Is acetylcholinesterase activity in neorectum after laparoscopic endorectal pull-through method for Hirschsprung’s disease a primary or a secondary condition?

Between 1996 and 2002, 22 cases of Hirschsprung’s disease were treated laparoscopically by endorectal pull-through operation. The proximal margin of the resected bowel materials from these 22 patients were examined histologically by frozen sections at surgery and also after surgery using HampE staining, and complete resection of the aganglionic segment was confirmed. Eleven patients, in whom an informed consent was obtained at randomly, underwent suction biopsy from the pulled-though neorectum after surgery. Of these 11 patients, 2 revealed many AchE-positive nerve fibers in the lamina propria, the muscularis mucosa and around the ganglion cells in the submucosal plexuses. These structural changes were similar to intestinal neuronal dysplasia that was characterized by hyperganglionosis and other neuronal abnormalities. The remaining 9 revealed no AchE activity. Unexpectedly, the two patients showing AchE activity in their neorectum continued to have persistent constipation and were treated with laxatives or glycerin enema. It was suggested that their persistent constipation was caused by intestinal neuronal dysplasia showing an abnormal increase of AchE activity in spite of presence of ganglion cells of the neorectum after surgery, but it was uncertain that they were primary condition as a HaIND or secondary reactions after surgery

Reliability and Validity of the Japanese Version of the Basel Assessment of Adherence to Immunosuppressive Medications Scale in Kidney Transplant Recipients

A valid and reliable instrument that can measure adherence is needed to identify nonadherent patients and to improve adherence. However, there is no validated Japanese self-report instrument to evaluate adherence to immunosuppressive medications for transplant patients. The purpose of this study was to determine the reliability and validity of the Japanese version of the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS).; We translated the BAASIS into Japanese and developed the Japanese version of the BAASIS (J-BAASIS) according to the International Society of Pharmacoeconomics and Outcomes Research task force guidelines. We analyzed the reliability (test-retest reliability and measurement error) and validity of the J-BAASIS (concurrent validity with the medication event monitoring system and the 12-item Medication Adherence Scale) referring to the COSMIN Risk of Bias checklist.; A total of 106 kidney transplant recipients were included in this study. In the analysis of test-retest reliability, Cohen's kappa coefficient was found to be 0.62. In the analysis of measurement error, the positive and negative agreement were 0.78 and 0.84, respectively. In the analysis of concurrent validity with the medication event monitoring system, sensitivity and specificity were 0.84 and 0.90, respectively. In the analysis of concurrent validity with the 12-item Medication Adherence Scale, the point-biserial correlation coefficient for the "medication compliance" subscale was 0.38 (; P; < 0.001).; The J-BAASIS was determined to have good reliability and validity. Using the J-BAASIS to evaluate adherence can help clinicians to identify medication nonadherence and institute appropriate corrective measures to improve transplant outcomes

Intravenous immunoglobulin for maintenance treatment of multifocal motor neuropathy: A multi-center, open-label, 52-week phase 3 trial

Intravenous immunoglobulin (IVIg) therapy is currently the only established treatment in patients with multifocal motor neuropathy (MMN), and many patients have an IVIg‐dependent fluctuation. We aimed to investigate the efficacy and safety of every 3 week IVIg (1.0 g/kg) for 52 weeks. This study was an open‐label phase 3 clinical trial, enrolling 13 MMN patients. After an induction IVIg therapy (0.4 g/kg/d for 5 consecutive days), maintenance dose (1.0 g/kg) was given every 3 weeks for 52 weeks. The major outcome measures were the Medical Research Council (MRC) sum score and hand‐grip strength at week 52. This trial is registered with ClinicalTrials.gov, number NCT01827072. At week 52, 11 of the 13 patients completed the study, and all 11 had a sustained improvement. The mean (SD) MRC sum score was 85.6 (8.7) at the baseline, and 90.6 (12.8) at week 52. The mean grip strength was 39.2 (30.0) kPa at the baseline and 45.2 (32.8) kPa at week 52. Two patients dropped out because of adverse event (dysphagia) and decision of an investigator, respectively. Three patients developed coronary spasm, dysphagia, or inguinal herniation, reported as the serious adverse events, but considered not related with the study drug. The other adverse effects were mild and resolved by the end of the study period. Our results show that maintenance treatment with 1.0 g/kg IVIg every 3 week is safe and efficacious for MMN patients up to 52 weeks. Further studies are required to investigate optimal dose and duration of maintenance IVIg for MMN

Muscleblind-Like 1 Knockout Mice Reveal Novel Splicing Defects in the Myotonic Dystrophy Brain

Myotonic dystrophy type 1 (DM1) is a multi-systemic disorder caused by a CTG trinucleotide repeat expansion (CTGexp) in the DMPK gene. In skeletal muscle, nuclear sequestration of the alternative splicing factor muscleblind-like 1 (MBNL1) explains the majority of the alternative splicing defects observed in the HSALR transgenic mouse model which expresses a pathogenic range CTGexp. In the present study, we addressed the possibility that MBNL1 sequestration by CUGexp RNA also contributes to splicing defects in the mammalian brain. We examined RNA from the brains of homozygous Mbnl1ΔE3/ΔE3 knockout mice using splicing-sensitive microarrays. We used RT-PCR to validate a subset of alternative cassette exons identified by microarray analysis with brain tissues from Mbnl1ΔE3/ΔE3 knockout mice and post-mortem DM1 patients. Surprisingly, splicing-sensitive microarray analysis of Mbnl1ΔE3/ΔE3 brains yielded only 14 candidates for mis-spliced exons. While we confirmed that several of these splicing events are perturbed in both Mbnl1 knockout and DM1 brains, the extent of splicing mis-regulation in the mouse model was significantly less than observed in DM1. Additionally, several alternative exons, including Grin1 exon 4, App exon 7 and Mapt exons 3 and 9, which have previously been reported to be aberrantly spliced in human DM1 brain, were spliced normally in the Mbnl1 knockout brain. The sequestration of MBNL1 by CUGexp RNA results in some of the aberrant splicing events in the DM1 brain. However, we conclude that other factors, possibly other MBNL proteins, likely contribute to splicing mis-regulation in the DM1 brain

Development of Effective Cancer Vaccine Using Targeting System of Antigen Protein to APCs.

PURPOSE: To develop a novel cancer vaccine using the targeting system of antigen protein to antigen-presenting cells (APCs) for efficient and safe cancer therapy. METHODS: The novel delivery system was constructed with antigen protein, benzalkonium chloride (BK), and γ-polyglutamic acid (γ-PGA), using ovalbumin (OVA) as a model antigen protein and evaluating its immune induction effects and utilities for cancer vaccine. RESULTS: BK and γ-PGA enabled encapsulation of OVA and formed stable anionic particles at nanoscale, OVA/BK/γ-PGA complex. Complex was taken up by dendritic cell line DC2.4 cells efficiently. We subcutaneously administered the complex to mice and examined induction of IgGs. The complex induced not only Th2-type immunoglobulins but also Th1-type immunoglobulins. OVA/BK/γ-PGA complex inhibited tumor growth of E.G7 cells expressing OVA regularly; administered OVA/BK/γ-PGA complex completely rejected tumor cells. CONCLUSION: The novel vaccine could be platform technology for a cancer vaccine

MEASUREMENT OF WAVY SURFACE OSCILLATIONS ON LIQUID METAL LITHIUM JET FOR IFMIF TARGET

ABSTRACT This paper reports on the measurement of surface waves on a liquid lithium jet and results of the study of the Li target at the International Fusion Materials Irradiation Facility (IFMIF). The characteristics of the surface waves at the nozzle exit and just downstream of it were examined experimentally, since the initial growth of free surface waves exerts a definite influence on surface behavior in the downstream region. Experiments were carried out using the lithium circulation loop at Osaka University, with a focus on the free surface oscillations. These oscillations were measured using an electrocontact probe apparatus, which detects electric contacts between the probe tip and the Li surface. The apparatus was installed 15 mm downstream from the nozzle exit and was scanned along the liquid-depth direction. The contact signal recorded in the experiment was analyzed, and the wave amplitude and frequency of the surface waves were examined