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Biomedical subjects

I Jokinen

Publications and source records attributed to I Jokinen.

15 recordsLinked to original sources
PubMed1990

HLA-DR antigens and HLA-DQ beta chain polymorphism in susceptibility to rheumatoid arthritis.

Forty four patients with rheumatoid arthritis (RA) were studied for HLA-DR antigens and for HLA-DQ beta chain gene restriction fragment length polymorphism using DNA hybridisation. A significant increase in the prevalence of the DR4 antigen and a tendency towards an increase of DR1 was found in patients with RA. No allelic form of HLA-DQ restriction fragment length polymorphism patterns was increased, but the prevalence of an allele characterised by a combination of 7.5 and 3 kb fragments was decreased among patients with RA. The DQw8 subtype represented by a 12 kb fragment was the most common DR4 associated allele, and a 3.7 kb fragment related to DQw7 was found in only 5/25 (20%) DR4 positive patients and 2/12 (17%) controls. The results support the hypothesis that RA susceptibility factors are primarily located within HLA-DR genes but HLA-DQ genes may have a role in protection from the disease.

Arthritis, Rheumatoid↗
PubMed1990

Analysis of impaired in vitro immunoglobulin synthesis in rheumatoid arthritis.

Decreased immunoglobulin production in pokeweed mitogen driven lymphocyte cultures has been reported in rheumatoid arthritis (RA). Here various activators and experimental designs have been used to determine the contribution of B cells, T cells, or monocytes to this low response. Sixty patients with RA and paired controls were studied at the onset of disease and again six months later. Concentrations of IgA, IgG, and IgM in cultures of RA peripheral blood mononuclear cells stimulated with thymus dependent activators were already decreased at the onset of the disease. Six months later RA mononuclear cells produced even lower concentrations of immunoglobulin. In contrast, stimulation with a T cell independent activator showed that RA B lymphocytes had retained normal potential to synthesise immunoglobulin. Poor helper function was indicated by costimulation experiments and cultures of mixed mononuclear cells from patients and controls. This notion was supported also by the fact that phytohaemagglutinin induced interleukin-2 production by RA mononuclear cells was less than half of the control values. Nonspecific suppressor activity was similar in RA and controls. Monocyte functions were normal when tested by addition of indomethacin or 2-mercaptoethanol to the mitogen activated cultures. The defect in mitogen stimulated immunoglobulin production in vitro of RA mononuclear cells thus was more pronounced with time and probably reflects impaired mediator associated help in the differentiation of B lymphocytes into immunoglobulin secreting cells.

Adolescent↗
PubMed1990

Lysosomal trafficking in rat cardiac myocytes.

By immunolabeling of cryosections, we have characterized in rat cardiac myocytes the cation-independent mannose-6-phosphate receptor (MPR), a lysosomal membrane glycoprotein, lgp120, and a lysosomal enzyme, MEP (homologous to cathepsin L). Most of the MPR label was located in large membrane-filled structures (MPR structures) in large clusters of mitochondria adjacent to but distinct from the Golgi complex. Lpg120 and MEP showed typical lysosomal localization throughout the cell, often associated with regions that appeared to contain autophagosome-like structures. In addition, MEP and lgp120 co-localized within MPR structures. MEP and MPR were localized inside the lumen of MPR structures. MPR was associated mostly with inner membranes, whereas lgp120 was predominantly bound to the outer limiting membrane. MPR, lgp120, and MEP were not detected in Golgi stacks, but some labeling was seen in the putative TGN. Our data suggest that the MPR structures are prelysosomes involved in lysosomal enzyme targeting in rat cardiac myocytes.

Animals↗
PubMed1988

Antibodies against native type II collagen do not precede the clinical onset of rheumatoid arthritis.

Serum levels of IgG and IgM antibodies to native human type II collagen were determined in 22 pre-illness sera from subjects who developed seropositive rheumatoid arthritis (RA) 4 months to 5 years after sera were obtained, in 51 specimens from 35 healthy controls, and in 4-5 specimens from 58 patients with recent-onset RA. The antibody levels in all pre-illness serum specimens fell within the range seen for the healthy controls. Four RA patients had an IgG class antibody level and 4 had an IgM class antibody level that was above the highest level observed for controls, in at least 1 serum sample. No significant difference in the mean level of anticollagen antibodies was observed in the followup specimens from RA patients.

Adolescent↗
PubMed1988

Relation between bone erosions and rheumatoid factor IgA and IgM isotypes in recent onset rheumatoid arthritis.

In this prospective study 58 patients with early rheumatoid arthritis were followed up for two years with six-monthly assessments including rheumatoid factors (RF) of IgA and IgM subtypes. Initial and mean serum levels of IgA-RFs were raised in patients with an erosive disease course in comparison to non erosive disease. The cases with initially increased serum levels of RFs of both isotypes developed more eroded joints in their hands and feet during the study period than the rest of the patients. None of the differences, however, were statistically significant. Of the tested parameters only clinical rheumatoid activity (Mallya-index) was significantly related to the number of eroded joints during the follow-up. We conclude that serum IgA-type RFs are raised in erosive RA, but the determination of RFs of any kind cannot be used to prognosticate erosiveness.

Adolescent↗
PubMed1986

Specific immunoglobulin-secreting human blood cells after peroral vaccination against Salmonella typhi.

Studies on intestinal immunity in animals have suggested that lymphocytes, after sensitization in Peyer's patches and maturation in regional lymph nodes, home via the circulation to the intestinal wall, where they secrete antibodies into the lumen. To detect such homing cells in the blood of human volunteers given oral, attenuated Salmonella typhi vaccine, we used the solid-phase enzyme-linked immunospot assay for S. typhi-specific antibody-secreting cells (ASCs). ASCs were found in eight of 10 individuals after the third postvaccination day, peaked in level on day 7, and were undetectable on day 14. Of the cells secreting specific immunoglobulin, approximately 62% produced IgA, 32% IgM, and 6% IgG. Antibodies could not be demonstrated in serum, saliva, or feces. This technique might give an opportunity to follow the response to antigens entering the body via mucous membranes. It will be of interest to correlate these findings with protection against diseases after peroral vaccination.

Administration, Oral↗
PubMed1986

Bacteria are polyclonal T-dependent stimulants of immunoglobulin formation.

Various gram-positive and gram-negative bacteria were tested for their ability to induce antibody secretion in human blood cell cultures. Total and specific immunoglobulin levels in the culture supernatants were quantitated with enzyme-linked immunosorbent assays (ELISA). All the twelve strains used stimulated IgM and IgG secretion in adult mononuclear cell cultures. With the four strains tested, also umbilical cord blood cells produced IgM. Specific antibodies directed against two bacteria were sought in adult and newborn cell culture but none were found. Bacterium-induced antibody synthesis thus seemed to be polyclonal. Experiments with purified T and B lymphocytes showed that bacterium-driven antibody formation was T-cell dependent.

Antibodies, Bacterial↗
PubMed1986

Effect of elevated temperature on human immunoglobulin synthesis, lymphokine production and lymphocyte proliferation in vitro.

Fever in infections is mediated by endogenous pyrogen, a protein inseparable from interleukin 1 (IL-1). It remains unclear what the role of fever in host defence is. We studied the effect of elevated temperature on mitogen-induced human lymphocyte stimulation in vitro. Lymphocyte proliferation, elaboration of leukocyte migration inhibiting factor (LIF) and immunoglobulin production were measured at normal and elevated temperatures. Pokeweed mitogen-(PWM) driven responses were quantitated with a plaque-forming cell assay and by measuring secreted immunoglobulins in culture medium. The responses at 38, 39 or 40 degrees C were, if anything, lower than those at 37 degrees C. The production of LIF after stimulation with PWM was not augmented at elevated temperatures. In contrast, the proliferative responses to PWM, phytohaemagglutinin (PHA) and concanavalin A (ConA) were increased at 38 degrees C. These results indicated that elevated temperature has diverse effects on mitogen-induced lymphocyte functions in vitro.

Cells, Cultured↗
PubMed1986

Polyclonal antibody formation of human lymphocytes to bacterial components.

The capacity of various bacterial components to induce antibody formation in human lymphocyte cultures was studied in the present investigation. Antibody levels were determined by an enzyme-linked immunosorbent assay (ELISA). Lipopolysaccharide (LPS), bacterial cell walls (CW, isolated from Bacillus subtilis and Staphylococcus aureus Wood 46) and peptidoglycans (PG) appeared to stimulate IgM, IgG and IgA secretion, whereas lysozyme-solubilized PG and teichoic acids (TA) were ineffective. Also, umbilical cord blood lymphocytes produced IgM after stimulation with LPS, CW and PG. Coculture experiments with purified lymphocytes and monocytes indicated that B-cell differentiation was dependent on both T cells and monocytes, and that T-cell derived factors could derived factors could partially substitute for T cells.

Adult↗
PubMed1986

Effects of a human urinary mitogen on subpopulations of peripheral blood mononuclear leukocytes.

We have earlier isolated, to apparent homogeneity, a 27-28 kD human basic protein (UM) from the urine of a patient with myelomonocytic leukaemia. UM is a mitogen for resting human peripheral blood mononuclear leukocytes (PBML). We have now further defined the effect of UM on human PBML and their subpopulations in 6-day cultures. Cell proliferation was measured by 3H-thymidine uptake and Ig production by the plaque forming cell (PFC) response. Whole PBML responded to UM with proliferation and an increase in PFC. The PFC response was at best equal to and frequently synergistic with that produced by pokeweed mitogen and occurred in the three major Ig classes. To test the effect of UM on subpopulations of PBML, adherent cells (AC) were isolated by plastic adherence and T and B enriched populations by rosetting with sheep red blood cells. The proliferative response of T cells needed the presence of AC whilst the effect on Ig production by B cells required both T cell help and the presence of AC. Human thymocytes also responded to UM by proliferation. The results show that, in addition to being a T cell mitogen, UM is also a T cell dependent polyclonal B cell activator.

B-Lymphocytes↗
PubMed1985

The effect of phenytoin in vitro on normal human mononuclear cells and on human lymphoblastoid B cell lines of different Ig isotype specificities.

The anticonvulsant drug phenytoin, in less than cytotoxic concentrations, caused significant reductions in Ig secretion by unstimulated or EBV-stimulated normal MNC, as measured by PFC or secretion of Ig into the culture medium. Isotype-specific LBL varied in their sensitivity, the secretion of IgA (1 line) and IgG (3 lines) being reduced by phenytoin near therapeutic concentrations, whereas that of IgM (1 line) was resistant. Six-day exposure of MNC to phenytoin caused no selective depletion of or enrichment for B cells, monocytes or T cell subsets. The results suggest that the reduction in serum Ig levels reported in phenytoin-treated epileptic patients is, at least in part, due to a direct effect of the drug on the B lymphocyte. However, among EBV-activated normal MNC, those secreting IgA were no more sensitive to the drug than those secreting IgG or IgM, and other factors may, therefore, operate to cause the preferential reduction in serum IgA in phenytoin-treated patients.

Antibody-Producing Cells↗
PubMed1985

Synthesis of human immunoglobulins in vitro: comparison of two assays of secreted immunoglobulin.

One consequence of B-lymphocyte activation is immunoglobulin production, which can be quantitated by various techniques. We have compared assay of plaque forming cell (PFC) and determination of immunoglobulins by ELISA in culture supernatants of human lymphocytes stimulated with pokeweed mitogen and with Staphylococcus aureus. These assays correlated well (r greater than 0.77) in all major immunoglobulin classes studied. The close correlation suggests that determination of secreted immunoglobulins by ELISA may be substituted for the PFC assay.

B-Lymphocytes↗
PubMed1983

Selenium and immune functions in humans.

Earlier animal experiments have shown that selenium depletion may decrease immune functions. In this human study, 40 volunteers from a population with low serum selenium concentrations were supplemented with selenium or placebo for 11 weeks. Blood samples were drawn at intervals for analysis of selenium status and immune function. At the end of the supplementation period, plasma selenium levels were 74 ng/ml in the placebo group and 169 ng/ml in the supplemented group. The improvement in selenium status was associated with a 57% increase in the activity of platelet glutathione peroxidase in the group supplemented with selenium, but there was no increase in the activity of this enzyme in the placebo-treated subjects. Immune function was measured in vitro by tests of lymphocyte and granulocyte activity. Intracellular killing of Staphylococcus aureus by granulocytes was slightly lower in the placebo group than in the selenium group at the end of the supplementation period (77.2 compared to 85.2%; P less than 0.05). No significant changes were observed in phagocytosis, chemotactic factor generation, antibody or leukocyte migration inhibitory factor production by lymphocytes, or proliferative responses to phytohemagglutinin or concanavalin A. These results suggest that the selenium deficiency of the order found in Finland and some other areas of the world has little, if any, influence on the immune functions measured in this study.

Adult↗
PubMed1982

Synthesis of IgM, IgG and IgA in rheumatoid arthritis.

We studied the production of immunoglobulins by lymphocytes separated from the blood of 15 rheumatoid arthritis (RA) patients, of 12 patients suffering from other connective tissue diseases (CTD), and of 18 healthy controls. The production of IgM, IgG and IgA in pokeweed-mitogen-stimulated cultures was measured by counting the number of plaque-forming cells (PFC) and by determining the concentration of secreted immunoglobulins by means of an enzyme immunoassay. Synthesis of immunoglobulins, particularly IgM and IgG, was lower than in other CTD patients or controls. The IgM response of RA patients was 20% and 29% (PFC and Ig concentrations) that of the controls. The respective figures for IgG were 33% and 53% and for IgA 61% and 72%.

Adult↗