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J Neppert

Publications and source records attributed to J Neppert.

At least 73 records · Page 4Linked to original sources

Receptor patching and capping of platelet membranes induced by monoclonal antibodies.

Redistribution of glycoproteins (GP) Ib, glycocalicin, IIb, and IIIa on the surface of human platelets in response to stimulation with corresponding monoclonal antibodies (MoAb) and a polyclonal antiglycocalicin antibody was studied by immunofluorescence, immunoelectron microscopy, and a quantitative radioimmune assay. Immobilization of the antigens by prefixation with formaldehyde showed a uniform distribution over the surface of the platelet. Incubation of unfixed platelets with specific MoAb against various epitopes on GPIIb and/or IIIa resulted in a time-dependent patching, subsequent capping, and after prolonged exposure to the antibody/label complex, internalization of the complex, possibly by endocytosis. In contrast, GPIb could not be shown to cap. From these results we conclude that platelet GPIIb and/or IIIa undergo spatial rearrangement in a manner analogous to that observed in lymphocytes, whereas GPIb does not. Since both GPIb and GPIIb and/or IIIa seem to be transmembraneous GP associated with the cytoskeleton, a special, though unidentified, role of GPIIb/IIIa in the induction of lateral membrane mobility is postulated.

Antibodies, Monoclonal↗

Murine monoclonal antibodies and human alloantisera specific for HLA inhibit monocyte phagocytosis of anti-D-sensitized human red blood cells.

Evidence is presented that monoclonal antibodies (mAb) against some human major histocompatibility complex (MHC) gene products and human sera containing HLA antibodies strongly inhibit immune phagocytosis of anti-D-sensitized red blood cells by human monocytes. w6.32HL, a mAb against a monomorphic class I antigen of high cell surface density, revealed the strongest inhibition among mAb reactive with MHC class I products. mAb with preferential reactivity for monomorphic and polymorphic DR and DQ epitopes (L203, L227, IIIE3, Tü22, Genox 3.53 and IV12) were noninhibitory. Definite inhibition was also apparent with a mAb against DRw52/MT2 (I-LR2) and with an antibody to class II antigens of high cell surface density (2MC3). Human sera containing HLA antibodies showed strong inhibition of immune phagocytosis up to a dilution of 1/1000. This inhibition could not be abrogated by platelet absorption. This indicates that human sera inhibiting immune phagocytosis may comprise at least two types of antibodies: cytotoxic HLA-specific antibodies which may or may not be inhibitory, and inhibitory antibodies against monocytic antigens not necessarily cytotoxic. These latter antibodies may recognize HLA DR or another as yet undefined gene product within, or closely associated to, the human MHC.

Antibodies, Monoclonal↗

Interdependent membrane mobility of human MHC coded antigens detected by monoclonal antibodies to various epitopes on class I and II molecules.

Binding of monoclonal antibodies (MAB) to human MHC coded class I antigens, w6.32HL or 61D2, specifically leads to clustering of these antigens and their assembly at one polar site on a cell, whereby these class I antigens tow class II-antigens with them into the polar cap revealing preexisting or arising molecular complexes in the membrane of the living cell. These class II antigens included DR (seen by MAB 2MC3, L203, L227, I-LR2, 109d6, SFR-3) and DQ (seen by Genox 3.53 and IVD12). In analogous cocapping experiments employing MAB to various class II antigens, interdependent surface mobility (bidirectional cocapping) could be demonstrated between DRw52 (MT2, seen by I-LR2) and DQw3 (MB3, seen by IVD12) as well as between DRw53 (MT3, seen by 109d6) and DQw3. There was incomplete interdependence between DRw52 or DRw53, respectively, and other DR antigens (seen by L227). These latter antigens were independent from DQ (seen by Genox 3.53 or IVD12). Analyzing pairs of monoclonal antibodies with various specificities to determinants on class I or II molecules a frequent finding was unidirectional cocapping: here a first antibody cocapped epitopes seen by a second, but this antibody did not cocap epitopes seen by the first. We conclude that epitopes are irregularly distributed on MHC coded molecules or on complexes of these molecules.

Antibodies, Monoclonal↗

Endothelial monocyte antigens are coded for by loci centromeric of HLA-B.

900 pregnancy sera were screened for monocyte antibodies. 23 sera (2.6%) were found to be reactive with monocytes in an allotypic pattern distinct from blood group ABO, HLA-A,B,C, DR and DQ specificities. Because of strong reactions and high reproducibility, 4 sera with pure endothelial monocyte (EM) reactivity and 2 sera also positive with B lymphocytes of certain donors were selected for population and family studies. The frequency of positive reactions in a panel of 26 random donors obtained with the pure EM sera was 13, 8, 8 and 13% with clearly distinct patterns. Analysis of the tentatively designated EM antigens 1.1, 1.2, 2.1, and 2.2 in 7 families revealed definite segregation with HLA. By means of two crossing-over events within the HLA region the two hypothetical EM loci were localized centromeric of HLA-A and one of both loci centromeric of HLA-B.

Antigens, Surface↗

HLA-A, B, C; -DR; -MT, -MB, and SB antigens on unstimulated human endothelial cells.

Since major histocompatibility complex (MHC) antigens of class II play an important role in organ transplantation, we attempted to demonstrate their expression on endothelial cells which are abundant in transplants with vascular blood supply. Our analysis was performed with monomorphic and polymorphic monoclonal antibodies employing a microscopic immunofluorescence assay and flow cytometry on unstimulated endothelial cells isolated from umbilical cord veins. No evidence was found for the presence of HLA-DR antigens and determinants associated with MT, MB and SB. MHC class I antigens exhibited reduced expression. These findings were confirmed in respect to alloantigens by the use of conventional cytotoxic tissue typing antisera. MB and SB antigens were present on most cord B lymphocytes, but could only be demonstrated on a subpopulation of monocytes exhibiting a lower antigen density at the cell surface. MT and DR antigens were found on most cord monocytes and B lymphocytes.

Antigens, Surface↗

Improved monocyte cytotoxicity test.

A micro-modification of the two-colour monocyte cytotoxicity test (MCTT) is described. It employs exclusively adherent monocytes for staining, sensitizing and labeling instead of monocyte suspensions. Thereby unspecific cytotoxicity is decreased while sensitivity and specificity of the test are improved. As a micro-technique, this modification of the MCTT is useful for antibody screening as well as antigen definition.

Cell Adhesion↗

[Trials with therapeutic plasmapheresis in pemphigus vulgaris].

A seventeen year old female with pemphigus vulgaris was treated by exchange plasmapheresis. Plasmapheresis was performed five times over three weeks. Each procedure significantly reduced the serum level of intercellular antibodies. Without immunosuppressive therapy and with only moderate doses of corticosteroids the clinical symptoms had improved after the three weeks period. Plasmapheresis represents an alternative therapeutical possibility in the treatment of pemphigus vulgaris in order to achieve a rapid reduction in circulating levels of the intercellular antibodies.

Antibodies↗

Immunologic response in onchocerciasis: relations to microfilaria density in the skin biopsy and to some frequent symptoms.

During physical and immunologic investigations on onchocerciasis in 1,298 persons in the Republic of Liberia, the following results were obtained. There is a significant correlation between immune response and Onchocerca volvulus infection detected by a microfilaria-positive skin biopsy. On the other hand, the immune response is not influenced by the number of parasites in the skin, and there is no correlation of the immune response with Onchocerca nodules and with pruritus. There is a high proportion of serologically false-positive and false-negative results, and thus a diagnosis cannot be made simply by establishing evidence for antibodies in one person.

Adolescent↗

[False-negative antiglobulin-(Coombs-) test caused by anticomplement bovine albumin batches in the transfusion preparation].

Different brands of bovine albumins were tested as reagent in the second step of the so called 3-stage-screening test for irregular blood group antibodies. In 3 of 9 brands of bovine albumin there was anticomplementary activity which was the cause of diminished or negative reactions in the third stage of the screening test (antiglobulin stage). The disadvantageous brands of bovine albumin contained Na2-EDTA which revealed to be responsible for the anti-complementary activity.

Blood Transfusion↗

[Studies on the serological manifestation of the hepatitis B-virus-infections in the Republic of Liberia (author's transl)].

The prevalence of hepatitis B virus infections was examined in four groups from Liberia using radioimmunoassays for HBsAg, anti-HBs and anti-HBc. At the age of 15-19 years 90% have been infected, at the age of 40 years 100%. In a rubber plantation 30% had HBsAg, in the remaining 3 groups only 13% were HBsAg-positive. In the first group onchocerciasis was also a more frequent finding. However the parasitic infection was not the cause of the HBs-antigenemia. The HBsAg-concentration is mostly lower in the positive Liberians than in German HBsAg-carriers. Apparently the HBV caused frequently latent infections with low production of viral antigens in Liberia.

Adolescent↗

[The estrogen dependence of the pregnancy associated alpha glycoprotein "SP3" and its occurrence in sera of patients with various malignant and benign diseases].

The pregnancy associated alpha-2-glycoprotein "SP3" is a macroprotein; the serum concentration of which is markedly enhanced by the increase of endogenous and exogenous estrogen. As regards the bronchial and uterine cancer the frequent presence of enhanced SP3 serum concentrations in tumour patients can be explained by an enhanced production of endogenous estrogen. This enhanced production has been described in literature. SP3 does not occur in healthy men and women without application of estrogen. In 26% of the cases it can be proved in cases of benign disease and in 52% in malignant cases having received no therapy of estrogen.

Contraceptives, Oral↗

[The closed hexagon immunodiffusion (CHI) for the diagnosis of onchocerciasis (author's transl)].

1273 sera from microfilaria-positive and -negative persons living in an onchocerciasis-endemic area in Liberia were examined. For this purpose a modification of the Ouchterlony-test was performed and compared with other methods. In the complement-fixation test many sera showed complement inhibition without any possibility to eliminate it. There were considerably varying titers in the indirect hemagglutination test. This helped to distinguish groups with different correlations to microfilaria-findings. The closed hexagon immunodiffusion after TRAAVIK, SIEBKE and KJELDSBERG (1972) - a modified OUCHTERLONY-test - proved to be nearly as good as indirect hemagglutination. An advantage of the CHI test is that it is easy to carry out. CHI reacted in 64% of microfilaria-positive and in 25% of microfilaria-negative cases.

Complement Fixation Tests↗