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Biomedical subjects

A Tarkowski

Publications and source records attributed to A Tarkowski.

At least 199 records · Page 11Linked to original sources
PubMed1988

Spontaneous temporomandibular joint arthropathy in MRL-lpr/lpr mice.

The temporomandibular joint (TMJ) in spontaneously arthritic MRL lpr/lpr (MRL/l) mice has been histologically analysed. After decalcification and standardized preparation of the joint tissue, histological sections were examined for presence of synovial hypertrophy, synovial villi, pannus tissue, erosions, cysts and signs of periarticular inflammation. In 12 of 13 TMJs examined, histopathological changes indicating a state of arthropathy were found. The most prevalent finding was synovial proliferation, which was frequently detected at the insertion of the synovial membrane to the bone. Two or more signs of inflammatory involvement including synovial proliferation, pannus tissue and bone erosion were seen in 5 mice with a predominance among the oldest mice (greater than or equal to 5 months of age). No lymphocytic cell infiltration was found in the analyzed synovial tissues of the TMJ. In contrast, lymphocytes were observed in the vicinity of periarticular blood vessels and tendons. It is concluded that the TMJ is frequently involved in the arthritic disease of autoimmune MRL/l mice.

Animals↗
PubMed1988

Autoimmunity to collagen in adult periodontal disease.

Although it has been documented that exogenous antigens of microbial origin are involved in the induction of the local inflammatory responses in human adult periodontitis (AP), endogenous antigens may contribute to the chronicity of this common disease. In this study, we used the enzyme-linked immunospot (ELISPOT) test to enumerate antibody-secreting cells to human collagen Types I-VI by cells isolated from the gingivae and peripheral blood of AP patients. Analyses of dissociated cells from gingivae of 39 AP patients revealed the presence of high numbers of cells that secrete antibodies to Type I collagen, and to a lesser extent, Type III. Although the majority of such cells produced specific antibodies of the IgG class, IgA- and IgM- anti-collagen -secreting cells were also detected. When compared to the total antibody-producing cells, the numbers of cells forming specific antibodies to collagen Type I were surprisingly high. In contrast, anti-collagen antibody-producing cells were rarely detected in the peripheral blood of patients with adult periodontal disease and only low levels of anti-collagen antibodies were present in the serum. The finding of local production of anti-collagen antibodies in AP suggests that autoimmunity may contribute to the pathogenesis of this common disease.

Antibody-Producing Cells↗
PubMed1988

Beneficial effect of captopril on systemic lupus erythematosus-like disease in MRL lpr/lpr mice.

MRL lpr/lpr (MRL/l) mice exhibit a disease similar to systemic lupus erythematosus (SLE) in humans. To investigate the influence of antihypertensive treatment on this disease, four groups of MRL/l mice were treated with the angiotensin-converting enzyme inhibitor captopril (n = 25), with the sympathetic blocker bretylium (n = 15), and with cyclophosphamide (n = 10). Thirty-five mice did not receive any treatment and served as controls. Survival rate, blood pressure, incidence of proteinuria and hematuria, renal pathology, lymphoid hyperplasia and dermatitis were studied. The survival at the age of 36 weeks was significantly improved by captopril as compared to controls (60 vs. 25%, p = 0.035). The cyclophosphamide group showed no mortality at that time and the bretylium group did not differ from the control group. Captopril and bretylium reduced systolic blood pressure significantly while cyclophosphamide was without effect. Captopril and cyclophosphamide diminished significantly the glomerular damage with less proliferative changes and a decreased incidence of proteinuria. The bretylium-treated animals also exhibited an improved renal pathology index but they did not differ from the controls with respect to proteinuria and hematuria. Lymphoid hyperplasia and dermatitis were decreased only by captopril and cyclophosphamide. It is concluded that captopril improves survival in SLE disease of MRL/l mice, counteracting lymphoid hyperplasia, renal disease, dermatitis and decreasing arterial blood pressure.

Animals↗
PubMed1988

Phenotypes of immunocompetent cells and Ia antigen expression in oral mucosa and skin of autoimmune mouse strains.

The phenotypic characteristics of resident and infiltrating cells in skin and oral mucosa of MRL/Mp-lpr/lpr (MRL-lpr), MRL/Mp+/+ (MRL-(+)), NZB x NZW F1 (NZB/W) and Balb/c mice have been studied using monoclonal antibodies (Mabs) and immunoperoxidase staining with the Avidin-Biotin Complex method. Macroscopically evident skin lesions appeared spontaneously exclusively in aging MRL-lpr mice. Infiltration of lymphocytes was detected within the mucosa and the skin of MRL-lpr-mice. These lymphocytes expressed predominantly L3T4 and to a lesser extent Lyt-2 phenotype (T helper/inducer and T suppressor/cytotoxic subset, respectively). Class II major histocompatibility complex antigen (Ia) expression was detected on macrophages, dendritic cells and few lymphoid cells in normal oral mucosa and skin of all strains examined. However, in the oral mucosa and skin lesions of the 4 months old MRL-lpr mouse also keratinocytes expressed Ia antigens. Keratinocytic Ia expression was also detected in oral mucosa of 8 months old MRL-(+) mice. The described immunopathological findings in skin and oral mucosa of old MRL-lpr mice show a number of important similarities to human SLE disease.

Aging↗
PubMed1988

Features of renal vasculitis in autoimmune MRL lpr/lpr mice: phenotypes and functional properties of infiltrating cells.

MRL lpr/lpr (MRL/1) mice spontaneously develop a widespread renal vasculitis. The majority of the cells in vasculitic lesions are bright Ly-1, L3T4 and la-positive in contrast to the cells found in lymph nodes and spleens of the old MRL/1 mice. However, despite differences in phenotypical patterns, B and T cells from arteritic lesions do not differ from mononuclear cells (MNC) eluted from MRL/1 lymph nodes with regard to the frequency of IgG secreting cells and the proliferative responses to Concanavalin A (Con A). Co-culture experiments with congeneic MRL+/+ (MRL/n) spleen cells indicate that the poor response to Con A of the MNC eluted from vasculitic lesions is, unlike the case of lymph node MNC, due to suppressive action of vasculitic cells on the indicator cell population. Further support for the activation status of infiltrating MHC in kidney vasculitic lesions, expressed by high in vivo uptake of 3H-thymidine, was obtained by autoradiography performed on frozen sections. The observed differences in phenotypic patterns and functional features between lymph node MNC and infiltrating vasculitic MNC indicate that different immune mechanisms may be responsible for the development of lymphadenopathy and vasculopathy, respectively in MRL/1 mouse.

Animals↗
PubMed1987

Immunohistochemical characterization of synovial cells in arthritic MRL-lpr/lpr mice.

MRL-lpr/lpr (MRL/l) mice spontaneously develop an autoimmune disease associated with arthritic manifestations. We used a recently developed mild demineralization procedure, followed by immunohistochemical staining of frozen sections, to investigate cell patterns in the hindlimbs of MRL/l mice at various stages of arthritic disease. Large numbers of Mac-1 (Mas 034)-positive, macrophage-like cells were seen both within the thickened synovial lining layer and in the deeper layers of the synovial tissue in all stages of arthritis. Ia-expressing cells were scarce in the lining layer, but occurred in moderate numbers in the deeper layers of synovial tissue. Lymphocytes were totally absent in MRL/l joints in all stages of arthritis, as demonstrated by lack of staining with Ly-1, Lyt-2, GK 1,5, and antiimmunoglobulin antibodies. Our findings are discussed and related to other types of experimental arthritis and to rheumatoid arthritis in humans.

Animals↗
PubMed1987

Expression of HLA-D-locus (DP, DQ, DR)-coded antigens, beta 2-microglobulin, and the interleukin 2 receptor in Sjögren's syndrome.

The expression of beta 2-microglobulin (beta 2m), class II major histocompatibility complex (MHC) antigens (HLA-DP, -DQ, -DR) and the interleukin 2 receptor (IL-2R) on resident and infiltrating cells in labial salivary glands of patients with Sjögren's syndrome (SS) was studied using an immunoperoxidase technique based on staining with monoclonal antibodies. The progression of the inflammatory process was accompanied by increasing numbers of immunocompetent cells as well as glandular epithelial cells expressing beta 2m and class II MHC antigens. Up to 60% of the infiltrating lymphocytes were DQ- and DR-positive while fewer cells stained for DP antigen. Glandular epithelium (acinar and ductal cells) stained for products of all three HLA-D subregions but with varying degrees of expression following the pattern DR greater than DP greater than DQ related to the severity of inflammation. A minor portion of the infiltrating lymphocytes expressed IL-2R. These findings emphasize the potential importance of epithelial expression of class II antigens in the local activation of T lymphocytes in salivary gland lesions of SS patients. They also indicate that differences may exist in this respect between T-cell reactions restricted by different class II MHC-encoded gene products.

Arthritis, Rheumatoid↗
PubMed1987

Immunohistochemical characterization of sialadenitis in NZB X NZW F1 mice.

The spontaneously developing sialadenitis in female autoimmune NZB X NZW F1 (NZB/W) mice has been studied with the help of immunohistochemistry and monoclonal antibodies to cell surface antigens. Semiquantitative assessment of stained cells within the infiltrates disclosed a progressive focal inflammation most pronounced in submandibular and parotid glands. The majority of cells expressed Ly-1 (all T cells) and L3T4 (T helper) phenotype, whereas only few Lyt-2 (cytotoxic/suppressor) expressing T cells were seen. A large proportion of the infiltrating cells stained for Ia antigens, which was also found on salivary gland ductal epithelium in the proximity of lymphoid infiltrates. The phenotypic pattern in sialadenitis of NZB/W mice thus closely resembles the pattern previously described for human Sjögren's syndrome (SS). Accordingly, immunomorphological analysis of the NZB/W sialadenitis may be useful in further studies of pathogenesis and therapy of both experimental and human SS.

Animals↗
PubMed1987

T cell subsets and expression of immunological activation markers in the arterial walls of patients with giant cell arteritis.

Immunohistochemical features of infiltrating mononuclear cells (MNC) and resident cells were studied in the temporal artery biopsy specimens of 13 patients with histological verified giant cell arteritis (GCA) and in six biopsy specimens from patients with GCA with negative histological findings. Eight temporal artery biopsy specimens from seven patients with unrelated diseases served as controls. In all patients with GCA proved by biopsy an infiltration of T lymphocytes in the arterial wall was observed, most being of the helper/inducer subset. No B lymphocytes, or very few, were seen. Lymphocytes in 10 out of the 13 positive biopsy specimens displayed staining for the class II major histocompatibility complex (MHC) antigen HLA-DR, whereas this was found in only two of eight controls. A minor number of the infiltrating T lymphocytes from seven out of 13 patients with GCA proved by biopsy stained for transferrin receptors, and in six out of the 13 cases they reacted with anti-interleukin 2 receptor antibody. In the arterial wall from all patients with histologically verified GCA we also found an increased number of macrophages, many of them expressing HLA-DR antigens and transferrin receptors. The immunohistochemical pattern of cell phenotypes found in the arterial wall of patients with GCA suggests that the infiltrating T cells are immunologically activated. This finding supports the hypothesis of a predominantly cellular immunological pathogenesis of giant cell arteritis.

Aged↗
PubMed1987

Rheumatoid factor isotypes and renal disease in systemic lupus erythematosus.

There is no agreement on whether rheumatoid factor (RF) exerts protection, injury, or is an epiphenomenon with regard to kidney disease in systemic lupus erythematosus (SLE). In this study we examined the occurrence and isotype distribution of rheumatoid factor in SLE in relation to some clinical parameters, including renal function and arthritis. A highly significant correlation (p less than 0.001) was noted between the presence of IgG RF and absence of kidney disease. The IgG RF also seemed to protect SLE patients from developing arthritis (p less than 0.01). On the other hand, elevated IgM RF levels indicated active SLE disease. The results obtained are discussed in relation to the ability of RF to interact with immune complexes in vitro and in vivo.

Adult↗
PubMed1987

Origin of the autoreactive anti-type II collagen response. I. Frequency of specific and multispecific B cells in primed murine lymph nodes.

DBA/1 mice develop systemic polyarthritis and high titres of collagen autoantibodies after immunization with type II collagen. In this study we have analysed the frequency and specificity of antibody-producing B cells in draining lymph nodes 11 days after a primary immunization with rat type II collagen. A remarkably high frequency of type II collagen-reactive hybridomas (30%, n = 71), the majority cross-reacting with autologous type II collagen, were generated. Most of the collagen-reactive hybridomas produced IgG antibodies specific for type II collagen. Many other hybridomas produced multispecific antibodies (9%): these were preferentially of the IgM class. Some of the monoclonal multispecific hybridomas produced antibodies that cross-reacted with specific epitopes on the collagen molecule. One type II collagen-reactive hybridoma also displayed rheumatoid factor activity. Different mechanisms for the generation of the high frequency of collagen reactive antibodies are discussed.

Animals↗
PubMed1987

Sialadenitis in the MRL-l mouse: morphological and immunohistochemical characterization of resident and infiltrating cells.

The MRL-lpr/lpr (MRL/l) mouse spontaneously develops an autoimmune disease associated with various rheumatic manifestations. We have studied the histological features of sialadenitis and utilized an immunohistochemical staining technique on frozen tissue sections to analyse the cellular composition of the salivary glands at varying stages of disease. Semiquantitative assessment of the infiltration disclosed a focal inflammation which started at 2 months of age and was progressive until 5 months of age in submandibular glands. A high frequency of Ly-1 and L3T4-positive cells was observed at all stages of sialadenitis, whereas Lyt-2 positive cells were found at a lower frequency. Ia expression was seen on a large proportion of the infiltrating cells and also on ductal and glandular epithelial cells in the vicinity of the inflammatory lesions. The presence of Ia antigens on many inflammatory as well as resident cells and the high frequency of lymphocytes with 'helper' phenotype may indicate a perpetuated immunological activation within salivary glands.

Animals↗
PubMed1986

A demineralization procedure for immunohistopathological use. EDTA treatment preserves lymphoid cell surface antigens.

An evaluation of the usefulness of EDTA treatment for decalcification of murine bone tissue in order to preserve both morphological details and immunologically intact cell surface antigens has been performed. The ABC immunohistochemical staining technique employing monoclonal antibodies to subsets of T-lymphocytes, B-lymphocytes and to Ia antigens was used on frozen sections. Treatment of mouse hindlegs with EDTA for 14 days resulted in an efficient decalcification and good preservation of morphological details. When lymphoid tissues were handled in the same manner monoclonal antibodies, defining Ly 1, Ly 2, L3T4, MAS 034 and Ia molecules, were shown to retain their reactivity comparable to that of directly frozen tissues. In contrast, formic acid, the commonly used decalcification agent, destroyed most of the antigenic reactivity. We conclude that EDTA treatment of non-fixed, bone-containing tissues provides a suitable demineralization procedure in the immunohistochemical study of, e.g., arthritis and periodontitis.

Animals↗