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Biomedical subjects

L Rink

Publications and source records attributed to L Rink.

67 records · Page 4Linked to original sources

Interferon and lymphokine production by human placental and cord blood cells.

The placenta plays an important role in protecting the fetus from maternal infections and in preventing an effective immune response of the mother against the fetus. We compared lymphokine production by human placental leukocytes with that of adult and cord blood leukocytes. Decidual and adult blood lymphocytes synthesized comparable quantities of interferon-gamma (IFN-gamma) following incubation with phytohemagglutinin (PHA). In contrast, lymphocytes of cord blood and fetal placental tissue stimulated with PHA produced very low titers of IFN-gamma. This defect was less marked after stimulation with staphylococcus enterotoxin B (SEB). In the presence of SEB, cord blood cells produced interleukin-2 (IL-2) and significant amounts of IFN-gamma. Production of IL-4 could not be detected. Collectively, these results indicate that fetal T lymphocytes show certain defects of lymphokine production.

Enzyme-Linked Immunosorbent Assay↗

Induction of cytokines in human peripheral blood and spleen cells by the Mycoplasma arthritidis-derived superantigen.

Recently, the mitogenic effects of the Mycoplasma arthritidis supernatant, MAS, and the induction of interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) by MAS have been described. In the present series of experiments we investigated human peripheral blood mononuclear cells (PBM) and human spleen cells with respect to their production of these and other cytokines. In human spleen cell cultures and PBM, MAS induced the synthesis of interleukin-1 alpha (IL-1 alpha) and IL-1 beta. Both interleukins were secreted faster and in higher amounts by PBM. IL-6 was also induced by MAS in PBM and human spleen cells. The amounts of IL-6 measured by ELISA were higher in PBM, whereas the biological activity of IL-6 was higher in spleen cell cultures. T-cell products such as IL-2, IL-4, and IFN-gamma were also induced by MAS in PBM and spleen cells. The kinetics of IFN-gamma and IL-4 induction were negatively correlated. In PBM we found low levels of IL-4 and high IFN-gamma induction, whereas in spleen cells high titers of IL-4 and low IFN-gamma titers were observed. Collectively, our results indicate that MAS induces different networks of cytokine interactions depending on the organ from which the cells are derived.

Antigens↗

Induction of interleukin-6 in murine bone marrow-derived macrophages stimulated by the Mycoplasma arthritidis mitogen MAS.

Cell-free supernatant of cultures from Mycoplasma arthritidis (MAS) functions as an extremely potent T-cell mitogen for human and murine lymphocytes. The T-cell response is dependent on the presence of accessory cells, presenting the intact E2 molecule on the cell surface. Until now, pure MAS protein has not been available. We developed a new multi-step method for MAS purification. The main steps in this protocol are ammonium sulfate precipitation, anion exchange and hydroxyapatite chromatography followed by gel filtration. With this efficient protocol we obtained fractions of extremely potent mitogenic properties, the purification rate was about 5 x 10(5). Although this protease-sensitive mitogenic activity was highly enriched, we failed to detect the protein by sensitive staining methods of SDS-PAGE. In previous studies, we showed that MAS induces the synthesis of interferon gamma in human and murine lymphocyte cultures. Here we demonstrate that MAS induces interleukin-6 (IL-6) in murine bone-marrow derived macrophage cultures. Since IL-6 is also induced by endotoxin, we used C3H/HeJ mice, which are known to be LPS-nonresponders, in all our studies.

Animals↗

Abnormalities in the immune system of children with beta-thalassaemia major.

We have studied both the humoral and cell mediated immune systems of 23 children with beta-thalassaemia major. In children who had not been splenectomized, a 3-fold expansion in the number of circulating B cells and a modest polyclonal gammopathy was present. Of these patients 70% had decreased numbers of circulating T4 cells; 83% were unresponsive to skin testing with Candida albicans, and the majority had decreased lymphocyte proliferative responses in vitro. In children who had been splenectomized, there was a 10-fold increase in the number of circulating B lymphocytes and a 2-fold increase in the number of T4 and T8 cells present in peripheral blood. Additionally, these patients as a group were more responsive to both skin testing and lymphocyte stimulation in vitro with Candida albicans. Seven patients had an inverted T4/T8 ratio. One child has positive serology to HIV by ELISA and Western Blot techniques with a normal T4/T8 ratio. Thus, while children with thalassaemia are at risk for exposure to HIV, the immunological abnormalities associated with the disease and/or its treatment necessitates cautious interpretation of any AIDS-related immunological changes.

Acquired Immunodeficiency Syndrome↗

Patient age distribution in thalassemia major: changes from 1973 to 1985.

Major advances have occurred in the treatment and prevention of thalassemia major, but their impact on incidence and survival have not been well assessed. In 1973, a survey was done of the ages of 243 living patients with thalassemia major followed at 12 centers in the United States and Canada. Twenty-two percent were younger than 5 years and 2.1% were older than 25 years of age (mean 11.4 +/- 6.7 [SD] years). In 1985, there were 303 patients at the same centers; 11% were younger than 5 years and 7.9% were older than 25 years (mean 14.2 +/- 7.3 years). A similar pattern was found in Connecticut, characterized by a marked decrease of new cases of thalassemia major during the past 15 years. This was not a result of fewer persons at genetic risk or a change in marital ethnic choices. Eleven of 14 families who had a child with thalassemia major assured that another affected child would not be born by having no more children, using prenatal diagnosis, or having therapeutic abortions. Extensive community programs of education and testing for thalassemia trait in Connecticut may also have contributed to the observed reduction in new cases.

Adolescent↗

Extracellular and immunological actions of zinc.

Zinc is an essential trace element for the immune system, but also very important in other organ systems. Every highly proliferating cell system is dependent on sufficient availability of zinc. During the last decades the influence of zinc on various cell systems have been investigated. Multiple effects of exogenously added zinc have been described in in vitro culture systems and in in vivo systems. However, most of these effects are so far poorly understood, and the dosages used in the in vitro systems are not comparable and sometimes unphysiologically high. Especially in the immune system a number of effects were described and over the last ten years we have come to understand some molecular mechanisms of zinc in this cell system. A zinc deficiency is accompanied by an immunodeficiency, resulting in an increased number of infections. However, the immune function is delicately regulated by zinc, since both increased and decreased zinc levels result in a disturbed immune function. Therefore, zinc supplementation must be accurately supervised. In this review, we discuss the activity of extracellular zinc in four sections. 1. The effect of zinc on different in vitro cell systems, including keratinocytes, osteocytes and leukocytes, and the concentrations of zinc needed for a specific cell response. 2. The modulation of the innate immune system in vitro and in vivo. 3. The role of zinc in the B cell response and antibody production. 4. Effects of zinc on the development and function of T cells.

Adjuvants, Immunologic↗

Impaired serum cortisol stress response is a predictor of early relapse.

AIMS: to investigate a possible association of cortisol stress response during early abstention with relapse. METHODS: Thirty-six alcohol-dependent males, half of them with a comorbid anxiety disorder, and 15 healthy controls were exposed to a standardized psychosocial stress test. Thirty-one of the patients were assessed for relapse 6 weeks after discharge. RESULTS: The relapsers showed almost no cortisol responses in the stress test. Comorbid anxiety disorder influenced neither stress response nor relapse. CONCLUSIONS: During early abstention from alcohol, reduced stress-responsivity of the hypothalamo-pituitary-adrenocortical axis seems to be connected to early relapse.

Adult↗

Clinical trial of young red blood cells prepared by apheresis.

Transfusion of young red blood cells (YRBC) with prolonged survival should result in increased intervals between transfusions and, therefore, decreased transfusion-associated iron loading. A prospective clinical trial comparing YRBC transfusions prepared by apheresis versus washed or frozen red cell transfusions was performed in five children with transfusion-dependent thalassemia. A total of 152 YRBC units, evaluated by reticulocyte enrichment and pyruvate kinase activity, were transfused. While a slightly longer interval between transfusions was observed during the time period of YRBC versus the time period after (30.0 +/- 1.5 days versus 27.9 +/- 1.1 days, respectively, p less than 0.02), there was no associated decrease in mg of iron transfused per kg. The effectiveness of transfused YRBC units was less than predicted by in vitro and in vivo studies.

Adolescent↗

[Characteristics of immunologic test values in the elderly].

The immune system changes during the lifespan of man. Many described changes in the immune system of the elderly were dependent on illness or chronic diseases. To exclude these pathological changes in the immune system and to exclusively describe age-dependent changes, Ligthart et al. defined immunogerontological criteria to study the immune system in the elderly, the SENIEUR-Protocol. Most changes in the immune system of elderly are within the normal ranges of the appropriate parameter. However, there are many significant differences between the status of the immune system in healthy young and elderly individuals, within these normal ranges. The comparison between SENIEUR-elderly and healthy young and the additional comparison of these two groups with centenarians allows the discussion of potential pathological effects of these changes. In this article we summarize the described changes of the immune system in SENIEUR-elderly and centenarians. The serum levels of the immunoglobulins G, M and A increased with age, as well as the number of benign monoclonal gammopathies and the number of autoantibodies. The titers of zinc are significantly decreased in the serum of the elderly. The production of the acute phase protein C-reactive protein is not age-dependent, whereas the serum levels of alpha 2-macroglobulin are significantly increased in the elderly. The number of lymphocytes decreased and the number of neutrophils increased with aging. Monocytes, basophils, and eosinophils are without changes during life. There are many descriptions about changes of the leukocyte sub-population in aging, which are not always comparable. However, the number of T cells (CD3) decreases. Within the T cells the CD8 cells decreased more than the CD4 cells, resulting in an increased CD4/CD8 ratio. Memory T cells (CD45RO) increase during life, whereas naive T cells (CD45RA) decrease. Interestingly, centenarians have more naive T cells SENIEUR-elderly. The number of B cells (CD19) decreased also, whereas the number of natural killer (NK) cells (CD16, CD56, CD57) increases with aging. The capacity of leukocytes from the elderly to produce cytokines is also significantly different from those of the young. The release of the TH1-cytokines interleukin (IL)-2 and interferon (IFN)-gamma is decreased, whereas the production of the TH2-cytokines IL-4 and IL-10 is increased in the elderly. The production of proinflammatory cytokines such as IL-1, IL-6, IL-8, and tumor necrosis factor-alpha is increased in the elderly. In contrast, the capacity to produce the antiviral cytokine IFN-alpha is reduced in elderly individuals. In conclusion, the immune system shows many age-dependent changes, but we know little about the reason and the potential pathological effects of these changes.

Aged↗