Tomohiko Shimo

Stimulation of liver regeneration after hepatectomy in mice by injection of bone marrow mesenchymal stem cells via the portal vein.

AIM To investigate whether mouse bone marrow mesenchymal stem cells (BMC) stimulate liver regeneration after partial hepatectomy. METHODS Isolated BMCs were purified by density gradient centrifugation. We performed a 70% hepatectomy in male BALB/c mice followed by injection of BMCs into the portal vein (PV-BMC group), or the tail vein (IV-BMC group), or of saline into the portal vein (control group). RESULTS The wet weight of the liver remnant increased significantly in the PV-BMC group at 3 and 5 days after hepatectomy compared with the IV-BMC and control groups. The Ki-67 labeling index revealed that the increase to result from stimulation of DNA synthesis. The constitutive interleukin-6 and hepatocyte growth factor mRNAs in the remnant liver tended to increase in the PV-BMC group at 3 days after hepatectomy. CONCLUSIONS These results demonstrated that BMC injection into the portal vein enhanced liver growth after partial hepatectomy in mice.

Predictive value of IgE/IgG4 antibody ratio in children with egg allergy

BackgroundThe aim of this study was to investigate the role of specific IgG4 antibodies to hen’s egg white and determine their utility as a marker for the outcome of oral challenge test in children sensitized to hen’s eggMethodsThe hen’s egg oral food challenge test was performed in 105 sensitized children without atopic dermatitis, and the titers of egg white-specific immunoglobulin G4 (IgG4) and immunoglobulin E (IgE) antibodies were measured. To set the cut-off values of IgG4, IgE, and the IgE/IgG4 ratio for predicting positive results in oral challenges, receiver operating characteristic curves were plotted and the area under the curves (AUC) were calculated.ResultsSixty-four of 105 oral challenges with whole eggs were assessed as positive. The AUC for IgE, IgG4, and IgE/IgG4 for the prediction of positive results were 0.609, 0.724, and 0.847, respectively. Thus, the IgE/IgG4 ratio generated significantly higher specificity, sensitivity, positive predictive value (%), and negative predictive value (%) than the individual IgE and IgG4. The negative predictive value of the IgE/IgG4 ratio was 90% at a value of 1.ConclusionsWe have demonstrated that the egg white-specific serum IgE/IgG4 ratio is important for predicting reactivity to egg during food challenges.

A Novel Nuclear Factor κB Inhibitor, Dehydroxymethylepoxyquinomicin, Ameliorates Puromycin Aminonucleoside-Induced Nephrosis in Mice

Background/Aims: Minimal-change nephrotic syndrome (MCNS) is a kidney disease defined by selective proteinuria and hypoalbuminemia occurring in the absence of cellular glomerular infiltrates or immunoglobulin deposits. Recent observations suggest that nuclear factor κB (NF-κB) of podocyte is strongly associated with the development of proteinuria in MCNS. Dehydroxymethylepoxyquinomicin (DHMEQ) is a novel NF-κB inhibitor that potently inhibits DNA-binding activity of NF-κB, resulting in several therapeutic effects in various pathological conditions. We conducted this study to ask whether DHMEQ may ameliorate the nephrosis in mice induced by puromycin aminonucleoside (PAN), which is considered to be an animal model for MCNS. Methods/Results: Pretreatment with DHMEQ alleviated the proteinuria and reversed the serum abnormalities in mice nephrosis induced by 450 mg/kg of PAN. Increased serum interleukin-6 level in PAN-induced nephrosis was also completely suppressed by DHMEQ. Electron microscopic analyses of glo-meruli indicated that DHMEQ can inhibit the podocyte foot process effacement via blocking the translocation of podocyte NF-κB from cytoplasm to nucleus. Conclusions: These results suggest that DHMEQ can be a potential therapeutic agent for MCNS.

Cause of uric acid stones in rotavirus-associated gastroenteritis

gastroenteritis. Fujita et al. suspected that there may be an association between renal hypouricemia and uric acid stone formation in patients with HRV-associated gastroenteritis due to the number of cases, including our own, that have been reported, primarily in Japan (2-6). Urate urolithiasis is rarely seen in children. It is generally associated with an increased urinary concentration of urate and its subsequent deposition. Hyperuricuria and uric acid nephrolithiasis are mainly caused by the increased excretion or disturbed reabsorption of uric acid by the renal proximal tubular cells: the former is accompanied with hyperurice- mia, while the latter may be associated with hypouricemia. Hyperuricemia is observed in children with tumor lysis syndrome, Lesch-Nyhan syndrome and hypoxanthine-

Pulmonary sclerosing hemangioma with lymph node metastasis: A case report and literature review

Pulmonary sclerosing hemangioma (SH) is an uncommon benign or low-grade malignant tumor. Multicentric SH and SH with lymph node metastasis have rarely been reported. The present report describes a case of pulmonary SH with lymph node metastasis in a middle-aged female. A nodule was found incidentally in the lower left lung. The patient underwent left lower pulmonary lobectomy and lymph node dissection. Histologically, the nodule demonstrated the characteristic features of SH and one of the resected lymph nodes contained a metastasis of this tumor. Thus, pulmonary SH has the potential to metastasize, a potential not suggested by histological features.

Change in urinary 8-hydroxydeoxyguanosine in idiopathic nephrotic syndrome

Sirs, We read with great interest the article entitled “Antioxidant status of children with idiopathic nephrotic syndrome” by Mishra et al. which was recently published in Pediatric Nephrology [1]. Oxidative stress (OS), defined as a disturbance in the reactive oxygen species (ROS) and antioxidant balance, can result either from low levels of antioxidants and/or from an increased production of ROS. It has been postulated that childhood idiopathic nephrotic syndrome (INS) is associated with OS due to increased levels of ROS and decreased levels of antioxidants [2], although results to the contradictory have been published [3]. Mishra et al. [1] report evidence of OS and impaired antioxidant defense during acute INS. 8-Hydroxydeoxyguanosine (8-OHdG), which originates from damaged DNA repaired by non-specific endonucleases and specific glycosylases and is eliminated into the urine, is currently accepted as a sensitive biomarker for oxidative DNA damage, as OS leads to the damage of not only lipids and proteins, but also nucleic acids [4]. In order to investigate oxidative cellular damage in INS, we are currently performing serial measurements of urinary 8-OHdG using a novel analyzer (model No. ICR001; Techno-Medica, Yokohama, Japan). Here, we report changes in urinary 8-OHdG during five nephrotic relapses in four patients with INS (ages 3, 4, 15, and 20 years, respectively) and three patients with poststreptococcal acute glomerulonephritis (PSAGN; ages 4, 7, and 16 years, respectively). As shown in Fig. 1, the urinary levels of 8-OHdG (ng/mL) corrected by creatinine (ng/mg Cr) in patients with INS were significantly higher in patients with nephrotic relapse (active phase) than in those in remission (convalescent phase; p=0.04, Wilcoxon signed-rank test); in contrast, there was no significant change between the active and convalescent phase in those patients with PSAGN (p=0.59). Thus, our finding of oxidative DNA damage assessed by urinary 8-OHdG is in agreement with the observation by Mishra et al. [1] that OS in INS is characterized by increased levels of ROS with decreased levels of antioxidant in the active phase and by normalized ROS in the

Key for Successful Home-Based Slow Oral Immunotherapy in Children with Egg Allergy: Age and Sensitivity

Background: Oral immunotherapy (OIT) has been recognized as a promising therapy for children with food allergy. However a part of applied patients was not able to increase doses of allergic food. Since a clear standard for the appropriate patient selection for OIT has not been established, we tried to determine the indication criteria for when and/or to whom OIT should be applied. Method: We retrospectively reviewed the medical records of 82 children treated by home-based slow OIT which shows the administration of baked eggs orally every 2-3 days at home for two months as maintenance dose after open food challenge and statistically analyzed their clinical courses to identify the prognostic factors associated with a successful result. We applied the variables such as age, sex, symptoms during OIT, initial dose when starting OIT, specific IgE level and dislike of eggs, to a multivariate stepwise logistic regression analysis. Results: A total of 40 (56%) children reached remission in the OIT trial for a median of 213 days without severer allergic reactions, the remaining 31 (44%) could not reach the remission stage. We found the clinical course of the patients to be significantly associated with age and the initial dose of OIT. The children under 4 years of age or who could ingest larger portions (more than 1g if under 4 years, and 6g if over 5 years) as an initial dose were found to be the best candidates for OIT. Conclusions: This study revealed that home-based slow OIT caused almost successful results without severe allergic results in the children with egg allergy, and especially when starting before 5 years of age it is remarkable even if their initial doses were limited. This is the first report to contribute to the establishment of the indication criteria for home-based OIT.

Dehydroxymethylepoxyquinomicin (DHMEQ) can suppress tumour necrosis factor-α production in lipopolysaccharide-injected mice, resulting in rescuing mice from death in vivo

Dehydroxymethylepoxyquinomicin (DHMEQ), a new nuclear factor (NF)‐κB inhibitor, has several beneficial effects, including the suppression of tumour growth and anti‐inflammatory effects. DHMEQ can also suppress the production of tumour necrosis factor (TNF)‐α induced by lipopolysaccharide (LPS) in vitro. In the present study, we examine the effects of DHMEQ on TNF‐α production in vivo and on the survival of mice injected with LPS. When DHMEQ was injected into mice 2 h before LPS injection, the survival of the LPS‐injected mice was prolonged. When DHMEQ was injected twice (2 h before LPS injection and the day after LPS injection), all the mice were rescued. The injection of DHMEQ 1 h after LPS injection and the day after LPS injection also resulted in the rescue of all mice. The serum levels of TNF‐α in the mice that received both LPS and DHMEQ were suppressed compared to the mice that received only LPS. These results suggest that DHMEQ can be utilized for the prevention and treatment of endotoxin shock.

A nuclear factor-κB inhibitor, dehydroxymethylepoxyquinomicin, ameliorates GVHD in allogeneic bone marrow transplantation

GVHD is a crucial mortality factor in allogeneic bone marrow transplantation (ABMT). In this paper, we show that dehydroxymethylepoxyquinomicin (DHMEQ), a novel inhibitor of nuclear factor-κB, suppresses GVHD, resulting in an improved mortality rate in a mouse ABMT model. Bone marrow cells from C57BL/6 mice (B6 mice) were transplanted into lethally irradiated BALB/c mice. Two weeks later, spleen cells from B6 mice were transplanted into the irradiated BALB/c mice. From one week after the injection of spleen cells, when the mice started to show GVHD, the mice were also injected intraperitoneally daily with DHMEQ or vehicle only (DMSO) for 4 weeks. By 80 days after the ABMT, 6/14 of the vehicle-injected mice (43%) had died because of GVHD, whereas all DHMEQ-injected mice survived this observation period and developed milder GVHD than the vehicle-injected mice. When regulatory T cells were reduced by the injection of anti-folate receptor 4 (FR4) antibody, the effects of DHMEQ were reduced. These findings suggest that administration of DHMEQ could become a new strategy for preventing fatalities from GVHD.

An autopsy case of pulmonary fissure induced by zygomycosis

For immunodeficient patients, fungi are life-threatening pathogens. In this paper, we present an autopsy case of combined zygomycosis and aspergillosis. A female in her 70s on chronic hemodialysis was admitted to a hospital suffering bloody sputum, dyspnea, and fever, probably due to perinuclear anti-neutrophil cytoplasmic antibody-related vasculitis. Antibiotics were administered and immunosuppressive therapy was started, resulting in an improvement in her condition. Pneumonia later developed, followed by pulmonary bleeding and intractable pneumothorax from which she ultimately died. On autopsy, the upper lobe of the left lung was found to have hemorrhagic necrosis and showed a large longitudinal fissure. Microscopically, Zygomycota were observed in both the lungs and heart, while Aspergillus was found in the middle lobe of the right lung. Zygomycosis, which usually has a poor prognosis, is assumed to have induced hemorrhagic infarction of the lungs, inducing pulmonary bleeding and necrosis, despite the use of lipid formulations of amphotericin B, which are effective medicines against Zygomycota.