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Biomedical subjects

L Kater

Publications and source records attributed to L Kater.

At least 91 records · Page 5Linked to original sources
PubMed1985

In vivo biological effect of allogeneic cultured thymic epithelium on thymus-dependent immunity in athymic nude rats.

We have extended our previous study of induction of T-lymphocyte immunocompetence in athymic nude rats by cultured epithelium (CTE) of syngeneic origin to that by CTE of allogeneic origin. Immune responsiveness (IgG-class antibody and delayed-type hypersensitivity) after ovalbumin immunization is detectable by 4-6 weeks after transplantation. However, the antibody appears at a slower rate when compared with heterozygous immunocompetent littermates. Seven weeks after transplantation phytohaemagglutinin responsiveness of spleen cells is detectable, and in T-dependent areas of lymphoid organs lymphocytes with helper and non-helper T-cell phenotype are present, but at lower levels than those in heterozygous immunocompetent littermates. Levels comparable to that of immunocompetent rats are reached about 20 weeks after transplantation. Since CTE contains thymocytes, control experiments consisted of transplantation with high numbers of allogeneic freshly isolated thymocytes in athymic nude rats. These animals showed IgG-class antibody formation after ovalbumin immunization, but at lower levels than CTE-treated rats, and were almost negative in T-cell immunocompetence assessed in the other assays. We conclude that CTE of allogeneic origin induces T-cell immunocompetence in athymic nude rats to the level of heterozygous immunocompetent littermates. This study adds to the rationale of CTE transplantation applied in treatment of thymic dysfunction.

Animals↗
PubMed1985

The human thymus microenvironment: heterogeneity detected by monoclonal anti-epithelial cell antibodies.

Monoclonal antibodies were raised against human thymus stromal cells and their specificity for the epithelial component of thymus stroma assessed by double immunofluorescence using anti-keratin antibodies to identify epithelium. Our monoclonal antibodies identify six distinct patterns of epithelial cell antigen expression within the thymus: pan epithelial (antibody IP1); cortex (MR3 and MR6); cortical/medullary junction (IP2); subcapsule and subpopulation of medulla (MR10/MR14); Hassall's corpuscles and adjacent subpopulation of medulla (IP3); Hassall's corpuscles only (MR13/IP4). This heterogeneity of antigen expression suggests that many different epithelial microenvironments exist within the human thymus.

Animals↗
PubMed1985

Heterogeneity and age dependency of human thymus reticulo-epithelium in production of thymosin components.

The specific compartmentalization of intrathymic lymphoid cells in different steps of T-cell maturation and the involvement of thymosin components in these steps prompted us to evaluate the localization of epithelial cells synthesizing various thymosin components. Thymosin fractions 5 and 6 were found in epithelial cells throughout the thymus cortex and medulla. Thymosin alpha 1 and beta 4 were observed in subcapsular and perivascular epithelial cells, and thymosin alpha 1 was observed in the medullary epithelium. Thymosin alpha 7 was exclusively found in Hassall's corpuscles and adjacent epithelial cells. We conclude that the organ localization of epithelium synthesizing different thymosin components is associated with the organ localization of intrathymic T-cell maturation steps. The involution of the human thymus, starting during the third decade of life, has been related to the age-dependency of thymus humoral factors in the circulation. However, quantitative data on humoral factor synthesizing epithelial cells are lacking. We found a strong intensity of thymosin fraction 6 expression by epithelium in thymus tissue from donors in the early postnatal period (2-4 months of age) and from all four donors aged 20-30 years. This phenomenon was paralleled by a high number of thymosin fraction 6 positive cells per unit area.

Adolescent↗
PubMed1984

A prospective study of the changes in immune status following radiotherapy for Hodgkin's disease.

In a prospective study, immune status was measured in 23 previously untreated patients with Hodgkin's disease Stage I-IIIA. Assessments of immunologic capacity were performed at diagnosis and repeated after staging laparotomy and after radiotherapy. The immune status was measured using delayed-type hypersensitivity tests to common recall antigens, the number of T- and B-lymphocytes in the peripheral blood, in vitro lymphocyte responsiveness to mitogens, antigens, and allogeneic lymphocytes, and serum levels of immunoglobulins. Skin reactivity was not significantly affected by either the staging laparotomy with splenectomy or the radiotherapy. Absolute T-lymphocyte count increased after splenectomy (P less than 0.025) and decreased after radiotherapy (P less than 0.005 compared to postsplenectomy values). In vitro lymphocyte responsiveness after splenectomy was comparable to the initial presenting level and diminished after radiotherapy (P less than 0.005). Serum levels of IgM were lowered after radiotherapy (P less than 0.05) while the fall was not significant after splenectomy. Three months after radiotherapy, lowest mean T-cells percentages were noted, but the responses to mitogens were significantly higher than those obtained immediately after treatment (P less than 0.01). While the reduction in the proportion of the T-lymphocytes persisted for 18 months, the mean lymphocyte responsiveness to mitogens, antigens, and allogeneic lymphocytes increased on follow-up. Apart from a severe impairment of the immune status following radiotherapy, this study also shows the existence of significant repair mechanisms during the follow-up period.

Adolescent↗
PubMed1984

Heterogeneity of epithelial cells in the human thymus. An ultrastructural study.

To evaluate interrelationships among epithelial cells, and between morphology and function in the microenvironment, we studied the ultrastructural morphology of epithelial cells in sections of human thymus from donors aged 2 months to 31 years. Six types of epithelial cells were observed: "subcapsular-perivascular" (type 1); "pale" (type 2); "intermediate" (type 3); "dark" (type 4); "undifferentiated" (type 5); and "large-medullary" (type 6). Cells of types 2, 3 and 4 were found throughout the organ. The type-2 to -4 epithelial cells may represent various stages in a differentiation process. In this, type-2 cells are very active and type-4 cells are possibly degenerating elements. Type-4 cells can also contribute to Hassall's corpuscles. Type-5 cells were located mainly in the cortico-medullary region and showed the morphological characteristics of undifferentiated elements. Type-6 cells were located exclusively in the medulla and displayed characteristics of cellular activity. Small Hassall's corpuscles consisted of type-6 epithelial cells; in larger corpuscles many nuclei of type-6 cells were found. Cells of types 2 and 6 contained tubular structures (diameter approximately 20 nm). Concerning the function of thymus epithelial cells, the features associated with protein synthesis observed in cellular types 2 and 6 make them likely candidates for humoral factor-producing and/or secreting elements. In addition, type-2 and -3 cells in the cortex appear to contribute to a special pattern of epithelium-lymphocyte interaction ("thymic nurse cells"), as demonstrated by the intracytoplasmic location of lymphocytes in the epithelial cells. The various steps in intrathymic T-cell maturation occur at locations in a microenvironment composed of morphologically distinct epithelial cells.

Adolescent↗
PubMed1984

Multinucleate giant cells in sublabial salivary gland tissue in Sjögren's syndrome. A diagnostic pitfall.

The presence of multinucleate giant cells in the sublabial salivary gland tissue in Sjögren's syndrome is an unusual phenomenon which can give rise to differential diagnostic problems. We found in 4 cases of 55 patients with Sjögren's syndrome multinucleate giant cells. In 2 of these 4 patients epimyoepithelial islands were also present. The combination of both multinucleate giant cells as epimyoepithelial islands can mimic the histological picture of a non- caseating granulomatous disease. To discriminate between an epimyoepithelial island and an epithelioid granuloma the immunoperoxidase technique with antibodies directed against muramidase appeared an useful tool. The epithelioid cells contain muramidase whereas the cells in the epimyoepithelial island do not contain this enzyme. Thus, multinucleate giant cells are a rare phenomenon in Sjögren's syndrome, therefore restricting its diagnostic significance. When they occur in Sjögren's syndrome staining for muramidase can be of help to avoid a false positive diagnosis of diseases in which non- caseating granulomatous inflammation occur, such as in sarcoidosis.

Adult↗
PubMed1984

Plasma-exchange in the treatment of severe thyrotoxicosis in pregnancy.

Three female patients with severe thyrotoxicosis, two of them pregnant 22 and 16 wk, respectively, were treated with plasma-exchange (PE) combined with anti-thyroid drugs. In both pregnant patients PE was an effective adjunct to therapy with low-dose carbimazol. They were both delivered of normal babies at 37 and 40 wk, respectively. One newborn was euthyroid, the other had transient neonatal thyrotoxicosis. In the non-pregnant patient an ominous situation of thyrotoxic crisis was rapidly reversed by a single PE. During PE an influx of thyroid hormones occurs from the extra- to the intravascular compartment, which increases the efficacy of PE. The 5% albumin solution derived from human donor plasma, used as replacement fluid, contained substantial amounts of thyroid hormones. A 5% albumin solution from human placental origin lacks these hormones and is therefore recommended as replacement fluid for PE in thyrotoxicosis. There are no valid arguments for advocating replacement with donor plasma.

Adult↗
PubMed1984

Cold lymphocytotoxic antibodies in systemic lupus erythematosus.

Optimum conditions were established for the assay of cold lymphocytotoxic antibodies (cLCTA) in serum from patients with systemic lupus erythematosus (SLE). The optimum temperature of the incubation step with complement was 15 degrees C. For target cells incubated with dextran a significantly higher percentage of damaged cells (p less than 0.005), a faster rate of cell damage (p less than 0.001) and a requirement for less complement was observed than for target cells not incubated with dextran. Under optimum conditions in the cytotoxicity assay, 62% of SLE sera damaged more than 60% of the target cells, whereas 73% of the sera from control donors damaged less than 20% of the target cells. In multiple serum samples obtained during follow-up of 30 patients with SLE, the serum cytotoxic activity or titer of cLCTA fluctuated and did not relate to clinical symptoms of disease activity. In sera obtained during active disease the cytotoxic activity was related to the anti-dsDNA antibody level and with levels of circulating immune complexes measured by the Raji cell assay and the indirect granulocyte phagocytosis test. We found no restricted reactivity of cLCTA against phenotypically distinct T-lymphocyte subpopulations with different immunoregulatory functions. The reactivity pattern of cLCTA towards the various T-lymphocyte subpopulations was not related to disease activity. We conclude that cLCTA in patients with SLE represent an epiphenomenon, being the result of a hyperreactive B-cell system rather than the cause of the disease.

Adolescent↗
PubMed1984

The efficacy of plasma exchange in the removal of plasma components.

The efficacy of plasma exchange in the removal of immunoglobulins (IgG, IgM, IgA), complement components (C1q, C4, C3), alpha 1-antitrypsin, alpha 2-macroglobulin, and transferrin was studied by analysis of pre- and postexchange serum samples and the plasma removed both in a healthy volunteer and in five patients undergoing therapeutic plasma exchange. In the healthy volunteer, the measured reduction in serum concentration and the measured amount removed for each component was compared with values predicted by a physical model. For all components except IgM, the sum of the measured amount removed during the procedure and the calculated amount present in the circulation progressively exceeded the calculated intravascular amount present before plasma exchange. This was particularly the case for C4, C3, alpha 1-antitrypsin, and alpha 2-macroglobulin and may be explained by influx from the extra- to the intravascular compartment during the procedure. Influx also occurred in the patients. We conclude that, except for IgM, the actual amount of a component that has been removed should be assessed for proper evaluation of the efficacy of PE.

Blood Proteins↗
PubMed1984

Rebound and overshoot after plasma exchange in humans.

On the basis of animal experiments, some authors recommend a routine combination of therapeutic plasma exchange in patients with immunologically mediated disorders, such as autoimmune and immune complex diseases, with administration of cytotoxic drugs to prevent overshoot in plasma levels of pathogenic components after plasma exchange. We examined one healthy volunteer, seven patients with nonimmunologic diseases, and seven patients with immunologically mediated disorders (six with non-organ specific and one with organ-specific autoantibodies) to test whether plasma exchange is succeeded by an overshoot in levels of immunoglobulins, isohemagglutinins, autoantibodies, and antibodies after booster immunization with diphtheria and tetanus toxoid combined with poliomyelitis vaccine. Our data indicate that overshoot is not a generally occurring phenomenon in humans. We also confirmed the capability of corticosteroids, administered immediately after a period of plasma exchange, to reduce autoantibody levels. We found no arguments to support the suggestions in the literature that plasma exchange be combined with cytotoxic drugs in treatment of immunologically mediated diseases to prevent stimulation of potentially pathogenic components such as autoantibodies.

Adolescent↗
PubMed1983

A prospective study of the changes in the immune status before, during, and after multiple-agent chemotherapy for Hodgkin's disease.

In a prospective study, immune status was measured in 20 previously untreated patients with Stage III and IV Hodgkin's disease. Assessments of immunologic capacity were performed at diagnosis and repeated after eventual staging laparotomy and after multiple-agent chemotherapy. The immune status was measured using delayed-type hypersensitivity tests to common recall-antigens and in vitro lymphocyte responsiveness to mitogens, antigens, and allogeneic lymphocytes. Immunoglobulin levels were determined on each point of assessment. In untreated patients, the disturbances in the cell-mediated immunity had no predictive value with respect to the chance to achieve a complete remission. During chemotherapy the mean value of the unstimulated culture in responders increased, whereas it decreased in nonresponders (P less than 0.05 between both groups). After treatment, the proliferative capacity of lymphocytes in vitro was severely affected, while the reactivity to skin tests improved. Chemotherapy also reduced the IgM level, irrespective of the performance of splenectomy. Thirteen patients achieved a complete remission after chemotherapy. In this group, measurements of immunologic capacity were continued. The patients showing a relapse did so despite gradual improvement of delayed-type hypersensitivity and the lymphocyte responsiveness to phytohemagglutinin in vitro.

Adolescent↗
PubMed1983

T-cell maturation in the human thymus and tonsil: peanut agglutinin binding T lymphocytes in thymus and tonsil differ in maturation stage.

The finding of peanut agglutinin (PNA) binding capacity, supposed to be a marker of immature lymphocytes, within the T-cell population of the human thymus (58%) and tonsil (10%) prompted the comparison of maturation stages of PNA binding (PNA+) and nonbinding (PNA-) T cells in both organs. The proliferative response after mitogenic stimulation of purified PNA+ fractions was significantly less than that of purified PNA- fractions. The results of mitogen dose-response experiments, of variation in time of culture harvest, and of addition of irradiated allogeneic peripheral blood non-T cells indicated the intrinsic mitogen unresponsiveness of cells in the PNA+ fractions. The mitogen response of tonsil fractions was higher than that of thymocyte fractions. Cells with an immature immunologic phenotype were enriched in the thymocyte PNA+ fraction, and almost absent in the tonsil fractions. Both tonsil fractions contained cells with the immunologic phenotype of mature T cells, and showed a purine interconversion enzyme makeup comparable to mature T lymphocytes. It is concluded that the tonsil PNA+ T cell is a functionally immature lymphocyte which is in a further maturation stage than PNA+ or PNA- thymocytes. The presence of PNA+ T cells outside the thymus is of relevance for the clinical evaluation of PNA binding assays and suggests the occurrence of T-cell maturation within the tonsil environment.

Cell Separation↗
PubMed1983

Divergence between the occurrence of antibody and cellular immune reactivity to cervical carcinoma cell lines in preinvasive and macroinvasive stages of cervical carcinoma.

A lymphocyte stimulation assay is described which detects immune reactivity to antigens derived from the CaSki cervical carcinoma cell line. Taking a stimulation index of greater than 4.1 as positive, the peripheral blood lymphocytes of 14/20 patients (70%) with untreated dysplasia or carcinoma-in-situ, 8/19 patients (42%) with untreated macroinvasive squamous cell carcinoma of the uterine cervix and 8/38 controls (21%) showed positive reactions. Statistical analysis revealed a significant difference between the group of patients with dysplasia or carcinoma-in-situ and the controls. The sera of patients and controls were simultaneously tested for the presence of tumour-directed antibody. There was no correlation between the occurrence of cellular immune reactivity and of serum antibody, both directed to cervical carcinoma antigens. Cellular immune reactivity tended to occur more frequently in patients with preinvasive stages of cervical carcinoma, and serum antibody in patients with macroinvasive carcinoma.

Antibodies, Neoplasm↗