[Clinical significance of LE cell phenomenon].
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Humans↗
Biomedical subjects
T Sakane
Publications and source records attributed to T Sakane.
Serum albumin metabolism in rheumatic diseases: relationship to corticosteroids and peptic ulcer.
Serum albumin concentrations and albumin metabolism were assessed in 150 patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and healthy subjects. Hypoalbuminemia was more marked in RA patients than in SLE patients. There was no correlation in RA patients between albumin levels and either disease activity or glucocorticosteroid administration; however, hypoalbuminemia in RA patients significantly correlated with juxta-articular erosions or with the incidence of peptic ulcer. The incidence of peptic ulcer was higher in RA patients with the combination of hypoalbuminemia and corticoid therapy, and reduced by the injection of anabolic steroid. In contrast, anabolic steroid did not improve hypoalbuminemia and bony erosions in the patients. The fractional catabolic rate of albumin was similarly elevated in both RA and SLE, while the absolute catabolic rate was increased to a greater extent in SLE patients. This explains the differences in serum albumin concentration between the patients with RA and SLE.
Adolescent↗
[Abnormalities in autologous mixed lymphocyte reaction-induced T cell activation cascade in rheumatoid arthritis and their possible correction by methyl-B12].
We have previously shown that when patients with active rheumatoid arthritis (RA) were examined for the ability of their lymphocytes to respond in the autologous mixed lymphocyte reaction (AMLR), profoundly reduced AMLR responses were found in the RA patients. The defects were mainly due to the impaired response of CD8+ and CD4+ Law8- subsets; however, both CD4+Leu8+ and CD4+ + Leu8- cells functioned normally as responding cells. The present study demonstrated that the abnormalities of RA CD8+ T cells in the AMLR were corrected when the AMLR cultures were set up in the presence of methyl-B12. In addition, a main target of the methyl-B12 effect observed was both CD8+Leu8+ and CD8+Leu8- cells. Thus, methyl-B12 may become a potential agent that would be able to control the pathophysiology of RA.
Adult↗
[The T cell receptor abnormalities and autoimmune diseases].
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Animals↗
Hyperreactivity of activated B cells to B cell growth factor in patients with systemic lupus erythematosus.
Inasmuch as B cell function is in large part determined by lymphokine-derived accessory signals, we studied the effects of recombinant IL-2 and low-molecular-weight B cell growth factor (BCGF) on peripheral blood B cells activated with Staphylococcus aureus Cowan I to explain the B cell hyperfunction in patients with SLE. When S. aureus Cowan I-activated normal B cells were separated into Tac-antigen (Tac-Ag)+ and Tac-Ag- cells by employing a rosette technique, IL-2 induced only the Tac-Ag+ cells to proliferate, whereas both the Tac-Ag+ and Tac-Ag- cells responded to BCGF. The Tac-Ag+ and Tac-Ag- fractions of activated SLE B cells behaved like respective fractions of activated normal B cells for the pattern of response to these growth factors. It should be pointed out, however, that although the Tac-Ag+ B cells of SLE patients and those of normal controls responded to IL-2 to almost the same degree, both the Tac-Ag+ and Tac-Ag- B cells of SLE patients exhibited markedly enhanced proliferative responses to BCGF. The selectively enhanced responsiveness of a broader range of activated SLE B cells may lead to B cell hyperactivity in this disease.
Adult↗
Familial occurrence of impaired interleukin-2 activity and increased peripheral blood B cells actively secreting immunoglobulins in systemic lupus erythematosus.
PURPOSE: We tested the hypothesis that some abnormalities of immune functions are genetically controlled in patients with systemic lupus erythematosus (SLE). SUBJECTS AND METHODS: We used a phytohemagglutinin-induced interleukin-2 (IL-2) activity assay and a spontaneous plaque-forming cell assay to evaluate T-cell and B-cell function, respectively, in 34 clinically healthy family members of six SLE probands. RESULTS: Impaired IL-2 activity was found in 15 of the 29 consanguineous relatives. There was no relation between the household relatives and the nonhousehold relatives; none of the five nonconsanguineous household persons had abnormal results. Results for the B-cell assay were abnormal in 22 of the 29 consanguineous relatives. The B-cell abnormalities were more commonly observed in the consanguineous household relatives; four of the five nonconsanguineous household relatives also had abnormal assay results. CONCLUSION: The findings indicate that the impaired IL-2 activity in relatives appears to strongly correlate with a genetic relationship. Although the evidence favors a genetic basis for the B-cell abnormalities, environmental effects may also contribute to the familial occurrence of these abnormalities.
Adolescent↗
The effect of immunization with protein-hapten conjugate on the intestinal uptake of p-aminobenzoic acid as a hapten.
Intestinal uptake of p-aminobenzoic acid was examined by means of an in vitro everted sac technique in rats immunized with ovalbumin-p-aminobenzoic acid conjugate. A dose-dependent and antigen-specific decrease in the serosal transfer of p-aminobenzoic acid was observed in rats immunized 6 times with protein-hapten conjugate compared with the control. There was a significant increase in the recovery of p-acetamidobenzoic acid, a metabolite of p-aminobenzoic acid, in mucosal fluid, tissue, and serosal fluid in the jejunum. In the case of ileum, increase of p-acetamidobenzoic acid was observed in mucosal fluid. However, there was no significant effect in the ileal p-acetamidobenzoic acid in tissue and serosal fluid between immunized and non-immunized rats. To examine the increased metabolism of immunized rats, N-acetyltransferase activity of the small intestinal mucosa was examined. There was a significant increase in mucosal N-acetyltransferase activity in immunized rats compared with the control animals. These observations suggested that the mucosal immune system may play an important role in regulating the intestinal uptake of the low molecular weight compounds.
4-Aminobenzoic Acid↗
Induction of excessive B cell proliferation and differentiation by an in vitro stimulus in culture in human systemic lupus erythematosus.
B cell hyperactivity present in the body in patients with systemic lupus erythematosus (SLE) can be detectable via almost any measure of B cell function. Nonetheless, the basis for the B cell hyperactivity is difficult to study in vitro. In this study, we have obtained the resting B cells from patients with entirely inactive SLE by collecting them sedimenting in a high density fraction on a Percoll density gradient. These resting SLE B cells proliferated in vitro at a higher rate than normal B cells when exposed to Staphylococcus aureus Cowan I (SAC). In addition, significant proliferation was observed earlier in the course of culture in SLE patients than in normal controls. Moreover, the SLE resting B cells, once triggered by SAC produced abnormally high numbers of immunoglobulin-secreting cells in response to T cell-derived soluble factors. There was less frequency of circulating Leu 1+ B cells in the SLE patients than in normal controls. Moreover, not only Leu 1+ B cells but also Leu 1- B cells of SLE patients were more responsive to SAC than those of normal controls. The results indicate that the B cell hyperactivity in human SLE can be induced by in vitro stimuli, and may not be limited to the Leu 1+ B cell subset.
Adult↗
Possible involvement of the CD4 molecule in a late activation event on CD4+ T cell proliferation in the human autologous mixed lymphocyte reaction.
CD4 monoclonal antibody (MoAb) was able to inhibit T cell proliferation induced in an autologous mixed lymphocyte reaction (AMLR). The effect of CD4 MoAb on cellular proliferation appears to be directly exerted on CD4+ T lymphocytes, and to be due to inhibition of a post-activation event, since the CD4+ T cell proliferation that occurs after an activation pulse of 24 h with autologous non-T cells could be inhibited when CD4 MoAb was added after, but not during, the pulse period, and the inhibition of autologous MLR-induced CD4+ T cell proliferation by CD4 MoAb was observed even if the Moab was added as late as 72 h after the initiation of culture. The presence of CD4 MoAb did not affect the production of interleukin 2 (IL-2). CD4 MoAb had, however, an inhibitory effect on the expression of IL-2 receptors, such that addition of exogenous IL-2 at the initiation of culture did not restore the AMLR-induced CD4+ T cell proliferation. These results indicate that the hindrance of the recognition of HLA class II products is not the only target of the CD4 MoAb effect in the autologous MLR. Rather, the binding of CD4 MoAb to CD4+ T cells interferes with a late event because it is capable of abolishing the proliferative activity of fully activated CD4+ T cells. The data are compatible with the idea that perturbation of the CD4 molecules can transmit a negative signal to CD4+ T cells.
Antibodies, Monoclonal↗
Intracellular activation signal requirements for the induction of IL-2 responsiveness in resting T cell subsets in humans.
Activation signal requirements for the induction of the IL-2 responsiveness in purified subsets of human resting T cells, T4+ or T8+, have been investigated under the monocyte-depleted conditions. Substantial levels of IL-2 responsiveness were induced in T8+ cells by lectin, Con A, mAb directed against the CD3 Ag, OKT3, Ca2+ ionophore, ionomycin or phorbol ester, PMA. In contrast, none of these stimuli was by itself sufficient for the induction of IL-2 responsiveness in the T4+ subset. The latter cells could, however, be induced to respond to IL-2 by combinations of PMA plus either of Con A, OKT3, or ionomycin (but not any combination of Con A, ionomycin, and OKT3). These data indicate that induction of IL-2 responsiveness in the resting T4+ subset is more complex, possibly requiring two intracellular activation signals, increase in the concentration of intracellular Ca2+ and activation of protein kinase C, whereas either signal may directly trigger IL-2 responsiveness in the resting T8+ cells. The data further suggest that under optimal conditions, growth of both resting T4+ and T8+ subsets may be independent of monocytes.
Antibodies, Monoclonal↗
Methyltransferase and phospholipase A2 activity in the cell membrane of neutrophils and lymphocytes from patients with Behçet's disease, systemic lupus erythematosus, and rheumatoid arthritis.
Phospholipid methylation and phospholipase A2 activation in the membrane of neutrophils and lymphocytes, which participate in the induction of cell activation, were assessed in patients with Behçet's disease, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). [3H-methyl] incorporation and phospholipase A2 activity of neutrophils from active cases of Behçet's disease and RA were significantly increased compared with normal controls. In lymphocytes from the patients with active Behçet's disease and RA, a significant increase in methyltransferase activity and a marked enhancement of phospholipase activity were found. A modest increase in these two membrane phospholipid enzyme activities was observed in lymphocytes of patients with active SLE. In addition, these enzyme activities were significantly enhanced in normal leukocytes preincubated with serum from patients with active SLE and malignant RA. The potentiated functions of neutrophils and lymphocyte abnormalities in the patients tested thus seem to be at least partly due to an increase in these enzymatic activities in the cell membrane.
Adolescent↗
B cell hyperactivity and its relation to distinct clinical features and the degree of disease activity in patients with systemic lupus erythematosus.
Peripheral blood B cells that were actively proliferating, those actively secreting immunoglobulin, and those expressing an early activation marker, Ba antigens, on the surfaces were quantitated in 25 patients with systemic lupus erythematosus (SLE). B cell hyperactivity was found in almost all of the SLE patients, as demonstrated by any one of these measures of B cell activity. Moreover, we observed a strong positive correlation between the degree of disease activity and the amount of spontaneous incorporation of 3H-thymidine by B cells; the magnitude of the increase in frequency of spontaneous Ig-secreting cells in peripheral blood correlated strikingly with certain clinical features in these patients. Our findings suggest that there is heterogeneity of B cell hyperactivity in individual patients with SLE and, thus, that clinical subsets of SLE can be identified on the basis of B cell hyperactivity.
Adolescent↗
Deficient phytohemagglutinin-induced interleukin-2 activity in patients with inactive systemic lupus erythematosus is correctable by the addition of phorbol myristate acetate.
In systemic lupus erythematosus (SLE) patients, the production of interleukin-2 (IL-2) by blood T lymphocytes in response to stimulation with phytohemagglutinin (PHA) either alone or with phorbol myristate acetate (PMA) or ionomycin, a Ca2+ ionophore, was examined. Deficiency in PHA-stimulated IL-2 production by cells from SLE patients was repaired by the addition of PMA, but not ionomycin. PMA alone did not stimulate IL-2 production but, in concert with PHA, induced IL-2 synthesis. Moreover, PMA was effective in the repair of the deficiency of PHA-induced IL-2 production by both T4+ and T8+ subsets. Thus, for effective IL-2 production, SLE T cells required signals either distinct from or in addition to those supplied by PHA.
Adult↗
The effect of aging on cutaneous lipid peroxide levels and superoxide dismutase activity in guinea pigs and patients with burns.
Cutaneous lipid peroxide levels and superoxide dismutase (SOD) activity in non-aged and aged guinea pigs were measured between 15 min and 7 days after experimental infliction of burns. Skin burns on non-aged and aged patients were also subjected to these assays. In non-aged guinea pig skin burns, lipid peroxide levels increased from 24 hr to the fourth day after the burn infliction, while SOD activity did not increase but showed a slight decrease 12 hr and 24 hr post-burn. On the other hand, while the aged group showed a more increase in skin lipid peroxide levels compared to that seen in non-aged mice, skin SOD activity began to decrease from 30 min post-burn, the maximum decrease being reached on the second day. The activity did not return to normal by the 7th day. In non-aged patients skin burns showed increases in both lipid peroxide levels and SOD activity, while in aged patients, though they showed a marked increase in lipid peroxide levels, SOD activity remained unchanged. The present study indicated that, although in our recent study, skin SOD activity of healthy elderly people was found to be comparable to that in non-aged individuals, the capacity for induction of SOD activity under oxygen stress differed with age in both guinea pig and human burn sufferers. Furthermore, this induction capacity seemed to vary from species to species.
Adult↗
Differential mechanism for differentiation into immunoglobulin-secreting cells in human resting B lymphocyte subsets isolated on the basis of cell density.
We have investigated differential mechanism for differentiation of human peripheral blood resting B cells to Ig-secreting cells. Purified resting B cells were further fractionated into subsets by discontinuous density gradients of Percoll, and proliferation and differentiation responses to Staphylococcus aureus Cowan I (SAC) and/or T cell-derived soluble factors were studied. High density resting B cells were stimulated to proliferate vigorously in response to SAC, but were poorly differentiated by SAC in presence of T cell factors. In contrast, low density resting B cells failed to proliferate in response to SAC and/or T cell factors; these cells could, however, be induced by stimulation with SAC plus T cell factors to become cells actively secreting Ig. These results indicate that there may exist heterogeneity in the human resting B cells: one subset of resting B cells (B cells with low density) can differentiate directly into Ig-secreting cells without the need for proliferation, and another subset (B cells with high density) can proliferate actively without subsequent differentiation into Ig-secreting cells. To address whether these resting B cell subsets belong to the same lineage, only high density B cells recovered from circulating resting B cells were first stimulated for 7 d with SAC, refractionated on Percoll gradients, and differentiation response of the refractionated B cells to SAC and T cell factors was examined. B cells shifting toward low density fraction were located in the resting status and could differentiate in response to SAC plus T cell factors. These results indicate that some of B cells with high density belong to the same cell lineage as those with low density and they must first proliferate before differentiation.
Antibody-Producing Cells↗
[Development of asymptomatic primary biliary cirrhosis in a patient with Hashimoto's thyroiditis and improvement of the liver disease by treatment of thyroiditis].
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Adult↗
Mechanism of T cell-derived helper factor production upon stimulation with pokeweed mitogen in humans.
T cell-derived helper factors can cause activated B cells to proliferate and differentiate into immunoglobulin (Ig)-secreting cells. In the pokeweed mitogen (PWM)-driven Ig production system, the cell-cell interaction necessary for the production of the helper factors was analysed. T cells were pulsed with PWM with or without autologous monocytes. The T cells were then isolated, and incubated for 48 h. Supernatants were tested for their ability to promote differentiation of activated B cells. We found that cell-cell contact between T cells and monocytes for the first 3 h of culture is required to produce the T cell-derived helper factors upon stimulation with PWM. We next examined which T cell subsets are involved in the production of helper factors and which surface molecules either on T cells or on monocytes are responsible for the cell-cell interaction to produce helper factors. A series of monoclonal antibodies were added to T cell subsets with monocytes during the PWM-pulsed period. Although T4+ and T8+ cells could produce almost equal amounts of helper factor activity upon PWM-stimulation, the interactions between T3 and T4 antigens on T4+ cells and Ia-like antigens on monocytes and those between T3 and T8 antigens on T8+ cells and HLA class I antigens on monocytes are respectively essential for the production of T4+ cell-derived and T8+ cell-derived helper factors.
Antibodies, Monoclonal↗
[Mechanism of cellular immunity in autoimmune diseases].
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Animals↗