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Biomedical subjects

R Jonsson

Publications and source records attributed to R Jonsson.

At least 127 records · Page 7Linked to original sources
PubMed1991

Differential effects of oestrogen in murine lupus: acceleration of glomerulonephritis and amelioration of T cell-mediated lesions.

Oestrogen is known to accelerate glomerulonephritis and autoantibody production in human and murine systemic lupus erythematosus (SLE). In this study we demonstrate that treatment of castrated autoimmune MRL +/+ mice with physiological doses of oestrogen results in enhanced immunoglobulin and autoantibody production as well as increased deposition of IgG in renal glomeruli. Accelerated development of glomerulonephritis was also evident from the increase of albuminuria. Interestingly, in contrast to these deteriorative effects of oestrogen on immune complex-mediated disease we now show that the lymphocytic infiltrations in the submandibular glands and perivascular lesions in the kidneys were significantly diminished after exposure to oestrogen. This remarkable impact of physiological oestrogen levels on the outcome of SLE in MRL +/+ mice is postulated to be the result of a differential effect on T and B cell-mediated immune responses.

Animals↗
PubMed1991

Murine models for systemic lupus erythematosus and Sjögren's syndrome.

Of the types of defects that have been observed in autoimmune mice, two are common to most strains and appear to be of critical importance in the development of autoimmune disease. The first of these is a deficiency in the maintenance of self-tolerance by B or T lymphocytes. This is an intrinsic defect due to genetic abnormalities that presumably affect an early developmental signaling mechanism. The disruption of early B- and T-cell development leads to the appearance of lymphocytes that are predisposed to loss of tolerance. In certain strains of autoimmune mice, it also leads to overproduction of Ly1+ (CD5+) B cells or CD4-CD8-B220+ T cells, which apparently do not contribute to autoimmunity. The second type of defect is a strain-specific, antigen-driven autoimmune disease syndrome. This defect is limited by the affinities of the available T-cell receptor and immunoglobulin variable regions and the efficiency of antigen presentation. Current evidence suggests that the major histocompatibility complex molecules play the most important role in determining which autoantigens lead to a pathogenic antigen-driven immune response. For example, the type and magnitude of the autoimmune response may be directed by the production of specific cytokines. The type of antigen and the context of its presentation can bias the production of cytokines that favor the production of the Th2 subset of CD4+ T helper cells. These cells secrete predominantly interleukin-4, interleukin-5, and interleukin-10, and may contribute to a chronic response and autoimmune disease.

Animals↗
PubMed1991

Immunoglobulin isotype distribution of locally produced autoantibodies to collagen type I in adult periodontitis. Relationship to periodontal treatment.

Production of antibodies to collagen type I was analyzed by means of an enzyme-linked immunospot (ELISPOT) assay in patients with chronic adult periodontitis (AP) before and after periodontal hygiene treatment. Anti-collagen type I antibody-secreting cells were found among mononuclear cells enzymatically eluted from inflamed gingiva in 9 of 15 patients with untreated AP and in 4 of 14 hygiene-treated patients with a varied isotype distribution. A notably high prevalence of IgG and IgM isotypes was observed for the anti-collagen antibodies in untreated patients. With wide variation, chronic AP was characterized by a high frequency of spontaneous IgG and low numbers of IgA and IgM-producing cells. Periodontal hygiene treatment significantly reduced the number of IgA and IgM-secreting cells. Although AP is not an autoimmune disease in the accepted sense, our results indicate that local autoimmune reactions to collagen type I are common in untreated AP, implying an interplay between periodontal infection and autoimmunity.

Autoantibodies↗
PubMed1991

Antibody-producing cells in peripheral blood and salivary glands after oral cholera vaccination of humans.

We examined whether immunization with a newly developed oral cholera vaccine would elicit gut-derived antibody-producing cells in the blood and in distant mucosal tissues, such as the minor salivary glands, in 30 adult Swedish volunteers. The results of this study demonstrated that this vaccine indeed induced production of specific antibody-producing cells against the cholera toxin B subunit in both peripheral blood and salivary glands. The response in blood, which after primary and booster immunizations comprised both immunoglobulin A (IgA) and IgG antibody-forming cells, was highly transient and preceded the response in salivary glands; the latter response was restricted to the IgA isotype. The results provide further evidence of the existence of a common mucosal immune system in humans. Furthermore, these findings support previous observations that in animals, the cholera toxin B subunit may be a useful carrier protein for preparing enteric vaccines against pathogens encountered at intestinal and extraintestinal mucosal sites.

Administration, Oral↗
PubMed1991

Swallowing problems in rheumatoid arthritis.

Twenty-nine female patients with definite or classical rheumatoid arthritis (RA) and 30 controls were investigated in order to evaluate oral symptoms, particularly xerostomia, and swallowing difficulties in RA by means of a questionnaire, physical examination, stimulated saliva secretion, labial salivary gland biopsy, esophageal manometry and laboratory blood tests. Xerostomia was reported by 6 patients (21%), compared with no-one in the control group. Four of these 6 patients had decreased stimulated saliva secretion, compared with 2 of the remaining 23 patients. Dysphagia was experienced by 8 patients (28%), compared with one control subject. Dysphagia was associated with disease severity. Esophageal manometry revealed a decrease of the amplitude of the peristaltic pressure complex in the proximal part of esophagus in the RA group, indicating dysfunction of the striated muscles. No correlation was found between dysphagia and esophageal manometry results.

Arthritis, Rheumatoid↗
PubMed1991

Local IgA and IgM rheumatoid factor production in autoimmune MRL/lpr mice.

Spontaneous local immunoglobulin (IgA, IgG, IgM) as well as IgA and IgM rheumatoid factor (RF) production in salivary glands, lymph nodes, and spleen was analyzed at various ages in autoimmune MRL/Mp-lpr/lpr (MRL/lpr) mice by using an ELISPOT assay. The longitudinal design of the study permitted correlations with severity of disease in salivary glands (sialadenitis). Local production of immunoglobulins in salivary glands and lymph nodes occurred with a pattern of IgG much greater than IgM greater than IgA. This isotype pattern differed from that simultaneously observed in spleen where IgG did not predominate to the same extent. Moreover, the spleen was the major site of IgM production. Rheumatoid factors constituted a significant fraction of local IgA and IgM in involved salivary glands. The pattern of IgA RF isotype expression in salivary glands contrasted with that observed in spleen. While the number of IgA and IgG secreting cells increase at an early age, the peak of RF production in salivary glands occurs in older mice. Furthermore, the level of immunoglobulin secretion was positively correlated with disease severity in salivary glands. The results suggest that local RF production is a secondary event in salivary gland inflammation in MRL/1pr mice rather than an initiating factor in this process.

Animals↗
PubMed1991

Multiple epitopes on cartilage type II collagen are accessible for antibody binding in vivo.

Monoclonal mouse antibodies specific for the major epitopes on mouse type II collagen (CII) were biotinylated and injected into neonatal and adult mice. Anti-CII antibodies, specific for four different epitopes on the CII molecule, could be shown to bind specifically to joint surfaces in the paws of 2-day-old syngeneic DBA/1 mice after an intraperitoneal injection of 100 micrograms of biotinylated antibody. The anti-CII antibodies did not bind to cartilage from DBA/1 mice in vitro, unless the sections were pretreated with hyaluronidase or the specimens decalcified prior to freezing, showing that the epitopes are accessible in vivo but not in vitro. By analyzing the in vivo binding capacity for a number of monoclonal anti-CII antibodies which represented different IgG subclasses, it could be demonstrated that binding to the same epitopes occurred independent of IgG subclass. However, one epitope (denoted "B1") was only weakly detected, possibly due to the fact that the antibody used (CIIB1) crossreacts with type I collagen and C1q. Monoclonal anti-CII antibodies, injected into neonates or adult mice, bound specifically to most, but not all, tissues containing CII; including hyaline joint cartilage, fibrous sternal and costal cartilage, tracheal cartilage and fibrous cartilage in the spine but not to CII-containing structures in the eye. The finding that CII, while present in cartilage, is accessible for antibody binding in vivo may have important implications for the availability of CII for the immune system and for the understanding of the development of pathological autoimmunity leading to collagen-induced arthritis in mice.

Animals↗
PubMed1991

Involvement of macrophages and dendritic cells in synovial inflammation of collagen induced arthritis in DBA/1 mice and spontaneous arthritis in MRL/lpr mice.

Type II collagen induced arthritis (C1A) is an antigen-specific and T-cell dependent autoimmune disease in which the time course of disease is known. Arthritis is induced with type II collagen (CII) immunization, but can also be induced with passive transfer of anti-CII antibody containing syngenic serum and with local administration of gamma interferon. In the present study we analysed the spectrum of inflammatory cells appearing in the arthritic joints. Three phases of the disease process could be defined: 1) Early infiltration of T cells and appearance of class II expressing macrophages in the synovial lining layer 2) Profound infiltration of granulocytes and oedema formation and 3) Pannus formation containing activated macrophages, granulocytes, T cells and dendritic cells. At this severe destruction of cartilage and bone beginning from the marginal zone was seen. In contrast, joints from spontaneously arising arthritis in MRL lpr/lpr mice showed no granulocytes or T cells, sparse expression of class II but relatively uniform appearance of C3bi-receptor+, Fc-receptor+ and MOMA2+ synovial cells.

Animals↗
PubMed1990

Arthritis in DBA/1 mice induced with passively transferred type II collagen immune serum. Immunohistopathology and serum levels of anti-type II collagen auto-antibodies.

Arthritis was induced in DBA/1 mice by passive transfer of syngeneic anti-type II collagen (CII) serum concentrate. After transfer of serum containing 0.2 or 0.5 mg anti-CII auto-antibodies the first clinical signs of arthritis appeared 48 h after injection. Severe clinical arthritis was detected 96 h after injection. Immunohistochemical analyses of joints 48 h after serum injection revealed synovial foci in intercarpal and metacarpophalangeal joints of macrophage-like cells, expressing C3bi-receptors and major histocompatibility complex class II molecules, and infiltration of few CD4+ lymphocytes. Later (96 h after injection), the inflamed synovia were dominated by C3bi-receptor+ polymorphonuclear cells. In contrast to conventionally induced collagen arthritis (CIA), the inflammatory infiltrates, filling joint spaces and synovial tissue, were extensively dominated by polymorphonuclear cells, whereas macrophage-like cells expressing class II molecules and a few T cells were seen only in the periphery of the developing pannus. The anti-CII serum induced arthritis may be used as a model for studies of humoral mediated mechanisms operating in conventionally induced CIA as well as in rheumatoid arthritis.

Animals↗
PubMed1990

Expression of heterozygous lpr gene in MRL mice. II. Acceleration of glomerulonephritis, sialadenitis, and autoantibody production.

Recently we showed that not only homozygous MRL lpr/lpr mice but also heterozygous MRL +/lpr mice display defective antigen- and mitogen-driven T-cell responses as well as polyclonal B-cell activation compared with congeneic MRL +/+ mice. In this study we examined the impact of the heterozygous lpr gene on organ pathology in kidneys, joints, and salivary glands, as well as serum levels of immunoglobulins and autoantibodies in young and old MRL mice. Only 1 out of 17 heterozygous lpr-bearing MRL mice developed clinically overt renal disease with significant proteinuria and haematuria during the first year of life. However, examination of Ig and C3 deposits in glomeruli of kidneys from these mice revealed that the expression of the heterozygous lpr gene in MRL mice accelerates glomerulonephritis. In addition, histological examination of the submandibular salivary glands showed an increased focus score in heterozygous MRL mice at 4-5 months of age compared with that of matched congeneic +/+ mice. In contrast, no signs of arthropathy were registered in the heterozygous lpr-bearing MRL mice. Heterozygous MRL mice displayed an expanding lymphoid system as evaluated by significantly increased spleen and lymph node weights compared with those of matched MRL +/+ mice. Further evidence for immunomodulatory properties of the heterozygous lpr gene was obtained when analysing serum levels of IgG, IgM, and autoantibodies. Thus, heterozygous MRL +/lpr mice produced significantly higher levels of both Ig and autoantibodies than matched MRL +/+ mice. We conclude that the expression of the heterozygous lpr gene in MRL mice results in acceleration of the autoimmune process, giving rise to precocious clinical disease.

Age Factors↗
PubMed1990

Infiltrating mononuclear cells in salivary glands and kidneys in autoimmune MRL/Mp-lpr/lpr mice express IL-2 receptor and produce interferon-gamma.

The salivary gland inflammatory lesions and renal vasculitic lesions of autoimmune MRL/lpr mice were analyzed for the presence of activated lymphocytes. Immunohistologic analysis revealed that the majority of lymphocyte-like cells in salivary glands and kidneys expressed CD4 antigen (greater than 50%). Lesser numbers of interleukin-2 receptor (IL-2R) expressing and interferon-gamma (IFN-gamma)-producing cells were present (1-5%). CD4+, IL-2R+, and IFN-gamma + mononuclear cells were found in small inflammatory foci. In larger inflammatory foci the IFN-gamma-producing cells were detected in the periphery in comparable numbers as the IL-2R expressing cells although with different location. Large numbers of cells in the inflammatory foci also expressed MHC Class II molecules (greater than 50%). The expression of IL-2R and production of IFN-gamma in the tissue lesions indicate presence of activated inflammatory T cells. Production of IFN-gamma by the infiltrating mononuclear cells may induce Class II antigens on epithelial cells and stimulate further T cell migration into the inflammatory site.

Animals↗
PubMed1990

Elucidating the pathogenesis of autoimmune disease: recent advances at the molecular level and relevance to oral mucosal disease.

Humoral and/or cellular immune responses directed against self antigen are currently thought to underlie a wide spectrum of systemic and organ-specific human and animal autoimmune diseases. Although the immunopathology of these diseases has been well characterized in most cases, the etiology still remains obscure. In order to gain a more fundamental insight of the abnormal processes leading to autoimmunity, efforts are currently being directed toward defining these diseases at a molecular level. Because of the clinical diversity and immunological complexity of these diseases, several directions are being pursued. Relevant to autoimmune oral disease, this review will focus on antigen processing and recognition (immunoglobulin and T cell receptor genes), the key role of the major histocompatibility complex, and the involvement of the cytokine network. Advances made in these fields have clear relevance for future diagnostic and therapeutic strategies related to autoimmune diseases affecting oral tissues.

Animals↗
PubMed1989

The relationship between intraoperatively assessed atrial and ventricular insertions of accessory pathways.

To gain insight into the complex problems regarding the extension of the atrial and ventricular insertions of anomalous pathways, the activation patterns obtained from intraoperative epicardial mapping in 23 patients with Wolff-Parkinson-White syndrome were carefully analyzed. The atrial and ventricular activation times along the atrioventricular groove were measured at 15 predefined anatomical landmarks. The width of the region of earliest atrial and ventricular activation times and the extent of atrial and ventricular overlap were assessed. The relationship between the atrial and ventricular insertions was studied by predicting the ventricular insertions from the observed atrial insertions and vice versa. The mean extension of an atrial and a ventricular insertion at surgery was 1.9 +/- 0.2 (SE) and 1.6 +/- 0.2 (SE) anatomical landmarks, respectively. The width of the region of early atrial and ventricular activation times measured 2.7 +/- 0.3 (SE) landmarks, thus indicating an overlap of the atrial and ventricular insertions. The lateral distance between the sites of earliest atrial and ventricular activation times was, on average, 1.7 +/- 0.3 (SE) landmarks. The predicted atrial insertion from a known ventricular insertion, and vice versa was found to cover 4 to 6 anatomical landmarks. These observations suggest that wide surgical dissections along the atrioventricular groove are warranted even if epicardial mapping discloses only a single accessory pathway.

Action Potentials↗
PubMed1989

Phenotypic characterization of mononuclear cells and class II antigen expression in angular cheilitis infected by Candida albicans or Staphylococcus aureus.

In the present study we characterized the phenotypes of infiltrating mononuclear cells in angular cheilitis lesions to further explore the pathogenesis of this disorder. Frozen sections from lesions infected by Candida albicans and/or Staphylococcus aureus were subjected to immunohistochemical analysis utilizing monoclonal antibodies directed to subsets of T-lymphocytes, B-lymphocytes, and macrophages. In addition, the expression of Class II antigens (HLA-DP, -DQ, -DR), the interleukin 2- and transferrin-receptors was studied on resident and infiltrating cells. An intense infiltration of T-lymphocytes was accompanied by expression of Class II antigens on the epidermal keratinocytes in lesion infected by Candida albicans. The Staphylococcus aureus infected lesions displayed a diffuse infiltration of T-lymphocytes but virtually no expression of Class II antigen by epidermal keratinocytes. These observations suggest that the cell-mediated arm of the immune system is involved in the inflammatory reaction of lesions infected by Candida albicans. In addition, the present study confirms that epidermal expression of Class II antigens is closely related to the type and magnitude of the infiltrating T-lymphocyte. Finally, these findings indicate that the type of inflammatory reaction in angular cheilitis is primarily dependent on the isolated microorganism, although the clinical pictures of the disorder are virtually identical.

Adult↗
PubMed1989

Non-stereo photographic screening after panretinal photocoagulation for proliferative diabetic retinopathy. Compared with 60D enhanced slit-lamp examination.

135 patients treated with panretinal photocoagulation for proliferative diabetic retinopathy were examined in order to detect 7 specific fibrovascular lesions after treatment. Two presumptive methods for long-term follow-up were evaluated and compared, i.e. slit-lamp biomicroscopy enhanced by a 60 D lens and reading from two non-stereo photographs of the posterior pole. Two observers repeated their examinations with respective methods. Comparison of the methods with respect to detecting ability of the fibrovascular lesions showed no significant disagreement except in some eyes with fibrous tissue on the optic disc where new vessels were better detected with the slit-lamp method (P less than 0.001). There was no difference between the methods with respect to the intra- and inter-observer variability. Twenty to 30 patients could be diagnosed per hour with the photographic method compared to 5-6 patients with the slit-lamp. Two non-stereo photographs of the posterior pole can be recommended as a safe and time-saving method for objective documentation and long-time follow-up after panretinal photocoagulation for proliferative diabetic retinopathy.

Adult↗
PubMed1989

Demonstration of immunoreactive sites on cartilage after in vivo administration of biotinylated anti-type II collagen antibodies.

Administration of biotinylated monoclonal antibodies provides the basis of a simple technique for identifying immunoreactive sites in vivo. Biotinylated anti-type II collagen antibodies were injected intraperitoneally into normal DBA/1 mice. The mice were sacrificed after 96 hr and the front paws removed and decalcified to allow tissue sectioning before snap-freezing. Binding of antibodies in vivo was visualized with affinity cytochemical staining using avidin-biotin-peroxidase complexes. Specific binding of antibodies to cartilaginous structures was seen after injection of 20-500 micrograms biotinylated monoclonal or polyclonal anti-type II collagen antibodies, but not after injection of a biotinylated control antibody. This technique should further the detection and localization studies of tissue components involved in the dynamics of physiological and pathological processes.

Animals↗