Monoclonal↗

Chronic leukemia with a hybrid surface phenotype (T lymphocytic/myelomonocytic): leukemic cells displaying natural killer activity and antibody-dependent cellular cytotoxicity.

A patient with chronic leukemia exhibited uncommon clinical features, such as hypergammaglobulinemia and activation of intravascular coagulation after low-dose irradiation of the enlarged spleen. By light and electron microscopy, the leukemic cells resembled large granular lymphocytes. The following markers were simultaneously expressed on their surface: receptors for sheep erythrocytes and the Fc part of IgG; common T-cell antigens as revealed by a heteroantiserum (HuTLA) and monoclonal antibodies (OKT3, T411); antigens shared by cytotoxic/suppressor T cells (OKT8, T811) as well as myelomonocytic antigens defined by the OKM1 and M522 monoclonal antibodies. The leukemic cells showed both spontaneous (NK) and antibody-dependent (ADCC) cytotoxicity, but they did not suppress B-cell differentiation in vitro.

Aged↗