Autophagy is an evolutionarily conserved intracellular mechanism for the degradation of organelles and proteins. Here we demonstrate the presence of perinuclear autophagosomes/ autolysosomes containing nuclear components in nuclear envelopathies caused by mutations in the genes encoding A-type lamins (LMNA) and emerin (EMD). These autophagosomes/ autolysosomes were sometimes bigger than a nucleus. The autophagic nature is further supported by upregulation of LC3-II in Lmna H222P/H222P fibroblasts. In addition, inhibition of autophagy led to the accumulation of nuclear abnormalities and reduced cell viability, strongly suggesting a beneficial role of autophagy, at least in these cells. Similar giant autophagosomes/ autolysosomes were seen even in wild-type cells, albeit rarely, implying that this "nucleophagy" is not confined to the diseased condition, but may be seen even in physiologic conditions to clean up nuclear wastes produced by nuclear damage.

The prevalence of osteoporosis in the RA patients was 1.9 times higher than in healthy subjects. Glucocorticoid use was a risk factor for generalized bone loss in female RA patients.

The aim of this study was to investigate the expressions of Toll-like receptor (TLR) 2, TLR4, TLR9, and their correlations with the expression of cytokines that are associated with activation of CD4+ T cells and inflammation including interferon γ (IFNγ), interleukin 4 (IL4), interleukin 17 (IL17), and tumor necrosis factor α (TNFα) in muscle tissues of patients with dermatomyositis (DM) and polymyositis (PM). The expressions of TLR2, TLR4, TLR9, IFNγ, IL4, IL17, and TNFα were measured by real-time reverse transcription–polymerase chain reaction in muscle tissues from 14 patients with DM and PM (nine patients with DM, five patients with PM) and three controls. The expressions of TLR2, TLR4, and TLR9 were also localized with immunohistochemistry. The expression levels of TLR2, TLR4, TLR9, IFNγ, IL4, IL17, and TNFα were significantly high in patients with DM and PM compared with those in the controls, and the expression levels of TLR4 and TLR9 had significant positive correlations with the expressions of IFNγ, IL4, IL17, and TNFα. Immunohistochemistry showed that TLR2, TLR4, and TLR9 were expressed by infiltrating cells of perimysium in DM, whereas they were expressed by infiltrating cells of endomysium in PM. These results suggest that the involvement of TLR4 and TLR9 in immunopathogenesis of DM and PM might be connected with activation of CD4+ T cells.

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Background: Missense mutations in the valosincontaining protein (VCP) gene on chromosome 9p13.3-p12 cause inclusion body myopathy with Paget disease of bone and frontotemporal dementia (hereafter referred to as IBMPFD; OMIM 167320). Objective: To describe detailed clinical, electrophysiological, biochemical, and neuroimaging findings in IBMPFD linked to VCP p.Arg155Cys in a Korean family. Design: Case series. Clinical, electrophysiological, biochemical, and neuroimaging findings were obtained by direct evaluation and from previous medical records. Setting: Tertiary referral hospital. Participants: Three affected family members in a Korean family. Results: The clinical features of myopathy, Paget disease of bone, and semantic dementia (a clinical subtype of frontotemporal dementia) in our patients were similar to those of previously reported cases. However, the brain magnetic resonance imaging features in our patients, including asymmetric anterior and lateral temporal and inferior parietal atrophy with ventricular dilatation on the affected side, differed from those of previously published features in patients with IBMPFD and in patients with typical semantic dementia who show anterior temporal and frontal atrophy. Conclusion: To our knowledge, this report provides the first documented IBMPFD family in Asia and broadens the phenotypic spectrum of VCP mutation-associated frontotemporal dementia.