Therapeutic potential of mature adipocyte-derived dedifferentiated fat cells for inflammatory bowel disease.

PURPOSE: Our previous studies demonstrated that mature adipocyte-derived dedifferentiated fat (DFAT) cells possess similar multipotency as mesenchymal stem cells. Here, we examined the immunoregulatory potential of DFAT cells in vitro and the therapeutic effect of DFAT cell transplantation in a mouse inflammatory bowel disease (IBD) model. METHODS: The effect of DFAT cell co-culture on T cell proliferation and expression of immunosuppression-related genes in DFAT cells were evaluated. To create IBD, CD4+CD45RBhigh T cells were intraperitoneally injected into SCID mice. One week later, DFAT cells (1 × 105, DFAT group) or saline (Control group) were intraperitoneally injected. Subsequently bodyweight was measured every week and IBD clinical and histological scores were evaluated at 5 weeks after T cell administration. RESULTS: The T cell proliferation was inhibited by co-cultured DFAT cells in a cell density-dependent manner. Gene expression of TRAIL, IDO1, and NOS2 in DFAT cells was upregulated by TNFα stimulation. DFAT group improved IBD-associated weight loss, IBD clinical and histological scores compared to Control group. CONCLUSION: DFAT cells possess immunoregulatory potential and the cell transplantation promoted recovery from colon damage and improved clinical symptoms in the IBD model. DFAT cells could play an important role in the treatment of IBD.

Obliterative cholangiopathy in acquired cystic biliary atresia type III after cyst perforation: a case report.

BACKGROUND: In biliary atresia, the disease process of obliterative cholangiopathy may begin in the perinatal period; however, no chronological evidence exists on how the cholangiopathy progresses to biliary obliteration. This is the first acquired case with the final diagnosis of type III cystic biliary atresia with an extrahepatic biliary cyst which showed the progression of obliterative cholangiopathy in chronological order after birth. CASE PRESENTATION: An 81-day-old girl presented with acute abdominal distress due to bilious peritonitis caused by biliary cyst perforation, for which she underwent emergency biliary drainage. Postoperative images showed a dilated common bile duct and hepatic ducts bilaterally, with flow of the contrast medium to the duodenum through the dilated common bile duct. Biochemistry of the bile collected during and after the operation revealed elevated levels of pancreatic enzymes in the bile from the gallbladder. The patient was diagnosed as having a congenital choledochal cyst and underwent laparotomy at 120 days of age which revealed that she had pancreaticobiliary maljunction. The biliary cyst was resected at the narrow portion just above the junction with the main pancreatic duct. During dissection up to the hepatic hilum, we found that the hilar hepatic ducts were bilaterally replaced by fibrous tissue and were obstructed, leading to a diagnosis of type III a1, µ biliary atresia. The fibrous tissue was excised, and hepatic portoenterostomy was performed according to the Kasai procedure. The patient's postoperative course was uneventful and the jaundice resolved within 1 month. She has had normal liver function tests with no episode of cholangitis for 3 years after discharge. CONCLUSIONS: We demonstrated the process of acquired type III biliary atresia in a patient with cystic biliary atresia and biliary cyst perforation. To the best of our knowledge, this is the first case of acquired cystic biliary atresia showing chronological progression of the course of obliterative cholangiopathy, providing a better understanding of the development of type III biliary atresia as an acquired disease.

[The price-based certainty of purchase influences consumer behavior for discount].

Tversky & Kahneman (1981) reported that most participants decided to drive when they could save money on a low-price good as compared to when they could save on a high-price good, even though the discount prices were same. Although this irrational decision making has been interpreted as a rate-dependent estimation of value (prospect theory), this study newly proposes that it can be explained by the certainty of purchase based on the price of goods. Experiment 1 replicated the previously reported difference in decision making, and additionally demonstrated that participants' certainty of purchase was lower for a high- than a low-price good. When it was emphasized that participants' intention to purchase high- and low-price goods were equally sure, decision making did not significantly differ (Experiment 2). Furthermore, decision making differed based only on the certainty of purchase even,when prices of goods were-same (Experiment 3). Consumers' decision making may be rather rational, depending straightforwardly on the certainty of purchase that is susceptible to price.

Evaluation of the efficacy of incision and drainage versus hainosankyuto treatment for perianal abscess in infants: a multicenter study.

PURPOSE: We retrospectively compared the short-term outcomes between incision and drainage (ID) and hainosankyuto (TJ-122, Tsumura & Co, Tokyo, Japan) treatment for perianal abscess (PA) in infants. METHODS: We retrospectively examined 48 consecutive patients (median age 129 days; range 19-330 days) who presented with PA over a 3 year period. Group 1 comprised 26 patients who were treated with ID at presentation, and Group 2 comprised 22 patients who were treated with oral TJ-122 at presentation; oral treatment was continued until the disappearance of purulent discharge and resolution of induration at the abscess site. RESULTS: PAs were identified in all 48 patients at presentation. The median duration of follow-up was 26 months (range 13-40 months). At presentation, there were no differences in the gender, age, birth weight, duration of symptoms, skin erosion or prevalence of diarrhea between the two groups. Purulent discharge resolved within a median period of 26 days (range 7-42 days) in Group 2, but persisted for 40 days (range 4-196 days) in Group 1. The induration resolved within a median period of 39 days (range 7-91 days) in Group 2, but persisted for 70 days (range 4-308 days) in Group 1 (p = 0.04). CONCLUSIONS: TJ-122 treatment was more beneficial than ID in treating PA in infants.

Identification of aberrant methylation regions in neuroblastoma by screening of tissue-specific differentially methylated regions.

BACKGROUND: The identification of tissue-specific differentially methylated regions (tDMRs) is key to our understanding of mammalian development. Research has indicated that tDMRs are aberrantly methylated in cancer and may affect the oncogenic process. PROCEDURE: We used the MassARRAY EpiTYPER system to determine the quantitative methylation levels of seven neuroblastomas (NBs) and two control adrenal medullas at 12 conserved tDMRs. A second sample set of 19 NBs was also analyzed. Statistical analysis was carried out to determine the relationship of the quantitative methylation levels to other prognostic factors in these sample sets. RESULTS: Screening of 12 tDMRs revealed 2 genomic regions (SLC16A5 and ZNF206) with frequent aberrant methylation patterns in NB. The methylation levels of SLC16A5 and ZNF206 were low compared to the control adrenal medullas. The SLC16A5 methylation level (cut-off point, 13.25%) was associated with age at diagnosis, disease stage, and Shimada classification but not with MYCN amplification. The ZNF206 methylation level (cut-off point, 68.80%) was associated with all of the prognostic factors analyzed. Although the methylation levels at these regions did not reach statistical significance in their association with prognosis in mono-variant analysis, patients with both hypomethylation of SLC16A5 and hypermethylation of ZNF206 had a significantly prolonged event-free survival, when these two variables were analyzed together. CONCLUSIONS: We demonstrated that two tDMRs frequently displayed altered methylation patterns in the NB genome, suggesting their distinct involvement in NB development/differentiation. The combined analysis of these two regions could serve as a diagnostic biomarker for poor clinical outcome.

Anaplastic sarcoma of the kidney: case report and literature review.

Anaplastic sarcoma of the kidney (ASK) is a relatively newly recognized pediatric renal tumor. The present patient, a 13-year-old boy with a large renal mass, underwent surgery. Pathological findings showed proliferation of short spindle-shaped cells with anaplastic features including multiple foci in hyaline cartilage. Complex chromosomal abnormalities were detected in the tumor cells. Postoperative chemotherapy with the regimen for Ewing's sarcoma achieved complete remission but the tumor recurred and the patient died during re-induction chemotherapy. Autopsy indicated the cause of death as duodenal hemorrhage. Because there were no viable tumor cells, the recurrent tumor was considered to have been completely cured by chemotherapy. ASK is a very rare tumor, of unknown pathogenesis, and no standard treatment has yet been established, but the tumor cells may be responsive to chemotherapy. Further study is needed to establish the optimal treatment strategy.

Annexin A4 is a possible biomarker for cisplatin susceptibility of malignant mesothelioma cells.

Mesothelioma is a highly malignant tumor with a poor prognosis and limited treatment options. Although cisplatin (CDDP) is an effective anticancer drug, its response rate is only 20%. Therefore, discovery of biomarkers is desirable to distinguish the CDDP-susceptible versus resistant cases. To this end, differential proteome analysis was performed to distinguish between mesothelioma cells of different CDDP susceptibilities, and this revealed that expression of annexin A4 (ANXA4) protein was higher in CDDP-resistant cells than in CDDP-susceptible cells. Furthermore, ANXA4 expression levels were higher in human clinical malignant mesothelioma tissues than in benign mesothelioma and normal mesothelial tissues. Finally, increased susceptibility was observed following gene knockdown of ANXA4 in mesothelioma cells, whereas the opposite effect was observed following transfection of an ANXA4 plasmid. These results suggest that ANXA4 has a regulatory function related to the cisplatin susceptibility of mesothelioma cells and that it could be a biomarker for CDDP susceptibility in pathological diagnoses.

A Pediatric Case of Autism Spectrum Disorder With a Prostatic Abscess.

There are few reports of prostatic and periprostatic abscesses in children, and diagnosis is often difficult due to the lack of early symptoms. In addition, children with autism spectrum disorder may have difficulty reporting symptoms, with and without cognitive impairments. This article reports the case of a five-year-old boy with autism spectrum disorder and multiple prostatic abscesses caused by Pseudomonas aeruginosa. He also had various vitamin and mineral deficiencies, presumably related to an unbalanced diet. The patient was treated with antibiotics, vitamins, and trace elements. After his blood vitamin and trace element levels returned to normal, he experienced no fever or relapse. The cause of this prostatic abscess was suggested to involve vitamin and trace element deficiencies.

The clinical course in pediatric solid tumor patients with focal nodular hyperplasia of the liver.

BACKGROUND: Focal nodular hyperplasia (FNH) of the liver is a rare benign lesion that may be related to the vascular and hepatic damage induced by completion of tumor therapy and a reaction to localized vascular abnormality. The aim of this study was to analyze the clinical course in pediatric solid tumor patients with FNH. METHODS: We analyzed thirty-two patients with pediatric solid tumors who received multiagent chemotherapy (15 advanced neuroblastomas, 7 hepatoblastomas, 5 rhabdomyosarcomas, 2 nephroblastomas, 1 rhabdoid tumor of the kidney, 1 clear cell sarcoma of the kidney and 1 pancreatoblastoma). All of them had been previously treated at our hospital, and have been alive for over 3 years without recurrence. RESULTS: FNH lesions were discovered in three (9.4%) of 32 patients, and were neuroblastoma (NB) stage 4. All 3 patients received induction chemotherapy and high-dose alkylating agents, and developed grade 3 (National Cancer Institute Common Toxicity Criteria; NCI-CTC) liver dysfunction during completion of tumor therapy without veno-occlusive disease. Two of the 3 patients received the same induction chemotherapy and high doses of alkylating agents with total body irradiation for cytoreductive agents prior to peripheral blood cell transplantation. FNH lesions in both female patients who received estrogen replacement therapy after completion of tumor therapy have expanded and are increasing. CONCLUSION: FNH appears to be a late complication of iatrogenic disease in NB stage 4 patients. The therapeutic agents for NB stage 4 and estrogen replacement therapy should be considered as risk factors for the development of FNH.

Effect of combined treatment with FK506, FTY720, and ex vivo graft irradiation in rat small bowel transplantation: expression of mucosal addressin cell adhesion molecule-1.

We studied the effect of the combined treatment with FK506, FTY720, and ex vivo graft irradiation. Five groups of SBT animals were studied on days 3, 5, and 7 after operation (untreated, FK506, FTY720, FK506 + FTY720, FK506 + FTY720 + irradiation). Indirect immunoperoxidase staining was performed against CD4 and MAdCAM-1. The numbers of CD4 positive cells in allografts were also analyzed by flow cytometry. The graft survival was prolonged in all of the FK506- and FTY720-treated groups. SBT allografts treated by FK506 and FTY720 demonstrated less infiltration of CD4 positive cells, but the irradiation group did not show any effects on its expression. In FK506- and FTY720-treated groups, MAdCAM-1 expression on the HEVs in PPs was up-regulated, and its expression on the ECVs in the LP was down-regulated compared with other allograft groups. Irradiation did not show any effects on MAdCAM-1 expression on both HEVs in PPs and ECVs in LP. FK506 and FTY720 prevented the infiltration of CD4 positive cells, the down-regulation of MAdCAM-1 expression on HEVs in PPs, and the up-regulation of MAdCAM-1 expression on ECVs in LP during the early phase of SBT.

Usefulness of power Doppler ultrasonography and superparamagnetic iron oxide enhanced magnetic resonance imaging for diagnosis of focal nodular hyperplasia of the liver after treatment of neuroblastoma.

Focal nodular hyperplasia (FNH) of the liver is rare in children, and it is usually diagnosed through a biopsy of the liver or hepatectomy. The authors report a case of a 10-year-old girl with multiple focal nodular hyperplasia lesions of the liver after the completion of tumor therapy for advanced neuroblastoma, and review the usefulness of the combination of power Doppler ultrasonography (US) and superparamagnetic iron oxide (SPIO) enhanced magnetic resonance imaging (MRI) for the diagnosis of FNH without a biopsy of the liver or hepatectomy.

Novel protein engineering strategy for creating highly receptor-selective mutant TNFs.

Tumor necrosis factor (TNF) plays important roles in host defense and in preventing tumor formation by acting via its receptors, TNFR1 and TNFR2, functions of which are less understood. To this end, we have been isolating TNF receptor-selective mutants using phage display technique. However, generation of a phage library with large repertoire (>10(8)) is impeded by the limited transformation efficiency of Escherichia coli. Therefore, it is currently difficult to create a mutant library containing amino acid substitutions in more than seven residues. To overcome this problem, here we have used two different TNF mutant libraries, each containing random substitutions at six selected amino acid residues, and utilized a gene shuffling method to construct a randomized mutant library containing substitutions at 12 different amino acid residues of TNF. Consequently, using this library, we identified TNF mutants with greater receptor-selectivity and enhanced receptor-specific bioactivity than the existing mutants.

Fourier transform infrared spectroscopic study of water-in-supercritical CO2 microemulsion as a function of water content.

Fourier transform infrared (FT-IR) spectrum of water-in-supercritical CO(2) microemulsion was measured at 60 degrees C and 30.0 MPa over a wide range of water/CO(2) ratio from 0.0 to 1.2 wt % to study the distribution of water into CO(2), interfacial area around surfactant headgroup, and core water pool. The microemulsion was stabilized by sodium bis(1H,1H,2H, 2H-heptadecafluorodecyl)-2-sulfosuccinate [8FS(EO)(2)] equimolarly mixed with sodium 1-oxo-1-[4-(tridecafluorohexyl)phenyl]-2-hexanesulfonate [FC6HC4] or with poly(ethylene glycol) 2,6,8-trimethyl-4-nonyl ether [TMN-6]. The signal area of the O-H stretching band of water suggested that the number of water molecules in the microemulsion increases linearly with the water/CO(2) ratio, except for a slow initial increase below 0.4 wt % due to a part of water dissolved in CO(2). The amount of water in CO(2) was evaluated by decomposing the bending band of water into two components, one at lower frequency ascribed to water in CO(2) and the other at higher frequency to water in the microemulsion. The decomposition confirmed that CO(2) is saturated with water at the water content of 0.4 wt %. It was also revealed, from the symmetric SO stretching frequency of the surfactant, that the sulfonate headgroup is completely hydrated at the water/CO(2) ratio of 0.4-0.5 wt %. The results demonstrated that water is introduced preferentially into CO(2) and the interfacial area at small water content, and then is loaded into the micelle core after the saturation of CO(2) with water and the full hydration of the surfactant headgroup.

Sutureless enterostomy for extremely low birth weight infants.

OBJECTIVE: In recent years, improved survival rates of extremely low birth weight infants (ELBWIs) have led to an increasing number of enterostomy performed for those with meconium obstruction of prematurity (MOP)1,2, spontaneous intestinal perforation (SIP)3,4. To prevent serious stoma-related complications such as stoma side perforation, prolapse, fall and surgical site infection, we introduce our new "sutureless enterostomy" technique. METHODS: We present the procedures in detail. We reviewed the medical records of twelve patients who underwent "sutureless enterostomy" in our neonatal intensive care unit from 2007 to 2013. Patient attributes, surgery-related items, stoma-related complications and outcomes were investigated. RESULTS: Mean birth weight was 671±158g (mean±S.D.). Six cases of MOP, three cases of SIP and three cases of NEC were diagnosed. Mean operative time was 75±35min (mean±S.D.) None of them presented any of early stoma-related complications (necrosis, fall, and surgical site infection). However the parastomal hernia occurred in one patient as late complication. Three deaths occurred postoperatively as a result of exacerbations of their conditions. CONCLUSIONS: Based on our preliminary observations, our new "sutureless enterostomy" was done safely and reduced the risk of stoma-related complications. It may be an ideal procedure for the ELBWI with MOP or SIP.

Creation of mouse TNFR2-selective agonistic TNF mutants using a phage display technique.

Tumor necrosis factor-α (TNF), which is an immuno-modulatory cytokine, has been suggested to cause inflammatory responses as well as protection against tissue dysfunction by binding two types of TNF receptor (TNFR1/TNFR2). However, the physiological effects of TNFR2-specific activation remain unclear. We therefore aimed to generate a TNF mutant with full TNFR2-selective agonist activity as a functional analytical tool. In this study, we utilized a phage display technique to create mouse TNFR2 (mTNFR2)-selective TNF mutants that bind specifically to mTNFR2 and show full bioactivity compared with wild-type TNF. A new phage library displaying TNF mutants was created, in which nine amino acid residues at the predicted receptor-binding site were randomized. From this library, an agonistic TNF mutant exhibiting high binding selectivity and bioactivity to mTNFR2 was isolated. We propose that this TNF mutant would be a powerful tool with which to elucidate the functional roles of mTNFR2.

Noncatalytic mono-N-methylation of aniline in supercritical methanol: the kinetics and acid/base effect.

Aniline is easily N-methylated in supercritical methanol without catalyst at 350 degrees C and 0.237 g cm-3 to give mono-N-methylaniline with high selectivity, and the reaction rate is increased by a small amount of base (LiOH, NaOH, KOH, and CH3ONa), indicating a difference in the reaction mechanism from the ordinary acid-catalyzed one.

Trabecular bone volume fraction measurements of a large number of subjects using a compact MRI.

Trabecular bone volume fraction (TBVF) and speed of sound (SOS) were measured for the right calcanei of 416 female volunteers. The TBVF was measured with a compact MRI developed in our laboratory. The SOS was measured with a commercial quantitative ultrasound system. It was observed that the correlation coefficient between TBVF and SOS and that between TBVF and age varied depending on the location of region of interest (ROI) in the calcaneus. As a result, an optimum circular ROI with a diameter of 20 mm was determined so that the correlation coefficients were maximized. In the optimum ROI, transverse relaxation time (T2) of the bone marrow protons of the calcaneus was found to be concentrated in a narrow range over the subjects. This result suggested that a 50% scan time reduction in the TBVF measurements could be made by skipping the T2 correction procedure.

Effectiveness of Interval Appendectomy After Conservative Treatment of Pediatric Ruptured Appendicitis with Abscess.

The management of patients with acute perforated appendicitis with abscess is controversial. The aim of the present study was to assess the outcomes of treatment in patients with this condition. We retrospectively analyzed 31 patients (16 men and 15 women with a mean age of 8.4 years) with appendicitis presenting with abscess. Patients were divided into two groups (emergency operation group and interval operation group), and clinical characteristics and outcomes of treatment were investigated. On presentation, no differences in gender, age, body weight, duration of symptoms, temperature, white blood cell count, C-reactive protein level, or maximum size of the abscess in the axial view were detected between the two groups. Fifteen patients (48.4 %) underwent emergency surgery. The remaining 16 patients (51.6 %) were initially treated conservatively with antibiotics. All 16 patients underwent planned operations after receiving conservative treatment, and two (12.5 %) of these patients underwent appendectomy before the planned operation day because of recurrent appendicitis without abscess. There were no differences in the length of hospital stay. In the emergency operation group, six (40 %) patients presented with wound infection and four (26.7 %) developed a postoperative intra-abdominal abscess. No infective complications were reported in the interval operation group. Interval appendectomy after conservative treatment of pediatric ruptured appendicitis with abscess significantly reduced postoperative infection rates.