Disruption of neurovascular unit prior to motor neuron degeneration in amyotrophic lateral sclerosis

Recent reports suggest that functional or structural defect of vascular components are implicated in amyotrophic lateral sclerosis (ALS) pathology. In the present study, we examined a possible change of the neurovascular unit consisting of endothelium (PCAM-1), tight junction (occludin), and basement membrane (collagen IV) in relation to a possible activation of MMP-9 in ALS patients and ALS model mice. We found that the damage in the neurovascular unit was more prominent in the outer side and preferentially in the anterior horn of ALS model mice. This damage occurred prior to motor neuron degeneration and was accompanied by MMP-9 up-regulation. We also found the dissociation between the PCAM-1-positive endothelium and GFAP-positive astrocyte foot processes in both humans and the animal model of ALS. The present results indicate that perivascular damage precedes the sequential changes of the disease, which are held in common between humans and the animal model of ALS, suggesting that the neurovascular unit is a potential target for therapeutic intervention in ALS.     

Primary thymic adenocarcinoma coexisting with type AB thymoma: a rare case with long-term survival

Thymic carcinoma is a rare tumor. The most common histological subtype is squamous cell carcinoma, and only a few cases of thymic adenocarcinoma have been reported. A case of papillary adenocarcinoma of thymic origin that coexisted with type AB thymoma as a separate nodule is presented herein. The patient was found to have an abnormal mediastinal shadow on chest X-ray. A computed tomography scan revealed a round, 6.5-cm-diameter mass in the right anterior mediastinum. The preoperative diagnosis was thymoma, and thymothymectomy was performed. On pathological examination, two tumors, which were diagnosed as papillary adenocarcinoma and type AB thymoma, respectively, were present in the thymus without any connection with each other. The patient has been alive without any signs of recurrence for 11 years after surgery. We diagnosed the adenocarcinoma in this case was a primary thymic carcinoma.     

Beneficial effect of a diet containing heat-killed Lactobacillus paracasei K71 on adult type atopic dermatitis

The purpose of this study was to investigate the clinical effect of a supplementary diet containing heat-killed lactic acid bacterium Lactobacillus paracasei K71 (LAB diet) on adult patients with atopic dermatitis (AD). A randomized, double-blind, placebo-controlled study was conducted in 34 adult type AD subjects who were treated with conventional topical corticosteroid and tacrolimus. LAB diet or placebo was added over 12 weeks. The primary end-point was the clinical severity of AD which was evaluated by a severity scoring system proposed by the guideline of the Japanese Dermatological Association. The effect was also secondarily evaluated by itch scores of visual analog scales (VAS), quality-of-life (QOL) impairment scores of Skindex 16 and consumption amounts of topical therapeutics. Data on these four assessment variables were collected at baseline and at week 4, 8 and 12. Within the study population, the skin severity scores were significantly decreased from baseline at week 8 (P<0.05) and at week 12 (P<0.01) in the LAB diet group but not in the placebo group. Influence of LAB diet on itch scores or QOL impairment scores was not evident. The consumption of topical therapeutics in the placebo group was 1.9-times greater in total amount compared with the corresponding value in the LAB diet group during the intervention period, although there was no significant difference. No LAB diet- or placebo-related adverse events were observed. We concluded that the LAB diet may have some benefits as a complementary therapy for adult AD patients who are managed with the conventional treatment.     

Resolution of SPECT-determined anterior cerebral hypoperfusion correlated with maintenance ECT-derived improvement in residual symptoms in a case of late-life psychotic depression

A 70-year-old widow with recurrent psychotic depression was successfully treated with maintenance electroconvulsive therapy (ECT) for 4 years up to the present. Anterior cerebral hypoperfusion visualized by single photon emission computerized tomography (SPECT) before ECT persisted (second SPECT study 14 days after the last ECT session) despite a response to the first course of acute ECT. Only mild symptoms remained. Relapse occurred 2 weeks after the post-ECT SPECT study. The hypoperfusion improved after response to a second course of acute ECT (per SPECT 5 days after the last ECT session), and perfusion was normalized after 2-year maintenance ECT (per SPECT 14 days after the last ECT session). The normalization coincided with improvement in depressive symptoms remaining after the second course of acute ECT. We speculate that the effectiveness of maintenance ECT might have been in part the result of the improvement in residual symptoms and that resolution of the persistent anterior hypoperfusion, which might underlie medical refractoriness, illness chronicity, and relapse tendency in late-life depression, might have been associated with the improvement in residual symptoms achieved by maintenance ECT.     

Mutant interleukin-4/13 signaling blockade successfully suppresses acute phase inflammation

Atopic dermatitis (AD) is a chronic disease with Th2-type-cytokine dominant profile. Several cytokines and related peptides had been tried for the treatment of AD but with unsuccessful results; a part of the reason is the limitation of their biological half time. We have recently developed a highly efficient mouse dominant negative IL-4/IL-13 DNA vaccine, which blocks both IL-4 and IL-13 signal transductions, resulting in the amelioration of atopic reaction. At the next step, the further consistent protein supplementation system is required for stable suppression of allergic reaction. To examine the effects of mutant IL-4/13 protein supplementation from skin, a keratinocyte-specific dominant negative IL-4-transgenic mouse line (IL-4DM) was established. The anti-inflammatory function was evaluated measuring ear thickness and analyzing histological change in mice AD model induced by repeated elicitation of oxazolone. In IL-4DM, ear thickness was suppressed significantly in the early phase of the elicitation schedule of contact hypersensitivity response. We next transplanted IL-4DM skin to normal control mice, and investigated effects in inflammatory reactions. In IL-4DM-skin-grafted mice, the inflammatory response was suppressed significantly similarly in the early phase accompanied with lesional suppressed Th2-type-cytokine signaling transduction. IL-4DM skin has the anti-inflammatory function especially in the acute phase of AD. Although there are several issues to be addressed for human application, the present results implicated that the gene manipulated skin transplantation is a potent therapeutic strategy to control allergic reactions.     

Impact of pediatric intestinal transplantation on intestinal failure in Japan: findings based on the Japanese intestinal transplant registry

Introduction

We assessed the impact of intestinal transplantation on Japanese pediatric patients with intestinal failure with data from the Japanese intestinal transplant registry.

Methods

Standardized forms were sent to all known intestinal transplantation programs, requesting information on transplants performed between 1996 and June 30, 2012. Patients younger than 18 years were analyzed. Patient and graft survival estimates were obtained using the Kaplan–Meier method.

Results

Of the 14 intestinal transplants, 4 were deceased and 10 were living donor transplants. The primary indications were: short gut syndrome (n = 7), intestinal functional disorder (n = 6), and re-transplantation (n = 1). The overall 1- and 5-year patient survival rates were 77 and 57 %, respectively. In transplants performed after 2006 (n = 6), the one-year patient survival rate was 83 %, and the 5-year survival rate was 83 %. Graft one- and 5-year survival rates were 83 and 83 %, respectively. The living-related transplant survival rate was 80 % at 1 year and 68 % at 2 years, compared to 67 and 67 % for cadaveric transplant recipients. There were no statistically significant differences in patient (p = 0.88) and graft (p = 0.76) survival rates between living donor and cadaveric transplant recipients. All current survivors discontinued PN.

Conclusion

Intestinal transplantation has become an effective therapy for patients with intestinal failure who cannot tolerate PN.