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Biomedical subjects

G Wick

Publications and source records attributed to G Wick.

At least 199 records · Page 11Linked to original sources
PubMed1989

Promotion of lymphocyte growth by high density lipoproteins (HDL). Physiological significance of the HDL binding site.

The characteristics and physiological relevance of the high density lipoprotein (HDL) binding site on unstimulated and mitogen activated human peripheral blood lymphocytes have been investigated. At 37 degrees C, specific binding/uptake of fluorescent (dioctadecylin-docarbocyanine, DiI) HDL was observed by cells from healthy donors as well as by those from low density lipoprotein receptor-defective patients; mitogen activated T-blasts exhibited a markedly elevated DiI-HDL uptake compared to resting T-cells. Binding was saturable at 37 degrees C and of high affinity, with a Kd of 5 x 10(-8) M. It was blocked by anti-apoAI polyclonal antibodies (F(ab)2 fraction), but not by anti-apolipoprotein (apo)E, anti-apoAII, or anti-apoB, and was inhibited competitively by HDL apoproteins and an apoAI-protein A fusion protein. T-cell associated DiI-HDL was increased by trypsin treatment (of the cells) and decreased by activation in the presence of HDL or low density lipoprotein. Comparison of the concentration dependencies of growth promotion and specific cell association of HDL indicated that two mechanisms of lipid exchange may be in operation: one a binding-dependent mechanism of cholesterol exchange, with maximal effect in the HDL concentration range (20-200 micrograms/ml) in which specific binding increases rapidly, and the other a binding-independent exchange of lipids effective at concentrations in which specific binding is saturated (300-5000 micrograms/ml).

Adult↗
PubMed1989

Immunogenetic analysis of spontaneous autoimmune thyroiditis of obese strain chickens.

A variety of immunological, endocrinological, and virological abnormalities have been implicated in the etiopathogenesis of spontaneous autoimmune thyroiditis (SAT) of Obese strain (OS) chickens, e.g., a general T cell hyperreactivity, an increased uptake of iodine into the thyroid gland, a diminution of the glucocorticoid tonus, and an OS-specific endogenous virus. In crosses of the close-bred OS B15/B15 subline with the inbred normal CB B12/B12 strain we have studied the mode of inheritance of these aberrations and their putative association with SAT. The results indicate that none of these OS-specific characteristics alone is an absolute prerequisite for the development of thyroid infiltration, which appears to be governed by one autosomal recessive gene.

Animals↗
PubMed1989

Intra-thymic nurse cell lymphocytes can induce a graft-versus-host reaction with high efficiency.

Thymic nurse cells (TNC) are multicellular complexes composed of morphologically intact thymocytes internalized within epithelial cells. Due to their unusual features, they have been suspected to provide an appropriate microenvironment for T-cell repertoire acquisition. In recent functional studies in the chicken system, we have shown that intra-thymic nurse cell-lymphocytes (TNC-L) are highly efficient inducers of a graft-versus-host reaction (GvHR) in an allogeneic chorionallantoic membrane (CAM) assay, manifested by the formation of visible colonies, so-called pocks. Immunohistochemical and electron microscopical assessment of pocks revealed no differences between the cellular components and ultrastructural features of GvHR induced by TNC-L or peripheral blood lymphocytes (PBL). In addition, the stimulation of this local GvHR by interleukin 2 (IL-2) was demonstrated.

Animals↗
PubMed1989

The role of interleukin 2 in autoimmunity.

In addition to playing a major role in physiological immune responses against foreign antigens, the interleukin 2 (IL-2)-IL-2 receptor (IL-2R) system may also be implicated in autoimmune phenomena. Initial studies on the role of IL-2 in autoimmunity indicate a deficiency in the production of this lymphokine in autoimmune disease. Here, Guido Kroemer and Georg Wick review recent data supporting the notion that an excess of endogenous or exogenous IL-2 may aggravate autoaggression by triggering autoreactive effector cells, and they speculate that IL-2 might favor the de novo development of autoimmunity by breaking autotolerance.

Autoantibodies↗
PubMed1989

An orally administered bacterial immunomodulator primes rabbit neutrophils for increased oxidative burst in response to opsonized zymosan.

To assess the potential effect of an orally administered immunomodulator, consisting of a lysate of seven different bacteria, on polymorphonuclear leukocyte (PMN) function, rabbits were fed this preparation for five consecutive days via a gastric tube. On day 6, PMN were separated from peripheral blood and oxidative burst was triggered by opsonized zymosan or 12-O-tetradecanoylphorbol-13-acetate and quantitated on a single-cell basis. This study presents the extension of an existing flow cytometric method, leading to the possibility of quantitating single-cell oxidative burst triggered by particulate (instead of only soluble) stimuli. By this means, treated animals showed statistically significant increased oxidative burst reactions compared with the control group. The data provide evidence that oral application of a bacterial immunomodulator leads to a primed state in PMN for increased oxidative activity in response to a particulate stimulus. This offers the possibility that the beneficial effect of similar treatment in humans may in part be due to comparable mechanisms.

Adjuvants, Immunologic↗
PubMed1989

Use of a FACS III for fluorescence depolarization with DPH.

We have previously demonstrated age-related differences in human lymphocyte membrane fluidity, by use of steady-state polarization measurements on bulk cell suspensions with the fluorescence probe DPH. However, for exact analysis of the possible functional importance of these changes, single-cell measurements were deemed of interest. We have now used an analog division device to measure fluorescence depolarization "p" of DPH in real time with a FACS III flow cytometer. The measurements are reliable, as we have been able to confirm the differences in DPH "p" between monocytes and lymphocytes previously shown in bulk suspension and to demonstrate the expected differences in fluidity of lipid-modulated cells. We also found significant differences in DPH "p" between lymphocytes of young and elderly blood donors. Lymphocyte subsets did not differ in polarization values but did differ in fluorescence intensity with Th less than Ts less than B = NK cells.

Adult↗
PubMed1989

Typing of MHC haplotypes in OS chicken by means of RFLP analysis.

For the analysis of the genetic background of autoimmune thyroiditis we used the Obese strain (OS) chicken model which develops a SAT. Practically all animals from this strain show severe lymphoid infiltration of the thyroid gland and circulating autoantibodies against thyroglobulin (Tg-AAb) within a few weeks after hatching. Of the 3 MHC haplotypes (B5, B13, B15) present in the OS, B13 was mostly associated with severe thyroid infiltration. Haplotypes B5 and B15 were associated both with severe, as well as with mild infiltration. To clarify these controversial results published by different groups and to further assess the role of the MHC in the development of SAT, we selected by appropriate breeding sublines with high and low levels of Tg-AAb. With the help of serological methods and GvH assays we were not able to find additional differences in the MHC antigens of that line. Therefore, for further characterization of these haplotypes, RFLP analysis was applied in the present study. Southern blots were done with restriction enzyme digests of erythrocyte DNA hybridized with a chicken cDNA probe (code-p234) for MHC class II antigens. The Southern blots with BamH-I digests showed at least 5 bands, four of which were polymorphic. Four RFLP patterns emerged, two of which were observed within chickens with the B15 haplotype. The confirmation of this RFLP heterogeneity within serologically identical haplotypes requires additional analysis.

Animals↗
PubMed1989

Immunodeficiency in old age.

Aging is a multi-facetted process, but the deterioration of the immune function seems to play a central role in this context. Paradoxically, immune reactivity against exogenous antigens declines during aging while autoimmune reactivity increases. One of the aims of our investigations on the function of the senescent immune system was to define immune parameters of 'normal' aging, i.e. those not dependent on underlying diseases. Specifically, our interest was focused on the possible role of an altered lipid metabolism of cells of the immune system during aging. The known decrease of plasma membrane fluidity of lymphoid cells and monocytes in higher age may be one of the factors responsible for the nonoptimal functioning of the immune system. This property, in turn, seems to be based on an altered lipid metabolism. Specifically, we have evidence that the finely tuned balance between the transport of cholesterol to and from lymphoid cells via the environment and the intracellular cholesterol biosynthesis seems to be disturbed with increasing age. This conclusion is drawn from experiments where low-density lipoprotein (LDL) and high-density lipoprotein (HDL) receptor activity is assessed using fluorescently labeled lipoproteins in fluorescence-activated cell sorter (FACS) analyses. LDL receptor uptake is unexpectedly increased in the elderly, but LDL receptor regulation, and serum LDL composition itself seem to be normal. Preliminary data point out the possibility that the efflux of cholesterol via HDL may be insufficient. Attempts to modulate plasma membrane fluidity by means of the phospholipid mixture 'active lipid 721' (AL 721) showed that this drug, in contrast to literature reports, is not a 'membrane fluidizer' but rather exerts this effect as a nutrient for lymphocytes and monocytes.

Aging↗
PubMed1989

Biostability of polyurethanes.

Aside from the medical requirements a material has to fulfill to qualify as biocompatible, for the bioengineer, who is involved in the design, construction and fabrication of prosthetic devices, the mechanical, physical and chemical properties of the material as well as its possible manufacturing procedures and, last but not least, its biostability are of the same importance. In the very aggressive biological environment, the material should behave inertly, showing no surface erosions, molecular chain disruptions, uptake of low molecular weight biological materials, local chemical imbalances, tendency to calcification or negative changes of mechanical properties. With regard to this aspect, different polyurethanes have been evaluated in-vitro and in-vivo as basic materials and already fabricated devices (blood pumps and heart valves). The comparison of the results stresses the necessity of further efforts to achieve a standardized test protocol for the prove of the biostability of polymers, containing appropriate, well-defined in-vitro and in-vivo test methods to establish the necessary data basa for the materials' clinical approval.

Animals↗
PubMed1988

[Molecular genetic analysis of autoantibody production in systemic lupus erythematosus].

This review summarizes studies from our and other laboratories attempting to define the molecular and clonotypic origin of autoantibodies that typify systemic autoimmune diseases such as lupus and rheumatoid arthritis. Comparative restriction fragment length polymorphism (RFLP) studies investigating the immunoglobulin (Ig) germline gene organization in lupus-prone strains of mice suggested that the disease can develop in different Ig heavy (H) and light (L) chain haplotypes, and that the Ig germline genes in lupus mice are probably normal. Analysis of the Ig gene segments expressed in monoclonal autoantibodies from autoimmune mice revealed that similar, and in some instances even identical, gene segments are expressed in autoantibodies and in antibodies to exogenous antigens, and that anti-self and anti-non-self responses are encoded by the same, or at least an overlapping germline gene repertoire. A large variety of Ig variable (V), diversity (D), and joining (J) gene segments can encode autoantibodies with different specificities, and both germline genes and somatically-mutated genes can be expressed in such antibodies.

Animals↗
PubMed1988

Genetic analysis of extrathyroidal features of Obese strain (OS) chickens with spontaneous autoimmune thyroiditis.

The Obese strain (OS) of chickens, which is afflicted with Hashimoto-like spontaneous autoimmune thyroiditis (SAT), displays elevated T cell proliferation, interleukin (IL)2 production and IL2 receptor expression upon mitogen stimulation, and defects in the neuroendocrine control of the immune system including elevated corticosteroid-binding globulin (CBG) and a deficient increase of serum corticosterone (CN) upon cytokine injection. Recently this strain has further been shown to harbor retrovirus-related sequences (endogenous virus no. 22, ev22) absent in healthy control strains. To determine the number of genes responsible for SAT-associated immunodysregulation and to unravel possible ev22 associations, we analyzed the above immune and endocrine parameters in F1 hybrids and backcrosses of the autoimmune OS B15B15 with healthy inbred CB B12B12 chickens. OS-like T cell hyperproliferation and IL2 hypersecretion in response to both concanavalin A and phytohemagglutinin were transmitted as autosomal dominant traits and co-segregated in backcross animals. In vivo hyporesponse of the OS to the corticosterone-inducing effect of cytokine preparations was inherited dominantly and the elevated CBG serum levels recessively. None of these traits appeared to be major histocompatibility complex (MHC) linked. However, while T cell abnormalities and elevated CBG serum levels were not associated with the autosomal ev22 locus, in vivo hyporesponsiveness to glucocortocoid-inducing cytokines co-segregated with this OS-specific provirus. These results add to the concept of SAT as a polyetiological and plurigenetic disease and do not support our previous hypothesis that T cell hyperreactivity and immunoendocrine dysfunction might be functionally related.

Animals↗
PubMed1988

ev 22, a new endogenous avian leukosis virus locus found in chickens with spontaneous autoimmune thyroiditis.

Chickens of the Obese strain (OS) develop a hereditary spontaneous autoimmune thyroiditis (SAT) which closely resembles human Hashimoto's disease. Analysis of the endogenous viruses harboured by these animals revealed a new endogenous virus (ev22) detected as a 5.5 kb Sac I fragment. Crossbreeding experiments showed that ev22 is vertically transmitted as an autosomal trait not associated with major histocompatibility (MHC) alleles. Preliminary experiments indicate that ev22 does not necessarily cause SAT, however, it may have a modulatory role in the development of the disease.

Animals↗
PubMed1988

Diminished glucocorticoid tonus in obese strain (OS) chickens with spontaneous autoimmune thyroiditis: increased plasma levels of a physicochemically unaltered corticosteroid-binding globulin but normal total corticosterone plasma concentration and normal glucocorticoid receptor contents in lymphoid tissues.

Obese strain (OS) chickens afflicted with spontaneous autoimmune thyroiditis (SAT) display several signs of a general immune dysbalance, some of which may be related to altered endocrine mechanisms such as the glucocorticoid tonus. The latter is the combined result of corticosterone (CN) production, metabolism as well as excretion, and the binding of CN to corticosteroid binding globulin (CBG) and glucocorticoid receptors (GR). The present study deals with the comparative investigation of these parameters in OS and normal White Leghorn (NWL) chickens. The results obtained with radioimmunoassay for CN and radioligand saturation assays for plasma CBG as well as GR in the thymus were as follows: (1) both OS and NWL have equal total CN levels; (2) however, OS chickens exhibit elevated CBG levels, whereas the physicochemical parameters (equilibrium affinity, specificity spectrum) of CBG were equal in OS and NWL; (3) the GR capacities and affinities were equal in both OS and NWL throughout development until thymic involution. Similarly, the specificity, affinity, and sedimentation behaviour were equal in OS and NWL. (4) Furthermore, no differences were found in the response of OS and NWL splenocytes to the suppressive effect of glucocorticoids in vitro, also excluding postreceptor alterations at the cellular level in the OS. From these findings we conclude that the increased CBG levels, which are not compensated for by either increased CN plasma levels or by increased receptor capacities or affinities in lymphatic organs, represent a diminished glucocorticoid tonus in OS chickens. This may have immunoregulatory consequences which, in turn, may contribute to the development of SAT.

Animals↗