Large Na+ influx and high Na+, K+–ATPase activity in mitochondria-rich epithelial cells of the inner ear endolymphatic sac

Fluid in the mammalian endolymphatic sac (ES) is connected to the endolymph in the cochlea and the vestibule. Since the dominant ion in the ES is Na(+), it has been postulated that Na(+) transport is essential for regulating the endolymph pressure. This study focused on the cellular mechanism of Na(+) transport in ES epithelial cells. To evaluate the Na(+) transport capability of the ES epithelial cells, changes in intracellular Na(+) concentration ([Na(+)](i)) of individual ES cells were measured with sodium-binding benzofurzan isophthalate in a freshly dissected ES sheet and in dissociated ES cells in response to either the K(+)-free or ouabain-containing solution. Analysis of the [Na(+)](i) changes by the Na(+) load and mitochondrial staining with rhodamine 123 showed that the ES cells were classified into two groups; one exhibited an intensive [Na(+)](i) increase, higher Na(+), K(+)-ATPase activity, and intensive mitochondrial staining (mitochondria-rich cells), and the other exhibited a moderate [Na(+)](i) increase, lower Na(+), K(+)-ATPase activity, and moderate mitochondrial staining (filament-rich cells). These results suggest that mitochondria-rich ES epithelial cells (ca. 30% of ES cells) endowed with high Na(+) permeability and Na(+), K(+)-ATPase activity potentially contribute to the transport of Na(+) outside of the endolymphatic sac.     

Multiple excimer laser phototherapeutic keratectomies for Avellino corneal dystrophy: a case report

Dear Editor,I am Chihiro Koiwa,from the Department of Ophthalmology,Juntendo University Hospital.I am writing this letter to present a case of multiple excimer laser phototherapeutic keratectomies(PTKs)for Avellino corneal dystrophy(ACD).Corneal dystrophy is a common type of hereditary,noninflammatory,and bilateral corneal disorder that involves various pathological,histological,and clinical manifestations[1].Advanced molecular gene sequencing has identified specific mutations that are associated with most dystrophies of this type.ACD,also known as granular corneal dystrophy typeⅡ[2],is autosomal dominant and associated with the R124H mutation of the transforming growth factor beta-induced(TGFBI)gene and characterized by deposits consistent with both discrete granular and lattice corneal opacities[3-4].An analysis of the TGFBI gene is essential to differentiate ACD because heterozygous R124H mutation carriers have minimal corneal abnormalities,whereas homozygotes have severe visual impairment,starting from early childhood,and early postoperative recurrence of corneal opacity.     

Japanese and Non-Japanese Patients with Transient Ischemic Attack or Minor Stroke: A Five-Year Risk Analysis of Stroke and Vascular Events

Aims: We have previously reported 5-year follow-up data on the TIAregistry.org, an international prospective cohort in patients with transient ischemic attack (TIA) or minor stroke. We conducted a Japanese subgroup analysis because outcomes and predictors might differ according to ethnicities and regions. In this study, we compared the baseline and 5-year follow-up data of Japanese and non-Japanese patients with TIA or minor stroke. Methods: Patients with TIA or minor ischemic stroke within 7 days after the onset were classified into two groups based on ethnicity, Japanese ( n =345) and non-Japanese ( n =3502); further, 5-year event rates were compared between the two groups. We also determined predictors of 5-year stroke for both groups. Results: Vascular death and death from any cause were identified to be less prevalent, unlike stroke and intracranial hemorrhage, which was determined to be more prevalent in Japanese than in non-Japanese patients. Five-year rate of stroke was significantly higher in Japanese patients. Cumulative stroke and major cardiovascular event rates did not decline but instead linearly increased from 1 to 5 years in both groups. Baseline risk factors for 5-year stroke were as follows: age, diabetes, history of stroke or TIA, and congestive heart failure in Japanese patients. Independent predictors of 5-year stroke were large artery atherosclerosis, congestive heart failure, diabetes, and age in Japanese patients. Conclusions: Recurrent stroke and intracranial hemorrhage were determined to be more prevalent at 5 years after TIA or minor stroke in Japanese patients than in non-Japanese patients. Strategies to mitigate the long-term risks of stroke, aside from adherence to current guidelines, should take Japanese-patient-specific residual risks into account.     

Significance of IgG4-positive cells in severe eosinophilic chronic rhinosinusitis

Background

IgG4 production is regulated by type 2 (IL-4 and IL-13) and regulatory (IL-10) cytokines involved in the pathophysiology of chronic rhinosinusitis (CRS). We sought to determine the pathophysiological characteristics of IgG4-positive cells in sinonasal tissues in CRS, especially eosinophilic CRS (ECRS).

Association between impaired IL-10 production following exposure to Staphylococcus aureus enterotoxin B and disease severity in eosinophilic chronic rhinosinusitis

Background

IL-10 is a major anti-inflammatory cytokine that prevents inflammation-mediated tissue damage. We characterized the production of IL-10 by sinonasal tissue cells following exposure to Staphylococcus aureus enterotoxin B (SEB), which elicits cellular responses and is associated with the pathogenesis of eosinophilic chronic rhinosinusitis (ECRS).

The genotype of the transporter associated with antigen processing gene affects susceptibility to colorectal cancer in Japanese

Objective

Although colorectal cancer (CRC) is one of the most frequent malignancies in Japan, the associated genetic factors remain to be elucidated. Functional loss of the transporter associated with antigen processing (TAP) 1 gene induces carcinogenesis. We investigated whether single nucleotide polymorphisms (SNPs) in the TAP1 gene (rs735883) are associated with susceptibility to CRC in a Japanese population.

Methods

The study participants were 143 cases and 243 clinical controls. After extracting DNA from their peripheral blood cells, genotyping was conducted by the polymerase chain reaction–restriction fragment length polymorphism method.

Results

Participants with a mutated allele had an increased risk for CRC. The adjusted odds ratios for the C/T, T/T, and the mutation type (C/T + T/T) compared to that of wild type (C/C) were 2.27 [95 % confidence interval (CI), 1.43–3.67], 1.95 (95 % CI, 0.88–4.30), and 2.22 (95 % CI, 1.42–3.55), respectively. Furthermore, a significant trend in the rate of cases was observed with an increasing number of mutated alleles (P for trend = 0.0068).

Conclusions

The genotype of the TAP1 gene is associated with susceptibility to CRC.     

Impact of CAD/CAM mandibular reconstruction on chewing and swallowing function after surgery for locally advanced oral cancer: A retrospective study of 50 cases

ObjectiveComputer-aided design and computer-aided manufacturing (CAD/CAM) techniques are increasingly applied to mandibular reconstruction, but the superiority of this method in oral food intake has not been well established. Considering the extent of mandibular defects, this retrospective study was aimed to clarify the impact of CAD/CAM mandibular reconstruction on chewing and swallowing function after surgery for locally advanced oral cancer.Materials and methodsWe performed a retrospective review of 50 patients who had undergone segmental mandibulectomy with free flap reconstruction for locally advanced oral cancer. The patients’ Functional Oral Intake Scale scores were measured at 3 months after surgery, and possible contributing factors including CAD/CAM mandibular reconstruction and the extent of mandibular defects for oral food intake were subjected to univariate analysis and multivariate logistic regression analysis.ResultsMultivariate logistic regression analysis showed that CAD/CAM mandibular reconstruction was independently associated with good oral intake, whereas both anterior or extensive mandibular resection and glossectomy were also independently associated with poor oral intake after surgery.ConclusionThe present study showed the positive impact of CAD/CAM mandibular reconstruction on chewing and swallowing function after surgery for locally advanced oral cancer for the first time.     

SIRPα on CD11c+ cells induces Th17 cell differentiation and subsequent inflammation in the CNS in experimental autoimmune encephalomyelitis

Signal regulatory protein α (SIRPα) is expressed predominantly on type 2 conventional dendritic cells (cDC2s) and macrophages. We previously showed that mice systemically lacking SIRPα were resistant to experimental autoimmune encephalomyelitis (EAE). Here, we showed that deletion of SIRPα in CD11c⁺ cells of mice (Sirpa^ΔDC mice) also markedly ameliorated the development of EAE. The frequency of cDCs and migratory DCs (mDCs), as well as that of Th17 cells, were significantly reduced in draining lymph nodes of Sirpa^ΔDC mice at the onset of EAE. In addition, we found the marked reduction in the number of Th17 cells and DCs in the CNS of Sirpa^ΔDC mice at the peak of EAE. Whereas inducible systemic ablation of SIRPα before the induction of EAE prevented disease development, that after EAE onset did not ameliorate the clinical signs of disease. We also found that EAE development was partially attenuated in mice with CD11c⁺ cell-specific ablation of CD47, a ligand of SIRPα. Collectively, our results suggest that SIRPα expressed on CD11c⁺ cells, such as cDC2s and mDCs, is indispensable for the development of EAE, being required for the priming of self-reactive Th17 cells in the periphery as well as for the inflammation in the CNS.