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Biomedical subjects

P Toivanen

Publications and source records attributed to P Toivanen.

303 records · Page 17Linked to original sources

Defect in the generation of light-chain diversity in bursectomized chickens.

The avian bursa of Fabricius has been regarded as a central organ for B-cell development, but there is controversy about the existence of other sites for differentiation of B cells. We have recently shown that chickens surgically bursectomized as early embryos, before the bursal primordium appears, can produce cytoplasmic, surface and serum immunoglobulins of IgM, IgG and IgA classes but are unable to generate specific antibodies in response to antigen. We have therefore examined the structure and diversity of immunoglobulins of bursectomized chickens. Analysis of serum IgG revealed normal gamma-heavy chains but altered light chains with more basic and less diverse isoelectric points than normal. These light chains may represent germ-line specificities not diversified by somatic mutations. Thus the bursa of Fabricius appears not to be necessary for the production of immunoglobulin molecules as such but to function in the creation and expansion of the antibody repertoire, possibly by providing a microenvironment for somatic mutations.

Animals↗

Experimental chronic arthritis and granulomatous inflammation induced by bifidobacterium cell walls.

Effects of cell walls (CWs) from two almost identical strains of Bifidobacterium adolescentis were studied in rats, using three different doses. A single i.p. injection of both CWs triggered a long-lasting arthritis with CW degradation products present in the joint tissue. Histologically, the arthritis was characterized by inflammatory cells, synovial hyperplasia, pannus formation and bone erosion, closely resembling human rheumatoid arthritis (RA). In addition, CWs of the other strain induced a remarkable granuloma formation in the spleen and liver. Both CWs have the same peptidoglycan (PG) type A4alpha/beta, but differ from each other in three aspects. CW of the granuloma inducing strain: firstly has more lysine and less ornithine in PG stem peptides; secondly is more resistant to lysozyme degradation, and thirdly is better retained in the spleen. All these in comparison to the other strain used. Such characteristics are associated with the capacity to induce chronic arthritis, but it remains open how crucial they are for the granuloma formation.

Animals↗

Passive immunization with monoclonal antibodies specific for lipopolysaccharide (LPS) O-side chain protects mice against intravenous Yersinia enterocolitica serotype O:3 infection.

Passive immunization with monoclonal antibodies specific for the lipopolysaccharide (LPS) O-side chain protected mice against intravenously given lethal doses of Yersinia enterocolitica O:3 bacteria. On the other hand, passive immunization with monoclonal antibody specific for the LPS core oligosaccharide did not protect mice. Neither antibody was able to protect mice against orally given lethal doses of bacteria. These results indicate that the O-side chain functions as an important antigenic structure during infection, and that immunity to it probably offer protection also in the in vivo situation.

Administration, Oral↗

Restorative effects of different embryonic cells transplanted into immunodeficient chick embryos.

Cyclophosphamide-treated 18-day chicken embryos were transplanted with cells from different organs of histocompatible embryonic donors. The cells transplanted include cells from the bursa of Fabricius, spleen, bone marrow, thymus or liver of 15- and 18-day embryos and yolk sac cells from 9, 11, 13, 15 and 18-day embryos. To evaluate the reconstitution capacity of the cells transplanted, gain of body weight, weight and microscopic morphology of the lymphoid organs and antibody forming capacity to sheep red blood cells and Brucella were assessed at the age of five weeks. According to all the criteria employed, bursa cells were the only cells capable of a functional and morphological reconstitution of the recipient's humoral immune system. Cells from the embryonic spleen, bone marrow, thymus, liver or yolk sac had no reconstituting effect, indicating that these organs do not harbor precursors for the B-cell lineage. Taken together with other observations, these findings reveal that, as a differentiation site of the B-cell lineage, the bursa of Fabricius precedes the bone marrow during ontogenetic development, and furthermore, that the role of the yolk sac as the first generator of prebursal stem cells must be questioned.

Age Factors↗

Tissue distribution and persistence of arthritogenic and non-arthritogenic Eubacterium cell walls.

OBJECTIVE: To study the tissue distribution and persistence of arthritogenic and non-arthritogenic Eubacterium cell walls (CWs), using arthritogenic Eubacterium aerofaciens and non-arthritogenic Eubacterium limosum. METHODS: Eubacterium aerofaciens or Eubacterium limosum CW was injected into Lewis rats intraperitoneally. Inflammatory changes in the synovium and periarticular tissues were graded histologically. On days 14, 28 and 56 after the injection, the presence of CW in the liver, spleen, mesenteric lymph nodes and synovium was studied by indirect immunofluorescence. In parallel, CW-derived muramic acid in the liver and spleen was measured by gas chromatography-mass spectrometry. In addition, serum TNF-alpha, IL-1 beta and IL-10 concentrations were determined by ELISA. RESULTS: Systemic injection of Eubacterium aerofaciens CW, but not of Eubacterium limosum CW, resulted in chronic arthritis. Both E. aerofaciens and E. limosum CWs were observed in the liver and spleen at all of the time points studied. In addition, Eubacterium limosum CW was present in non-arthritic synovium on day 14. It was not, however, detected in the synovium or lymph nodes on days 28 and 56, in clear contrast to the rats injected with E. aerofaciens CW. According to the analysis by gas chromatography-mass spectrometry, non-arthritogenic E. limosum CW had accumulated in the liver cells on days 14 and 28 after the injection to a greater extent than arthritogenic E. aerofaciens CW, leading to a lesser distribution in the other organs. A weak trend was observed suggesting that the production of TNF-alpha and IL-1 beta, but not of IL-10, is stimulated better by arthritogenic CW than by non-arthritogenic CW. CONCLUSION: Our results indicate that non-arthritogenic CWs are handled by the rat's defence mechanisms in a different way than arthritogenic CWs. The tissue distribution and persistence of CWs play a role in arthritogenicity, but additional factors must exist to determine why the CWs of certain bacteria are arthritogenic and those of others are not.

Animals↗

Mononuclear cell response to enterobacteria and Gram-positive cell walls of normal intestinal microbiota in early rheumatoid arthritis and other inflammatory arthritides.

OBJECTIVE: To study whether enterobacteria and Gram-positive bacterial cell walls (BCW) derivedfrom normal intestinal microbiota are involved in the etiopathogenesis of early rheumatoid arthritis (RA). METHODS: Peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) were isolatedfrom patients with early RA (the average duration of 5 months) and the controls (other types of inflammatory arthritis). The mononuclear cell proliferation and tumor necrosis factor-alpha (TNF-alpha) responses to heat-killed Salmonella enteritidis (SE). Yersinia enterocolitica (YE), and Escherichia coli (EC), and to Gram-positive BCW derived from four common intestinal indigenous bacteria, Eubacterium aerofaciens (EA), Eubacterium limosum (EL), Lactobacillus casei (LC), and Lactobacillus fermentum (LF), and a BCW derived from a pathogen, Streptococcus pyogenes (SP) were investigated. RESULTS: 39% or 56% of patients with early RA showed significant proliferation responses by PBMC or SFMC against enterobacteria, respectively. In other types of arthritis, corresponding figures were 59% or 66%. When BCW were used as antigens, 8.1% or 23% of patients with early RA showed proliferation responses by PBMC or SFMC, respectively. In other types of arthritis the corresponding figures were 7.5% or 35%, respectively. However, TNF-alpha production by SFMC stimulated by EA BCW, SE, YE or EC, was significantly higher in early RA than in other types of arthritis. CONCLUSION: These results suggest that SFMC reacting with enterobacteria or BCW exist in some patients with early RA, but also in other types of inflammatory arthritis. Intestinal bacterial agents may play a role in the etiopathogenesis of RA, but the effect appears to be non-specific.

Adolescent↗

Yersinia-associated arthritis in rats: effect of 65 kDa heat shock protein, bovine serum albumin and incomplete Freund's adjuvant.

OBJECTIVE: We have previously shown that the microbial load of rats has a significant effect on their susceptibility to Yersinia-associated arthritis. In this study our aim was to see whether mycobacterial 65 kDa heat shock protein (hsp) could induce the same suppressive effect in experimental Yersinia-associated arthritis as has been reported for arthritides induced by adjuvant, pristane, or streptococcal cell walls (SCW). METHODS: Arthritis was induced by the intravenous injection of Yersinia enterocolitica 0:8 into Lewis rats. Hsp, bovine serum albumin (BSA) or NaCl, administered in incomplete Freund's adjuvant (IFA), was given subcutaneously on day -5 or +5 with regard to the bacterial inoculation. RESULTS: Mycobacterial hsp given in IFA on day -5 significantly suppressed the development of arthritis. However, a similar suppression was observed with BSA or NaCl given in IFA. CONCLUSION: These results, together with those known from the effect of microbial load, suggest that susceptibility to Yersinia-associated arthritis is easily affected by external factors.

Animals↗

Antibodies to streptococcal cell wall in psoriatic arthritis and cutaneous psoriasis.

OBJECTIVE: To evaluate the possible role of streptococcal cell wall antigens in the development of psoriatic arthritis. METHODS: IgM, IgA and IgG class serum antibodies against peptidoglycan-polysaccharide (PG-PS) and peptidoglycan (PG), both from group A streptococcus, were measured in patients with psoriatic arthritis (PA), non-arthritic psoriasis (NAP), rheumatoid arthritis (RA) and in healthy controls, using ELISA. RESULTS: Both groups of psoriatic patients had elevated IgA levels specific to streptococcal PG-PS. No association with the severity of the skin disease or with the different subsets of PA was detected. Higher concentrations of IgG against the two streptococcal preparations was observed in PA than in RA. Analysis of antibody levels in patients with recent onset arthritis showed lower concentrations of IgM antibodies against streptococcal as well as control antigens in early than in late PA, whereas an overall increase of specific IgA and IgG antibodies was observed in early RA. CONCLUSION: The results suggest chronic mucosal stimulation of lymphocytes by long-lived streptococcal antigens in patients with psoriasis, without any difference observed between PA and NAP. The differences between recent onset versus established PA and RA could reflect a distinct immunopathology in the two arthritides.

Adult↗

Enterobacterial antibodies in Chinese patients with rheumatoid arthritis and ankylosing spondylitis.

OBJECTIVE: To study the role of microbial infection in rheumatic diseases. METHODS: Sera from 39 Chinese patients with rheumatoid arthritis (RA), 52 patients with ankylosing spondylitis (AS) and 51 healthy subjects (HS) were examined for IgG, IgA, and IgM class antibodies against Proteus mirabilis, Escherichia coli, Campylobacter jejuni, Salmonella typhimurium and enteritidis, Yersinia enterocolitica, and Klebsiella pneumoniae (capsular serotypes 31 and 43), using an enzyme-linked immunosorbent assay. RESULTS: In patients with RA, IgA class antibodies against all bacterial strains used as the antigen were increased when compared to healthy controls. In patients with AS, significantly elevated IgA levels were observed against Campylobacter and Klebsiella K43. IgM class antibodies were less frequently elevated in RA and in AS than IgA class antibodies. In RA patients, IgG antibodies against Klebsiella K43 and Proteus were significantly increased. No differences were observed in IgG class antibodies between AS patients and healthy controls. CONCLUSION: Increases in serum bacterial antibodies in RA and AS suggest that in both diseases stimulation of the intestinal immune system by enterobacteria may have a role. However, the question whether this phenomenon is due to increased intestinal permeability and/or represents cross reactions between different enterobacteria remains open.

Antibodies, Bacterial↗