The aim of the study was to estimate the prevalence, characteristics, and prognostic factors of interstitial lung disease (ILD) in patients with polymyositis (PM) and dermatomyositis (DM). The medical records of 151 PM/DM patients treated at Chang Gung Memorial Hospital between January, 2000 and June, 2007 were retrospectively reviewed. Thirty of 151 (19.9%) PM/DM patients had developed ILD. Older age at PM/DM onset, anti-Jo-1 antibody, and arthritis/arthralgia were associated with the presence of ILD (p = 0.004, p = 0.008, and p = 0.026, respectively). Anti-Jo-1 was initially excluded from the multivariate analysis because only 80 patients underwent the test. An older age at onset above 45 years (odds ratio 3.28, 95% confidence interval (CI) 1.15-9.34, p = 0.026) and arthritis/arthralgia at onset (odds ratio (OR) 2.57, 95% CI 1.09-6.08, p = 0.032) were the two independent risk factors for developing ILD. If anti-Jo-1 was included in the multivariate analysis (n = 80), then an older age at onset above 45 years (OR 7.30, 95% CI 1.70-31.40, p = 0.008) and anti-Jo-1 positive (OR 7.89, 95% CI 1.18-52.87, p = 0.033) were associated with ILD, while arthritis/arthralgia was no longer significant (OR 2.64, 95% CI 0.70-10.01, p = 0.153). Of the 30 ILD patients, 16 (53.3%) died. The survival time was significantly shorter in ILD patients than in patients without ILD (p < 0.001). Poor survival in ILD patients was associated with male gender (p = 0.039), a Hamman-Rich-like presentation (p = 0.039), and a clinical diagnosis of acute interstitial pneumonia (p = 0.007).
Human coronavirus OC43 (HCoV-OC43) is a causative agent of the common cold. The nucleocapsid (N) protein, which is a major structural protein of CoVs, binds to the viral RNA genome to form the virion core and results in the formation of the ribonucleoprotein (RNP) complex. We have solved the crystal structure of the N-terminal domain of HCoV-OC43 N protein (N-NTD) (residues 58 to 195) to a resolution of 2.0Å. The HCoV-OC43 N-NTD is a single domain protein composed of a five-stranded β-sheet core and a long extended loop, similar to that observed in the structures of N-NTDs from other coronaviruses. The positively charged loop of the HCoV-OC43 N-NTD contains a structurally well-conserved positively charged residue, R106. To assess the role of R106 in RNA binding, we undertook a series of site-directed mutagenesis experiments and docking simulations to characterize the interaction between R106 and RNA. The results show that R106 plays an important role in the interaction between the N protein and RNA. In addition, we showed that, in cells transfected with plasmids that encoded the mutant (R106A) N protein and infected with virus, the level of the matrix protein gene was decreased by 7-fold compared to cells that were transfected with the wild-type N protein. This finding suggests that R106, by enhancing binding of the N protein to viral RNA plays a critical role in the viral replication. The results also indicate that the strength of N protein/RNA interactions is critical for HCoV-OC43 replication.
This study underlines the high frequency of major infections in PM/DM, which is significantly detrimental to patient survival rates. Close follow-up of PM/DM patients with risk factors for developing major infections is mandatory.
To estimate the mortality rate and identify factors predicting survival in patients with polymyositis (PM) and dermatomyositis (DM). The medical records of 192 PM/DM patients who were treated at Chang Gung Memorial Hospital from 1999 through 2008 were retrospectively reviewed. The Taiwan National Death Registry (1999-2008) was used to obtain their survival status. Thirty-one (16.1%) of the 192 patients with PM/DM had an associated malignancy; 41 (21.4%) had interstitial lung disease (ILD). During the follow-up period, 55 (28.6%) patients died and the overall cumulative survival rate was 79.3% at 1 year, 75.7% at 2 years, 69.9% at 5 years, and 66.2% at 10 years. In univariate analysis, older age at PM/DM onset, anemia, thrombocytopenia, leukopenia, diabetes mellitus, ILD, cancer, and non-use of azathioprine were associated with higher mortality (p = 0.0172, 0.0484, <0.0001, 0.0008, 0.0001, 0.0036, 0.0010, and 0.0019, respectively). In multivariate Cox regression analysis, thrombocytopenia (hazard ratio [HR] 4.94, 95% confidence interval [CI] 2.60-9.37, p < 0.0001), diabetes mellitus (HR 2.57, 95% CI 1.38-4.80, p < 0.0001), cancer (HR 2.30, 95% CI 1.26-4.22, p = 0.0030), and ILD (HR 1.98, 95% CI 1.11-3.51, p = 0.0182) were positively associated with mortality. Use of azathioprine (HR 0.35, 95% CI 0.16-0.74, p = 0.0064) was negatively associated with mortality. This study confirmed the high mortality rate (28.6%) in PM/DM patients. Survival time was significantly reduced in patients with thrombocytopenia, diabetes mellitus, ILD, and cancer patients than in those without these conditions.
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