Takehito Mayumi

Clinical importance of persistence of anticardiolipin antibodies in systemic lupus erythematosus.

The clinical importance of IgG anticardiolipin antibodies was investigated in systemic lupus erythematosus (SLE). IgG anticardiolipin antibodies were found in 69 of 155 (44.5%) patients with SLE. Serial measurements of IgG anticardiolipin antibodies allowed the patients to be classified into two groups: group A, persistently positive for IgG anticardiolipin antibodies; group B, positive only in active phases. The IgG anticardiolipin antibody titre in group A was significantly higher than in group B. The incidence of thromboses, spontaneous abortions, and lupus anticoagulant in group A was significantly higher than in group B (p less than 0.05). By contrast, the incidence of renal diseases and anti-dsDNA antibodies in group B was significantly higher than in group A (p less than 0.05). This study showed that group A formed a separate subgroup of patients with SLE who had a high risk of thromboses and spontaneous abortions despite having milder disease activity.

Frequency of valvular regurgitation by color Doppler echocardiography in systemic lupus erythematosus

Abstract We studied valvular regurgitation in patients with systemic lupus erythematosus (SLE) by color Doppler echocardiography. Because valvular regurgitation occurs frequently in normal subjects, 1,2 we matched the patients by age with a control group. Furthermore, the same person examined both patients and normal subjects using the same Doppler echocardiographic apparatus.

Liver abnormalities and liver membrane autoantibodies in systemic lupus erythematosus.

The hepatic involvement of 57 patients with systemic lupus erythematosus (SLE) was studied with special reference to liver membrane autoantibody (LMA). Liver abnormalities were found predominantly in patients with active SLE (27/48 (56%) in active SLE v 3/20 (15%) in inactive SLE). They were, however, rather mild or moderate and tended to disappear as the disease activity of SLE decreased. In this respect the liver abnormalities observed in this study differed from those in patients with lupoid hepatitis. The incidence of LMA in active SLE (8/11 (73%] was significantly greater than that in inactive SLE (4/12 (33%)). The mean LMA index value in active SLE was 8.3, which was also greater than the 2.9 in inactive SLE. Furthermore, in active SLE the mean LMA titre was significantly higher in patients with liver abnormalities than in those without. These results suggest that LMA may be associated with the activity of SLE and may be one of the factors which cause transient liver abnormalities.

Haemostatic factors associated with vascular thrombosis in patients with systemic lupus erythematosus and the lupus anticoagulant.

To elucidate the mechanism of vascular thrombosis in patients with systemic lupus erythematosus and the lupus anticoagulant changes in factors associated with haemostasis were investigated. The lupus anticoagulant was associated with an increased incidence of thrombosis, particularly cerebral thrombosis. Concentrations of fibrinopeptide A and fibrinopeptide B beta 15-42 were significantly raised in the plasma of patients with systemic lupus erythematosus and the anticoagulant compared with concentrations in patients without the lupus anticoagulant. The tendency towards formation of thrombosis was not found in all lupus patients with the anticoagulant, however. Concentrations of thromboxane B2 were remarkably raised in the plasma of the two patients with the lupus anticoagulant who had recently had thrombosis. Concentrations of 6-keto-prostaglandin F1 alpha, protein C, antithrombin III, and plasminogen were similar in both groups. No significant decrease in serum stimulatory activity on prostacyclin production by cultured aortic endothelial cells was noted in lupus patients with the anticoagulant, but inhibition was present in the two patients with recent thrombosis. These results indicate that although patients with the lupus anticoagulant are not always in a hypercoagulable state, haemostatic abnormalities found in some patients with the anticoagulant may be predictive of thrombotic events.

Okadaic acid enhances human T cell activation and phosphorylation of an internal substrate induced by phorbol myristate acetate

Okadaic acid is a potent tumor promoter and an inhibitor of serine/threonine-specific protein phosphatases. We studied the effect of okadaic acid in human T cell activation and phosphorylation of internal substrates. Okadaic acid at up to 4 nM enhanced phorbol myristate acetate (PMA)-induced proliferation and CD25 (IL-2 receptor, p55) expression, although it showed no activation by itself. Okadaic acid induced hyperphosphorylation of a 60 kDa protein in T cells as well as non-T cells, as reported in fibroblasts and keratinocytes. Preincubation with 4 nM okadaic acid enhanced PMA induced phosphorylation of the 80 kDa protein, an internal substrate of protein kinase C in T cells. These results suggest that okadaic acid inhibited dephosphorylation of protein kinase C specific substrates, and as a result, enhanced T cell activation mediated by protein kinase C pathway.

Phorbol Ester Receptors and the Induction of Differentiation in the Human T Lymphoblastic Cell Line MOLT-3

To examine the mechanism of induction of differentiation in the human malignant T-lymphoblastic cell line, MOLT-3, by 12-O-tetradecanoylphorbol-13-acetate (TPA), the role of receptors for phorbol esters was investigated. Binding of [20-3H]-phorbol-12,13-dibutyrate to TPA-resistant subclones derived from MOLT-3 was less than 50% of that of the parental MOLT-3. Scatchard analysis showed that the concentration of phorbol ester receptors in a TPA-resistant subclone was about 50% of that in the parental MOLT-3, but affinities of binding were similar, indicating that more than a certain number of phorbol ester receptors is required to induce differentiation by TPA in this human T cell line.