Cytosolic nucleic acid sensors and innate immune regulation

During viral and bacterial infections, pathogen-derived cytosolic nucleic acids are recognized by the intracellular RNA sensors retinoic acid-inducible gene I and melanoma-differentiated gene 5 and intracellular DNA sensors, including cyclic-di-GMP-AMP synthase, absent in melanoma 2, interferon (IFN)–gamma inducible protein 16, polymerase III, and so on. Binding of intracellular nucleic acids to these sensors activates downstream signaling cascades, resulting in the production of type I IFNs and pro-inflammatory cytokines to induce appropriate systematic immune responses. While these sensors also recognize endogenous nucleic acids and activate immune responses, they can discriminate between self- and non-self-nucleic acids. However, dysfunction of these sensors or failure of regulatory mechanisms causes aberrant activation of immune response and autoimmune disorders. In this review, we focus on how intracellular immune sensors recognize exogenous nucleic acids and activate the innate immune system, and furthermore, how autoimmune diseases result from dysfunction of these sensors.     

High Expression of SQSTM1/p62 Protein Is Associated with Poor Prognosis in Epithelial Ovarian Cancer

High expression of SQSTM1/p62 (p62) protein, which functions as a hub for various cellular signaling pathways, has been detected in several human cancers. However, the clinicopathological impact of high p62 expression is largely unknown in epithelial ovarian cancer (EOC). Here, the expression level of p62 in primary EOCs (n=266) was assessed by immunohistochemistry, and its clinical significance was analyzed. Univariate and multivariate analyses were used to determine the impact of p62 expression on overall survival. p62 was expressed in the cytoplasm (Cyto) and/or nucleus (Nuc) in primary EOCs, and an expression subtype (Cyto^High/Nuc^Low), showing high expression in the cytoplasm but low expression in the nucleus, was significantly correlated with serous carcinoma (P<0.001), advanced stage (P=0.005), presence of residual tumor (P<0.001), and low overall survival rate (P=0.013). Furthermore, in serous carcinomas (n=107), the p62 Cyto^High/Nuc^Low subtype was significantly correlated with low overall survival rate (P=0.019) as an independent factor (P=0.044). Thus, our findings suggest that high expression of cytoplasmic p62 may be a novel prognostic biomarker in EOC, particularly in serous carcinoma.     

Risk factors for acetabular retroversion in developmental dysplasia of the hip: does the Pemberton osteotomy contribute?

BackgroundThe purpose of this study was to investigate residual acetabular retroversion after skeletal maturity in patients with Pemberton osteotomy.Patients and methodsWe compared 40 hips in 36 patients treated with a Pemberton osteotomy (Pemberton group) and 30 hips in 26 patients treated only with a Pavlik harness (Rb group) for developmental dysplasia of the hip. The average age at operation in the Pemberton group was 94.5 months and the follow-up duration was 151.8 months. Radiographic parameters included the acetabular index (a angle) and the center-edge angle of Wiberg, preoperatively and at skeletal maturity. We examined the crossover sign (COS) at the latest follow-up as a sign of acetabular retroversion (AR). We compared the parameters between the two groups and examined the risk factors for acetabular retroversion using a multivariate Cox model.ResultA COS (+) was significantly more frequent in the Pemberton group compared to the Rb group [15 hips (37.5 %) vs 3 hips (10 %); p = 0.0077]. In the Pemberton group, the average age at operation in COS (+) hips was significantly older than that in COS (—) hips (126.9 vs 72.8 months; p = 0.0005). The preoperative α angle did not vary between hips with and without COS; however, the postoperative α angle was significantly smaller in COS (+) hips. A multiple logistic regression analysis for prediction of COS (+) showed that the age at operation and the amount change of α angle were significant predictors for COS (+) hips. The cut-off of the age at operation was 7 years and 9 months old.ConclusionsAR was present in 37.5 % of the hips in the Pemberton group after skeletal maturity. Remodeling of acetabular version was observed in younger patients; however, hips in older patients (> 8 years) at the time of operation and greater degrees of correction tended to result in AR.     

Is acute subdural hematoma reduced during the agonal stage and postmortem?

The issue of proper use of postmortem computed tomography (PMCT) in forensic fields is currently being actively discussed. The PMCT image has specific findings that differ from the antemortem image, and it is essential to understand and interpret postmortem changes in order to utilize PMCT properly. In this article, we present two cases of acute subdural hematoma (ASDH) in which images were obtained both ante- and postmortem. These images showed marked reduction of hematoma and diminishing midline shift between the agonal and postmortem periods, without evacuation of the hematoma. Attention should be paid to this phenomenon because key findings in determining cause of death could disappear if investigating the cause of death takes too long in cases that prove to be ASDH. In other words, this phenomenon potentially becomes a risk for misdiagnosis when we decide the cause of death without knowing the details of the circumstances of death.     

Two Japanese cases of dermatitis herpetiformis associated each with lung cancer and autoimmune pancreatitis but showing no intestinal symptom or circulating immunoglobulin A antibodies to any known antigens

Dermatitis herpetiformis (DH) is common in some Caucasian populations but extremely rare in Japanese, probably because of different immunogenetic backgrounds. We report two Japanese DH cases with typical clinical, histological and direct immunofluorescence features. However, no symptom of gluten‐sensitive enteropathy was shown. The diagnosis was confirmed by eliminating other autoimmune blistering diseases by indirect immunofluorescence, enzyme‐linked immunosorbent assays and immunoblotting. However, circulating immunoglobulin (Ig)A anti‐endomysium, reticulin and gliadin antibodies were not detected. IgA antibodies to tissue and epidermal transglutaminases were also negative. One case was associated with lung cancer and the other one with autoimmune pancreatitis. On review of 17 cases of DH reported in Japan over the previous 10 years, including our cases, one case was associated with gluten‐sensitive enteropathy, four with malignant neoplasms, two with autoimmune systemic disorders and one with psoriasis. Although our cases were typical of DH in clinical, histopathological and IgA deposit features, they showed different human leukocyte antigen haplotypes, no gluten‐sensitive enteropathy and no DH‐specific IgA antibodies, including those to epidermal and tissue transglutaminases. These results suggest that studies of unique characteristics in Japanese DH patients should facilitate further understanding of pathogenesis in DH.