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Biomedical subjects

L Kater

Publications and source records attributed to L Kater.

At least 109 records · Page 6Linked to original sources

Lymphocyte maturation in the human thymus. Relevance of purine nucleotide metabolism for intrathymic T cell function.

The combination of centrifugal elutriation as an efficient and reproducible method to separate thymocytes by size, micromethods to assess purine interconversion enzymes, and assessment of purine (deoxy)nucleoside inhibition of mitogen responses enabled us to study purine metabolism at the intrathymic level. Out of six fractions, four (nos. 3-6), containing medium- and large-sized lymphocytes, showed a proliferative response after stimulation with phytohaemagglutinin (PHA). In fractions 1-6 the number of cells with an immature immunological phenotype gradually decreased, and cells with the phenotype of mature cells gradually increased. The enzyme activity ratio of adenosine deaminase to purine nucleoside phosphorylase gradually decreased from 21 in fraction 1 to 7 in the last fraction (blood T-cell value, 0.7). We conclude that this enzyme activity ratio is a useful marker for intrathymic T-cell maturation stages. In PHA-responsive cell fractions (3-6), the sensitivity to inhibition of the PHA response by (deoxy)adenosine and deoxyguanosine was inversely related to the enzyme activity ratio of ecto-5'-nucleotidase to deoxycytidine kinase. These findings are compatible with the hypothesis that intracellular concentrations of phosphorylated (deoxy)nucleosides are related to this inhibition. We conclude that the differences in purine metabolism among the various (mitogen-responsive) human thymocyte fractions are related to lymphoid cell function. Since the number of cells contributing to the enzyme activities and the number of cells contributing to the proliferative response (about 15% of unseparated cells) differ considerably, it is not possible to evaluate enzyme activities in unseparated thymocytes in terms of relationships between purine metabolism and lymphocyte function.

Adenosine Deaminase↗

Selective deficiency of immunoglobulin A2.

A case of familial selective IgA2 deficiency is described. The mother had no detectable IgA2, but a low level of IgA1. She had anti-alpha 2 antibodies of the IgG class. One of her daughters also lacked IgA2 with a normal level of IgA1. The analysis of the immunoglobulin haplotypes of the family suggested the deletion of the alpha 2-gene. In addition, the analysis of B lymphocytes of mother and daughter showed the absence of IgA2-bearing cells. Upon stimulation with pokeweed mitogen, the B cells differentiated into IgA1-containing plasma cells, but IgA2-containing cells were not found. The results suggest a defect in the generation of intraclonal B cell isotype diversity. The molecular basis of this phenomenon is unknown.

Adolescent↗

Identification and in situ localization of the "thymic nurse cell" in man.

The observation of the "thymic nurse cell" (TNC), a reticuloepithelial cell with intracytoplasmic lymphocytes, in suspension of murine thymic tissue prompted us to investigate the existence of this cell in cell suspension, as well as in tissue sections of the human thymus. TNC-like cells were enriched in suspension by enzymatic disintegration of thymic tissue and 1 X G sedimentation over 50% fetal calf serum gradients. TNC-like cells were negative for lysosomal enzymes: in this respect, as well as in light microscopic morphology, the cells were different from tissue macrophages with intracytoplasmic lymphocytes. In electron microscopy, TNC-like cells showed reticuloepithelial characteristics. In 1-micron tissue sections, clusters of lymphocytes with a possible reticuloepithelial nucleus were observed close to blood capillaries in the cortical area. Ultrastructural analysis confirmed the epithelial nature of this cell, as well as its location adjacent to blood capillaries. We concluded that there is in situ existence of TNC in man. This observation enables studies on the role of TNC in intrathymic T cell maturation.

Cell Differentiation↗

Functional analysis of the defective T cell regulation of the antigen-specific PFC response in SLE patients: differentiation of suppressor precursor cells to suppressor effector cells.

The investigation described here is concerned with the T cell regulation of the antigen-specific antibody response which has been studied in patients suffering from systemic lupus erythematosus (SLE). Apart from the fact that T helper cell activity was found to be less efficient, it appeared that the peripheral blood leucocytes (PBL) of patients in an active stage of the disease did not contain the suppressor precursor cells, which functions as the target cell for the inductive signal of T mu+ suppressor inducer cells. The absence of the suppressor precursor cells in SLE patients coincided with the absence of T gamma+ suppressor effector cells. Characterization of the (post-thymic) precursor cells (derived from normal donors) with the aid of monoclonal antibodies of the OKT series and several other markers pointed out that this population contains OKT4+ as well as OKT8+ cells. Further experiments demonstrated that the cells are capable of rosetting with autologous erythrocytes, and do not bear Fc receptors for IgM or IgG. Considering the various findings as a whole the conclusion is warranted that the post-thymic suppressor precursor T cell can differentiate into a suppressor effector cell only after interaction with T suppressor inducer cells.

Antibodies, Monoclonal↗

Studies on the mechanism of action of human thymic epithelial conditioned medium on mouse thymocytes. Evidence for induction of immune competence.

It has been shown that addition of human thymic epithelial conditioned medium (HTECM) leads to an increased response of mouse thymocytes to concanavalin A and phytohemagglutinin. HTECM caused a maximal potentiating effect when added to thymocyte cultures at the time of their initiation. Addition at later times had a smaller enhancing effect and after 24 hr no effect of HTECM could be measured. Responses to mitogen were higher at all time periods measured and peak responses were shifted to later times in the presence of HTECM. Determination of cell viability made it highly unlikely that the effect of HTECM was simple due to enhanced numbers of viable cells in culture. These data support the view that HTECM induces T-lymphocyte maturation.

Animals↗

Effect of plasmapheresis (PP), corticosteroids and cyclophosphamide in essential mixed polyclonal cryoglobulinaemia associated with glomerulonephritis.

In two patients with type III essential cryoglobulinaemia with glomerulonephritis and neurological involvement, the effect of prednisone, plasmapheresis, the combination of both and subsequently the addition of cyclophosphamide was studied. Prednisone alone had no effect, plasmapheresis alone was only temporarily effective in one patient. The combination of prednisone and plasmapheresis was also only temporarily effective. Addition of cyclophosphamide resulted in complete clinical remission in both patients.

Antigen-Antibody Complex↗