Biomedical subjects
R Jonsson
Publications and source records attributed to R Jonsson.
[Oral manifestations associated with Sjogren syndrome--clinic, diagnosis and treatment].
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Treatment with gamma-interferon triggers the onset of collagen arthritis in mice.
We investigated the effect of gamma-interferon (gamma-IFN) on the development of type II collagen (CII)-induced arthritis. DBA/1 mice were immunized with rat CII and 16 days later, were treated with subcutaneous injections of recombinant rat gamma-IFN into the right paws twice a week. Compared with controls, the gamma-IFN-treated mice developed arthritis with a higher frequency and severity. Immunohistochemical analysis of gamma-IFN-treated paws from CII-immunized mice revealed an increase in the numbers of class II antigen-expressing cells and an infiltration of CD4+ lymphocyte-like cells. The auto-antibody response toward CII was suppressed by gamma-IFN treatment. The findings implicate gamma-IFN in a role that triggers arthritis by enhancing local inflammatory processes in the joints, or possibly, by permitting homing of T cells to the joints.
Effects of immunomodulating treatment on autoimmune sialadenitis in MRL/Mp-lpr/lpr mice.
The autoimmune MRL/Mp-lpr/lpr (MRL/l) mouse spontaneously develops sialadenitis with a morphological and phenotypical pattern similar to that seen in human Sjögren's syndrome (SS). This makes the MRL/l mouse a suitable model for therapeutical studies of autoimmune sialadenitis. We have, by histological and immunohistochemical techniques, analyzed the therapeutical effect of treatment with LS2616, a recently synthesized oxokinolinamide derivative, on sialadenitis in submandibular glands of MRL/l mice. The results were compared with effects obtained after treatment with cyclophosphamide (CY) and physiologic saline. Administration of both LS2616 and CY to MRL/l mice has previously been found to result in prolongation of survival and amelioration of organ pathology. However, only CY treatment reduced sialadenitis, while LS2616 increased the semiquantitatively assessed focal inflammation of salivary glands in 6 months old mice. No differences in T-cell phenotypes of infiltrating lymphoid cells in salivary glands between different treatment regims could be noted. However, the frequency of B-cells in the sialadenitis was decreased in the CY treated group. In contrast, CY but not LS2616 treatment normalized expression of T-helper and cytotoxic T-cell phenotypes as well as reduced the B-cell portion in lymph nodes. It is concluded that CY treatment can suppress sialadenitis although both LS2616 and CY are effective in prolongation lifespan of MRL/l mice. This may implicate different immunopathogenic mechanisms for development of sialadenitis versus other organ lesions in the autoimmune disease of MRL/l mice.
Ventricular dimensions and wall motion assessed by echocardiography in patients with arrhythmogenic right ventricular dysplasia.
Twenty patients with arrhythmogenic right ventricular dysplasia (ARVD) and 20 healthy volunteers underwent cross-sectional echocardiographic examination for the assessment of ventricular dimensions and wall motion. Right ventricular cavity diameters and wall segments were selected from the inflow and outflow tracts and the right ventricular body. The measurement error for measuring cavity dimensions was low throughout and the reproducibility of wall motion scoring was high in both the normal subjects and the patients. All except one patient had increased dimensions and/or abnormal wall motion in the right ventricle. The right ventricular inflow tract was dilated in nine patients, the outflow tract in 11 patients and the short- or long-axis diameters of the right ventricular body were increased in seven patients. Right ventricular wall motion abnormalities, being the most frequent finding, ranged from mild hypokinesia only to dyskinesia or sacculations, and were fairly evenly distributed among the segments studied. Left ventricular abnormalities, found in eight patients, were generally mild. Cross-sectional echocardiography thus provides highly reproducible measurements of right ventricular size and contraction patterns even in patients with wall shape deformities, and is therefore a feasible non-invasive method for the evaluation of right-sided myocardial abnormalities in patients with ARVD. The diagnostic accuracy of this technique warrants further clarification.
Transiently increased insulin-like growth factor. I. Immunoreactivity in UVB-irradiated mouse skin.
UVB-irradiation during 3 d for 90, 180, and 180 sec, respectively, at a daily dose of 0.1 and 0.2 joule/cm2, respectively, induced slight inflammatory reactions in the mouse ear. The insulin-like growth factor I (IGF-I) immunoreactivity, normally demonstrable only in scattered basal epidermal cells, rapidly increased in intensity and frequency in the epidermis. After 3 d of UVB irradiation almost all epidermal cells were outlined by IGF-I immunoreactivity in their plasma membrane. The Langerhans cells expressed intense IGF-I immunoreactivity throughout their cytoplasm. The elevated IGF-I immunoreactivity ceased after 5-7 d and was normalized in 3 weeks. The number of Ia positive epithelial Langerhans cells did not seem to be affected by UVB irradiation. It is concluded that the increased IGF-I immunoreactivity is likely to reflect formation of the trophic peptide IGF-I, most evidently by Langerhans cells, in early events of the inflammatory, reactive response of the skin to UVB irradiation.
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.
Oral lesions of lupus erythematosus patients in relation to other chronic inflammatory oral diseases: an immunologic study.
The nature and distribution of mononuclear cells in non-ulcerated oral lesions of discoid (DLE) and systemic lupus erythematosus (SLE), were investigated and compared to other chronic inflammatory oral diseases (lichen planus (LP), contact lesion (CL), unspecified inflammation (UI), geographic tongue (GT), and leukoplakia (LK). For this purpose an immunoperoxidase technique based on staining with monoclonal antibodies was employed. In most LE specimens examined infiltrating cells consisted predominantly of a mixture of T cells (Leu 3a+ and Leu 2a+) that were distributed in the lamina propria, the submucosa, and occasionally also in the epithelium. In general, only few B cells were detected while macrophages were more frequent. In all LE specimens examined beta 2-microglobulin expression was observed on a large proportion of cells including infiltrating mononuclear cells as well as resident keratinocytes. In addition, most infiltrating cells displayed MHC Class II antigens according to a pattern HLA-DR greater than DQ greater than DP. Interestingly, expression of Class II antigens was also observed on epithelial keratinocytes but was restricted to HLA-DR and -DP gene products (DR much greater than DP). HLA-DQ expression was never observed on keratinocytes. In most LE specimens studied a small proportion (less than 5%) of inflammatory cells had detectable interleukin-2 receptors (IL-2R) and/or transferrin receptors (transf-R). However, expression of transf-R was also observed on basal epithelial cells, being more pronounced in DLE than in SLE lesions. The above staining patterns observed in LE lesions, when compared to other chronic inflammatory oral lesions, did not disclose any striking differences that could support the specific diagnosis of LE. However, the findings of Class I and II MHC gene products on oral keratinocytes suggest an important accessory role for these cells in directing the migration of activated lymphoid cells in the epithelium in chronic inflammatory lesions of the oral mucosa.
Cardioangiographic findings in patients with arrhythmogenic right ventricular dysplasia.
The dimension, contractility, and regional wall motion of the right and left ventricles were scored on the angiograms of 13 patients with arrhythmogenic right ventricular dysplasia. In 10 patients the right ventricle was enlarged, in eight the contractility of the right ventricle was reduced, and in all but one patient there were regional wall motion abnormalities of the right ventricle. The most common abnormality of regional wall motion was mild hypokinesia. There were bulging or dyskinetic areas in seven patients. Regional wall motion abnormalities of the left ventricle were found in five patients, two of whom also had bulging or dyskinetic areas. The reproducibility of right ventricular dimension, contractility, and regional wall motion scores was generally fair but varied unexpectedly both within and between two observers (Kendall's Tau 0.38-0.92). The score values of regional wall motion for some of the segments differed considerably within and between observers. One of the observers consistently gave higher scores than the other. These data suggest that a more objective approach is needed for evaluating angiographic changes in arrhythmogenic right ventricular dysplasia.
Relationships between periodontal health, salivary steroids, and Bacteroides intermedius in males, pregnant and non-pregnant women.
Relationships between four steroids, determined by radio-immunoassay of whole saliva, and clinical and bacteriological parameters were studied in 90 subjects: males, menstruating females, and pregnant females. Pocket depths and both plaque and gingival bleeding scores were recorded. Total counts and percentages of Gram-negative organisms Bacteroides and B. intermedius were determined from anaerobic cultures of subgingival plaque from 9-14 subjects in each group. None of the clinical parameters for the pregnant females differed significantly from those of non-pregnant females, nor did these parameters show any significant correlation with progression of pregnancy. No correlations were detected between bacterial and clinical parameters in the pregnant group. There were no statistically significant differences between the total bacterial counts from the three groups, yet males had significantly higher proportions of Gram-negative bacteria, Bacteroides, and B. intermedius, than did pregnant and non-pregnant females. Proportions of B. intermedius did not differ significantly between the two female groups, nor was there any correlation with progression of pregnancy. While some steroids appeared to affect some clinical or bacteriological parameters in some groups, no obvious patterns consistent with different steroid levels were detected. The results do not indicate that increased hormone levels cause more severe periodontal disease in pregnant women, nor that high salivary steroid levels result in increased recovery of B. intermedius from subgingival plaque.
Histological and functional features of salivary glands in rheumatic patients with oral sicca symptoms.
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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.
SSC microgravity sounding rocket program MASER.
The Swedish Microgravity Sounding Rocket program MASER is presented. Especially the MASER 1 payload is depicted, but also an outlook for the future possibilities within the Short Duration Flight Opportunities is given. Furthermore the coordination and relation with the German TEXUS program is touched upon. With the two TEXUS and MASER programs--possibly together with other fascinating projects like M-ARIES and MG-M-ARIANNE--the microgravity scientific community in Europe should get reasonable amounts of flight opportunities in preparation for the big space venture the European Space Station.
HLA-DR expression in the vascular lesion and circulating T lymphocytes of patients with giant cell arteritis.
Giant cell arteritis (GCA) is a vascular inflammatory disease characterized by accumulations of T lymphocytes and macrophages in the arterial wall. In order to characterize the immune response in GCA, we have analysed temporal artery biopsies using a double-staining immunofluorescence method and studied T lymphocytes in peripheral blood with a fluorescence-activated cell sorter (FACS). HLA-DR was expressed on 28% (range 16-42%) of all T lymphocytes in the wall of the inflamed temporal artery, but only on average on 6% of peripheral blood T lymphocytes, indicating a high degree of local T cell activation in the inflammatory lesion. The proportions of T lymphocytes, T helper/inducer and T suppressor/cytotoxic cells in the blood of GCA patients before treatment with prednisolone did not deviate from those in normal individuals, but there was a minor increase in T helper cells after initiation of steroid therapy. The number of T helper cells expressing HLA-DR antigen and IL-2 receptor was not altered after 6-10 days of treatment with prednisolone. We found no evidence of HLA-DR expression by arterial smooth muscle cells in the GCA lesions, suggesting that these cells do not serve as antigen-presenting cells in GCA.
Early appearance of activated CD4+ T lymphocytes and class II antigen-expressing cells in joints of DBA/1 mice immunized with type II collagen.
Arthritis induced with type II collagen in DBA/1 mice, was analyzed by immunohistochemical techniques. In the earliest detectable pathologic changes, before any macroscopic signs, an accumulation of Mac1+, macrophage-like cells, and an increased expression of major histocompatibility class II antigens were observed focally in the synovial lining layer. In these foci, CD4+ and interleukin 2 receptor expressing T lymphocytes were regularly detected, but not usually other sets of lymphocytes such as B lymphocytes and CD8+ lymphocytes. In clinically detectable arthritis, there was a prominent infiltration of Mac1+ cells, both polymorphonuclear-like and macrophage-like cells. T cells were relatively few, suggesting that they do not play a primary effector role, but rather that they may regulate or permit the self-perpetuative inflammation.
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.
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.
Differential tissue distribution of HLA-DR, -DP and -DQ antigens.
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