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G Riethmüller

Publications and source records attributed to G Riethmüller.

At least 163 records · Page 9Linked to original sources
PubMed1989

Functional aspects of three molecules associated with metastasis development in human malignant melanoma.

To identify molecules which may be functionally associated with the development of metastasis in human melanoma, monoclonal antibodies which discriminate between benign and malignant melanocytic lesions in situ were selected. Biochemical studies and cDNA cloning identified the antigens HLA-DR, ICAM-1 and MUC18 which showed an expression pattern on primary tumors correlating with vertical tumor thickness, the most predictive parameter for the development of metastasis in melanoma. ICAM-1 and MUC18 show sequence similarity to a family of cell adhesion molecules which include the neural cell adhesion molecule NCAM. Both HLA-DR and ICAM-1 can be induced on melanoma cells by lymphokines, suggesting a role of the mononuclear cell infiltrate in the control of tumor cell phenotype. Knowledge of the normal function of these molecules allows one to hypothesize how they may contribute to the successful development of metastases.

Antigens, CD↗
PubMed1989

Clonal analysis of liver-derived T cells of patients with primary biliary cirrhosis.

Lymphocyte infiltration in liver tissue is one important histological finding in primary biliary cirrhosis (PBC). So far, functional analyses of lymphocytes in PBC have focused on circulating lymphocytes, whereas lymphocytes at the involved site, the liver, have not been examined functionally. We have established interleukin 2 (IL-2)-dependent T lymphocyte lines (TLL) and clones (TLC) from liver biopsies of 14 patients with PBC. Phenotypic analysis using the monoclonal antibodies MT910 (CD2), MT811 (CD8), and MT151 (CD4) revealed that in nine of 14 TLL cytotoxic-suppressor T cells predominated (CD8+:52-84%; CD4+:14-48%), whereas in five of 14 TLL a preponderance of the CD4+ subpopulation was found (CD4+:56-73%; CD8+:28-45%). From 10 patients 137 TLC were generated which phenotypically correlated to the TLLs. We have tested the cytotoxic potential of seven TLL and 43 TLC in LDCC (lectin-dependent cell-mediated cytotoxicity), NK (natural killing) and ADCC (antibody-dependent cell-mediated cytotoxicity) assays. All TLL and all but one CD8+ TLC tested showed high activity in the LDCC assay, reflecting the cytolytic activity of cytotoxic T cells (CTL). CD4+ clones with LDCC activity were rarely found. NK activity and K cell activity could only be found in two clones. For the first time TLC and TLL from liver tissue of PBC patients could be generated. The high cytotoxic activity displayed by T cells derived from the liver indicates an important role for this immunological mechanism in the tissue damaging process.

Adult↗
PubMed1989

Complement activation in human lymphoid germinal centres.

The presence of complement activation products has been studied in morphologically normal human lymphatic tissue from tonsil, spleen and lymph node. Newly established monoclonal antibodies (mAbs) with reactivity against the C4 cleavage fragments C4a, C4b, C4c and C4d were applied on cyrostat sections in the indirect immunoperoxidase staining technique. Irrespective of organ type, C4d activation product could be detected in germinal centres of all secondary lymphoid follicles. To substantiate this finding, the complete sequence of complement activation products was investigated by a series of mono- and polyclonal antibodies to the complement proteins C1, C2, C3, factor B, C5, C9 to C5b-9 neoantigens and to the regulatory complement proteins C4 binding protein (C4bp), factor I, factor H and properdin. Similar to C4d, all secondary follicles exhibited a strong staining reaction for C3d antigens restricted to germinal centres. At the same site, albeit with distinctly weaker intensity, components of the membrane attack complex (MAC) C5b-9 were found. The simultaneous deposition of C1, C4b and C4bp in certain germinal centres indicates that complement activation is induced via the classical pathway. Concomitant deposition of IgM suggests IgM-antigen complexes that have been trapped on follicular dendritic cells (FDC) during normal immune response as the most likely candidates for activators of the classical pathway. Our data demonstrate that human lymphoid germinal centres as important sites of immune regulation closely interrelate with the complete cascade of complement-activation products, including the membrane attack complex (MAC).

Antigen-Antibody Complex↗
PubMed1988

MACG1, a mouse monoclonal antibody detecting a monosialoganglioside expressed in tumor-infiltrating macrophages.

MacG1 is a mouse monoclonal antibody (mAb) directed against a ganglioside, which is differentially expressed by macrophages infiltrating malignant melanomas and benign melanocytic lesions. mAb MacG1 was obtained by immunization with liposomes containing a mixture of gangliosides extracted from malignant melanoma. The antibody was selected for binding to melanoma gangliosides and for reactivity with frozen tissue sections of malignant melanoma. mAb MacG1 showed reactivity in 25 of 46 melanomas examined but in only 1 of 51 nevi tested. The mAb did not react with melanoma cells but did with cytoplasmic granules and deposits associated with large dispersed cells, which were also found in some nonmelanomatous tumors and in some lymphoid tissues. Using mAbs directed against differentiation antigens these cells were identified as macrophages. In nearly all reactive tissues MacG1-positive macrophages accounted for a minority of the total macrophages. The difference in reactivity between malignant melanomas and nevi could not be explained by the variable numbers of total macrophages in these lesions. It is suggested that mAb MacG1 may define a functionally distinct subpopulation of tumor-infiltrating macrophages. Staining of cells other than macrophages was observed in some normal and malignant neural tissues. MacG1 bound to a monosialoganglioside extracted from melanoma and reacted only with NeuAc alpha 2-3Gal beta 1-4Glc-Cer when tested with a panel of ganglioside standards.

Animals↗
PubMed1988

Glycoprotein P3.58, associated with tumor progression in malignant melanoma, is a novel leukocyte activation antigen.

The P3.58 antigen is defined by monoclonal antibodies (MAbs) selected to discriminate between benign and malignant melanocytic cells. Its expression in malignant cells has been shown to correlate with an increased risk of metastasis. A survey of a wide range of tissues revealed that, on normal tissue, expression of P3.58 antigen is restricted to a subset of cells involved in the immune response. The antigen was found not only on certain endothelia, but also on activated macrophages in vivo and in vitro and as well as on activated B lymphocytes. A comparison with known B-lymphocyte and leukocyte activation antigens indicated that P3.58 is a novel leukocyte activation antigen. Biochemical analysis of the P3.58 antigen isolated from cells of different histogenic origin indicated that different molecular forms of the antigen exist, apparently depending on the cell type of origin. P3.58 molecules precipitated from tunicamycin-treated cells were identical in all cell types, suggesting that the variation observed is due to variable N-glycosylation.

Antigens, Neoplasm↗
PubMed1988

Biochemical characterization and tissue distribution of the Cora antigen, a cell surface glycoprotein differentially expressed on malignant and benign gastrointestinal epithelia.

A monoclonal antibody designated Cora was isolated which discriminates between malignant and benign colon epithelium. It identifies a novel, variably glycosylated membrane glycoprotein. Expression of the Cora antigen was shown to be characteristic for gastrointestinal carcinomas (100% of tested colorectal carcinomas, 70% of tested gastric carcinomas) but could not be detected on normal gastrointestinal tissues using histochemical methods on frozen tissue sections. An extensive survey of normal tissues revealed that the Cora antigen has a very restricted distribution pattern, being detected only on alveoli of the lung, granulocytes, and bone marrow. Polyacrylamide gel electrophoresis of immunoprecipitates prepared from [35S]methionine, 125I, or [3H]glucosamine labeled colon carcinoma cell lines showed that the Cora antigen consists of a group of glycoproteins ranging in apparent molecular weight from 75,000 to 95,000. Following treatment with neuraminidase, the apparent molecular weights were reduced (65,000 to 85,000) but the size heterogeneity remained. Culturing the cells in the presence of tunicamycin, which inhibits N-linked glycosylation, removed this heterogeneity and under these conditions monoclonal antibody Cora precipitated a major band with an apparent molecular weight of 33,000. Because this monoclonal antibody can distinguish between normal and malignant gastrointestinal epithelia, expression of the Cora antigen may be associated with the process of malignant transformation in this tissue.

Animals↗
PubMed1988

Establishment of a human cell line (Mono Mac 6) with characteristics of mature monocytes.

A monocytic cell line, termed Mono Mac, was established from peripheral blood of a patient with monoblastic leukemia. Two clones, designated Mono Mac I and Mono Mac 6, were isolated and both were assigned to the monocyte lineage on the basis of morphological, cytochemical and immunological criteria. Most importantly, the clones express NaF-sensitive non-specific-esterase, produce reactive oxygen and stain with MAb My4. Mono Mac 6, in addition, constitutively exhibits phagocytosis of antibody-coated erythrocytes in 80% of the cells and reacts with a panel of MAbs that are specific for mature monocytes, i.e., M42, LeuM3, 63D3, Mo2 and UCHMI. By contrast, the monoblastic cell lines U937 and THP-I are negative for all these markers. Only expression of My4 could be detected after differentiation induced by interferon-gamma (IFN-gamma). Similar treatment of Mono Mac I, however, resulted in staining with all the monocyte-specific MAbs mentioned above, while IFN-gamma treatment of Mono Mac 6 enhanced antigen expression. In addition, the cells showed an increased frequency of multinucleated cells with a rise from 4.8% to 21.9%. Mono Mac 6 appears to be the only one of the cell lines studied to constitutively express phenotypic and functional features of mature monocytes.

Cell Line↗
PubMed1988

The tumor progression-associated human melanoma antigen P3.58 mediates monocyte-lymphocyte interactions in vitro.

The melanoma-associated antigen P3.58 is rarely found on benign proliferating melanocytes but is consistently expressed on advanced malignant melanomas which have a high probability of metastasis. Previous studies have shown that its expression on normal tissues is limited to vascular endothelia and lymphoid follicle germinal centers and that it is also expressed by activated monocytes in vitro. In the studies reported here, anti-P3.58 monoclonal antibodies (mAb) were shown to partially inhibit antigen-specific and anti-CD3-induced T cell proliferation and to completely block a lymphocyte/monocyte clustering which occurs in the absence of added antigen. This inhibition is highly specific for P3.58 mAb and was not affected by mAb directed to major histocompatibility complex or T cell antigens. P3.58 therefore seems to be involved in an antigen-independent attraction or adhesion of lymphocytes. P3.58 is the second example (HLA-DR being the first) of an association between the expression of an immune function-associated molecule and the development of metastatic disease in melanoma.

Antibodies, Monoclonal↗
PubMed1988

Class II (DR) antigen expression on CD8+ lymphocyte subsets in acquired immune deficiency syndrome (AIDS).

In a selected group of human immunodeficiency virus (HIV)-infected patients we confirm the expansion of a CD8+ T-lymphocyte subset, i.e., the CD8+/Leu7+ cells, which account for 30% of the lymphocytes, compared to 3% in the control donors. In addition, a CD8+ T-lymphocyte subset that coexpresses class II (DR) antigens, i.e., CD8+/DR+ cells, is also increased from 1.5% in controls to 27% in the HIV-infected patients. Using three-color immunofluorescence and flow cytometry we can demonstrate that the CD8+/Leu7+ and the CD8+/class II+ cells are not distinct but overlapping subsets. In the HIV-infected patients 42% of the CD8+/Leu7+ cells were strongly positive for class II and these CD8+/Leu7+/class II+ cells accounted for 13% of all lymphocytes. These findings indicate that the expanded CD8+/Leu7+ cells are activated and hence might be actively involved in immune defense in acquired immune deficiency syndrome (AIDS).

AIDS-Related Complex↗
PubMed1988

The melanoma progression-associated antigen P3.58 is identical to the intercellular adhesion molecule, ICAM-1.

The 89kd cell surface glycoprotein, P3.58, is expressed on human malignant melanomas in situ where it is associated with an increased risk of metastatic disease. Monoclonal antibodies detecting denatured P3.58 were produced and used to isolate a P3.58 encoding cDNA clone from a human melanoma lambda expression library. Sequencing of the cDNA revealed that the P3.58 antigen is identical to the leukocyte intercellular adhesion molecule 1 (ICAM-1).

Amino Acid Sequence↗
PubMed1988

Enzymatic degradation in phagocytic monocytes generates the ganglioside epitope defined by antibody MacG1.

Monoclonal antibody (mAb) MacG1 was recently shown to detect a monosialoganglioside expressed in tumor infiltrating macrophages. The present study demonstrates with in vitro experiments that the MacG1 epitope is generated during cellular digestion in phagocytic monocytes. Following phagocytosis and degradation of MacG1 negative sheep red blood cells, the MacG1 epitope was expressed in intracytoplamsic granules of murine plastic-adherent peritoneal cells. Stimulation of adherent cells and phagocytosis alone did not lead to the expression of the MacG1 epitope. Chloroquine, which inhibits the activity of lysosomal enzymes, prevented the generation of the MacG1 epitope. Reactivity with mAb MacG1 appears to reflect a specific step during the enzymatic degradation of gangliosides and the antibody may provide a unique tool for analyzing this pathway.

Animals↗
PubMed1988

Molecular biology of the HLA-B27 locus.

The molecular biology of the HLA-B27 locus is reviewed. The HLA-B27 gene itself does not differ between healthy individuals and ankylosing spondylitis patients. Several unique features of the HLA-B27 molecule have been identified and one epitope was proposed to cross-react with bacterial proteins.

Amino Acid Sequence↗
PubMed1988

T4/T8 ratio and absolute T4 cell numbers in different clinical stages of Kaposi's sarcoma in AIDS.

Thirty-seven men (36 homosexual or bisexual and one heterosexual) with epidemic Kaposi's sarcoma and underlying HIV infection were followed up over a period of up to 32 months. Fourteen patients (38%) died, with a median survival time of 7.2 months after the diagnosis of AIDS. Seventeen patients (46%) presented with one or more opportunistic infections, mostly Pneumocystis carinii pneumonia. Eighteen patients (49%) had lymphadenopathy syndrome according to the definition of the CDC. Using the Laubenstein-classification of Kaposi's sarcoma, all patients either remained stable or deteriorated, improvement was never observed. Absolute T4 lymphocyte counts and the T4/T8 ratio were not related to the disease stage. With the onset of B symptoms (systemic symptoms), however, the absolute T4 numbers and the T4/T8 ratio markedly decreased. Delayed type hypersensitivity also showed no relationship to the clinical stages of Kaposi's sarcoma. Thus, the clinical progression of Kaposi's sarcoma lesions seems to be largely independent of the immunological parameters investigated. However, the onset of B symptoms was observed to be related to changes in immune status.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Influence of nicotine on monocyte phenotype and function.

Monocyte expression of class II antigens was studied in smokers and in nonsmokers using double marker analysis and flow cytometry. There was no difference in class II expression with 78.8% and 79.3% class II+ monocytes in smokers and nonsmokers, respectively. Further, in vitro treatment with nicotine at levels seen in smokers (50 ng/ml) did not alter class II expression either. When analyzing TNF production using the Wehi 164/ActD 51Cr-release assay we observed a two-fold lower TNF production in smokers versus nonsmokers. In vitro treatment of monocytes with nicotine, however, did not reduce the LPS triggered TNF production.

Fluorescent Antibody Technique↗
PubMed1988

Tumor necrosis factor in human monocyte-mediated antitumor cytotoxicity.

The WEHI-164 target cells pretreated with actinomycin D can be employed in a 7-hour 51Cr release assay that exhibits exquisite susceptibility for cytotoxic monocytes without contribution by natural killer cells. The system can be used either to detect cell-mediated monocyte cytotoxicity directly or to measure cytotoxic-factor activity in cell-free supernatants. Analysis of cytotoxic factor demonstrates molecular characteristics similar to tumor necrosis factor (TNF), and polyclonal as well as monoclonal antibodies specific for TNF can readily neutralize the monocyte-generated cytotoxic factor. In the cell-mediated approach, neutralization can be achieved as well, although somewhat higher amounts of antibody are required. Hence, the WEHT-164/actinomycin D system appears to detect monocyte cytotoxicity that is mediated by TNF.

Animals↗
PubMed1988

[Monoclonal antibodies--new probes for diagnosis and therapy. Their use as an example of the micrometastasizing of solid tumors].

Monoclonal antibody CK2, recognizing component No. 18, appeared to be the most suitable reagent for the detection of epithelial tumor cells in bone marrow. Its specificity was confirmed in a double-marker staining procedure (combination of APAAP-technique and radioautography). CK2 positive cells were demonstrated not to reveal any cross-reactivity with an antibody directed against the "leucocyte common antigen". A significant correlation between the presence of epithelial tumor cells in bone marrow and certain conventional risk factors was found. A more detailed phenotypic characterisation could demonstrate the expression of proliferation associated antigens on these cells. Furthermore in an immunotherapeutic approach with monoclonal antibody 17-1A, labelling of the disseminated tumor cells in bone marrow after infusion of the antibody was shown.

Antibodies, Monoclonal↗
PubMed1987

[Serological and immunological diagnosis of HIV-1 infection. Studies of 198 infected cases].

Since 1985, a total of 4281 patients at the Department of Dermatology, University of Munich, were tested for HIV-1 antibodies. Using the ELISA test, 273 were found to be positive, of whom 198 were examined clinically. At the time of the first serological test, 76 of these 198 patients (38.4%) had no clinical symptoms, 98 (49.5%) had a lymphadenopathy syndrome, and 29 had the full-blown picture of AIDS (12.1%). The following additional tests were performed on the 198 patients: antibodies against virus envelope and core proteins, concentration of serum immunoglobulins G, A and M and beta 2-microglobulin, absolute leukocyte and lymphocyte counts, T4/T8 ratio, and intracutaneous cellular immune reaction. Antibodies against virus envelope proteins were present in all the patients. Antibodies against virus core proteins were present in 82% of patients in the latent stage, 64% of patients with the lymphadenopathy syndrome, but only 45% of those with AIDS. Clearcut deviations within the three groups were also present with respect to serum levels of IgG and beta 2-microglobulins, as well as the T4/T8 ratio and the intracutaneous reaction against recall-antigens.

AIDS-Related Complex↗