Search PubMed⌕ Search

Biomedical subjects

P Toivanen

Publications and source records attributed to P Toivanen.

At least 109 records · Page 6Linked to original sources
PubMed1994

Does parvovirus B19 have a role in rheumatoid arthritis?

OBJECTIVES: To determine whether parvovirus B19 (B19) infection is associated with rheumatoid arthritis (RA). METHODS: The polymerase chain reaction was applied to serum, cells isolated from synovial fluid, and synovial fluid. Enzyme immunoassay technique was used to detect antibodies against B19. RESULTS: Of 142 patients with early RA (onset of disease under one year) and 67 control patients, serological evidence of recent parvoviral infection was found in 4/135 and 2/62, respectively. However, no evidence for the presence of parvoviral DNA was observed in 18 synovial fluids, 21 samples of synovial fluid granulocytes or 40 sera, all obtained from 65 patients diagnosed with early RA. CONCLUSION: Although there is published evidence of chronic rheumatoid-like arthropathy following acute parvovirus infection, our findings do not support the involvement of B19 in the aetiopathogenesis of RA.

Adult↗
PubMed1994

Does Yersinia induce autoimmunity?

Yersinia enterocolitica O:3 and the human thyrotropin receptor share a structural similarity, revealed by their serological cross-reactivity. The exact molecular basis of the similarity is open. In spite of this cross-reactivity, Yersinia seems not to be a major inducer of thyroid autoimmunity. Yersinia infections or avirulent Yersinia strains in the intestinal flora may rather contribute to the development of thyroid autoimmunity arising for other reasons in genetically susceptible individuals. Regarding Yersinia and spondyloarthropathies, it is undetermined whether the chronic sequelae of acute Yersinia-triggered reactive arthritis are due to the persistence of phlogistic microbial components or to autoimmunity, or to both. No convincing evidence exists for a role of molecular mimicry between Yersinia and HLA B27 or other host structures. Cytotoxic T-cell clones derived from synovial fluid, and capable of killing Yersinia-infected and uninfected autologous targets in an HLA B27-restricted fashion have recently been described. Evaluation of their significance for the potential Yersinia-induced autoimmunity is waiting for characterization of the bacterial and host peptides involved.

Animals↗
PubMed1994

Variability in the induction of experimental arthritis: Yersinia associated arthritis in Lewis rats.

Lewis rats of different microbiological status were studied for susceptibility to experimentally-induced Yersinia associated arthritis. Status A rats were serologically positive for Bacillus piliformis, Kilham rat virus and Toolan H-1 virus, whereas status B rats were serologically negative for these same microorganisms. When status A and status B rats were kept in the same room, incidence of arthritis was low (0-13% for status A rats and 27-33% for status B rats). When status B rats only were kept in different environments, increased incidence (up to 89%) of arthritis was observed. These findings suggest that the microbiological status of the host has an effect on the susceptibility to experimentally-induced arthritis. They call attention to the need for strictly defined conditions, including those of the host and the environment, in studies on experimental arthritides.

Animals↗
PubMed1994

No evidence of adenoviral hexon regions in rheumatoid synovial cells and tissue.

OBJECTIVE: To investigate whether adenoviral DNA is present in synovial specimens from patients with rheumatoid arthritis (RA). METHODS: Synovial fluid (SF) cells from 53 patients with early RA (duration less than 1 year) and synovial tissue samples of 20 patients with advanced RA were studied by using polymerase chain reaction for the presence of adenoviral DNA. The controls were 21 patients with other arthropathies. RESULTS: No adenoviral DNA was found in the SF leukocytes or synovial tissue of any of the patients with arthritis. CONCLUSION: These findings do not indicate that adenoviruses play a role in the etiology of RA. However, they do not exclude adenoviruses as an occasional cause of persistent or recurrent inflammatory arthritis.

Adenoviruses, Human↗
PubMed1994

Antibodies to Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis in ankylosing spondylitis: effect of sulfasalazine treatment.

OBJECTIVE: To make a longitudinal study of antibodies to Klebsiella pneumoniae in patients with ankylosing spondylitis (AS) and to assess treatment effects. As a comparison we measured antibodies of 2 other gut associated bacteria, Escherichia coli and Proteus mirabilis. METHODS: In a double blind study in 84 Finnish outpatients with AS before and after 26 weeks' treatment with sulfasalazine or placebo we measured serum antibodies to Klebsiella pneumoniae, E. coli and Proteus mirabilis with ELISA: Serum samples of 100 healthy blood donors served as controls. RESULTS: The levels of IgA class antibodies to all 3 bacteria were statistically significantly higher in the sera of the patients compared to the controls. During sulfasalazine treatment significant decreases were observed in concentrations of the IgA class antibodies to Klebsiella and E. coli whereas only a slight decrease was observed in the concentrations of IgA antibodies to Proteus mirabilis. There were no correlations between the clinical and laboratory results observed with sulfasalazine and decrease in concentrations of IgA class antibodies. CONCLUSION: Our results agree with the role of gut associated lymphoid tissue in the pathogenesis of AS, but do not totally exclude Klebsiella pneumoniae as a specific agent contributing to the development of AS.

Adult↗
PubMed1993

Detection of herpesviruses by polymerase chain reaction in lymphocytes from patients with rheumatoid arthritis.

OBJECTIVE: To investigate the occurrence of herpesviruses, including Epstein-Barr virus (EBV), herpes simplex viruses types 1 and 2 (HSV-1; HSV-2), and human herpesvirus 6 (HHV-6), in lymphocytes from patients with rheumatoid arthritis (RA) of less than 1 year's duration. METHODS: The polymerase chain reaction was applied to cells isolated from synovial fluid and peripheral blood. Indirect immunofluorescence and enzyme immunoassay techniques were used to detect antibodies against EBV and HSV, respectively. RESULTS: EBV DNA was present in synovial fluid lymphocytes from 19% (7 of 37) of the RA patients and 33% (5 of 15) of the patients with reactive arthritis (ReA). Peripheral blood lymphocytes harbored EBV DNA in 39% of the RA patients, 39% of the ReA patients, 27% of the patients with other arthropathies, and in 31% of the healthy control subjects. HSV-1, HSV-2, and HHV-6 viral DNA was not detected in cells from the synovial fluid or peripheral blood. CONCLUSION: Our findings do not support the participation of EBV, HSV-1, HSV-2, or HHV-6 in the pathogenesis of RA. A role for the highly prevalent EBV cannot be excluded, however, since potential contributions may become manifest only when other necessary factors are involved. RA pathogenesis caused by an overproduction of the EBV virus is nevertheless highly unlikely.

Adult↗
PubMed1993

Chicken B cells adhere to the CS-1 site of fibronectin throughout their bursal and postbursal development.

In chickens, the pre-B cell development takes place in a specialized organ, the bursa of Fabricius. In this study, we show that fibronectin can be detected in the bursa at least from the day 15 of embryonic incubation up to 10 weeks of age after which the bursa starts to involute. During the embryonic incubation, fibronectin localizes mainly in the areas between the follicles and later on also in the border zone between the cortical and medullary parts of the lymphoid follicles. By adhesion studies with synthetic peptides we show that immature bursal B cells bind in a dose-dependent manner to the CS-1 site of the type III connecting segment at the carboxy-terminal end of fibronectin throughout their bursal development. Postbursal B cells from chicken spleen also display a similar preference of binding to the CS-1 site of fibronectin, whereas peripheral blood B lymphocytes bind to the 40-kDa fragment of fibronectin, but do not adhere as strongly to the CS-1 site. Instead, they recognize to some extent also the heparin-binding YEKPGSPPREVVPRPRPGV peptide. The adhesion of the bursal B cells to the CS-1 site can partially be blocked by preincubation of cells with a synthetic CS-1 peptide and also by preincubation with a monoclonal anti-fibronectin receptor antibody. In contrast, the RGD motif present in several adhesion-associated stromal molecules did not promote any adherence of bursal lymphocytes. The bursal B cells which adhere to the fibronectin molecule in vitro form only a small fraction of the total number of B cells present in the bursa as only less than 4% of the cells remained bound to the surface coated with fibronectin in the adhesion studies. In conclusion, these results suggest that fibronectin may be involved in the differentiation of pre-B cells in the bursa of Fabricius and also in the adherence of postbursal B cells in the spleen.

Amino Acid Sequence↗
PubMed1993

Helper activity of CD4+ alpha beta T cells is required for the avian gamma delta T cell response.

We have studied the in vitro activation of chicken gamma delta T cells. Both splenic alpha beta and gamma delta T cells obtained from complete Freund's adjuvant-primed chickens proliferated in vitro when stimulated with mycobacterial sonicate or purified protein derivative of Mycobacterium tuberculosis. When CD4+ cells or alpha beta T cell receptor (TcR)-positive cells were removed, both the proliferation and the blast formation of gamma delta T cells in response to mycobacterial antigens were abrogated. The response was restored if supernatant from concanavalin A (Con A)-activated lymphocyte cultures (CAS) as a source of helper factors was added together with the specific antigen purified protein derivative. The CD4- or alpha beta TcR-depleted cells still proliferated in response to Con A, although a decrease of the response was observed. To analyze the gamma delta T cell response more specifically we stimulated peripheral blood cells with immobilized monoclonal antibodies against T cell receptor. Anti-gamma delta TcR antibody alone did not induce significant proliferation. When CAS was added together with the anti-gamma delta TcR monoclonal antibody, a strong proliferation of gamma delta T cells was observed. In contrast, both V beta 1- and V beta 2-expressing alpha beta T cells proliferated in vitro in response to stimulation with the relevant anti-TcR monoclonal antibody alone. Depletion of either V beta 1+ or V beta 2+ T cell subset alone had no negative effect on the proliferation or blast formation of gamma delta T cells stimulated with mycobacterial antigens. Taken together our results suggest that CD4+ alpha beta T cells (both V beta 1- and V beta 2-expressing) play a role in the activation and response of chicken gamma delta T cells.

Animals↗
PubMed1993

Molecular mimicry: any role in the pathogenesis of spondyloarthropathies?

Ankylosing spondylitis and reactive arthritis are seronegative spondyloarthropathies, which are strongly associated with HLA-B27. Despite intensive investigation, the basis for this association is not clear. However, in recent years one favored hypothesis to explain this linkage has been that of molecular mimicry, i.e., sharing of linear or conformational epitopes common to microbial antigens and host structures. During the past few years several examples of molecular mimicry between HLA-B27 and microbial antigens have been described. Heat shock proteins, among others, have been considered as target candidates for autoimmune phenomena, because of the high degree of homology between bacterial and mammalian species. Reactive arthritis triggered by Yersinia or Salmonella provides a unique model for studying the pathogenetic mechanisms underlying human inflammatory joint diseases in general, because the arthritogenic microbes are known and well-characterized. We have described two bacterial proteins that share amino acid homology with HLA-B27, namely YadA (Yersinia adhesin) and OmpH, outer surface proteins of Yersinia and Salmonella, respectively. Notably, the area of identity of these amino acid sequences is located in the same place on the HLA-B27 molecule as a hexapeptide identical between Klebsiella nitrogenase and HLA-B27, and a pentapeptide shared by a Shigella flexneri protein and HLA-B27. We have investigated immune responses to a panel of synthetic peptides based on the HLA-B27-homologous portions of pathogen-specific antigens in patients with reactive arthritis and ankylosing spondylitis. One third of the patients have antibodies to the synthetic peptides. However, instead of recognizing the HLA-B27-homologous portion, the antibodies are directed against the flanking sequences of the synthetic peptides. The concept of the role of molecular mimicry between HLA-B27 and microbial antigens in the pathogenesis of spondyloarthropathies is discussed, with a conclusion that no convincing evidence for its significance exists at the present.

Adhesins, Bacterial↗
PubMed1993

Yersinia enterocolitica lipopolysaccharide: genetics and virulence.

The O side chain (O antigen) of the lipopolysaccharide of Yersinia enterocolitica serotype O:3 has been shown to be a virulence factor. The genes directing the biosynthesis of the O antigen have been cloned, sequenced and characterized. Like the expression of most of the virulence factors of Y. enterocolitica, O-antigen expression is temperature regulated.

Gene Expression Regulation, Bacterial↗
PubMed1993

Analysis of chicken CD4 by monoclonal antibodies indicates evolutionary conservation between avian and mammalian species.

We have created a panel of mouse monoclonal antibodies detecting different epitopes on avian CD4 molecule. Two-color immunofluorescence analysis shows that chicken peripheral alpha beta T cells are either CD4 or CD8 single positive whereas most gamma delta T cells are CD4-negative both in the thymus and peripheral tissues. Unlabeled antibody competition analysis by flow cytometry demonstrates that several different epitopes on chicken CD4 are recognized by these antibodies. Antibodies precipitate a monomeric glycoprotein from surface-labeled chicken thymocytes and T cells with relative molecular mass (M(r) of 64 kd as analyzed by SDS gel electrophoresis. Removal of N-linked carbohydrates by endoglycosidase-F increases the electrophoretic mobility and reveals the core protein size with M(r) of 45 kd. The anti-CD4 antibodies inhibit antigen-induced cellular proliferation of a keyhole limpet hemocyanin (KLH) -specific T cell line. They synergize in the blocking of T cell proliferation with anti-class II major histocompatibility complex (MHC)-specific antibodies indicating that chicken CD4 is involved in antigen recognition process by CD4+ T cells. We also show that chicken CD4 is down-modulated in a similar manner as its mammalian equivalent when thymocytes are stimulated in vitro with phorbol esters. Altogether these findings suggest functional and biochemical conservation of the CD4 molecule in evolution.

Animals↗
PubMed1993

Effect of a non-steroidal anti-inflammatory drug, naproxen, on faecal microbial flora.

Faecal Clostridium perfringens counts have been observed to be elevated in RA patients. The use of NSAIDs has been suggested as being responsible for this increase. To clarify the potential of NSAIDs to change faecal flora, 10 male volunteers were given naproxen 500 mg twice daily for 2 weeks in a randomized, placebo-controlled and double-blind study, and 10 other volunteers were given a placebo in tablets of identical appearance. Stool samples were collected and subjected to direct stool sample gas-liquid chromatography of bacterial fatty acids. The method has proved to be practical and sensitive in detecting overall changes in faecal flora. The samples were also cultured for Cl. perfringens. No significant change of faecal flora was observed by either method. The results show that naproxen given in doses and over a period in excess of the levels reported to increase intestinal permeability, does not change intestinal flora.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

Effect of dietary fish powder on intestinal flora and development of arthritis in the pig.

In 1971 Månsson et al. reported that a 20% dry fish powder diet fed to young pigs induced arthritis and increases in faecal Clostridium perfringens counts. To confirm this interesting finding we have repeated their experiment by following their regimen as closely as possible. Twelve piglets of Finnish landrace were divided at 8 weeks of age into two groups according to litter, sex and initial weight. The control group received a cereal-based diet. In the experimental group 20% of cereal in the diet was replaced by fish meal. Stool samples were cultured for Cl. perfringens and subjected to direct gas-liquid chromatography (GLC) to provide bacterial cellular fatty acid profiles. Development of arthritis was monitored macroscopically, and synovial samples were taken at autopsy for microscopical examination. Faecal Cl. perfringens counts increased 10-40 times more in the fish diet group than in the control group. GLC revealed a significant difference in bacterial florae between the groups. No arthritis was observed and only slight synovial inflammation in four experimental pigs and in one control pig. We conclude that fish diet changed faecal flora significantly, but did not induce arthritis.

Animals↗
PubMed1993

Hydrophobic domains affect the collagen-binding specificity and surface polymerization as well as the virulence potential of the YadA protein of Yersinia enterocolitica.

The YadA surface protein of enteropathogenic Yersinia species contains two highly hydrophobic regions: one close to the amino terminal, and the other at the carboxy-terminal end of the YadA polypeptide. To study the role of these hydrophobic regions, we constructed 66 bp deletion mutants of the yadA genes of Yersinia enterocolitica serotype O:3 strain 6471/76 (YeO3) and of O:8 strain 8081 (YeO8). The mutant proteins, YadAYeO3-delta 83-104 and YadAYeO8-delta 8O-101, lacked 22 amino acids from the amino-terminal hydrophobic region, formed fibrillae and were expressed on the cell surface. Bacteria expressing the mutated protein lost their auto-agglutination potential as well as their collagen-binding property. Binding to fibronectin and laminin was affected differently in the YeO3 and the YeO8 constructs. The deletion did not influence YadA-mediated complement inhibition. Loss of the collagen-binding property was associated with loss of virulence in mice. We also constructed a number of YadAYeO3 deletion mutants lacking the hydrophobic carboxy-terminal end of the protein. Deletions ranging from 19 to 79 amino acids from the carboxy terminus affected polymerization of the YadA subunits, and also resulted in the loss of the YadA expression on the cell surface. This suggests that the carboxy terminus of YadA is involved in transport of the protein to the bacterial outer surface.

Adhesins, Bacterial↗
PubMed1993

Genetic organization and sequence of the rfb gene cluster of Yersinia enterocolitica serotype O:3: similarities to the dTDP-L-rhamnose biosynthesis pathway of Salmonella and to the bacterial polysaccharide transport systems.

The Yersinia enterocolitica O:3 lipopolysaccharide O-antigen is a homopolymer of 6-deoxy-L-altrose. The cloned rfb region was sequenced, and 10 open reading frames were identified. Transposon mutagenesis, deletion analysis and transcomplementation experiments showed that eight of the genes, organized into two operons, rfbABC and rfbDEFGH, are essential for O-antigen synthesis. Functional tandem promoters were identified upstream of both operons. Of the deduced polypeptides RfbA, RfbF and RfbG were similar to Salmonella proteins involved in the dTDP-L-rhamnose biosynthesis. Rhamnose and 6-deoxy-L-altrose are C3-epimers suggesting that analogous pathways function in their biosynthesis. RfbD and RfbE were similar to capsular polysaccharide export proteins, e.g. KpsM and KpsT of Escherichia coli. This and transposon mutagenesis showed that RfbD and RfbE function as O-antigen exporters.

Amino Acid Sequence↗
PubMed1993

Yersinia lipopolysaccharide is modified by human monocytes.

Reactive arthritis is usually self-limiting polyarthritis, which develops after certain gastrointestinal or urogenital tract infections, mostly in susceptible HLA B27-positive individuals. In the pathogenesis of this arthritis, it is probably important that structures of the causative bacteria are found in the affected joints. The structure found in the synovial fluid phagocytes of the patients with reactive arthritis after Yersinia, Salmonella, and Shigella infections has always been lipopolysaccharide (LPS) of the causative bacteria. It has been in a highly processed form but still immunoreactive. To follow the degradation process of LPS, we fed peripheral blood monocytes of healthy blood donors with heat-killed Yersinia enterocolitica O:3 bacteria in vitro and monitored the fate of LPS by immunofluorescence and immunoblotting methods. Heat-killed bacteria were used since Y. enterocolitica O:3 bacteria are able to live inside monocytes in vitro and dividing intracellular bacteria would have made it impossible to monitor the degradation process of LPS with these methods. Both the core region and the O-polysaccharide chain of LPS persisted in cytoplasmic vacuoles and on plasma membrane of monocytes through the 7-day follow-up time. Migration properties of processed LPS in sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggested structural modifications of LPS. We also demonstrated that core epitopes appearing on the surface of Yersinia-fed monocytes on day 4 of incubation were processed intracellularly, suggesting that LPS-containing phagocytes are a constant source of membrane-active LPS in their microenvironment as well as in the joints of arthritic patients.

Antigens, Bacterial↗