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P Toivanen

Publications and source records attributed to P Toivanen.

At least 73 records · Page 4Linked to original sources
PubMed1996

The presence of interleukin-13 in rheumatoid synovium and its antiinflammatory effects on synovial fluid macrophages from patients with rheumatoid arthritis.

OBJECTIVE: To study the production of interleukin-13 (IL-13) in rheumatoid synovium and the effects of recombinant IL-13 on the phenotype and function of synovial fluid (SF) macrophages and T cells derived from patients with rheumatoid arthritis (RA). METHODS: The presence of IL-13 in SF was studied using an IL-13-specific enzyme-linked immunosorbent assay (ELISA); the production of IL-13 was studied in SF mononuclear cells (SFMC) by reverse transcriptase-polymerase chain reaction. The effects of recombinant IL-13 on cytokine production by and phenotype of SFMC were evaluated using cytokine-specific ELISAs and flow cytometry, respectively. The effect of IL-13 on the proliferation of SFMC was determined by 3H-thymidine incorporation. The production and the effects of IL-13 were compared with those of IL-4. RESULTS: IL-13 was present in 27 of 28 SF samples, and IL-13 messenger RNA (mRNA) was detectable in SFMC. Importantly, IL-13 levels were significantly higher than those of IL-4, and IL-13 protein and mRNA were expressed in several samples, although IL-4 synthesis was undetectable. Recombinant IL-13 significantly reduced the production of IL-1 beta and tumor necrosis factor alpha and the expression of CD16 and CD64 by SF macrophages, whereas the expression of HLA-DR and CD23 was increased. These effects on SF macrophages were similar to those observed with IL-4, but in contrast to IL-4, IL-13 had no growth-promoting effect on SF T cells. CONCLUSION: IL-13 is consistently present in rheumatoid synovium. The ability of exogenous IL-13 to decrease the production of proinflammatory cytokines by SFMC suggests that it may have therapeutic potential in the treatment of patients with RA.

Adult↗
PubMed1996

HLA-B27 and bacteria.

Most HLA-B27 positive individuals live without noticing the risk factor they carry. Only when certain bacteria come into play, usually in the form of intestinal or genital infection, some of the HLA-B27 positive individuals will develop a reactive disease. Such an association is so well established that it has formed a basis to study the relation of autoimmune reactions to microbial infections. Early epidemiological investigations have been followed by studies on immunological cross-reactivity and recently by studies on presentation of bacterial peptides by the HLA-B27 molecule. This introductory review briefly summarizes the evolution of the research, the goal of which still remains to clarify the etiopathogenetic mechanisms of HLA-B27 associated diseases.

Bacterial Infections↗
PubMed1996

IgA antibodies in HLA-B27 associated acute anterior uveitis and ankylosing spondylitis.

Acute anterior uveitis (AAU) and ankylosing spondylitis (AS) are, like reactive arthritis (ReA), strongly associated with HLA-B27. Mucosal infections play a role in the pathogenesis of ReA. To investigate whether these microorganisms are also involved in the pathogenesis of AAU and AS, we examined blood samples from patients with AAU, AS or both, and healthy controls for presence of antibodies against Klebsiella pneumoniae (K 30), Salmonella enteritidis and S. typhimurium, Chlamydia trachomatis, Proteus mirabilis and Borrelia burgdorferi. The IgA, IgG and IgM classes of these antibodies were measured using an enzyme-linked immunosorbent assay. No significant differences were found in the frequency in which these antibodies occurred in HLA-B27 positive patients with AAU or AS and healthy controls. However, IgA antibodies against K. pneumoniae (p < 0.01) and IgA and IgG antibodies against P. mirabilis (p < 0.01 and p < 0.05) were detected more frequently in HLA-B27 negative patients with AAU than in healthy controls. The results of this study are in contrast with various earlier reports in which antibodies against Klebsiella strains were more frequently found in patients with HLA-B27 associated ankylosing spondylitis than in healthy controls.

Acute Disease↗
PubMed1996

Expression of MHC class II molecules on human monocytes is regulated independently from each other after phagocytosis of bacteria.

Reactive arthritis is usually self-limiting polyarthritis which develops in HLA-B27 positive individuals after certain gastrointestinal or urogenital infections. The pathogenesis of reactive arthritis is unknown but T cells seem to have a crucial role. Most of the antigen-specific T cells isolated from the synovial fluid have been MHC class II restricted. The role of antigen presentation in the pathogenesis of reactive arthritis has been studied relatively little. In this work the authors studied the effect of arthritis-triggering bacterium (Yersinia enterocolitica O:3) on the expression of MHC class II molecules on human monocytes and found that the expression of different MHC class II molecules was regulated independently from each other in half of the individuals after certain incubation periods. In these cases the expression of HLA-DP was parallel to the expression of HLA-DQ, while HLA-DR expression went to the opposite direction or did not change at all. No difference between HLA-B27 negative and HLA-B27 positive healthy individuals was seen. The authors conclude that independent regulation of the expression of different MHC class II antigens on antigen-presenting cells is a more common phenomenon than usually thought.

Antibodies, Monoclonal↗
PubMed1996

Oncoprotein expression in human synovial tissue: an immunohistochemical study of different types of arthritis.

Based on the fact that synovial lining cells have some properties of transformed-appearing cells, we have examined the expression of Myc, Myb, Fos, Jun and Ras oncoproteins in synovial tissues from patients with different types of arthritis. Formalin-fixed and paraffin-embedded sections of synovial tissue from 12 patients with rheumatoid arthritis (RA), 14 with reactive arthritis (ReA), nine with other seronegative arthritis (OSA), seven with bacterial arthritis (BA), eight with probable bacterial arthritis (PBA) and eight with osteoarthritis (OA) were studied using the immunoperoxidase staining technique. The oncoproteins studied were expressed both in the synovial lining layer and in the sublining layer, consisting of lymphocytes, other inflammatory cells and blood vessels. Among the six disease entities, RA and OA appeared to be the most distinct, whereas the results obtained for ReA and OSA, and on the other hand for BA and PBA, closely resembled each other. The expression of Myc, Myb, Fos and Jun was significantly correlated both to the degree of synovial hypercellularity and the synovial lymphocytic infiltration. For Ras, such a correlation could not be seen. We conclude that we find no evidence of a cell lineage-specific or a disease-specific abnormality of proto-oncogene products in RA, and the expression of these oncoproteins is consistent with inflammation rather than with any primary abnormality of cell growth.

Adult↗
PubMed1996

Expression of bcl-2 in rheumatoid arthritis.

Since defective apoptosis has been suggested to play a role in the development of autoimmune diseases, we have investigated the expression of the proto-oncogene bcl-2 in patients with rheumatoid arthritis (RA). The expression of bcl-2 was studied in peripheral blood (PB) and synovial fluid (SF) lymphocytes and synovial tissues (ST) from patients with RA using immunohistochemistry, flow cytometry and nucleic acid hybridization. Patients with reactive arthritis (ReA) or osteoarthritis (OA) and healthy individuals were used as controls. The expression of bcl-2 protein in PB lymphocytes and the expression of bcl-2 mRNA in PB mononuclear cells (PBMC) was similar in healthy controls and patients with RA. However, bcl-2 protein expression was significantly reduced in SF lymphocytes when compared to PB lymphocytes. Similar results were observed with lymphocytes from patients with ReA, and irrespective of whether total lymphocytes, T cells or different T-cell subsets were studied. In the synovial sections, the expression of bcl-2 was restricted to lymphocytes, and bcl-2+ cells were observed in the majority of samples from patients with RA, OA and ReA. These data indicate that the expression of bcl-2 is not increased in the lymphocytes or ST derived from patients with RA. Instead, decreased expression of bcl-2 protein in SF lymphocytes compared to PB lymphocytes was demonstrated. We suggest that bcl-2 does not play a significant role in the pathogenesis of RA.

Adult↗
PubMed1996

Reactive arthritis.

During the past year, new information has been obtained regarding the pathogenetic process in reactive arthritis. Characterization of the triggering microbes as well as of their interaction with T cells and other host components has brought us closer to achieving a comprehensive picture of the events leading from infection to reactive arthritis. Efforts are ongoing to define clinically applicable diagnostic criteria. It is becoming apparent that chronic forms of the disease are not uncommon.

Arthritis, Reactive↗
PubMed1996

Bacterial 16S rDNA polymerase chain reaction in the detection of intra-amniotic infection.

OBJECTIVE: Bacterial polymerase chain reaction (PCR) was used to detect early subclinical intraamhiotic infection. We used universal primers which amplify a DNA fragment of 16S ribosomal DNA (rDNA) from all known bacteria and sequenced the positive samples to identify the bacterial species. DESIGN: Transabdominally obtained amniotic fluid samples from 20 pregnant women with prelabour rupture of the fetal membranes (PROM), showing no signs of clinical infection, and 16 control samples were analysed with universal bacterial PCR. In addition, routine bacterial culture and amniotic fluid glucose were studied. RESULTS: Out of 20 PROM patients, five were positive in the PCR. PCR detected Ureaplasma urealyticum in two cases, Haemophilus influenzae in one case, Streptococcus oralis in one case and Fusobacterium sp. in one case. Only two of these were positive in a routine bacterial culture. Both were multibacterial infections, which caused discrepancies between the PCR and culture results. Two patients developed infectious complications: both were identified with the PCR assay. Amniotic fluid glucose was lower in PCR positive patients compared with PCR negative patients. CONCLUSION: Bacterial 16S rDNA PCR, in properly controlled conditions, promises to be a fast and reliable test for early intra-amniotic infection especially concerning Ureaplasma urealyticum.

Amniotic Fluid↗
PubMed1995

Primed avian gamma delta T cells respond to mycobacterial antigens, but show no preference for the 65-kDa heat shock protein.

We have studied the reactivity of chicken T cells to mycobacterial antigens. Neither peripheral blood nor splenic lymphocytes isolated from unprimed chickens proliferated in response to mycobacterial antigens (mycobacterial sonicate, purified protein derivative, or recombinant 65-kDa heat-shock protein HSP65). After immunization with complete Freund's adjuvant (CFA) a strong response appeared, and a transient increase of peripheral blood gamma delta T cells was observed. Analysis of spleen cells isolated from CFA-primed chickens showed that both alpha beta and gamma delta T cells were activated by the mycobacterial antigens, apparently at equal levels. Both subsets also responded to HSP65, but no preference of gamma delta T cells to respond to it or any of the other mycobacterial antigens was observed. These results indicate that although HSP65 is an important mycobacterial antigen, it is not dominant in the chicken gamma delta T cell repertoire. Moreover, the results show a clear distinction between the naive and primed repertoire of gamma delta T cells.

Animals↗
PubMed1995

Sialyl LewisX carbohydrate is expressed differentially during avian lymphoid cell development.

Sialyl LewisX is a carbohydrate moiety involved in the regulation of white blood cell adhesion to endothelial cells. In this work, we have studied the expression, localization and function of sialyl LewisX carbohydrate on maturing B and T cells and the stroma of avian bursa, thymus and spleen as well as the role of sialyl LewisX in the generation of immune response and formation of germinal centers in the spleen. The expression of sialyl LewisX on bursal B cells decreases during the embryonic period, while on T cells it remains at a stable low level throughout their thymic development. Immediately after hatching, by which time the expression of sialyl LewisX on bursal B cells has already decreased, the stromal microenvironment of the bursa starts to express it. After hatching, sialyl LewisX is localized exclusively in the medullae of the follicles and the number of sialyl LewisX-positive follicles declines gradually during the following weeks. Thymic stroma does not express sialyl LewisX at any stage of development. In spleen, sialyl LewisX is expressed on a number of B and T cells as well as on other cell types in a way that seems not to be restricted to any structurally defined area. The cells or stroma of the germinal centers, however, do not express sialyl LewisX. When given simultaneously with an immunizing agent, anti-sialyl LewisX monoclonal antibody reduced the formation of germinal centers and suppressed antibody response in young birds. These results demonstrate that sialyl LewisX-bearing cell surface molecules are required during the generation of immune responses. They also suggest a role for sialyl LewisX in B cell maturation.

Animals↗
PubMed1995

Use of the polymerase chain reaction and DNA sequencing for detection of Bartonella quintana in the aortic valve of a patient with culture-negative infective endocarditis.

We used the polymerase chain reaction (PCR) and broad-range bacterial primers, combined with DNA sequencing, to identify Bartonella quintana as the etiologic agent in a case of culture-negative infective endocarditis; all blood cultures, as well as the bacterial cultures of the resected aortic valve and vegetations, remained negative. PCR was used to amplify bacterial 16S rDNA from a template prepared from the aortic valve vegetation. The amplified 16S rDNA produced a nucleotide sequence that was 99.79% identical to the B. quintana rDNA sequence. The patient had a highly elevated level of serum antibodies to Bartonella antigen (1:8,192).

Antibodies, Bacterial↗
PubMed1995

Muramic acid in peripheral blood leukocytes of healthy human subjects.

Peptidoglycan, a specific marker for all bacterial cell walls, was studied in peripheral blood of healthy human subjects by mass spectrometric analysis of muramic acid. Peripheral blood mononuclear and polymorphonuclear cells from 98 healthy adults were hydrolyzed and analyzed by gas chromatography-mass spectrometry as alditol acetate derivatives using selective ion monitoring. Muramic acid was observed in cell samples from 21 of 98 subjects. Blood cultures were done simultaneously and remained negative. As a control, mononuclear and polymorphonuclear cells separated from umbilical vein blood of 41 healthy newborns were studied; all were muramic acid-negative. Since newborns lack gut flora, intestinal absorption of bacteria or of their degradation products appears to be the most likely explanation for the finding.

Adult↗
PubMed1995

Antibodies to Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis in the sera of patients with axial and peripheral form of ankylosing spondylitis.

IgM, IgG and IgA class serum antibodies against the whole Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis bacteria, as well as against K. pneumoniae and E. coli lipopolysaccharides (LPSs) were studied earlier in two separate patient populations of 99 and 85 patients with ankylosing spondylitis (AS) and in 102 healthy blood donors by enzyme immunoassay. In this study the patients were divided into groups according to the presence or absence of peripheral arthritis. The patients with peripheral type AS had increased levels of IgM and IgA class antibodies against K. pneumoniae, whereas the patients with axial type AS had increased levels of IgG and IgA class antibodies to K. pneumoniae, as well as IgA class antibodies against E. coli and P. mirabilis bacteria. Sulphasalazine treatment decreased the IgM and IgA class antibodies in peripheral AS and IgA class antibodies in axial AS against K. pneumoniae LPS. The antibody levels were also decreased against E. coli and P. mirabilis bacteria in the sera of patients with axial AS. The immunological findings in patients with peripheral and axial form of AS were different from each other and thus may reflect different aetiopathogenetic mechanisms for these two types of AS.

Antibodies, Bacterial↗
PubMed1995

Antibodies to Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis in the sera of ankylosing spondylitis patients with/without iritis and enthesitis.

IgM, IgG and IgA class serum antibodies against the whole Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis bacteria, as well as against K. pneumoniae and E. coli lipopolysaccharides (LPSs) were studied earlier in the sera of 98 patients with ankylosing spondylitis (AS) and in 102 healthy blood donors by enzyme immunoassay. In this study the patients were divided into groups according to the clinical picture, i.e. presence or absence of iritis and enthesitis. The previous major finding of increased IgA class antibody levels against the whole K. pneumoniae bacteria in AS patients when compared to the healthy controls was not specifically associated with any single patient group in the present study. However, the patients with iritis had higher levels of IgA class antibodies to LPS of K. pneumoniae and E. coli when compared to the patients without iritis. In addition, the patients without enthesitis had higher level of IgG class antibodies against whole K. pneumoniae bacteria compared to the patients with enthesitis. The increased IgA class antibody levels against K. pneumoniae and E. coli LPS in AS patients with iritis may reflect an inflammatory process in the gut area. Furthermore, there were certain other differences in the immunological parameters between the AS patients with and without iritis or enthesitis and the possibility that they reflect different mechanisms involved in the disease processes cannot be excluded.

Antibodies, Bacterial↗
PubMed1995

Oncogene expression in synovial fluid cells in reactive and early rheumatoid arthritis: a brief report.

Since it has been implied that cellular oncogenes might have a role in the pathogenesis of rheumatoid arthritis (RA), we have examined the expression of c-myc, c-myb, c-fos, c-jun and c-Ha-ras oncogenes in the cells from synovial fluid (SF) and peripheral blood (PB) of patients with reactive arthritis (ReA) and early RA. Oncogene expression was studied using RNA hybridizations with 32P-labelled probes. From the SF, mononuclear and granulocyte cell fractions were used separately. Significant differences between ReA and RA were observed only for c-myb in PB mononuclear cells and c-jun in SF granulocytes. Regarding the expression of c-myc, c-fos and c-Ha-ras oncogenes, no difference between ReA and RA was observed. Comparison to normal controls was made using PB mononuclear cells; only the expression of c-fos tended to be slightly increased in RA, without statistical significance, however. We conclude that oncogene activation in the synovial inflammation is not a phenomenon specific for RA.

Arthritis, Reactive↗
PubMed1995

Epidemiologic, clinical, and therapeutic aspects of reactive arthritis and ankylosing spondylitis.

The role of microbes in the pathogenesis of various arthritides continues to be the focus of keen interest. In the study of genetic factors that predispose to spondyloarthropathies, HLA-B27 transgenic animal models present exciting new research possibilities. The basic principles in the management of these arthritides have not changed, but an increasing number of patients are being treated with disease-modifying antirheumatic drugs when the response to nonsteroidal anti-inflammatory drugs is inadequate.

Animals↗