To determine the efficacy of low-dose FK506 in the treatment of myasthenia gravis (MG), untreated de novo patients were randomly selected to receive treatment with (n = 18) or without (n = 16) FK506, and were evaluated for 1 year after treatment with limitation of daily dose of prednisolone. Low-dose FK506 reduced the duration of early-phase therapy in hospital (p < 0.05) and the need for combined therapy with plasmapheresis and high-dose intravenous methylprednisolone or high-dose intravenous methylprednisolone alone (p < 0.05). It also reduced the daily dose of prednisolone (p < 0.05) required to maintain minimal manifestations of MGFA postintervention status. None of the patients exhibited significant side effects up to 1 year after treatment. These findings suggest that low-dose FK506 is safe and efficacious for the treatment of de novo MG patients.

To investigate the role of dendritic cells (DCs) in the hyperplastic myasthenia gravis (MG) thymus, we studied the frequency and distribution of three mature DC phenotypes (CD83(+)CD11c(+), CD86(+)CD11c(+), and HLA-DR(+)CD11c(+)) in samples from patients with MG whose symptoms dramatically improved following thymectomy and in non-MG control thymuses. In hyperplastic MG thymuses, mature DCs were much more numerous in nonmedullary areas, such as the subcapsular/outer cortex; around the germinal centers; and in extralobular connective tissue, particularly around blood vessels. Mature DCs strongly coexpressed CD44 and appeared to be components of a CD44-highly positive (CD44(high)) cell population migrating from the vascular system. Furthermore, in the hyperplastic MG thymus, the expression of secondary lymphoid-tissue chemokine (SLC) markedly increased especially around extralobular blood vessels, where the CD44(high) cell population accumulated. These findings suggest that DCs may migrate into the hyperplastic thymus from the vascular system via mechanisms that involve CD44 and SLC. DCs may present self-antigens, thereby promoting the priming and/or boosting of potentially autoreactive T cells against the acetylcholine receptor.

No abstract

We investigated the neuroprotective function of a7 nicotinic acetylcholine receptor (a7nAChR) after transient hypoxia (12 h) and reoxygenation (0-72 h), comparing rat pheochromocytoma (PC12) cells overexpressing FLAG-tagged a7nAChR (a7pCMV cells) and control PC12 cells (nontransfected or transfected with vector only) in medium with and without nicotine. Plasma membrane degradation in the early phase after hypoxia was inhibited in PC12 cells with nicotine, and more profoundly in a7pCMV cells with nicotine. Inhibition of DNA fragmentation in the late phase after hypoxia was most remarkable in a7pCMV cells with nicotine, but, surprisingly, it was more remarkable in a7pCMV cells without nicotine than in PC12 cells with nicotine. G1-arrest of the cell cycle, observed in control PC12 cells at 12 h after hypoxia, preceding DNA fragmentation, was not evident in a7pCMV cells, with or without nicotine. Furthermore, in a7pCMV cells with and without nicotine, the basal expression levels of total Akt were approximately 1.5-fold higher, and the up-regulation of Akt phosphorylated at Ser473 after hypoxia was strikingly enhanced, compared with control PC12 cells. These findings suggest that a7nAChR functions constitutively in PC12 cells, that its overexpression raises tolerance against G1-arrest and DNA fragmentation after hypoxia, and that it can be considered a candidate target for treatment against hypoxia-induced acute membrane degradation and delayed DNA fragmentation in neurons.

Performing a cohort-based SARS-CoV-2 antibody assay is crucial for understanding infection status and future decision-making. The objective of this study was to examine consecutive antibody seroprevalence changes among hospital staff, a high-risk population. A two-time survey was performed in May and October 2020 for 545 hospital staff to investigate the changes in the results of the rapid kit test and chemiluminescence immunoassay (CLIA). The seroprevalence of each assay was summarized at both the survey periods. The proportion of seropositive individuals in the CLIA for each survey period and the number of confirmed COVID-19 cases in Central Fukushima were then compared. We chose 515 participants for the analysis. The proportion of IgM seroprevalence in CLIA increased from 0.19% in May to 0.39% in October, and IgG seroprevalence decreased from 0.97% in May to 0.39% in October. The proportion of IgM seroprevalence in the rapid kit test decreased from 7.96% in May to 3.50% in October, and IgG seroprevalence decreased from 7.77% in May to 2.14% in October. The IgG and IgM antibody seroprevalence among hospital staff in rural Central Fukushima decreased; the seroprevalence among hospital staff was consistent with the number of confirmed COVID-19 cases in the Central Fukushima area. Although it is difficult to interpret the results of the antibody assay in a population with a low prior probability, constant follow-up surveys of antibody titers among hospital staff had several merits in obtaining a set of criteria regarding the accuracy of measures against COVID-19 and estimating the COVID-19 infection status among hospital staff.