Resting T cells negatively regulate osteoclast generation from peripheral blood monocytes.

There is accumulating evidence that T cells may be involved in osteoclastogenesis in a variety of murine systems. However, the precise role of human T cells in the regulation of osteoclast generation is still unclear. To address this issue, we investigated the effect of resting peripheral T cells on receptor activator of NF-kappaB ligand (RANKL)-induced osteoclast generation from human peripheral monocytes. Although osteoclasts were not generated in the culture of human peripheral blood mononuclear cells (PBMC) in the presence of RANKL and macrophage colony-stimulating factor (M-CSF), the addition of cyclosporine A (CsA), a potent inhibitor of T-cell function, resulted in the formation of an increasing number of lacunae resorption on dentine, suggesting T cells may inhibit osteoclast formation. In a coculture of T cells and monocytes, which were isolated from PBMC, T cells inhibited the osteoclast generation from monocytes, as determined by tartrate-resistant acid phosphatase (TRAP) staining and a pit assay using dentine. This inhibition of osteoclast generation by T cells was also observed in a culture of the parathyroid hormone-stimulated SaOS4/3 osteoblast cell line and monocytes. The culture in Transwell plates revealed that the cell-to-cell interaction was not required for the inhibition, suggesting that T-cell cytokines may be responsible for the inhibition. Among inhibitory T-cell cytokines on osteoclastogenesis, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) were actively produced by CD4 T cells but not CD8 T cells in the coculture of T cells with monocytes, and the neutralizing antibodies to these cytokines partially rescued the T-cell-induced inhibition of osteoclast formation. Although CsA did not affect RANKL-induced osteoclast generation in the culture of monocytes alone, it completely rescued the T-cell-induced inhibition of osteoclast formation and strongly inhibited the production of GM-CSF and IFN-gamma. Thus, we demonstrate that resting T cells negatively regulate the osteoclast generation via production of GM-CSF and IFN-gamma by CD4 T cells and that CsA stimulates the osteoclast generation through the inhibition of the production of these cytokines. These findings provide new insight into therapeutic strategies for immunosuppression-induced bone loss in transplant and other diseases.

[A case of pseudoaneurysm of the thoracic aorta with Behçet's disease].

A 54-year-old female with incomplete type of Behçet's disease was operated on because of impending rupture of the thoracic aneurysm. There was a saccular pseudoaneurysm below the left subclavian artery, and a punched out lesion of the aorta was recognized. The defect of the aortic wall was closed with a PTFE patch. Before and after the operation, we have given prednisolone. The postoperative course was uneventful. Two years later, there was no recurrence of pseudoaneurysm near the PTFE patch. In many reports, aneurysms of Behçet's disease are saccular pseudoaneurysms, and have high incidence of complications about anastomosis postoperatively. We need a further follow-up about this patient.

[The evaluation of the modified Blalock-Taussig shunt with a prosthesis of microknitted Dacron for tetralogy of Fallot in early infancy].

We evaluated the surgical results of the modified Blalock-Taussig shunt (MBTS), performed with a prosthesis of microknitted Dacron, for the ductus-dependent tetralogy of Fallot (TOF) in early infancy. Nine MBTSs for eight patients, 4 with and 4 without pulmonary atresia, were performed, and one patient died. The mean age was 30 +/- 27 days, and the mean weight was 3460 +/- 770 g at the initial MBTS. In the initial two cases, the patients experienced convulsions due to severe hypoxia on account of the troubles of the preoperative administration of Prostaglandin E1 (PGE1). Thereafter, in order to prevent brain damage, we performed the MBTS following short-term administration of PGE1 (2-13 days). Consequently, we did not experience brain damage in later cases. Half of the patients with the MBTS with a 5 mm diameter prosthesis experienced postoperative congestive heart failure due to excessive pulmonary flow, and one of them died. The patients with the MBTS with a 4 mm diameter prosthesis had good postoperative courses. The suitable shunt flow in these patients was estimated to be 70-90 ml/kg/min. The MBTS with a 4 mm prosthesis obtained the lower level of this suitable shunt flow, but that a 5 mm prosthesis induced excessive shunt flow. Observing the patients' weight gain and the progress of polycythemia until two years of age, there were no differences between the MBTS with a 4 mm prosthesis and that with a 5 mm prosthesis. From these results, we recommend a 4 mm microknitted Dacron prosthesis for the MBTS of the TOF in early infancy.(ABSTRACT TRUNCATED AT 250 WORDS)