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Biomedical subjects

M Leirisalo-Repo

Publications and source records attributed to M Leirisalo-Repo.

At least 163 records · Page 9Linked to original sources
PubMed1991

Molecular mimickry between HLA B27 and Yersinia, Salmonella, Shigella and Klebsiella within the same region of HLA alpha 1-helix.

Two new examples of amino acid homology between HLA B27 and microbes triggering HLA B27-associated diseases are described. An outer membrane protein YadA (Yersinia adhesin, previously called Yop1) of Yersinia enterocolitica and Y. pseudotuberculosis shares a linear tetrapeptide with HLA B27. A cationic outer membrane protein OmpH of Salmonella typhimurium shares homology with five amino acids of HLA B27 in a non-linear fashion. The four amino acids of YadA are also notably included in the hexapeptide identical between Klebsiella pneumoniae nitrogenase and HLA B27, and three of them occur in the pentapeptide shared by a Shigella flexneri protein and HLA B27. Antibodies against synthetic peptides including HLA B27 homologues sequences of YadA and OmpH were observed in one-third of the patients with HLA B27 associated diseases. Antibodies were directed against a flanking sequence next to the amino acid sequences shared by arthritis-triggering microbes and HLA B27. The area of identity in each example of this molecular mimicry (Yersinia, Salmonella, Shigella and Klebsiella) is located in the same place on the HLA B27 molecule: between amino acids 70 to 78 in the variable region of alpha 1-helix. This area of HLA B27 molecule includes sites predicted to be important for binding processed antigens.

Adhesins, Bacterial↗
PubMed1991

Determination of oxygen radical production in spondyloarthropathies by whole blood chemiluminescence.

Oxygen derived free radicals are considered to play an important part in the development of inflammation. A whole blood chemiluminescence assay was used to study N-formyl-methionyl-leucyl-phenylalanine induced oxygen radical production in subjects with ankylosing spondylitis or previous yersinia arthritis. In luminol enhanced chemiluminescence, the subjects with previous yersinia arthritis showed significantly increased initial activation (at one minute), whereas the subjects with ankylosing spondylitis showed decreased responses at both the initial activation and at peak activation (at two to three minutes). This finding gives credence to the view that, in terms of oxygen radical production, the pathogenesis of yersinia arthritis is different from that of ankylosing spondylitis.

Acridines↗
PubMed1990

Circulating immune complexes containing chlamydial lipopolysaccharide in acute myocardial infarction.

The presence of circulating immune complexes (IC) was studied using two detection methods specific for chlamydial lipopolysaccharide (LPS) in paired serum samples of 44 patients (30 men and 14 women) with acute myocardial infarction (AMI). Forty-four random controls were individually matched for locality, age and sex with the AMI patients. As specificity controls for the IC assays single serum samples from 29 patients with diseases characterized by the presence of circulating IC were used. Fifty-seven per cent of AMI patients, 12% of their random controls and 10% of the patient controls were shown to have chlamydial LPS-specific immune complexes in their sera (P less than 0.0001, AMI versus random and patient controls). This finding provides further evidence of the possible association of chronic chlamydial infection with AMI.

Adult↗
PubMed1990

Phagocyte function in familial hypercholesterolaemia: peripheral blood monocytes exposed to lipopolysaccharide show increased tumour necrosis factor production.

We studied functions of polymorphonuclear leucocytes (PMN) and monocytes from peripheral blood of subjects with familial hypercholesterolaemia (FH). FH monocytes exposed to Escherichia coli lipopolysaccharide (LPS) in 10% human AB serum generated tumour necrosis factor (TNF) significantly more than did control monocytes. After lowering of serum low-density lipoprotein (LDL) levels by drug treatment, FH monocytes exposed to LPS in the absence of exogenous lipoproteins generated significantly more TNF than did control monocytes. These findings suggest that increased TNF production is not affected by hypolipidaemic treatment and may not derive from differences between uptake of exogenous LDL by FH monocytes and control cells. Chemotaxis, chemokinesis, and random migration of both FH PMN and FH monocytes were normal, as determined by agarose assay and membrane filter assay. FH PMN showed increased luminol-enhanced chemiluminescence in response to 2.5 x 10(-8) M, but not to 2.5 x 10(-6) M, N-formyl-methionyl-leucyl-phenylalanine, and not to serum-treated zymosan or to phorbol myristate acetate. Luminol- and lucigenin-enhanced chemiluminescence responses of FH monocytes were normal. In summary, the major aberration found in the present study was that FH monocytes stimulated with LPS show enhanced production of TNF. The possibility that exaggerated TNF production contributes to an early development of atherosclerotic lesions in FH subjects warrants further studies.

Adult↗
PubMed1990

Platelet autoantibodies detected by immunoblotting in systemic lupus erythematosus: association with the lupus anticoagulant, and with history of thrombosis and thrombocytopenia.

71 patients with systemic lupus erythematosus (SLE) were studied for the occurrence of platelet antibodies by immunoblotting. Binding of IgG antibodies to platelet protein antigens was observed in 39 of the 71 patients. The most frequently detected and exceptionally strongly reacting antibodies were directed against platelet protein antigens with an approximate molecular weight of 65 kDa under nonreducing conditions. These antibodies were autoreactive and, when followed, they usually persisted. Interestingly, in this group of well-defined SLE patients, platelet antibodies against the most common targets (65 kDa) were significantly associated with the lupus anticoagulant, a history of thrombocytopenia and thrombosis, particularly with arterial occlusions. The lupus anticoagulant, on the other hand, correlated significantly only with venous thrombosis. In addition to the lupus anticoagulant, platelet antibodies against this unknown platelet protein may thus be a marker of a higher risk of thrombosis in SLE patients.

Adolescent↗
PubMed1990

Phagocyte function in juvenile periodontitis.

We studied the chemotaxis of peripheral blood polymorphonuclear leukocytes (PMNs) and monocytes and the production of tumor necrosis factor alpha by monocytes of patients with juvenile periodontitis (JP). As a group, the patients' PMNs showed significantly increased chemotaxis determined by counting the number of migrating cells within a 3-microns-pore-size filter. Determined as distance of migration within the filter, as chemotactic increment based on checkerboard analysis, as leukotactic index calculated on the basis of distance of migration and cell count at different depths within a 3-microns-pore-size filter, as distance of migration under agarose, and as the number of PMNs migrating across a 5-microns-pore-size filter, the chemotactic migration rates of PMNs of patients were similar to those of controls. Evaluation of the data on an individual basis suggested that in terms of PMN chemotaxis some patients were hyperresponsive and some were hyporesponsive. Chemotaxis, spontaneous migration, and the rates of lipopolysaccharide-induced tumor necrosis factor alpha production by JP monocytes were similar to those of control cells. Our results give credence to the view that there are minor aberrations in the functions of JP phagocytes, but the extent to which these aberrations are relevant to accumulation of PMNs at sites of infection and inflammation in vivo and possibly contribute to the pathogenesis of JP remains unclear.

Adolescent↗
PubMed1990

Chemotaxis and chemiluminescence responses of synovial fluid polymorphonuclear leucocytes during acute reactive arthritis.

The chemotaxis and chemiluminescence responses of polymorphonuclear leucocytes (PMN) of synovial fluid and peripheral blood from patients with acute reactive arthritis were studied. Rates of chemotactic and chemokinetic migration of synovial fluid PMN were significantly decreased. In addition, chemiluminescence responses tended to be depressed, suggesting that the cells were deactivated for both chemotaxis and production of oxygen derived free radicals. Such deactivation has been described previously as a characteristic of synovial fluid PMN in rheumatoid arthritis. Compared with those with a mild disease, patients with severe acute reactive arthritis had higher chemiluminescence responses of synovial fluid PMN to phorbol myristate acetate during acute disease and developed increased migration of peripheral blood PMN towards zymosan treated serum after recovery from the disease. This supports the view that hyperreactive PMN contribute to the development of severe inflammatory symptoms in acute reactive arthritis.

Acute Disease↗
PubMed1990

Inflammation in HLA-B27-associated diseases.

The pathogenetic mechanisms in the development of spondyloarthropathies are multifactorial. These include the possible role of infective micro-organisms which can by direct invasion lead to persistence of microbial antigens and thus trigger arthritis or by cross-reactions with the host tissue lead to inflammatory symptoms or by cross-reactions with HLA-B27 trigger cytotoxic T-cell response. After the primary event, exaggerated inflammatory response can lead to amplification of inflammation. The components in the amplification of inflammation include hyperreactive neutrophils and serum factors such as enhanced production of activation products of complement in subjects with HLA-B27. The enhanced neutrophil function seems to persist in patients with previous severe inflammatory symptoms during acute reactive arthritis or in those with late inflammatory complications. The enhancement is probably caused by priming effect by lipopolysaccharide, which seems to persist for a long period in patients with acute reactive arthritis. Enhanced production of monokines can contribute to the enhanced inflammation in patients with spondyloarthropathies. The primed phagocytes can respond vigorously when rechallenged with antigenic load during a new infection, thus leading in some patients to recurrent or chronic inflammatory symptoms. Antimicrobial therapy or sulphasalazine by modifying antigen elimination or absorption can diminish inflammatory response during acute arthritis and in chronic spondyloarthropathies. Long-term follow-up studies are needed to find out whether prolonged therapies with these agents affect the prognosis of spondyloarthropathies.

Anti-Bacterial Agents↗
PubMed1990

Enhanced inflammatory reactivity in the pathogenesis of spondyloarthropathies.

Pathogenesis of seronegative spondyloarthropathies such as ankylosing spondylitis and reactive arthritis is not known. Growing evidence indicates that microbial structures such as Chlamydia antigen and Yersinia antigen are present in the inflamed joints of patients with reactive arthritis. Microbial antigens can activate the host's inflammatory mechanisms. After the activation, the course of inflammation can be postulated to be affected by the host factors responsible for amplification of the inflammatory reaction and elimination of the foreign structures. Thus, the amplification, whether strong, moderate, or weak, may contribute to the degree of inflammatory tissue injury in patients with seronegative spondyloarthropathies. This review will discuss the role of increased inflammatory reactivity in the pathogenesis of HLA-B27 associated spondyloarthropathies, with special reference to reactive arthritis triggered by yersinia enteritis.

Animals↗
PubMed1988

Ten-year follow-up study of patients with Yersinia arthritis.

Eighty-five patients with acute Yersinia arthritis were seen in followup for a mean of 10 years. During that time, peripheral joint symptoms occurred frequently (51.8%), but these symptoms were mild (45.9%). Development of a new reactive arthritis (4.7%) or chronic arthritis (2.4%) was uncommon. One-third of the patients experienced low back pain, and one-third of the patients had radiologic evidence of sacroiliitis. The presence of sacroiliitis was more frequent in patients with low back pain (46.7%) than in those who did not have symptoms (21.2%). More patients with HLA-B27 had low back pain and sacroiliitis, but there was no association of this genetic factor with the residual symptoms in peripheral joints.

Arthritis, Infectious↗
PubMed1988

Sulfasalazine in the treatment of ankylosing spondylitis. A twenty-six-week, placebo-controlled clinical trial.

Eighty-five patients with active ankylosing spondylitis (AS) were randomized to receive either sulfasalazine (less than or equal to 3 gm/day, mean 2.5) or placebo for 26 weeks. There was a statistically significant improvement, compared with baseline, in most of the clinical variables in patients receiving the active drug. Laboratory parameters (erythrocyte sedimentation rate, C-reactive protein, IgG, IgM, and IgA) also improved during the active treatment, suggesting a beneficial effect of sulfasalazine on AS. At the end of the treatment, significant differences between the sulfasalazine and placebo groups were observed in morning stiffness, chest expansion, erythrocyte sedimentation rate, and in all immunoglobulin classes. Two patients in each treatment group discontinued the trial because of side effects. Enteric-coated sulfasalazine seemed to be effective and well tolerated in patients with active AS.

Analysis of Variance↗
PubMed1988

Significance of rheumatoid factors in an eight-year longitudinal study on arthritis.

A community-based cohort comprising 150 patients with recent-onset seropositive arthritis or seronegative oligoarthritis or polyarthritis was monitored for 8 years. Of the different rheumatoid factor (RF) tests, the initial positivity in the most sensitive assays (latex slide test and IgM-RF by enzyme immunoassay) was the most reliable factor when distinguishing between the erosive and nonerosive cases. The individual RF isotypes fluctuated in four serial specimens, but each patient tended to preserve his or her reactivity pattern. Seroconversion from positive to negative within the 1st year of follow-up did not indicate a particularly good long-term prognosis.

Arthritis, Rheumatoid↗
PubMed1988

Complement activation and HLA-B27.

The efficiency of complement activation was studied in sera from HLA-B27 positive and negative subjects (27 with previous yersinia arthritis and 35 controls). Activation of complement with zymosan induced higher mean levels of the anaphylatoxin C3a in HLA-B27 positive sera (mean (SD) 7.40 (1.66) mg/l) than in HLA-B27 negative sera (6.41 (1.79) mg/l). Similarly, higher levels of C3d,g, another C3 breakdown fragment, were obtained in HLA-B27 positive sera after Escherichia coli 0111:B4 lipopolysaccharide treatment (17.6 (3.7)% v 15.0 (3.8)%). The differences occurred irrespective of previous arthritis, complement C4 or Bf phenotype, or variation in background complement levels. The findings suggest that an increased responsiveness to complement activators may contribute to the pathogenesis of HLA-B27 associated inflammatory diseases.

Adult↗
PubMed1988

Polymorphonuclear leucocyte function and previous yersinia arthritis: correlation of enhanced superoxide production with late manifestations.

Polymorphonuclear leucocyte (PMN) functions (migration in vitro, chemiluminescence, O-2 production, and aggregation) were studied in 32 patients with previous yersinia arthritis (YA). PMNs of 11 HLA-B27 positive patients who had chronic or recurrent inflammatory symptoms showed O-2 production significantly higher than that of PMNs of 11 HLA-B27 positive patients without late manifestations. Also, PMNs of both HLA-B27 positive and negative patients tended to show chemotactic and chemokinetic migration rates higher than those of control cells of healthy HLA-B27 negative subjects. These functional aberrations may play a part in the development of the patients' inflammatory symptoms.

Adult↗