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Biomedical subjects

W Müller-Ruchholtz

Publications and source records attributed to W Müller-Ruchholtz.

At least 163 records · Page 9Linked to original sources
PubMed1984

Immunosuppression by cytostatic drugs?

In the present study, an attempt was made to characterize the immunomodulating abilities of the cytostatic drugs cyclophosphamide, ifosfamide, vinblastine, vincristine, procarbazine, dacarbazine, 6-mercaptopurine, methotrexate, 5-fluorouracil and adriamycin in a defined experimental model. Varying combinations of drug plus transplantation alloantigen, (C3H-lymphocytes) were injected into Balb/c mice at different time intervals in vivo. The resulting T-effector cell reactivity was determined in vitro with the microcytotoxicity assay on day +5 for primary (1 degree) and day +7 for secondary (2 degrees) sensitized mice. According to the type of drug (alkylating agent vs. vinca alkaloid vs. antimetabolite vs. cytostatic antibiotic), the dosage (20% LD50 vs. 60% LD50), the state of sensitization (1 degree vs. 2 degrees sensitized recipients), and the time of drug application in relation to the antigen treatment on day 0 (in varying steps from day -6 to day +4), so-called "pharmacon-antigen-variation-effects" (PAVE) were established for each of the investigated drugs in form of reaction profiles. The results were as follows: For almost all substances, characteristic reaction profiles involving immunostimulation and/or immunosuppression could be established. Similarities in the profiles of different substances made it possible to classify the drugs according to different reaction types. The reaction type however is not definitely correlated to the biochemical mechanism of drug action. The PAVE are decisively influenced by some of the biological parameters, such as the time of drug application in relation to the antigen treatment and the state of sensitization but relatively little by the dosage of the drug. Considering the different processes occurring during primary and secondary immune responses, the PAVE may give hints for a distinct manipulation of the immunoregulation and thus information on the immunobiological mechanism of drug action.

Animals↗
PubMed1984

Tracheal transplantation. II. Influence of genetic difference and degree of sensitization on reactions to the tracheal transplant.

To determine what influence the extent of genetic difference and degree of presensitization exercise on reactions to tracheal transplants, orthotopic tracheal transplantations were performed in 189 rats. In groups with minor genetic differences (non-RT1-different combination) and major genetic differences (RT1-different combination), the survival rates were significantly lower in comparison with syngeneic controls. In both strain combinations, presensitization prior to orthotopic tracheal transplantation led to significantly lower survival rates. The survival times of the RT1-different strain combination were obviously shorter than those of the non-RT1-different strain combination. Therefore, the degree of histo-incompatibility and presensitization, detectable only and purposively variable in investigations on inbred strains, strongly influences the reactions to a tracheal transplant. Indications of an organospecific antigenicity of the tracheal transplant have not been found. Thus, the trachea is subject to the same immunological laws for transplantation as all other tissues.

Animals↗
PubMed1984

HLA typing of nonviable tissues with a multiple microabsorption method.

HLA typing is usually performed by directly measuring complement-dependent cytotoxicity on viable peripheral blood lymphocytes as target cells. To overcome the limitations inherent to viable targets, absorption inhibition techniques have been developed. The main drawbacks of most of these techniques are, however, that they are not very feasible and require relatively large amounts of absorbing material and rare antisera. Therefore, we adjusted the multiple microabsorption method (MMA) and tested simultaneously for 16 HLA specificities of the A, B, and C locus on 6 different nonviable tissues. The results of the MMA, when compared with those of the usual microlymphocytotoxicity test (LCT) that was run in parallel, correspond in 96% of the 28 comparable antigen pairs. Only one false negative and no false positive result was found. The absorbing quality of the individual organs differed, as was to be expected: lymph node and spleen rank on the top, followed by liver and kidney, whereas brain and muscle show several negative reactions. Altogether, the MMA proves to be a reliable and practical method for typing nonviable tissues, eg, in hematological diseases or in certain forensic situations.

Brain↗
PubMed1983

Increase of MLC sensitivity by elimination of a non-adherent responder cell subpopulation with anti-macrophage serum.

A specific rabbit anti-rat macrophage antiserum (SAM) was prepared with a cytotoxic reactivity pattern complementary to that of a specific anti-lymphocyte serum. This was used to characterise adherent and non-adherent spleen cell subpopulations in mixed lymphocyte cultures. Adherent SAM+ cells reacted as accessory cells whereas non-adherent SAM+ cells were suppressors. Selective elimination thus achieved resulted in a highly significant increase of MLC reactivity in certain strain combinations and in conversion from non-reactivity to reactivity in others.

Animals↗
PubMed1982

Neutrophil granulocytic cell antigen defined by a monoclonal antibody--its distribution within normal haemic and non-haemic tissue.

Monoclonal antibodies were raised against normal human bone marrow cells. One of the antibodies obtained, monoclonal antibody 3C4 (MA 3C4), the subject of this paper, was characterised by immunofluorescence studies with viable normal peripheral blood and bone marrow cells and by immunoperoxidase studies using paraffin sections. In bone marrow and peripheral blood MA 3C4 reacts selectively with cells of late neutrophilic granulopoiesis (myelocytes, metamyelocytes, and neutrophilic granulocytes). Cells of erythropoiesis, thrombopoiesis and lymphopoiesis are negative. In lymph node and spleen only neutrophils react with MA 3C4. In non-haemic tissue reactivity was seen with epithelial cells of a variety of different gland ducts. Thus the antigen detected by MA 3C4 can serve as a marker for neutrophil differentiation in normal haemopoiesis and as a marker for ductal epithelial cells of a variety of organs within non-haemic tissue. The antigen is formalin-resistant and can be detected in paraffin sections. The antibody thus appears to be a valuable reagent for both haematological research and for routine pathology.

Antibodies, Monoclonal↗
PubMed1981

Patterns of antibody reactivity against selected human leukemia cell lines.

Absorption procedures which allow the production of a selectively cytotoxic anti-human lymphocyte serum are described. Although the production of a reagent whose reactivity is restricted. Although the production of a reagent whose reactivity is restricted exclusively to lymphocytes may be achieved by exhaustive absorption steps using fresh human erythrocytes, CML cells, and fetal liver cells, a more realistic alternative is the use of appropriately selected cultured human leukemia cell lines. Data are presented which show how these cell lines may be employed to selectively manipulate the cross-reactivity spectrum of ALS. Pre-treatment of donor bone marrow cells prior to transplantation with a selectively lymphocytotoxic ALS has been shown to allow transplantation of bone marrow across major histocompatibility barriers in rodents without the occurrence of GvH reactions, and it is the purpose of the present investigations to show that an analogous anti-human ALS can be prepared which possesses the required degree of selectivity to allow its application for human bone marrow transplantation.

Antilymphocyte Serum↗
PubMed1981

Cell separation by antibody-coupled magnetic microspheres and their application in conjunction with monoclonal HLA-antibodies.

The modification and efficiency of a technique for cell separation is described. This technique combines the specificity of serologic reactions with the strength and physical selectivity of a magnetic field. A monoclonal HLA-BW 6 antibody was coupled to 100 nm diameter Fe3O4 containing albumin microspheres via surface-incorporated St. aureus Protein-A. The mixture of HLA-BW 6 and -BW 4 human peripheral blood lymphocytes was incubated with these immunomicropheres and applied to a glass column located in a magnetic field. Only HLA-BW 4 lymphocytes passed through the column and were collected. The recovered cells were 97% viable.

Antibodies, Monoclonal↗
PubMed1981

[Evidence that electrophoretic-mobility (EM) test is of no value for the diagnosis of cancer in children (author's transl)].

After incubation with encephalitogenic factor (EF) the capacity of lymphocytes to inhibit the migration of tanned, stabilized sheep-erythrocytes in the electric field was tested in 133 children (52 tumor- and 81 control patients). Tumor patients (on and off treatment) as well as children suffering from non-inflammatory diseases showed a significant migration inhibition as compared with healthy controls (p less than 0.05). However, in only 3/23 patients on, and 3/35 off therapy, an unequivocal inhibition of more than 8% could be demonstrated. The repeated examination of 8 individual patients yielded an unsatisfactory reproducibility; results were independent of the EF concentration ranging between 200-600 microgram EF/ml. We think that the EM-Test provides no useful information for the detection of malignant disease in children.

Adolescent↗
PubMed1979

[Immunopathogenesis of the Vogt-Koyanagi-Harada syndrome].

Regarding immunopathogenesis of the Vogt-Koyanagi-Harada syndrome (VKHS), peripheral blood lymphocytes of a female patient with this disease were tested for sensitization against several antigens such as myelinic basic protein (BP) and uveoretinal, brain and spleen tissue homogenates. For comparison, cells of seven patients with chorioretinitis only and cells of six patients with encephalitis of unknown etiology were also tested. Cells of healthy donors served as controls. The electromobility test and the leucocyte migration test were used as in vitro test systems for cell-mediated immunological reactivity. The results show a strong sensitivity against BP and uveoretinal and brain tissue homogenates in VKHS. In the patients suffering from chorioretinitis, a strong reactivity against uveoretinal homogenate only was found, while in patients with encephalitis, responses to brain antigens only were observed. Reactions towards spleen tissue homogenate were negative in all experiments. The extent to which this tissue-specific immunological reactivity, which is different from the monoreactivity in chorioretinitis or encephalitis, might be a characteristic phenomenon of the VKHS is discussed.

Eye Proteins↗