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Biomedical subjects

G Wick

Publications and source records attributed to G Wick.

At least 289 records · Page 16Linked to original sources
PubMed1984

Basement membrane components outline the tumour islands in cylindroma.

The main histological feature of cylindroma is the deposition of sheaths of a 'hyalinized' material contiguous to the tumour cell clusters. Although ultrastructural studies of this material have revealed a basement membrane-like structure, its exact nature has remained unclear. Using immuno-staining with affinity-purified antibodies directed against distinct basement membrane components, we have shown that type IV collagen and laminin are major constituents of this zone. In addition, cell culture studies indicated that both proteins are synthesized by the tumour cells. The immunohistological data make it clear that the tumour matrix between the tumour cell islands is composed not only of basement membrane components, but also is composed of other connective tissue constituents, i.e. type I and III collagen and fibronectin.

Basement Membrane↗
PubMed1984

Functional analysis of B-L (Ia-like) antigen-bearing chicken peripheral blood cells.

The functional of B-L (Ia-equivalent)-positive (B-L+) adn -negative (B-L-) chicken peripheral blood lymphocytes (PBL) was studied in vitro and in vivo. The PBL were first stained in direct immunofluorescence tests with a fluorescein isothiocyanate-labelled anti-B-L alloantiserum and then separated by means of a fluorescence-activated cell sorter. In agreement with our previous findings, B-L- cells showed functional properties of T lymphocytes, responding to concanavalin A and phytohaemagglutinin-P in vitro and inducing a graft-versus-host (GVH) reaction when injected into allogeneic embryos. Sorted B-L+ gave no responses in any of these assays. Neither B-L+ nor B-L- cells, when tested alone, responded significantly to pokeweed mitogen, but mixtures of the two restored the responsiveness to that of the original unsorted suspension. Of the B-L+ PBL, 10% were T cells, which may account for the low GVH reactivity given by this population.

Animals↗
PubMed1984

Monoclonal antibodies against human chorionic gonadotropin (hCG): II. Affinity and ability to neutralize the biological activity of hCG.

Monoclonal antibodies (MCA) against hCG have been characterized with regard to their affinity and their ability to neutralize the biological activity of hCG in vivo. The production and specificities of these reagents were described in the preceding paper of this series. Equilibrium association constants (Ka) of the MCA, determined by radioimmunological saturation assays, ranged from less than 1 X 10(8)M-1 up to 3.7 X 10(9)M-1 whereas values for conventional polyclonal antisera against hCG ranged from 8.9 X 10(9)M-1 to 1.8 X 10(10)M-1. The ability of MCA to neutralize the biological activity of hCG was tested in a rat bioassay in vivo; 9 of 13 different MCA preparations tested could neutralize hCG. Surprisingly, this property did not correlate with affinity or specificity, and was not restricted to those MCA recognizing the hormone specific beta-subunit. It could be demonstrated that determinants on each individual subunit as well as epitopes formed by both subunits are involved in the expression of the biological activity of hCG.

Abortion, Induced↗
PubMed1984

Obese strain (OS) chickens with spontaneous autoimmune thyroiditis have a deficiency in thymic nurse cells.

Chicken thymic nurse cells (TNC) were isolated and their plasma membrane antigens were characterized by immunofluorescence with a panel of allo-, hetero-, and monoclonal antibodies. Analogous to the murine system, chicken TNC are localized in the subcapsular region of the cortex and were strongly B-L and B-F positive (MHC Ia and H-2 D, K equivalents). The TNC were non-phagocytic and lacked fc receptors, but expressed an antigen specific for thymic epithelial cells, and their cytoplasm was stained by an anti-keratin antiserum. The internalized lymphocytes were all intact T cells of a distinct differentiation stage, their antigenic profile consistent with that of immature cortical thymocytes. To determine whether TNC may play a role in the activation of autoimmune disease, Obese strain chickens with spontaneous autoimmune thyroiditis were investigated. These chickens were found to have a twofold defect in their TNC content: the thymuses contained approximately one-half of the number of TNC found in normal chickens beginning as early as 17 days of embryogenesis, and the lymphocyte content of the Obese strain TNC was one-half that of the normals. The deficiency is specific for TNC and may be a major reason for the abnormal T cell differentiation in the Obese strain.

Animals↗
PubMed1983

Nidogen: a new, self-aggregating basement membrane protein.

Nidogen was purified from a mouse tumor basement membrane where it accounted for 2-3% of the total proteins. It was isolated as two forms (A and B) of a monomer (Mr = 80000) each consisting of a single polypeptide chain folded into a globular head connected to a small tail. The B form of the monomer was shown to be capable of aggregating into a nest-like structure (Mr greater than 250000). A smaller form (Mr = 45000) was observed in some of the extracts. The amino acid composition of nidogen was different to that of other basement membrane proteins. It contained about 10% carbohydrate, with N-linked and O-linked oligosaccharide chains in similar proportions. Isoelectrofocussing demonstrated a limited heterogeneity of nidogen with pI in the range 6.5 - 7. Monomeric nidogen failed to interact with other basement membrane components and heparin. Aggregation could be induced by limited proteolysis and was reversed by detergents or high salt concentrations. Together with the observation that most of the nidogen could be solubilized only after destroying the collagenous matrix, the data indicate that aggregation of nidogen reflects an activity involved in matrix assembly. Specific antibodies raised against nidogen did not distinguish between the monomeric and aggregated form of the protein but showed that the fragment was antigenically deficient. These antibodies did not cross-react with collagen type IV, laminin, entactin and heparansulfate proteoglycan. Immunofluorescence staining and absorption studies demonstrated that nidogen is a common component of authentic basement membranes. Larger forms of nidogen (Mr about 100000 and 150000) were found in organ cultures of Reichert's membrane suggesting that it is synthesized in precursor forms.

Animals↗
PubMed1983

Characterization of chicken lymphocyte subsets separated by peanut agglutinin.

The reactivity of chicken lymphocytes isolated from bursa, thymus, spleen, and peripheral blood (PBL) with peanut agglutinin (PNA) has been investigated. High numbers of cells binding PNA (PNA+ cells) were found in bursa (74.5%) and thymus (85.2%), as well as in the peripheral organs (spleen and PBL, 43.8 and 70%, respectively). In the latter organs, the levels of PNA+ cells exceeded by far the values reported for mammals. Separation of PNA+ and PNA- cells from different organs was achieved by selective agglutination with the lectin or by affinity chromatography on immobilized PNA. Experiments combining the use of limiting concentrations of neuraminidase to cleave off sialic acid from the surface membrane of splenocytes that do not bind PNA (PNA- cells), followed by agglutination with the lectin, suggested that the high binding of PNA to mature lymphocytes is most likely due to a low degree of sialylation of chicken cell surface glycoconjugates. The functional properties in vitro of PNA+ and PNA- spleen cell fractions were assayed in mitogen responses (PHA, Con A, PWM), the mixed-lymphocyte reaction (MLR), and the in vitro anti-SRBC antibody response. In all three systems the responses of the PNA+ fraction were found to be significantly higher than those of the PNA- cells. Mixing experiments revealed that irradiated (1500 R) PNA- cells preferably suppress pure T-cell responses of unfractionated spleen cells, whereas PNA- cells exerted a stronger suppressive effect on responses involving B cells. Thus, in the chicken, PNA may be a valuable tool to distinguish subsets of suppressor cells with different target specificity.

Animals↗
PubMed1983

Chicken thrombocytes. Isolation, serological and functional characterisation using the fluorescence activated cell sorter.

Different procedures for enrichment of peripheral blood leukocytes (PBL) from whole chicken blood have been compared in terms of the percentage yield of lymphocytes and thrombocytes. The yield of thrombocytes was low in the buffy coat cells of heparinised blood, but high in PBL enriched from heparinised blood over a Ficoll-Paque density gradient and in PBL prepared from citrated blood by either technique. The fluorescence activated cell sorter (FACS) has been used to separate thrombocytes from lymphocytes in PBL by sorting of the negative cells after staining with specific anti-T and anti-B cell sera (or anti-immunoglobulin). The sorted cells were more than 99% viable, more than 98% thrombocytes by antigenic and morphological criteria and did not respond in vitro to T and B cell mitogens. Absorption studies on a turkey anti-bursa cell serum (ABST) which is cross-reactive for B cells and thrombocytes (8) indicated that the cross-reactivity is attributable to two (or more) antibody specificities in the serum rather than to one antibody directed at shared determinants on the two cell types.

Animals↗
PubMed1983

Immunofluorescence studies on the codistribution immune deposits and complement in the thyroid glands of Obese strain (OS) chickens.

This study demonstrates immune complexes in thyroid glands of Obese strain (OS) chickens, that consist of thyroglobulin (Tg) and antibodies to Tg. In IIF tests it was shown that these complexes fix complement with an age-dependent increase from 12% in 19-day-old embryos up to 100% in 6-week-old animals. This finding and the observation that the deposition of complement-binding immune complexes precede cellular infiltration of the thyroid gland and correlate with the serum titer of Tg-Ab (as one parameter of the disease) points towards a role as one initial effector mechanism for the development of spontaneous autoimmune thyroiditis (SAT).

Animals↗
PubMed1983

Detection of antibodies interacting with glycosaminoglycan polysulfate in patients treated with heparin or other polysulfated glycosaminoglycans.

A new method has been developed for the demonstration of the antibody nature of a factor occurring in some patients during treatment with heparin or other polysulfated glycosaminoglycans (GAGPS). So far, antibodies reacting with GAGPS, except heparin, have not been described. We used heparin- or GAGPS-coated normal blood group O thrombocytes for the detection of suspected antibodies. After addition of patients' plasma or serum to a suspension of purified heparin- or GAGPS-coated platelets, agglutination was determined microscopically. In indirect immunofluorescence, positive staining of agglutinated platelets was observed with fluorescein isothiocyanate anti-Ig and anti-IgG conjugates, but not with anti-IgA or anti-IgM, with one exception in which IgM antibodies were also involved. Binding of complement was also shown using a tetramethylrhodamin isothiocyanate-labelled anti-C3 conjugate in double-staining experiments. Fibronectin could be excluded as a possible factor responsible for thrombocyte agglutination.

Fluorescent Antibody Technique↗
PubMed1983

Genetically-controlled severity of autoimmune thyroiditis in Obese strains (OS) chickens is expressed at both the humoral and cellular effector mechanism levels.

Two lines of Obese strain (OS) chickens of identical MHC (B) genotype, B5B5, bred over 10 years with different selection parameters, differ in their severity of spontaneous autoimmune thyroiditis. To determine whether alterations in immune responsiveness underly this discrepancy, the two lines were compared for their thyroiditis effector mechanisms. The OS B5B5 chickens, selected for high levels of serum thyroglobulin autoantibody, had correspondingly higher levels of thyroid-specific cytotoxic cells and also antibody dependent cellular cytotoxicity (ADCC) than the equivalent B5B5 line selected solely for the phenotypic trait of hypothyroidism. These results thus emphasize the importance of the non-MHC locus controlling immune responsiveness, in the 3 locus-model for this autoimmune disorder.

Animals↗
PubMed1982

The role of self-antigen in the development of autoimmunity in Obese strain chickens with spontaneous autoallergic thyroiditis.

Neonatal thyroidectomy of Obese strain (OS) chickens showed that the spontaneous development of thyroid autoimmunity in these animals was fully dependent upon the presence of autoantigen, and could not be ascribed essentially to antigen-independent mechanisms such as polyclonal lymphocyte activation or innate distortions within the idiotype network. Similarly, removal of the gland in animals with established thyroiditis demonstrated the need for antigen to maintain the autoimmune response. Thyroglobulin from normal chickens induced autoantibodies in neonatally thyroidectomized OS birds, suggesting that an abnormality in the structure of this protein is not a prerequisite for the development of autoimmunity. This contention is supported by the finding that OS and normal thyroglobulin were immunochemically indistinguishable, whether compared using OS autoantibodies or rabbit anti-chicken thyroglobulin sera.

Aging↗
PubMed1982

Effect of cyclosporin A on spontaneous autoimmune thyroiditis of Obese strain (OS) chickens.

The spontaneous autoimmune thyroiditis (SAT) which develops in the Obese strain (OS) of chickens depends on an intact B-dependent portion of immune system. T helper cells have been shown to be required for the production of thyroglobulin autoantibodies (Tg-AAb), but a possible contribution of cytotoxic T cells in the initial phases of SAT still remains to be elucidated. Cyclosporin A (CsA), an immunosuppressive drug with selective activity on T blast formation was used as a probe to clarify this issue: (a) the immunosuppressive potential of CsA was first verified for an avian species by demonstrating prolongation of skin allograft survival; (b) posthatching treatment of OS chickens with CsA until they were killed at 3 weeks of age did not alter the frequency and severity of SAT and the incidence and titer of Tg-AAb; (c) treatment of OS embryos on days 15, 17 and 19 of incubation entailed the development of significantly more severe disease and higher titers of Tg-AAb as compared to controls. A possible effect of CsA on precursors of suppressor T cells in the chicken is postulated. Cytotoxic T cells seem to play a minor role in the beginning of thyroid infiltration. It is concluded that CsA may not be the drug of choice for treatment of at least some autoimmune diseases.

Administration, Oral↗
PubMed1982

IgG-Fc and C3 receptors in the chicken: distribution, tissue localization and functional significance.

This paper summarizes data obtained in our laboratory on the demonstration of receptors for IgG-Fc (FcR) and complement (CR) on mononuclear cells of the fowl. A clearcut distinction of these two structures on spleen cells was achieved in rosette assays using SRBC coated with rabbit IgG as indicator cells which bind avian complement, but are not bound by the FcR. The tissue distribution and localization of FcR and CR positive cells was studied in mixed hemadsorption assays on sections of both central (bursa, thymus) and peripheral (spleen) lymphoid organs from normal chickens, as well as lymphocytic infiltrated thyroid glands from animals of the Obese strain (OS) afflicted with spontaneous autoimmune thyroiditis. The possible significance of both receptors in the pathogenesis of this autoimmune process is discussed.

Animals↗
PubMed1982

Antiserum to LH reverses the abortifacient effect of Bromergocryptine treatment in early rat pregnancy.

In vivo experiments showed that anti-bovine luteinizing hormone rabbit serum (a-LH) reversed the abortifacient effect of Bromergocryptine (BEC) on day 6 of pregnancy in 13 of 19 rats when injected 5-15 h after the initial BEC administration. Radioreceptor assay studies revealed that BEC treatment entailed an 85% drop of ovarian LH-receptor (LH-rec) concentration and a drastic decrease in progesterone serum levels. a-LH restored both the ovarian LH-rec content and progesterone serum levels in those rats that were found to have macroscopically intact implantations. A time course study of LH serum levels after BEC treatment showed a trend for BEC to stimulate LH secretion with a maximum 12-18 h after the initial BEC injection. These experiments indicate that (i) BEC terminates early rat pregnancy primarily by inducing a process of desensitization of ovarian LH-rec by blocking prolactin (PRL) secretion and possibly also by additionally stimulating LH secretion, which in the absence of endogenous PRL causes HL-rec and serum progesterone levels to drop; (ii) a-LH administration without simultaneous PRL substitution may rescue LH-rec of BEC treated rats from being desensitized as well as prevent fetuses from being resorbed. It is suggested that the contribution of PRL in the luteotropic complex is permissive for the luteotropic action of LH and/or for keeping the corpus luteum in a functional state rather than being luteotropic by itself.

Abortifacient Agents↗