Publications (14)19.91 Total impact
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Article: A lectin array analysis for wild-type and α-Gal-knockout pig islets versus healthy human islets.
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ABSTRACT: PURPOSE: We performed lectin microarray analyses of islets from wild-type (WT) pigs and α1-3galactosyltransferase gene knockout (GKO) pigs and compared the results with the corresponding values for islets from healthy humans. METHODS: Islets were isolated from the pancreas. After sonication and centrifugation, the proteins in the supernatant from each islet were labeled with Cy3 and applied to a lectin array. RESULTS: Despite negligible expression of the Gal antigen on the adult pig islets (APIs), GKO-islets showed weaker signals, not only for GS-I-B4 but also for PNA, WFA, PTL-I, and GS-I-A4, than the WT islets, indicating reduced contents of α-linked GalNAc and Galβ1-3GalNAc. In comparing the islets of pigs vs. humans, human islets showed stronger signals for UEA-I, AAL, TJA-II, EEL, WFA, HPA, DBA, SBA and PTL-I, indicating that besides ABO blood type antigens, high levels of fucose and α-linked GalNAc are present. On the other hand, the high mannose form was very rich in the APIs. CONCLUSION: GKO reduced alpha-linked GalNAc, despite negligible expression of the Gal antigen on WT-API. On the other hand, the high-mannose form was richer in both APIs than in healthy human islets. These results provide useful information for future studies.Surgery Today 04/2013; · 1.22 Impact Factor -
Article: Trial using pig cells with the H-D antigen knocked down.
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ABSTRACT: PURPOSE: This report describes an attempt to reduce the expression level of Hanganutziu-Deicher (H-D) antigens by small interfering RNA (siRNA) for pig cytidine monophospho-N-acetylneuraminic acid hydroxylase (pCMAH). METHODS: A pig endothelial cell (PEC) line, and PEC and fibroblasts from an α1,3galactosyltransferase knockout (GalT-KO) piglet were used. Real-time PCR was used to evaluate the degradation of mRNA by siRNA. The H-D antigen was stained, and then the cells were incubated with human serum for the FACS analysis. The extent of lysis in human serum was next calculated using an LDH assay. RESULTS: Suppression of the mRNA of pCMAH by each siRNA was first determined. The mixture of siRNAs for pCMAH reduced the expressions of the H-D antigen on the PEC and fibroblasts to a considerable extent. The further reduction in the xenoantigenicity for human serum of the GalT-KO cells was then confirmed. In addition, the PEC line showed a significant downregulation in complement-dependent cytotoxicity by the siRNAs, thus indicating that the anti-H-D antigen in human serum is capable of causing lysis of the pig cells. CONCLUSION: pCMAH silencing by siRNA reduced the expression of the H-D antigen and its antigenicity, thus confirming that the H-D antigen is one of the major non-Gal antigens in this situation.Surgery Today 08/2012; · 1.22 Impact Factor -
Article: Carbohydrate antigens.
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ABSTRACT: To summarize the current knowledge of carbohydrate antigens as related to xenotransplantation. The emphasis is on non-Gal carbohydrate antigens identified in many institutes. In addition, several topics such as glycosyltransferase-transgenic pigs, innate cell receptors and porcine endogenous retrovirus (PERV) will be discussed. Studies related to iGb3 and neoantigens after knocking out GalT (GGTA1) were reviewed. Available data do not support the conclusion that GalT-KO remains iGb3 and/or that neoantigens are produced in the pigs. Concerning non-Gal antigen, in addition to the Hanganutziu-Deicher (H-D) antigen (NeuGc), Forrsman antigen, Galα1-3Lew(x), α-linked or β-linked GalNAc, β3 linked Gal, NeuAc, such as Neu5Acα2-3Galβ1-3GlcNAc, and Sid blood group (Sd(a))-like antigens are candidates. However, to date some of these remain controversial and others need further study to completely identify them. Regarding the H-D antigen, different from the α-Gal, it has a complicated expression system, but has cytotoxic effects toward pig cells. To modify other carbohydrate antigen apart from α-Gal, only the overexpression of GnT-III appears to have an effect on the suppression of the N-linked sugar of non-Gal antigen. Concerning innate cell receptors related to carbohydrates (ligands), the focus turned from natural killer (NK) receptor to others, such as monocytes. Finally, PERV contains a ligand with an N-linked sugar. Modification of the glycosylation pattern appears to be associated with regulating PERV infectivity. A considerable amount of data related to carbohydrate antigens is now available. At the same time, however, discrepancies between studies complicate this issue. Further studies will be needed to completely understand this complicated area of interest.Current opinion in organ transplantation 01/2012; 17(2):174-9. · 1.22 Impact Factor -
Article: Graft fibrosis in patients with biliary atresia after pediatric living-related liver transplantation.
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ABSTRACT: Although an LDLT can successfully treat biliary atresia (BA), some patients develop liver fibrosis or inflammation. To study the incidence and risk factors associated with these complications, we performed serial protocol biopsies. Twenty-four patients with BA who received a pediatric LDLT underwent protocol biopsies. All patients received standard tacrolimus-based immunosuppression and steroids. The last available biopsies were assessed. The mean age at the time of transplant was 4.8yr and the follow-up period ranged from 1.2 to 12.3yr. The GRWR ranged from 0.8% to 4.5%. The mean time from transplantation to the latest biopsy was 4.7yr. No complications occurred with the biopsy protocol. The last available biopsies for 13 (54%) and 4 (17%) patients indicated grade 1 and grade 2 portal fibrosis, respectively, and 14 patients (54%) had inflammation. No ductopenia was detected. A younger age at LDLT was significantly correlated with graft fibrosis (p=0.036). These results indicate that biopsy-proven fibrosis can be detected in patients with BA after LDLT, even in the context of normal liver function blood tests. Therefore, a serial biopsy is a safe and effective follow-up procedure for pediatric LDLT.Pediatric Transplantation 08/2011; 15(5):470-5. · 1.48 Impact Factor -
Article: Effects of a calcineurin inhibitor, FK506, and a CCR5/CXCR3 antagonist, TAK-779, in a rat small intestinal transplantation model.
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ABSTRACT: The effects of FK506, and TAK-779, antagonists of CCR5 and CXCR3, were investigated using a rat intestinal transplantation model. Small intestines from DA rats were heterotopically transplanted into LEW rats. The recipients were treated with FK506 (1mg/kg/day, day 0-5) and TAK-779 (10mg/kg/day, day 0-10). Graft survival and immunological responses to these materials were estimated by mixed lymphocyte reactions and IFN-γ production. The expression of chemokine receptors on lymphocytes was also examined. The average duration of survival was 7.0±0.3, 12.0±1.0, 9.8±0.5 and 18.0±1.5days in the allogeneic, FK506, TAK-779 and the two-drug combined groups, respectively. Cell proliferative responses and IFN-γ production were suppressed to a significant extent in the FK506 group compared with the TAK-779 group. In addition, the two-drug combination showed a tendency for stronger suppression than FK506 alone, correlated with in vivo and histopathological data. The numbers of both CD4(+) and CD8(+) cells were significantly suppressed in the blood of the recipients of both the FK506 and the TAK-779 groups, and in Peyer's patches of the graft of the TAK-779 group, but the FK506 group was not, as evidenced by FACS analysis. In addition, double-staining of graft-infiltrating lymphocytes showed a significant reduction in lymphocyte numbers, expressing CCR5 and CXCR3 in the TAK-779 group, but not evident in the FK506 group, compared to the allogeneic group. While FK506 suppresses cell proliferation and effecter function, it has less effect on the expression of CCR5 and CXCR3 in lymphocytes. Further exploration of the effects of a combined therapy with TAK-779 could represent a novel treatment for intestinal transplantation.Transplant Immunology 04/2011; 25(1):49-55. · 1.46 Impact Factor -
Article: Current status of intestinal transplantation.
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ABSTRACT: The prognosis of short gut syndrome has improved dramatically in the past few decades through the development of total parenteral nutrition (TPN). However, TPN-related complications still produce major problems for such patients. Intestinal transplantation can significantly improve patients' prognosis and increase their quality of life. The international intestinal transplant registry is updated every other year in an international small bowel transplant symposium. In this report we review the indications, procedures, management, and current status of intestinal transplantation based on the 11th International Small Bowel Transplant Symposium held in Bologna in 2009. The major findings of international studies have shown that optimization of the following factors may contribute to better outcomes: advancement of surgical techniques, new immunosuppressive techniques, improvement of postsurgical management, adequate timing of transplantation, and refined selection of candidates. Ideally, intestinal transplantation will be established as a standard therapy for intestinal failure and secondary multiorgan failure by improving the long-term survival and quality of life for patients receiving such transplants.Surgery Today 12/2010; 40(12):1112-22. · 1.22 Impact Factor -
Article: Diagnosis and management of biliary cystic malformations in neonates.
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ABSTRACT: Recent advances in ultrasonography have made it possible to identify biliary atresia (BA) and choledochal cyst (CC) with biliary cystic malformations (BCM) both prenatally and neonatally. The early differential diagnosis between BA and CC is extremely important because operations must be performed as soon as possible before the livers of BA patients advance to an irreversible cirrhotic stage. The aim of this study was to differentiate patients with BCM and to determine the best course of management in the neonatal period. The medical records of patients that were diagnosed with BCM by a prenatal or neonatal ultrasound between 1997 and 2008 were reviewed. We retrospectively divided the BCM patients into the BA and CC groups and then compared the results of ultrasound, computed tomography, and laboratory tests between the 2 groups. Ten patients were enrolled in the study. The median age at the time of corrective surgery was 74 days (range, 24-206 days). All of the BA cases received an operation by the time they were 60 days old. In the BA group (5 patients), the mean cyst size was 15 mm, the mean direct bilirubin (D-Bil) was 3.3 mg/dL, and the mean total bile acid (TBA) was 138.1 µmol/L at 30 days of age, whereas in the CC group (5 patients), cyst size, D-Bil, and TBA were 40 mm, 0.9 mg/dL, and 46.9 µmol/L, respectively. These differences between the 2 groups were statistically significant. All of the patients with CC successfully cleared their jaundice, whereas 4 patients with BA subsequently required liver transplantation for liver failure. In our study, all patients with BCM less than 21 mm, D-Bil greater than 2.5 mg/dL, and TBA greater than 111 µmol/L in the neonatal period were diagnosed with BA. Our data suggested that patients with BCM smaller than 21 mm, D-Bil higher than 2.5 mg/dL, and TBA higher than 111 µmol/L in the neonatal period were more likely to have BA than CC. This potential diagnosis should be surgically examined and corrected as soon as possible.Journal of Pediatric Surgery 11/2010; 45(11):2119-23. · 1.45 Impact Factor -
Article: Complement regulation in the GalT KO era.
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ABSTRACT: A number of institutes have reported on the successful production of alpha-galactosyltransferase knockout (GalT-KO) pigs. After producing such pigs, hyperacute rejection appeared to no longer be a problem. However, acute vascular rejection (AVR)/acute humoral xenograft rejection (AHXR) is defined as a rejection that begins within 24 h after transplantation and gradually destroys the graft. The origin of AVR/AHXR continues to be a controversial topic, but is generally thought to be initiated by xeno-reactive antibodies, including non-Gal antibodies and subsequent activation of the graft endothelium, the complement and the coagulation systems. The complement is activated via the classical pathway by non-Gal antigens and ischemia-reperfusion injury, via the alternative pathway, especially on islets, and via the lectin pathway. Therefore the complement system is still an important recognition and effector mechanism of AVR/AHXR. In addition, quite recently, based on the relationship between complement and coagulation systems, a new pathway has been proposed. All complement regulatory proteins (CRPs) have the ability to regulate complement activation in different ways. Therefore, to effectively protect xenografts against AVR/AHXR, it appears reasonable to employ not only one but several CRPs including anti-complement drugs. Non-Gal antigens, such as the Hanganutziu-Deicher antigen, is still present on GalT-KO grafts. The further assessment of antigens continues to be an important issue in the area of clinical xenotransplantation. The above conclusions suggest that the expression of human CRPs on GalT-KO grafts is necessary. Moreover, multilateral inhibition of complement activation is required in conjunction with the regulation of the coagulation system.Xenotransplantation 01/2010; 17(1):11-25. · 2.33 Impact Factor -
Article: A case of tracheal agenesis surviving without mechanical ventilation after external esophageal stenting.
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ABSTRACT: Tracheal agenesis is a rare and usually lethal congenital malformation of the forgut. Although some infants can be resuscitated with an intra-esophageal intubation temporarily, long-term airway management is difficult because of the collapsing airway. We report a long-term survivor with tracheal agenesis in whom a Gortex external esophageal stent using radial traction sutures was applied to prevent the esophagus from collapsing. The patient was discharged from our hospital without mechanical ventilation or oxygen inhalation at 10 months of age. Our procedure has a potential to establish a long-term steady airway in patients with tracheal agenesis. The detail of the procedure is presented and the related literature is reviewed.Journal of Pediatric Surgery 11/2008; 43(10):1906-8. · 1.45 Impact Factor -
Article: Reply.
Journal of Pediatric Surgery 07/2008; 43(6):1231-1232. · 1.45 Impact Factor -
Article: Anorectal sleeve micromanometry for the diagnosis of Hirschsprung's disease in newborns.
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ABSTRACT: An accurate diagnosis is mandatory for surgery in newborns with Hirschsprung's disease (HD). Acetylcholinesterase staining of rectal suction biopsy specimens is widely performed in the diagnosis of HD, but results are sometimes incorrect or atypical in newborns. We report the usefulness of our method of anorectal manometry using a specially designed sleeve microassembly for the diagnosis of neonatal HD. Anorectal manometry was conducted without sedation in 41 newborns, aged 2 to 30 days (19 newborns were within the first week of life), with abdominal distension. A silastic assembly with a 2-cm-long sleeve sensor and 5 side holes arrayed along the sleeve was designed to reduce the effects of displacement of pressure sensors relative to the anal sphincter. Rectoanal inhibitory reflex (RAIR) was examined with rectal balloon distension. Thirty-two subjects who showed falls of anal sphincter pressure fulfilling the criteria for RAIR were diagnosed to be without HD. Nine patients without an appropriate RAIR were subsequently confirmed to have HD based on operative pathologic findings. Parameters of anal sphincter function did not differ significantly between the subjects with and without RAIR. An anorectal sleeve micromanometric technique is useful in the diagnostic workup of newborns suspected of having HD.Journal of Pediatric Surgery 01/2008; 42(12):2075-9. · 1.45 Impact Factor -
Article: Lack of distal esophageal contractions is a key determinant of gastroesophageal reflux disease after repair of esophageal atresia.
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ABSTRACT: The objective of this study is to investigate the characteristics of esophageal motor activity responsible for the development of gastroesophageal reflux (GER) in patients with esophageal atresia (EA). The subjects consisted of 29 patients with EA (1 month to 19 years). Computerized esophageal manometry was conducted to investigate esophageal contractions at swallow. A topographic esophageal manometric analysis was conducted in each subject, providing 3-dimensional displays to reveal the pressure continuum representing esophageal contractions. Significant contractions in the middle esophagus just below the anastomosis were absent in all subjects. Contractions in the distal esophagus were conspicuously absent in 17 subjects. Of these 17, 6 had already undergone fundoplication, and 9 had symptomatic GER requiring fundoplication subsequent to this study. The remaining 12 patients had contractions in the distal esophagus and did not require medical/surgical intervention. A lack of distal esophageal contractions was significantly correlated with the development of GER (P < .001). There was a significant difference in esophageal acid exposure between the 2 groups (median, 38% vs 4%, P < .001). Lack of distal esophageal contractions indicating an impaired clearing capacity is considered a potential key determinant of GER in patients with EA.Journal of Pediatric Surgery 12/2007; 42(12):2017-21. · 1.45 Impact Factor -
Article: Focal intestinal perforation in extremely-low-birth-weight neonates: etiological consideration from histological findings.
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ABSTRACT: In Japan, mortality due to intestinal perforation has been increasing for the last 15 years, as the survival rate of extremely-low-birth-weight neonates (ELBWs) has been increasing. In our NICU, although the incidence of necrotizing enterocolitis has been decreasing, that of focal intestinal perforation (FIP) has been increasing. To elucidate the pathogenesis of FIP, a histological study was performed. For the last 20 years, in our NICU, 11 ELBWs with FIP, including one with multiple perforations and impending rupture, underwent laparotomy and enterostomy. The intestinal wall around the perforation was resected for histological study. Histological studies revealed well-developed ganglion cells in all the cases. Although some lymphocytic infiltration and hemorrhage were observed, no apparent neutrophilic infiltration, or necrotic change was identified in any case. No evidence of microcirculatory impairment was identified. The intestinal musculature discontinued abruptly with thinning in three cases, and without thinning in the others. The histology of impending rupture showed an absence of the muscularis with preservation of the remaining components of the bowel wall. The findings that the punched-out perforations had the appearance of Hirschsprung's disease, FIP exclusively occurred in ELBWs, and that neither mechanical obstruction nor necrotic change could be identified as the cause of the perforation suggest that immature bowel movement and congenital muscle defects may be involved in the pathogenesis of FIP.Pediatric Surgery International 11/2007; 23(10):997-1000. · 1.25 Impact Factor -
Article: Effects of rikkunshito on the clinical symptoms and esophageal acid exposure in children with symptomatic gastroesophageal reflux.
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ABSTRACT: Rikkunshito (TJ-43), a herbal medicine consisting of eight herbs, is used to treat chronic dyspepsia. Studies have shown that TJ-43 improves human gastric emptying. This study investigated the effects of TJ-43 on the clinical symptoms and esophageal acid exposure in children with symptomatic gastroesophageal reflux (GER). Eight children, aged from 2 months to 15 years (median age 4 years), were studied. Six of them had neurological impairment. TJ-43 (0.3 g/kg/day) was given orally or via nasogastric tubes in three divided doses before meals for 7 days. Their symptoms were frequent emesis in four, nausea in two, and hematemesis and stridor in one each. Twenty-four-hour esophageal pH monitoring was conducted using multichannel pH electrodes located at the distal esophagus (P1) and 10 cm proximal to P1 (P2). The clinical symptoms and esophageal pH were compared before and after TJ-43 therapy for 1 week. The frequency of emesis decreased in three patients. Other symptoms, including nausea, hematemesis, and stridor, were relieved in the remaining patients. Measured at the distal pH electrode, the percentage time of esophageal pH < 4.0 and the mean duration of reflux decreased significantly (P < 0.05). However, the number of acid reflux per hour did not change significantly, and no pH parameters measured at the proximal electrode differed significantly. The short-term administration of TJ-43 relieved symptoms and reduced the distal esophageal acid exposure through improved esophageal acid clearance.Pediatric Surgery International 10/2007; 23(10):1001-5. · 1.25 Impact Factor
Top Journals
Institutions
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2010–2011
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Osaka City University
Ōsaka-shi, Osaka-fu, Japan
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2007–2008
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Osaka Medical Center and Research Institute for Maternal and Child Health
Izumi, Osaka-fu, Japan
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