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Biomedical subjects

A Toivanen

Publications and source records attributed to A Toivanen.

At least 109 records · Page 6Linked to original sources

Luminol-enhanced chemiluminescence of peripheral blood leukocytes as an early indicator of graft take after allogeneic bone marrow transplantation in patients with acute myelogenous leukaemia.

The luminol-enhanced chemiluminescence (CL) of peripheral blood leukocytes was studied daily in five patients with acute myelogenous leukaemia (AML) in first remission, who were undergoing allogeneic bone marrow transplantation (BMT). The CL was measured after stimulation of leukocytes with opsonized zymosan in highly diluted whole blood. All patients had an undetectable CL level on day +7, post BMT, simultaneously with severe pancytopenia caused by the pre-conditioning for BMT. Subsequently, CL started to rise, reaching the maximum level, twice that of healthy controls, on day +11. This preceded the rise of blood leukocytes above 1.0 x 10(9) l.-1 and that of neutrophils above 0.5 x 10(9) l.-1 by 3-14 days, but coincided with the appearance of large unstained cells (LUC; a parameter given by a Technicon H 6000 blood analyzer). One of the patients later had a transient decline of CL. This preceded the fall in white blood count and platelets by 7 days, suggesting marrow suppression. We conclude that in AML the measurement of leukocyte CL is a more sensitive test for prediction of graft take than the conventional blood counts.

Blood Cell Count↗

Serum IgA deficiency and anti-IgA antibodies in pernicious anemia.

Three pernicious anemia (PA) patients with selective IgA deficiency and anti-IgA antibodies in their sera were followed for over 3 years. After instituting therapy with cyanocobalamin there was a slight increase in the anti-IgA antibodies. After 1 year the titers of anti-IgA antibodies in the sera of these patients declined significantly as compared to the values before treatment (P less than 0.02), and after 2 years one patient had no measurable anti-IgA antibodies, yet no IgA appeared in the serum of any of the three. Further, in a medium with no anti-IgA the lymphocytes of these patients were not capable of producing IgA in vitro. Thus, the reason for the IgA deficiency in PA appears to be linked to the function of B cells rather than to anti-IgA antibodies.

Adolescent↗

Abnormal mitochondria in cultured synovial fibroblasts in rheumatoid and reactive arthritis?

This paper summarizes our recent studies on synovial fibroblast cultures started from patients with rheumatoid or reactive arthritis and from healthy controls. Analysis of these cultures by flow cytometry, spectroscopy and electron microscopy revealed consistent differences between arthritic and normal fibroblasts. Increased autofluorescence, exceptional light scatter properties, rhodamine-123 staining and electron microscopic findings of fibroblasts from arthritis patients suggest involvement of mitochondria in the disease process. Conditioned media of activated monocytes induced in the mitochondria of normal synovial fibroblasts changes similar to those observed in the fibroblasts originating from patients with rheumatoid or reactive arthritis.

Arthritis, Rheumatoid↗

Factors associated with the development of reactive arthritis.

The role of the causative microorganism in the generation of reactive arthritis is decisive, but host factors are also of major importance. Patients who develop reactive arthritis after Yersinia enteritis show several interesting features in the immunological defence against Yersinia when compared to those who recover uneventfully. When all these peculiarities are taken together, they strongly indicate that in the patients developing reactive arthritis the causative microorganism enters host tissues to persist within the body for prolonged periods of time.

Antibody Formation↗

Role of antibodies in the opsonization of Yersinia spp.

We have determined the opsonic capacity of specific antibodies in patient sera obtained after Yersinia infection. The results indicate that Yersinia antibodies lead to complement activation through the classical pathway, thus overcoming the inhibition of complement-mediated opsonization in the absence of specific antibodies provided by the virulence plasmid in Yersinia enterocolitica and Yersinia pseudotuberculosis. Further, antibodies against plasmid-encoded structures, the Yersinia outer membrane proteins (YOPs), are not necessary in this effect. This is indicated by two facts. (i) Monoclonal antibodies directed against the O polysaccharide of Y. enterocolitica O:3 are capable of opsonizing the plasmid-containing bacteria through C1q binding. (ii) Rabbit antisera show opsonic activity when obtained by immunization both with plasmid-containing Y. enterocolitica expressing the YOPs and a plasmid-cured variant not expressing these proteins.

Antibodies, Bacterial↗

IgA class antibodies against Yersinia enterocolitica O:3 in patients with thyroid disease.

IgM, IgG and IgA class serum antibodies against Yersinia enterocolitica O:3 and O:9 and Yersinia pseudotuberculosis 1a and 3 in 41 patients with thyroid disease and 50 healthy control persons were measured by enzyme-linked immunosorbent assay (ELISA). Concentrations of antibody levels against Yersinia enterocolitica O:9 and Yercinia pseudotuberculosis 1a and 3 did not differ significantly between the patients and controls. The median value of IgA class antibody Yersinia enterocolitica O:3 was 7.5 relative units (EIU, percentage of the reference serum) in the patients with thyroid disease and 0.7 EIU in the controls (P less than 0.01; Mann-Whitney's U-test), whereas IgM and IgG class antibodies did not show this difference. IgA class serum antibodies were especially high in patients with autoimmune thyroid diseases. These findings and two case reports support the concept that there may be a causal relationship between infections with Yersinia enterocolitica O:3 and autoimmune thyroid diseases.

Adolescent↗

Rheumatoid factors in Yersinia-triggered reactive arthritis.

Total rheumatoid factor (RF) activity and RF isotypes were measured in the sera of 33 patients with Yersinia infection using enzyme-linked immunosorbent assay. Twenty out of 33 patients developed reactive arthritis as a postinfectious complication. Yersinia infection does not seem to stimulate formation of RFs. The serum samples were practically negative, except two consecutive samples of one patient with Yersinia enterocolitica 0:3 triggered reactive arthritis which were strongly positive for all RFs tested. Although in Yersinia triggered reactive arthritis continuous response against Yersinia is seen, especially in the form of persisting IgA response, RF do not seem to be involved.

Adolescent↗

Activated monocytes induce arthritis-associated changes in mitochondria of cultured synovial fibroblasts.

We have recently shown that synovial fibroblasts cultured from patients with reactive or rheumatoid arthritis exhibit increased autofluorescence when compared with controls. Morphological studies suggested that this increase was related to the anomalous structure of mitochondria in cells cultured from rheumatoid or non-rheumatoid inflammatory synovial tissue. The present study describes attempts to find an explanation for these observations. The effects of conditioned media of cultured mononuclear cells were tested on normal synovial fibroblasts. Conditioned media of monocytes stimulated with lipopolysaccharide or poly-IC induced an increase in the cellular autofluorescence and changes in the morphology of mitochondria in normal fibroblasts. These changes were indistinguishable from those seen in synovial fibroblasts cultured from various arthritides. Indomethacin or gold salts did not abolish the effects of monocyte-conditioned media. Abnormal mitochondria could not be induced in the presence of cycloheximide. This study describes a new aspect of monocyte-fibroblast interactions during rheumatoid and non-rheumatoid inflammation of synovial tissue.

Arthritis, Rheumatoid↗

Allogeneic bone marrow transplantation in multiple myeloma: a report of four cases.

Allogeneic bone marrow transplantation offers a new and promising form for treatment of multiple myeloma incurable with chemotherapy. We present four cases of advanced multiple myeloma given bone marrow transplantation from HLA-identical and MLC-negative sibling donors. One patient had a recurrent plasmacytoma 8 months later and one died 12 days after the transplantation whereas the other two are in good clinical remission 15 and 19 months post-transplantation.

Adult↗

Lack of hybridization between Yersinia enterocolitica and HLA-B27 DNA.

No homology was observed between Yersinia enterocolitica O:3 and HLA-B27 at DNA level when Yersinia enterocolitica chromosomal probes were hybridized with human HLA-B27 positive leukocyte DNA or in the hybridization of Yersinia DNA with HLA-B27 specific probe. Our results do not exclude the existence of molecular mimicry between Yersinia proteins and HLA-B27 antigen, since the crossreactive epitope might be a conformational determinant not detected with hybridization.

Arthritis, Infectious↗

Avidity of anti-Yersinia antibodies in yersiniosis patients with and without Yersinia-triggered reactive arthritis.

Avidity of IgM, IgG, and IgA class anti-Yersinia antibodies was compared in sera of 22 patients with yersiniosis and subsequent reactive arthritis versus sera of 22 patients without postinfection complications. An enzyme-linked immunosorbent assay was used for antibody determination. Less than 2 months after onset of the infection, the patients with arthritis had fewer high-avidity IgM antibodies against the bacterial lipopolysaccharide (P = 0.035) and more high-avidity IgA antibodies against bacterial cell extract (P = 0.039) than did the patients without arthritis. This difference increased with time.

Adult↗

Characterization of circulating Yersinia-specific immune complexes in patients with yersiniosis.

The size of immune complexes (ICs) containing Yersinia enterocolitica antigens was studied by size exclusion high-pressure liquid chromatography and sucrose density gradient ultracentrifugation in sera of patients with recent yersiniosis. The ICs detected were relatively small, i.e., of equal size to or slightly larger than the corresponding anti-Yersinia antibodies. The size of the ICs was equal in the patients with Yersinia-triggered reactive arthritis and in those recovering without complications. No changes were observed during a follow-up. The equal size of ICs in the patients with and without arthritis also suggests that antigens and antibodies involved are similar in both patient groups. Taken together with our earlier findings indicating occurrence of high concentrations of Yersinia IgM ICs in the arthritic patients, the present results suggest that Yersinia--IgM ICs have a role in the pathogenesis of Yersinia-triggered reactive arthritis.

Antibodies, Bacterial↗

Immunoblot analysis of human IgM, IgG and IgA responses to plasmid-encoded antigens of Yersinia enterocolitica serovar O3.

Human IgM, IgG and IgA responses after infection with Yersinia enterocolitica serovar O3 were studied by immunoblotting sera against whole-cell homogenates of a plasmid-containing strain of Y. enterocolitica O3 and a plasmid-free strain derived from it; each strain was grown in conditions expressive for the plasmid. The antibodies observed were directed against several plasmid-encoded polypeptides. The response against different bacterial components decreased uniformly with time and the persisting antibody production was directed against several epitopes. Strong reactions to the prominent plasmid-specified antigens of mol. wts (10(3] 26, 34, 45 and 52.5 were found more often with IgG-class antibodies than with IgM or IgA; the latter immunoglobulins recognised, respectively, antigens of mol. wt (10(3] 26 and 45 (IgM) and 26, 34 and 52.5 (IgA). Immunoblotting of sera from patients with yersinia-triggered reactive arthritis did not reveal any antigens that were involved additionally or specifically. However, IgA-mediated recognition of certain antigens of mol. wts (10(3] 26, 34 and 52.5 tended to persist longer in the arthritic patients.

Adolescent↗

Graft-versus-leukaemia activity associated with cytomegalovirus seropositive bone marrow donors but separated from graft-versus-host disease in allograft recipients with AML.

To elucidate whether a relationship existed between bone marrow donor cytomegalovirus (CMV) immune status and the probability of staying in remission after transplantation, a retrospective multicentre analysis was performed in 69 patients who received allogeneic bone marrow transplantation during relapse or second remission of AML, or second remission of ALL. None of 12 AML patients with CMV seropositive donors had posttransplant relapse, in contrast to 7 of 10 AML patients with seronegative donors. Kaplan-Meier estimates of the 2-yr probability of staying in remission for the two groups were 100% and 0%, respectively (p less than 0.0005). This effect was independent of disease stage, donor and recipient age, recipient pretransplant CMV immune status and the occurrence of posttransplant CMV infection in recipients, and was not mediated through an increased occurrence of overt graft-versus-host disease (GvHD) in recipients with CMV seropositive donors. The increased probability of staying in remission was associated with an increased probability of 3-yr disease-free survival (p less than 0.01). No similar effect was observed in patients with ALL. This study may suggest an allograft-versus-leukaemia effect in AML, associated with CMV seropositive donors, which seems separate from GvHD and independent of the occurrence of posttransplant CMV infection.

Adolescent↗