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Biomedical subjects

M Leirisalo-Repo

Publications and source records attributed to M Leirisalo-Repo.

At least 19 recordsLinked to original sources
PubMed1992

Selective endothelial binding of interleukin-2-dependent human T-cell lines derived from different tissues.

The ability of lymphocytes to recognize and bind to high endothelial venules (HEVs) is essential for lymphocyte migration from the blood into lymphoid tissues and into sites of inflammation. Endothelial cell binding capacity also critically determines the clinical usefulness of T-cell lines and clones in immunotherapy. In the present study, interleukin-2-dependent T-cell lines were derived from the blood, lamina propria of the gut, inflamed synovium, synovial fluid, and peripheral lymph nodes. After 3-8 weeks of culture, the expression of homing-associated molecules and binding to mucosal, synovial, and peripheral lymph node HEVs were analyzed. Cell lines derived from the blood and mucosal sites bound significantly better to mucosal and synovial HEVs than to peripheral lymph node HEVs. Three out of seven synovial T-cell lines showed preferential binding to synovial HEVs, whereas the rest bound almost equally well to synovial and mucosal HEVs. T-cell lines from peripheral lymph nodes bound preferentially to lymph node HEVs despite the lack of L-selectin (the peripheral lymph node homing receptor). Expression of the known homing-associated molecules did not predict the HEV-binding specificity of these lines. Importantly, two cell lines bound well to synovial venules, but poorly, if at all, to mucosal or peripheral lymph node HEVs, supporting the concept that synovial-specific HEV recognition mechanisms exist. In conclusion, the tissue origin of T-cell lines critically determines their selectivity for endothelial cell recognition, and besides the known "homing receptors," other molecules may also mediate tissue-specific HEV-binding of interleukin-2-activated T cells.

Antigens, CD↗
PubMed1992

Cyclosporin reduces renal prostanoid excretion in type 1 diabetic patients.

Prostacyclin and thromboxane A2 are important regulators of kidney blood flow. To examine whether changes in their metabolism could be involved in the nephrotoxicity of cyclosporin, we determined urinary excretion of 6-keto PGF1a and dinor-6-keto PGF1a (prostacyclin metabolites) and dinor-TxB2 (thromboxane metabolite) in five newly diagnosed type 1 diabetic patients during and after stopping cyclosporin therapy. In the resting state, cyclosporin had no effect on prostanoid excretion. In response to exercise, urinary excretion of 6-keto PGF1a was reduced by 50% (P less than 0.02), dinor-6-keto PGF1a by 15% (P less than 0.05) and dinor-TxB2 by 45% (P less than 0.02), while albumin excretion increased 4.5-fold (P less than 0.05) during cyclosporin therapy. Simultaneously, there was a rise in serum creatinine concentration, and renal biopsy specimens obtained from three patients showed periglomerular and interstitial fibrosis and tubular atrophy. After the discontinuation of cyclosporin therapy, serum creatinine concentrations returned to normal, histological changes improved and there was an associated rise in urinary prostanoid excretion. These data suggest that a reduction in renal prostanoid synthesis by cyclosporin may diminish renal blood flow and function, and lead to histological changes in the kidney.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Oxygen radical production and trapping in subjects with previous Yersinia infection.

Previous studies indicate that oxygen radical production by 1-min activation of N-formyl-methionyl-leucyl-phenylalanine-induced chemiluminescence (CL) by whole blood is increased in subjects with previous Yersinia arthritis (YA). This finding is confirmed in the present study and extended further by demonstrating that subjects with previous YA show increased oxygen radical generation and enhanced release of myeloperoxidase from neutrophils and increased CL activity by serum, all factors that can contribute to an increase in the initial activation of CL. Initial activation was not increased in subjects who had had Yersinia enteritis without arthritis; however, intracellular oxygen radical production by purified neutrophils was significantly increased, suggesting that the cells had been primed in vivo. The water-soluble antioxidants of plasma samples tested by a peroxyl radical-trapping assay were much the same in subjects with previous YA, in subjects with previous Yersinia enteritis without arthritis, and in healthy subjects. The results suggest that aberrations in neutrophil oxygen radical production play a role in the pathogenesis of YA.

Adult↗
PubMed1992

HLA typing and seropositivity in Finnish and in Polish patients with rheumatoid arthritis and amyloidosis.

We determined HLA-A, -B, -C and -DR antigens in 83 patients with rheumatoid arthritis (RA) and reactive secondary amyloidosis (RSA), 60 in Finland and 23 in Poland, and compared the results with control RA patients and blood donors. There were no significant differences in the frequencies of HLA between the RA patients with and those without RSA in either Finland or Poland, and no significant differences between the Finnish and Polish patients with RSA. All the RSA patients from Finland and 70% of the RSA patients from Poland were seropositive. In the development of RSA, the prolonged period of inflammatory stimuli may play a more important role than genetic factors.

Adolescent↗
PubMed1992

Antikeratin antibodies: diagnostic and prognostic markers for early rheumatoid arthritis.

Antibodies to the stratum corneum of rat oesophagus (antikeratin antibodies) were assayed by indirect immunofluorescence in a prospective study of patients with early rheumatoid arthritis (RA). At the beginning of the study, antikeratin antibodies of IgG class were detected in serum samples from 27/71 (38%) patients compared with 1/20 (5%) control patients with reactive arthritis, and 1/38 (3%) healthy blood donors. At the end of the two year follow up, 27/67 (40%) patients with RA were positive for antikeratin antibodies. The patients with RA who were initially positive for antikeratin antibodies had a more active disease course than the patients negative for antikeratin antibodies as measured by clinical, laboratory, and radiological variables. The prevalence of positivity for antikeratin antibodies fluctuated during the follow up, the variation paralleling the disease activity. The occurrence of HLA-DR4 was similar in patients with RA who were positive and negative for antikeratin antibodies. Antikeratin antibodies were also found in seronegative patients with RA, confirming that antikeratin antibodies do not have rheumatoid factor activity. These results show that antikeratin antibodies are detectable at the time of the initial diagnosis of RA and that the positivity for antikeratin antibodies may have prognostic significance in early RA.

Adult↗
PubMed1992

Antiphospholipid antibodies and thrombosis in systemic lupus erythematosus: comparison of three lupus anticoagulant assays and anticardiolipin ELISA in 188 patients.

The presence of antiphospholipid antibodies (aPL) in 188 unselected patients with systemic lupus erythematosus was studied using the recalcification time, kaolin clotting time (KCT), dilute Russell's viper venom time (dRVVT) and anticardiolipin ELISA (aCL) to identify patients with a high or low risk of thrombosis among patients with aPL. aPL were detected by at least one method in 104 (55%) of the patients. Despite heterogeneity, lupus anticoagulant (LA) methods correlated reasonably well with each other (r = 0.736-0.968), but poorly with aCL (r = 0.241-0.549). Positivity in LA assays and immunoglobulin G (IgG)-aCL were associated with patients who experienced thrombosis (P less than 0.001 for all assays). Patients with both LA and aCL had experienced thrombosis more often than those having only one (odds = 6.3, P less than 0.001). When patients with aPL were ranked by relative strength of the finding and divided into tertiles, a history of thrombosis was associated with membership in the strongest tertile of at least one assay (odds = 4.2, P = 0.002). LA and aCL had similar sensitivities for thrombosis (61% and 63%, respectively), but LA was more specific than aCL (79% vs 53%). The best combination of two assays was KCT with dRVVT (61% sensitivity, 87% specificity). Maximal sensitivity (71%) for thrombosis could be achieved by adding IgG-aCL to these two assays, but specificity was lower (73%). In conclusion, a high thrombotic risk among patients with aPL was indicated by the simultaneous presence of both LA and aCL, strongly positive aPL, and, among aCL, IgG-class antibodies.

Adolescent↗
PubMed1992

Gut and spondyloarthropathies.

There is a link between gut and spondyloarthropathies, which extends from the acute ReA triggered by enteritis due to gram-negative bacteria to ankylosing spondylitis and peripheral arthritis in association with Crohn's disease and ulcerative colitis. In addition, in studies using ileocolonoscopy, an unexpectedly high proportion of patients with prolonged or chronic seronegative oligoarthritis or sacroiliitis have inflammatory changes in the terminal ileum or colon or both. These changes have either features of acute gut inflammation or infection, but about one quarter of the patients have chronic lesions, probably early Crohn's disease. The conventional treatment of spondyloarthropathies consists of liberal use of NSAIDs, local corticosteroid injections if indicated, and physiotherapy. In patients with acute ReA, the conventional antimicrobial therapy to eradicate the triggering infection is necessary if there is evidence of chlamydial or gonococcal etiology. This therapy does not, however, influence the course of the subsequent arthritis. Patients with chlamydia arthritis probably host living bacteria for prolonged periods, and they seem to benefit from a prolonged antimicrobial therapy with tetracyclines. In the face of frequent gut involvement in patients with prolonged or chronic spondyloarthropathies, the use of sulfasalazine is the logical alternative, as short-term studies on patients with ankylosing spondylitis indicate.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Double-blind, placebo-controlled study of three-month treatment with lymecycline in reactive arthritis, with special reference to Chlamydia arthritis.

We conducted a double-blind, placebo-controlled, randomized study of 3-month treatment with lymecycline, a form of tetracycline, in reactive arthritis (ReA). Lymecycline therapy significantly decreased the duration of the illness in patients with Chlamydia trachomatis-triggered ReA, but not in other ReA patients. In 2 ReA patients, C trachomatis was found in the throat, an uncommon locale for this organism. Our results suggest that it is important to verify the triggering microbe and that it is beneficial to treat Chlamydia arthritis patients with a prolonged course of tetracycline.

Adult↗
PubMed1991

Serum hyaluronate level as a predictor of radiologic progression in early rheumatoid arthritis.

Increased serum levels of hyaluronate (HA) have been found in patients with rheumatoid arthritis (RA). This probably reflects increased leakage of HA from the inflamed joints into the circulation. In a prospective study of 40 patients with early RA, we evaluated the relationship of serum HA to clinical, laboratory, and radiologic parameters of disease activity. The patients were followed for 12 months; all had active disease at study entry. We confirmed the previous finding of higher serum HA concentrations in RA patients compared with healthy controls. At study entry, the patients' serum HA levels correlated positively with clinical and laboratory parameters of acute inflammation. Despite marked clinical improvement during therapy with second-line drugs, the serum HA levels increased during the followup period. At the end of 1 year, these levels correlated with the radiologic progression of joint lesions, whereas they showed a less pronounced correlation with clinical or laboratory parameters of inflammation. We conclude that, in early RA, serum HA levels may reflect ongoing joint destruction and may even predict subsequent joint damage.

Adult↗
PubMed1991

Increased whole blood chemiluminescence in patients with Shwachman syndrome: therapy trial with thiamine and alpha-tocopherol.

Neutrophils purified from peripheral blood of patients with the Shwachman syndrome show enhanced chemiluminescence (CL) and depressed chemotaxis. Here we present data showing that the increased CL response can be demonstrated by using a whole blood CL assay. This assay is well-suited for studies in infants, because the blood sample volumes needed are small. Increase in CL was most distinct in the initial (1 min) activation induced by N-formyl-methionyl-leucyl-phenylalanine. The 1-min response is considered to derive from extracellular production of oxygen radicals. Such an extracellular oxygen radical production may render the patients susceptible to undue oxidant stress. We therefore treated the patients with two antioxidants, thiamine and alpha-tocopherol, for 3 months. This supplementation, however, failed to exert any significant effect on either whole blood CL or migration of the patients' neutrophils under agarose.

Antioxidants↗
PubMed1991

Salmonella-specific antibodies in reactive arthritis.

The development and persistence of Salmonella-specific serum antibodies of different immunoglobulin classes and subclasses were compared between those who developed reactive arthritis (n = 39) and those who did not (n = 58) after Salmonella infection. Antibodies against lipopolysaccharide and SDS-extract antigen were measured by ELISA. A significant difference was seen between the two patient groups after 4-14 months of follow-up; those with reactive arthritis had higher levels of Salmonella-specific IgM, IgG, and IgA class antibodies than those without arthritis. In the increased antibody response, secretory IgA, IgA1, and IgG2 classes were especially well represented. The persisting antibody response is a common feature in reactive arthritis and supports persistence of the pathogen or its components in the host. The differences observed in antibody profiles between Salmonella- and Yersinia-triggered reactive arthritides suggest certain dissimilarities (e.g., in the location of persisting microbes) in the arthritogenic process due to these two microbes.

Adolescent↗
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↗