Localization of prosaposin in rat cochlea

Prosaposin, the precursor of the sphingolipid hydrolase activator proteins called saposins A, B, C, and D, is abundant in the nervous system and muscles. Besides its role as the precursor of saposins, prosaposin is reported to function as a neurotrophic factor, initiating neural differentiation and preventing neuronal cell death in vivo and in vitro. In this study, we examined the localization and synthesis of prosaposin in the rat cochlea. Intense prosaposin immunoreactivity was observed in the organ of Corti, stria vascularis, and spiral ganglion. In an immuno-electron microscopic study, prosaposin immunoreactivity was found mainly in lysosomal granules of the cells in these regions. In the lysosome, prosaposin does not always colocalize with cathepsin D, but was localized mainly in the dark area of the lysosome. Prosaposin mRNA was observed in these same regions. Our results suggest that prosaposin plays a role in homeostasis in the peripheral auditory system.     

Adenomyoma of the common hepatic duct

A very rare case of adenomyoma of the common hepatic duct is described. A 54-year-old woman was admitted with impending obstructive jaundice secondary to adenomyoma of the common hepatic duct. Our impression, formulated from her clinical presentation, endoscopic investigations, and biochemical and radiological findings, was a cancer of the proximal common hepatic duct. The patient was treated successfully by combination surgical resection and hepaticojejunostomy. Despite our obtaining an intraoperative frozen section, final histological examination was required to confirm the diagnosis. The patient remains well 16 months postoperatively. A survey of the world literature revealed that this is the second report of adenomyoma occurring in the common hepatic duct.     

Quantification of circulating varicella zoster virus-DNA for the early diagnosis of visceral varicella

Varicella zoster virus (VZV)-DNA was quantified in peripheral blood of 2 patients with visceral varicella due to endogenous reactivation. An 18-year-old male contracted varicella following the courses of chemotherapy for T cell lymphoma. Another 18-year-old male suffered from varicella 16 months after the complete engraftment of hematopoietic stem cell transplantation. Both patients had past VZV infection, but no recent contact with the disease. Paralytic ileus and ascites preceded the skin lesions. Quantitative real-time polymerase chain reaction revealed >200 copies of VZV per 1 ml of whole blood before or at the time when cropping vesicles emerged. The viral load reflected their prolonged clinical courses. Similar levels of VZV-DNA were detected in primary varicella patients, but not in herpes zoster patients or immunocompromised children without varicella or zoster. Quantitative monitoring of circulating VZV-DNA may be useful for the diagnosis and assessing the treatment response of visceral varicella in immunocompromized hosts.     

Peripheral blood lymphocyte telomere length as a predictor of response to immunosuppressive therapy in childhood aplastic anemia

Predicting the response to immunosuppressive therapy could provide useful information to help the clinician define treatment strategies for patients with aplastic anemia. In our current study, we evaluated the relationship between telomere length of lymphocytes at diagnosis and the response to immunosuppressive therapy in 64 children with aplastic anemia, using flow fluorescence in situ hybridization. Median age of patients was ten years (range 1.5–16.2 years). Severity of the disease was classified as very severe in 23, severe in 21, and moderate in 20 patients. All patients were enrolled in multicenter studies using antithymocyte globulin and cyclosporine. The response rate to immunosuppressive therapy at six months was 52% (33 of 64). The probability of 5-year failure-free survival and overall survival were 56% (95% confidence interval (CI): 41–69%) and 97% (95%CI: 87–99%), respectively. Median telomere length in responders was −0.4 standard deviation (SD) (−2.7 to +3.0 SD) and −1.5 SD (−4.0 to +1.6 (SD)) in non-responders (P<0.001). Multivariate analysis showed that telomere length shorter than −1.0 SD (hazard ratio (HR): 22.0; 95%CI: 4.19–115; P<0.001), platelet count at diagnosis less than 25×10⁹/L (HR: 13.9; 95%CI: 2.00–96.1; P=0.008), and interval from diagnosis to immunosuppressive therapy longer than 25 days (HR: 4.81; 95%CI: 1.15–20.1; P=0.031) were the significant variables for poor response to immunosuppressive therapy. Conversely to what has been found in adult patients, measurement of the telomere length of lymphocytes at diagnosis is a promising assay in predicting the response to immunosuppressive therapy in children with aplastic anemia.     

First-line treatment for severe aplastic anemia in children: bone marrow transplantation from a matched family donor versus immunosuppressive therapy

The current treatment approach for severe aplastic anemia in children is based on studies performed in the 1980s, and updated evidence is required. We retrospectively compared the outcomes of children with acquired severe aplastic anemia who received immunosuppressive therapy within prospective trials conducted by the Japanese Childhood Aplastic Anemia Study Group or who underwent bone marrow transplantation from an HLA-matched family donor registered in the Japanese Society for Hematopoietic Cell Transplantation Registry. Between 1992 and 2009, 599 children (younger than 17 years) with severe aplastic anemia received a bone marrow transplant from an HLA-matched family donor (n=213) or immunosuppressive therapy (n=386) as first-line treatment. While the overall survival did not differ between patients treated with immunosuppressive therapy or bone marrow transplantation [88% (95% confidence interval: 86–90) versus 92% (90–94)], failure-free survival was significantly inferior in patients receiving immunosuppressive therapy than in those undergoing bone marrow transplantation [56% (54–59) versus 87% (85–90); P<0.0001]. There was no significant improvement in outcomes over the two time periods (1992–1999 versus 2000–2009). In multivariate analysis, age <10 years was identified as a favorable factor for overall survival (P=0.007), and choice of first-line immunosuppressive therapy was the only unfavorable factor for failure-free survival (P<0.0001). These support the current algorithm for treatment decisions, which recommends bone marrow transplantation when an HLA-matched family donor is available in pediatric severe aplastic anemia.     

Electromyographic activity of superficial masseter and anterior temporal muscles during unilateral mastication of artificial test foods with different textures in healthy subjects

Objectives

This study aimed to examine the electromyographic activity of superficial masseter and anterior temporal muscles during chewing gum and gummy jelly mastication in healthy subjects to reveal the difference of neuromuscular control of jaw-closing muscles, according to the food texture.

Materials and methods

Electromyographic activity was recorded in 30 adults with Angle Class I occlusion and unimpaired function from the bilateral superficial masseter and anterior temporal muscles during unilateral mastication of two test foods: standardized gummy jelly and color-changeable chewing gum. Differences in normalized electromyographic activity and asymmetry index values between gummy jelly and chewing gum mastication were analyzed during the early, middle, and late phases of mandibular closure. Furthermore, changes among the three closing phases were compared for each test food.

Results

High electromyographic activity of both muscles tended to occur bilaterally during the middle and late closing phases during gummy jelly mastication, but increased muscle activity in the late closing phase was not observed during chewing gum mastication. The asymmetry index of the superficial masseter muscle increased significantly from early to late closure, regardless of the food texture, but it tended to decrease for the anterior temporal muscle during gummy jelly mastication.

Conclusion

The different aspects of the chewing process between the comminution and mixing test measures are necessary to elicit the different human neuromuscular strategies of chewing for different test foods.

Clinical relevance

These characteristic EMG activities of the superficial masseter and anterior temporalis muscles may be used as supporting diagnostic information during patient assessments and a reference during evaluation of masticatory system disharmony or dysfunction.

     

Modulation of matrix metalloproteinase-9 secretion from tumor-associated macrophage-like cells by proteolytically processed laminin-332 (laminin-5)

Macrophages infiltrating tumor tissues (tumor-associated macrophages, TAM) affect the malignant behaviors of tumor cells. We previously reported that monocytes were differentiated into TAM-like cells secreting matrix metalloproteinase (MMP)-9 by co-culture with tumor cells, and that cell adhesion to extracellular matrix (ECM) proteins played a critical role in the differentiation. In this study, we found that the monocyte differentiation was promoted by laminin-332 (laminin-5), a major epithelial ECM component. We also demonstrated that the proteolytic processing of the γ2 chain of laminin-332 was essential for its activity but that the N-terminal short arm of the γ2 chain inhibited MMP-9 secretion. These results indicate that the activity of laminin-332 for monocyte differentiation is dynamically regulated by the proteolytic processing of the γ2 chain.     

The Long Elusive IgM Fc Receptor,FcμR

IgM exists as both a monomer on the surface of B cells and a pentamer secreted by plasma cells. Both pre-immune “natural” and antigen-induced “immune” IgM antibodies are important for protective immunity and for immune regulation of autoimmune processes by recognizing pathogens and self-antigens. Effector proteins interacting with the Fc portion of IgM, such as complement and complement receptors, have thus far been proposed but fail to fully account for the IgM-mediated protection and regulation. A major reason for this deficit in our understanding of IgM function seems to be lack of data on a long elusive Fc receptor for IgM (FcμR). We have recently identified a bona fide FcμR in both humans and mice. In this article we briefly review what we have learned so far about FcμR.     

Health Effects of Drinking Water Produced from Deep Sea Water: A Randomized Double-Blind Controlled Trial

Global trends focus on a balanced intake of foods and beverages to maintain health. Drinking water (MIU; hardness = 88) produced from deep sea water (DSW) collected offshore of Muroto, Japan, is considered healthy. We previously reported that the DSW-based drinking water (RDSW; hardness = 1000) improved human gut health. The aim of this randomized double-blind controlled trial was to assess the effects of MIU on human health. Volunteers were assigned to MIU (n = 41) or mineral water (control) groups (n = 41). Participants consumed 1 L of either water type daily for 12 weeks. A self-administered questionnaire was administered, and stool and urine samples were collected throughout the intervention. We measured the fecal biomarkers of nine short-chain fatty acids (SCFAs) and secretory immunoglobulin A (sIgA), as well as urinary isoflavones. In the MIU group, concentrations of three major SCFAs and sIgA increased postintervention. MIU intake significantly affected one SCFA (butyric acid). The metabolic efficiency of daidzein-to-equol conversion was significantly higher in the MIU group than in the control group throughout the intervention. MIU intake reflected the intestinal environment through increased production of three major SCFAs and sIgA, and accelerated daidzein-to-equol metabolic conversion, suggesting the beneficial health effects of MIU.