N Yoshimura

Kyoto Prefectural University of Medicine, Kioto, Kyōto, Japan

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Publications (282)444.82 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Given the recent increase in the prevalence of diabetes mellitus, it is not uncommon for kidney transplantation donors to have diabetes. We perform kidney transplantation in our hospital if the diabetic donors are receiving oral hypoglycaemic agents, but not insulin, and their haemoglobin A1C (HbA1C) is below 6.5%. There are few reports about histological changes to diabetic nephropathy after transplantation of kidney grafts from donors with diabetes mellitus to non-diabetic recipients. Therefore, we studied the histological diabetic changes in grafts from diabetic donors at protocol biopsies (1 hour, 1 month, 1 year), and evaluated whether they improved under the recipient's good glycaemic control. Three cases of kidney transplantation from donors with diabetes mellitus to non-diabetic recipients were selected. We used a pathological classification established by the Renal Pathology Society for evaluating histological improvements in diabetic nephropathy. The results revealed that early diabetic changes found at the 1-hour and 1-month protocol biopsies were reversed and improved at the 1-year biopsy. We concluded that early diabetic changes in grafts from diabetic donors may improve if the graft recipient has good glycaemic control after kidney transplantation. © 2015 Asian Pacific Society of Nephrology.
    Nephrology 07/2015; 20 Suppl 2(S2):40-4. DOI:10.1111/nep.12451 · 2.08 Impact Factor
  • T. Nakamura · T. Nakao · N. Yoshimura · E. Ashihara ·
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    ABSTRACT: Mammalian target of rapamycin (mTOR) inhibitors are the main immunosuppressive drugs for organ transplant recipients. Nevertheless, the mechanisms by which mTOR inhibitors induce immunosuppression is not fully understood. Myeloid-derived suppressor cells (MDSCs) maintain host immunity; however, the relationship between mTOR inhibitors and MDSCs is unclear. Here, the results from a murine cardiac transplantation model revealed that rapamycin treatment (3 mg/kg, intraperitoneally on postoperative days 0, 2, 4, and 6) led to the recruitment of MDSCs and increased their expression of inducible nitric oxide synthase (iNOS). Immunohistochemical analysis revealed that rapamycin induced the migration of iNOS-expressing MDSCs into the subintimal space within the allograft vessels, resulting in a significant prolongation of graft survival compared with that in the untreated group (67 days vs. 7 days, respectively). These effects were counterbalanced by the administration of an anti-Gr-1, which reduced allograft survival to 21 days. Moreover, adoptive transcoronary arterial transfer of MDSCs from rapamycin-treated recipients prolonged allograft survival; this increase was reversed by the anti-Gr-1 antibody. Finally, co-administration of rapamycin and a mitogen-activated protein kinase kinase (MEK) inhibitor trametinib reversed rapamycin-mediated MDSC recruitment. Thus, the mTOR and Raf/MEK/extracellular signal regulated kinase (ERK) signaling pathways appear to play an important role in MDSC expansion. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
    American Journal of Transplantation 05/2015; 15(9). DOI:10.1111/ajt.13276 · 5.68 Impact Factor
  • T Nakamura · H Ushigome · T Takata · T Nakao · S Harada · K Koshino · T Suzuki · T Ito · S Nobori · N Yoshimura ·
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    ABSTRACT: Introduction of everolimus (RAD) has been established as a new immunosuppressive medication for kidney transplant (KT) recipients. Administration of RAD is capable of reducing the dosage of coadministrated calcineurin inhibitors (CNI). However, histological investigations have rarely been performed. To clarify histopathologic effects of RAD, a total of 9 adult KT recipients were enrolled (RAD group, n = 5; Mycophenolate mofetil (MMF) group, n = 4). Renal graft biopsies had been performed at 3 weeks and 1 year following KT. There were no differences in 1-, 3-, and 5-year graft survival rates (RAD group: 100%, 100%, and 80%, respectively; MMF group: 100%, 100%, and 75%, respectively), and patient survival between the 2 groups (no deaths during the 5 years post-transplantation). Interestingly, although 2 patients in the RAD group had developed CNI nephrotoxicity clinically, renal biopsies had proven no CNI-related lesions 1 year later, which might be due to the reduction in CNI. On the other hand, 1 patient, in the MMF group, had been diagnosed histologically with new-onset CNI nephrotoxicity 1 year following KT. Importantly, the frequency and mean arteriolar hyalinosis (ah) scores, which reflect CNI nephrotoxicity, were significantly higher in the MMF group at 1-year biopsy (P < .05, P < .0001). Two patients in the RAD group improved their ah scores between 3 weeks and 1 year. Pathological findings revealed that reversible CNI nephrotoxicity can be improved by RAD with reduced CNI maintenance therapy. It is reasonable to believe, therefore, that introduction of RAD is useful for patients who have been diagnosed with CNI nephrotoxicity. Copyright © 2015 Elsevier Inc. All rights reserved.
    Transplantation Proceedings 04/2015; 47(3):630-4. DOI:10.1016/j.transproceed.2014.09.180 · 0.98 Impact Factor
  • H Ushigome · S Harada · M Nakao · T Nakamura · K Koshino · T Suzuki · T Ito · S Nobori · N Yoshimura ·
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    ABSTRACT: Improving the short-term outcome of kidney transplantation, the rejection induced by anti-donor specific antibody (DSA) has been the large complication. We analyzed 324 living-donor kidney transplant recipients (procedures performed between April 2003 and August 2014) to investigate the outcome of kidney transplant recipients with DSA. We divided them into four groups (anti-blood type antibody alone, group A [n = 73]; anti-human lymphocyte antigen [HLA] antibody alone, group B [n = 11]; both antibodies, group C [n = 8]; and no DSA, group D [n = 232]) and investigated the incidence of rejection and those histologic findings. Each case with DSA underwent some desensitization therapy before transplantation. There was no significant difference in graft survival (all cases: 100% at 1 year, group A: 97.6%, B: 95.9%, C: 100%, and at 5 years, group D: 96.1%). There were some significant differences in incidence of acute antibody-mediated rejection (AAMR) and chronic active antibody-mediated rejection (CAAMR) among four groups (group A: 4.1% and 2.7%, B: 18.2% and 9.1%, C: 12.5% and 12.5%, D: 0% and 0.9%, respectively). Each AAMR case was improved by ordinary desensitization therapy, but half of the CAAMR cases, diagnosed early after transplantation, had no effect of any therapy to result in graft failure. Our results suggested that even the case with DSA could be transplanted safely by some desensitization therapy. However, we should be cautious regarding recipients with DSA for the long term even if there is no histologic change early after transplantation because graft loss may occur due to CAAMR. Copyright © 2015 Elsevier Inc. All rights reserved.
    Transplantation Proceedings 04/2015; 47(3):612-6. DOI:10.1016/j.transproceed.2014.12.039 · 0.98 Impact Factor
  • T Nakamura · H Ushigome · T Nakao · S Harada · K Koshino · T Suzuki · T Ito · S Nobori · N Yoshimura ·
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    ABSTRACT: There is a growing tendency to perform pre-emptive kidney transplantation (PKT). However, less research has been performed on outcomes of PKT and kidney transplantation (KT) after long-term dialysis (LD). To elucidate advantages of PKT to KTLD, 96 patients who underwent living-donor KT at our university from 2000 to 2011 were enrolled for this study: 64 patients in the PKT0 (0 months dialysis) group; 14 patients in the PKT-3 group (less than 3 months dialysis); 18 patients in the LD (dialysis > 120 months) group. All recipients were assessed for patients' survival, graft survival, urinary tract infection, laboratory data, episodes of acute rejection, cytomegalovirus-related diseases, and other significant infectious diseases which required hospitalization. Although there were no significant differences in 5-year graft survival (93.8% in PKT0, 85.7% in PKT-3, and 83.7% in control), 5-year patient survival is better in the PKT0 group (96.9%) and the PKT-3 group (92.9%) compared to 88.9% in the control group. Urinary tract infection is clearly correlated with the LD group (44.4% in the LD group vs 19.2% in the PKT group) primarily due to atrophic bladder and subsequent vesicoureteral reflux. Slightly higher rates of acute rejection were found in the PKT groups (30.8% vs 26.3%). This study revealed that there are both advantages and disadvantages of PKT. It is clear, therefore, that PKT can be recommended for end-stage renal disease patients provided enough attention is paid to the onset of acute rejection. Copyright © 2015 Elsevier Inc. All rights reserved.
    Transplantation Proceedings 04/2015; 47(3):626-9. DOI:10.1016/j.transproceed.2014.09.179 · 0.98 Impact Factor
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    T Nakao · H Ushigome · T Nakamura · S Harada · K Koshino · T Suzuki · T Ito · S Nobori · N Yoshimura ·
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    ABSTRACT: Chronic allograft injury (CAI) is one of the most important factors for graft failure after renal transplantation. Protocol biopsy is the most valuable tool for revealing subclinical renal allograft failure. Transient elastography (TE) is a noninvasive technique that has shown utility for the assessment of hepatic and renal fibrosis. This study sought to evaluate whether TE was a viable and effective method for the assessment of renal allograft failure. Thirty-five patients underwent TE by Fibro Scan (Echosense, Paris, France). Biopsies were performed in 27 patients, allowing classification according to Banff chronic changes in the interstitium grade 0, grade 1 or grade 2. Measurement of parenchymal stiffness was successful in 31of 35 patients (91%). Stiffness was significantly correlated with interstitial fibrosis (P < .05) and inversely related with estimated glomerular filtration rate (eGFR; P < .05). Stiffness values of patients with eGFR > 50 mL/min were lower than those of patients with eGFR < 50 mL/min (P < .05). Patients classed as CAI Banff grade 0 had significantly less parenchymal stiffness than patients with Banff grade 1 or grade 2 CAI (P < .05). Parenchymal stiffness measured by TE reflected interstitial fibrosis in renal allograft. Assessment of parenchymal renal allograft stiffness by TE was effective for identifying patients with CAI who may subsequently benefit from biopsy and modification of the immunosuppressive regimen. Assessment of parenchymal renal allograft stiffness can be effective for identifying patients with CAI. TE has the potential to reduce the number of renal allograft biopsies required for accurate assessment of CAI. Copyright © 2015 Elsevier Inc. All rights reserved.
    Transplantation Proceedings 04/2015; 47(3):640-3. DOI:10.1016/j.transproceed.2014.12.034 · 0.98 Impact Factor
  • T Nakao · H Ushigome · K Kawai · T Nakamura · S Harada · K Koshino · T Suzuki · T Ito · S Nobori · N Yoshimura ·
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    ABSTRACT: The introduction of rituximab has led to a growing tendency to perform ABO-incompatible living-donor kidney transplantation (LDKT) without splenectomy. However, the optimal dosage of rituximab is undefined. Fifty-five LDKT recipients who had neither a history of hepatitis B infection nor positive crossmatch were enrolled between October 2005 and June 2014. Recipients were divided into three groups by year of transplantation: 2005 to 2008; 2009 to 2011; and 2012 to 2014. Percentages of CD20-positive B lymphocytes and blood-group antibody titers were monitored before renal transplantation. An initial rituximab dosage of 100 mg/body (for titers below 64) or 200 mg/body (for titers above 128) was administered 2 weeks before transplantation. If the percentage of peripheral B lymphocytes remained greater than 0.5%, additional rituximab (100 mg or 200 mg) was administered. Patient demographics, patient survival, graft survival, and complication rates were compared. Nine patients received rituximab 100 mg/body (low-dose rituximab [LDR] group). Overall survival and graft survival rates did not differ significantly between the LDR group and other cases. The incidences of myelosuppression and viral infection were lower in the LDR group than the other cases. A low dose of rituximab (100 mg/body) is adequate in ABO-incompatible LDKT, especially in cases with low blood-type antibody titer against ABO-antigens. Rituximab dosage reduction has been successful in our hospital without serious complications. Moreover, as over-dosage of rituximab may cause myelosuppression, it is reasonable to believe that LDR is a suitable option to safely perform ABO-incompatible LDKT without splenectomy. Copyright © 2015 Elsevier Inc. All rights reserved.
    Transplantation Proceedings 04/2015; 47(3):644-8. DOI:10.1016/j.transproceed.2014.12.033 · 0.98 Impact Factor
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    ABSTRACT: Radiofrequency ablation (RFA) has been established as the mainstay therapy for hepatocellular carcinoma (HCC) in patients deemed unsuitable for surgical resection. However, delayed diaphragmatic hernia can occur as a result of this procedure. There have been only seven other cases reported on this complication in the literature. Considering the recent growth in the popularity of the procedure, it is predictable that the incidence of the diaphragmatic hernia, due to RFA, will definitely increase. This case report is therefore vitally important as it increases clinical awareness of this currently rare complication, which could lead to improved survival rates in these patients. This case concerns an 81-year-old Asian man with a past medical history of cirrhosis and HCC (segment IV and VIII) who presented with a delayed, right diaphragmatic hernia and strangulated ileus 18 months after his original RFA procedure. It is important to implement extra measures to limit the risk of diaphragmatic, thermal injuries when RFA is performed. In particular, gastroenterologists, surgeons and accident and emergency staff should all be aware of this complication proceed with rapid diagnosis and management when patients, who previously underwent RFA, present with acute abdominal pain.
    Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery: TJTES 07/2014; 20(4):295-9. DOI:10.5505/tjtes.2014.03295 · 0.38 Impact Factor
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    ABSTRACT: Mortality following blunt chest injury and cardiac rupture remains high despite advances in the care of traumatic injuries. Indeed, most patients succumb to these injuries even prior to reaching a hospital. However, timely recognition and surgical intervention can save lives. We present the case of a 40-year-old woman who presented to our emergency department in cardiac arrest due to rupture of her left atrium following a major motor vehicle collision. The patient underwent emergency department thoracotomy with successful repair of the cardiac rupture. Emergency department thoracotomy, when indicated and performed by trained surgeons, can be the only life-saving procedure available. Rapid median sternotomy using a cost-effective fret sternum saw does not require significantly more time than a left lateral thoracotomy or clamshell incision in an emergency situation. It can be an effective and alternative method of thoracic entry in the emergency department. Prognosis of cardiac rupture depends largely on the mechanism of injury, location of injury, signs of life: vital signs, and availability of timely intervention. When indicated, hesitation should be avoided. Expedient cardiac exposure is essential and leads to better results with improved survival rates in patients with blunt cardiac rupture.
    Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery: TJTES 05/2014; 20(3):217-220. DOI:10.5505/tjtes.2014.60598 · 0.38 Impact Factor
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    ABSTRACT: Background Mizoribine (MZR) has been developed as an immunosuppressive agent in Japan, but has a less potent immunosuppressive effect up to 3 mg/kg/d. We previously reported that high-dose MZR, at 6 mg/kg/d, would be effective and safe for ABO-incompatible(ABO-i) living donor kidney transplantation (LDKT) patients when combined with cyclosporine (CsA) or tacrolimus(FK), anti-CD20 and anti-CD25 monoclonal antibodies, and corticosteroid without splenectomy in a 1-year study. Therefore, we observed these patients for 3 years. Methods From 2007 to 2010, we encountered 24 cases of ABO-i LDKT using anti-CD20 and anti-CD25 monoclonal antibodies without splenectomy. The pretransplantation immunosuppressive regimen consisted of two doses of anti-CD20 antibody, mycophenolate mofetil (MMF, 25 mg/kg/d), prednisolone, calcineurin inhibitor (CNI; CsA 7 mg/kg or (FK 0.2 mg/kg) and two doses of anti-CD25 antibody. Antibody removal by plasmapheresis was performed before LDKT up to several times according to the antibody titer. The post-transplantation regimen consisted of high-dose MZR (6 mg/kg/d) instead of MMF (MZR group, N = 12) . Results The 3-year graft survival rates for the MZR and MMF groups were 91.7% and 100%, respectively. Serum creatinine levels for the MZR and MMF groups were 1.44 mg/dL and 1.31 mg/dL at 1 year, 1.55 mg/dL and 1.41 mg/dL at 2 years, and 1.51 mg/dL and 1.48 mg/dL at 3 years, respectively (not significant [NS]). The MZR group did not show a higher rate of elevated serum uric acid values. The percentage of patients who were administered anti-uric medication was 42.5% (5/12) in the MZR group and 50% (6/12) in the MMF group (P = NS) at the third year. Severe infection, such as cytomegalovirus, herpes zoster, was not observed at the second and third years in both groups. Conclusion A high-dose MZR regimen including CNI (CsA or FK), steroid, and anti-CD20 and anti-CD25 antibodies without splenectomy was effective and safe in ABO-i renal transplantation.
    Transplantation Proceedings 03/2014; 46(2):391–394. DOI:10.1016/j.transproceed.2013.10.061 · 0.98 Impact Factor
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    ABSTRACT: In Japan, diabetic nephropathy accounted for 16,225 (43.7%) of the 38,473 patients who began hemodialysis in 2010 and the number increases year by year. In 1991, we started a kidney transplantation program for patients with diabetic nephropathy in our institution, and the ratio of patients who underwent kidney transplantation for diabetic nephropathy traces the course of increase. Among the 516 patients who underwent primary kidney transplantation in our institution from January 1991 to February 2013, we divided them into 2 groups. One group was the diabetes mellitus (DM) group, which included patients with primary disease of diabetic nephropathy, and the other group was the non-DM group. The DM group included 50 patients, and in our institution the ratio traces the course to increase. There was no significant difference for the 1-year and 5-year patient survival rates and graft survival rates between the DM group and the non-DM group. Moreover, the rate of acute rejection in the 2 groups was not significantly different. Furthermore, when we investigated the causes of death in the 2 groups, there was no significant difference with the mortality of cases due to heart vascular disease in the DM group and the non-DM group. Also, no case in which the graft lost function due to recurrence of diabetic nephropathy was observed. Although the early outcome of kidney transplantation for diabetic nephropathy in our institution did not have inferiority in comparison with kidney transplantation for the other primary disease, we think that careful diabetic control after kidney transplantation is required for long-term outcome.
    Transplantation Proceedings 03/2014; 46(2):464–466. DOI:10.1016/j.transproceed.2013.11.076 · 0.98 Impact Factor
  • K. Koshino · H. Ushigome · T. Nakao · S. Harada · K. Sakai · T. Suzuki · S. Nobori · T. Ito · N. Yoshimura ·
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    ABSTRACT: Background Due to the shortage of deceased donor kidneys, we have expanded the indications for living-donor kidney transplantation (LKT) including ABO-incompatible (ABO-i) donors in Japan. In this study, the utility of protocol biopsies was discussed in ABO-i LKT. Methods Protocol biopsies have been performed on kidney graft 1 hour, 3 weeks, and 1 year after LKT in our institution. The relationship between biopsies and clinical courses was considered retrospectively in 38 cases of ABO-i LKT. The immunosuppressive regimen consisted of anti-CD20 antibody, mycophenolate mofetil, prednisolone, calcineurin inhibitor (cyclosporine or tacrolimus), and anti-CD25 antibody. Anti-ABO blood type antibody removal by plasmapheresis was performed before LKT up to 32 times. The post-transplantation regimen consisted of mycophenolate mofetil or mizoribine as an antimetabolite. Results Episode biopsies have been performed in 6 cases within 3 weeks post-transplantation. Each pathological diagnosis was as follows: antibody-mediated rejection (AMR; 5 cases) and calcineurin inhibitor (CNI) nephrotoxicity (1 case). Subclinical chronic active AMR was found at 1 year post-transplantation follow-up biopsies in 4 of the 6 cases. Episode biopsies have been done in the other 6 cases from 1 month to 1 year post-transplantation. Each pathological diagnosis was as follows: acute T-cell–mediated rejection (TMR; 1 case), vesicoureteral reflux (VUR; 3 cases), CNI nephrotoxicity (2 cases), and VUR + CNI nephrotoxicity (1 case). AMR was also not found at 1 year post-transplantation follow-up biopsies in them. In all cases episode biopsies were performed based on pathological diagnosis and had no graft dysfunction after that. Conclusions Pathological study revealed that acute AMR was found early (ie, within 3 weeks) following transplantation. Although appropriate treatment made AMR go into remission once, chronic active AMR was often found at 1-year follow-up biopsies.
    Transplantation Proceedings 03/2014; 46(2):385–387. DOI:10.1016/j.transproceed.2013.11.073 · 0.98 Impact Factor
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    ABSTRACT: Lymphoepithelial cysts with sebaceous glands of the pancreas are extremely rare, with only 7 cases, including this case, published in English literature. We herein present the case of a 67-year-old Asian man who underwent a resection of a lymphoepithelial cyst of the pancreas during the follow up care for lung cancer. Fourteen years previously he underwent a right lower lobectomy at the right segment nine for lung cancer. A 20 mm mass in the body of the pancreas was identified by CT scan 4 years ago, and the diagnosis was intraductal papillary mucinous neoplasm (IPMN) at that time. Over a 5-year period, this mass grew to 42 mm without dilatation of the main pancreatic duct. The preoperative evaluation, including endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), indicated a cystic neoplasm with suspicion of malignancy. Intraoperative frozen section revealed a squamous-lined cyst accompanied by sebaceous glands without any malignant findings. Following this pathological finding, resection of the cyst was performed. Consequently, microscopic examination revealed that it was a lymphoepithelial cyst with sebaceous glands of the pancreas. Pancreatic lymphoepithelial cysts can be cured by conservative resection, but if they are asymptomatic and are diagnosed before surgery, no treatment is necessary. To our knowledge, this is the first ever published case of a lymphoepithelial cyst with sebaceous glands of the pancreas, which was found during the follow up care for lung cancer.
    JOP: Journal of the pancreas 11/2013; 14(6):632-5.
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    ABSTRACT: Since 2007, we have performed tonsillectomies for patients with recurrent immunoglobulin A nephropathy (IgAN) after kidney transplantation. Seven patients with primary IgAN showed biopsy-proven recurrent IgAN after living-donor kidney transplantation. They had persistent proteinuria or hematuria for an average of 40.3 months, and tonsillectomy was performed, on average, 75.6 months after kidney transplantation. In six patients with observation periods of more than one yr, good remission of urinary findings was observed after tonsillectomy. We classified the seven patients into three types of renal injury based on histological findings: severe, moderate, and mild. Two patients classified with severe renal injury at the time of tonsillectomy had other problems, such as refractory hypertension and bilateral sinusitis. They followed a rapidly progressive clinical course. One case already had moderate histological renal injury. He demonstrated prompt amelioration of urinary findings after tonsillectomy but immediate deviation from remission of proteinuria and hematuria. In the four cases presenting mild renal injury at tonsillectomy, the improved urinary findings and serum creatinine value after tonsillectomy have persisted. In conclusion, tonsillectomy may be a favorable treatment for cases of mild-grade IgAN. However, other treatments such as antihypertensive agents and diet therapy may be necessary in other grades.
    Clinical Transplantation 11/2013; 27 Suppl 26(s26):22-8. DOI:10.1111/ctr.12194 · 1.52 Impact Factor
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    ABSTRACT: The optimal use and monitoring of cyclosporine A (CyA) have remained unclear and the current strategy of CyA treatment requires frequent dose adjustment following an empirical initial dosage adjusted for total body weight (TBW). The primary aim of this study was to evaluate age and anthropometric parameters as predictors for dose adjustment of CyA; and the secondary aim was to compare the usefulness of the concentration at predose (C0) and 2-hour postdose (C2) monitoring. An open-label, non-randomized, retrospective study was performed in 81 renal transplant patients in Japan during 2001-2010. The relationships between the area under the blood concentration-time curve (AUC0-9) of CyA and its C0 or C2 level were assessed with a linear regression analysis model. In addition to age, 7 anthropometric parameters were tested as predictors for AUC0-9 of CyA: TBW, height (HT), body mass index (BMI), body surface area (BSA), ideal body weight (IBW), lean body weight (LBW), and fat free mass (FFM). Correlations between AUC0-9 of CyA and these parameters were also analyzed with a linear regression model. The rank order of the correlation coefficient was C0 > C2 (C0; r=0.6273, C2; r=0.5562). The linear regression analyses between AUC0-9 of CyA and candidate parameters indicated their potential usefulness from the following rank order: IBW > FFM > HT > BSA > LBW > TBW > BMI > Age. In conclusion, after oral administration, C2 monitoring has a large variation and could be at high risk for overdosing. Therefore, after oral dosing of CyA, it was not considered to be a useful approach for single monitoring, but should rather be used with C0 monitoring. The regression analyses between AUC0-9 of CyA and anthropometric parameters indicated that IBW was potentially the superior predictor for dose adjustment of CyA in an empiric strategy using TBW (IBW; r=0.5181, TBW; r=0.3192); however, this finding seems to lack the pharmacokinetic rationale and thus warrants further basic and clinical investigations.
    International journal of medical sciences 09/2013; 10(12):1665-73. DOI:10.7150/ijms.6727 · 2.00 Impact Factor
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    ABSTRACT: Peripheral intrabiliary liver metastases (PILM) from colorectal carcinoma are rare, and this feature, which resembles primary cholangiocarcinoma, potentially misleads the accurate diagnosis and subsequent surgical treatment. A 67-year-old man with a medical history of descending colon carcinoma demonstrated an abnormal rise in CA19-9. There was a strong possibility of peripheral cholangiocarcinoma, because Computed tomography detected tumour infiltration into bile duct three. The patient underwent anatomic segment eight and lateral lobe resection. Pathological findings revealed that every tumour was metastatic liver carcinoma due to descending colon carcinoma. Cases of liver metastasis which resemble peripheral cholangiocarcinoma might be difficult to distinguish preoperatively. The correct diagnosis is important in making decisions regarding the surgical management of such patients. Nonanatomic hepatectomy is often performed for liver metastases from colorectal carcinomas. Anatomic hepatectomy, however, should be recommended in cases of PILM.
    08/2013; 2013(8). DOI:10.1093/jscr/rjt055
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    ABSTRACT: No study to date has evaluated the efficacy and safety of everolimus with reduced-exposure cyclosporine in Japanese de-novo renal transplant (RTx) patients. This 12-month, multicenter, open-label study randomized (1:1) 122 Japanese de-novo RTx patients to either an everolimus regimen (1.5 mg/day starting dose (target trough: 3 to 8 ng/ml) + reduced-dose cyclosporine) or a mycophenolate mofetil (MMF) regimen (2 g/day + standard dose cyclosporine). All patients received basiliximab and corticosteroids. Key endpoints at month 12 were composite efficacy failure (treated biopsy-proven acute rejection, graft loss, death, or loss to follow-up) and renal function (estimated glomerular filtration rate; Modification of Diet in Renal Disease-4). Clear cyclosporine exposure reduction was achieved in the everolimus group throughout the study (52% reduction at month 12). Month 12 efficacy failure rates showed everolimus 1.5 mg to be non-inferior to MMF (11.5% vs. 11.5%). The median estimated glomerular filtration rate at month 12 was 58.00 ml/minute/1.73 m2 in the everolimus group versus 55.25 ml/minute/1.73 m2 in the MMF group (P = 0.063). Overall, the incidence of adverse events was comparable between the groups with some differences in line with the known safety profile of the treatments. The everolimus group had a higher incidence of wound healing events and edema, whereas a higher rate of cytomegalovirus infections was reported in the MMF group. This study confirmed the efficacy of everolimus 1.5 mg/day (target trough: 3 to 8 ng/ml) in Japanese RTx patients for preventing acute rejection, while allowing for substantial cyclosporine sparing. Renal function and safety findings were comparable with previous reports from other RTx populations.Trial registration: ClinicalTrials.gov number: NCT00658320 http://clinicaltrials.gov/ct2/results?term=NCT00658320&Search=Search.
    07/2013; 2(1):14. DOI:10.1186/2047-1440-2-14
  • N Yoshimura · H Ushigome · S Nobori · T Suzuki · K Sakai · K Koshino · H Okajima · M Okamoto ·
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    ABSTRACT: Background: Mizoribine (MZR) at 3 mg/kg/d shows less potent immunosuppressive effects, but high-dose MZR (6 mg/kg/d) was effective and safe in a 2-year study in conjunction with a regimen of cyclosporine (CsA), basiliximab, and corticosteroids. Methods: We compared 40 living-related kidney recipients administered MZR (6 mg/kg/d), CsA (7 mg/kg/d), prednisolone (maintenance dose 10 mg/d), and basiliximab (20 mg/body) with control group (n = 38) treated with CsA, mycophenolate mofetil (MMF; 25 mg/kg/d), basiliximab, and corticosteroids. Results: The 4-year graft survival rates for the MZR vs MMF groups were 92.5% vs 94.7%, respectively, with serum creatinine levels of 1.66 ± 1.0 mg/dL vs 1.41 ± 0.42 mg/dL at 3 years, and 1.72 ± 1.16 mg/dL vs 1.56 ± 1.26 mg/dL at 4 years. There was no significant difference in serum creatinine levels between the 2 groups. The MZR group demonstrated a significantly higher rate of elevated serum uric acid values (29.7%). The numbers of patients treated with allopurinol at 4 years were 11/37 (29.7%) for MZR vs 2/36 (5.6%) for the MMF subjects (P < .05). Mean serum uric acid levels of the MZR vs MMF group at 4 years were 7.1 ± 1.9 mg/dL vs 7.0 ± 1.6 mg/dL, respectively (NS). There was no significant difference between the 2 groups regarding bone marrow suppression or liver dysfunction. Severe cytomegalovirus infection was not observed at 3 and 4 years in either group. There were no severe gastrointestinal symptoms among the MZR or the MMF group at 3 or 4 years. Conclusions: The combination of high-dose MZR with CsA, basiliximab, and corticosteroids displayed excellent results over a 4-year follow-up.
    Transplantation Proceedings 05/2013; 45(4):1472-1475. DOI:10.1016/j.transproceed.2013.01.055 · 0.98 Impact Factor
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    ABSTRACT: Proliferation of pancreatic β-cells is an important mechanism underlying β-cell mass adaptation to metabolic demands. Increasing β-cell mass by regeneration may ameliorate or correct both type 1 and type 2 diabetes, which both result from inadequate production of insulin by β-cells of the pancreatic islet. Transforming growth factor β (TGF-β) signaling is essential for fetal development and growth of pancreatic islets. In this study, we exposed HIT-T15, a clonal pancreatic β-cell line, to TGF-β signaling. We found that inhibition of TGF-β signaling promotes proliferation of the cells significantly, while TGF-β signaling stimulation inhibits proliferation of the cells remarkably. We confirmed that this proliferative regulation by TGF-β signaling is due to the changed expression of the cell cycle regulator p27. Furthermore, we demonstrated that there is no observed effect on transcriptional activity of p27 by TGF-β signaling. Our data show that TGF-β signaling mediates the cell-cycle progression of pancreatic β-cells by regulating the nuclear localization of CDK inhibitor, p27. Inhibition of TGF-β signaling reduces the nuclear accumulation of p27, and as a result this inhibition promotes proliferation of β-cells.
    Acta histochemica et cytochemica official journal of the Japan Society of Histochemistry and Cytochemistry 04/2013; 46(2):51-58. DOI:10.1267/ahc.12035 · 1.39 Impact Factor

  • International Journal of Clinical Medicine 01/2013; 04(10):432-439. DOI:10.4236/ijcm.2013.410078

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2k Citations
444.82 Total Impact Points


  • 1990-2015
    • Kyoto Prefectural University of Medicine
      • • Division of Transplantation and General Surgery
      • • Graduate School of Medical Science
      • • Research Institute for Neurological Diseases and Geriatrics
      • • Department of Surgery
      • • Department of Orthopaedics
      Kioto, Kyōto, Japan
  • 2013
    • Jichi Medical University
      • Department of Development of Advanced Treatment
      Totigi, Tochigi, Japan
    • Kobe Gakuin University
      • Faculty of Pharmaceutical Sciences
      Kōbe, Hyōgo, Japan
  • 1999-2013
    • Kyoto Prefectural University
      Kioto, Kyoto, Japan
  • 2009
    • Kyoto Pharmaceutical University
      Kioto, Kyōto, Japan
  • 1987
    • University of Texas Medical School
      • Department of Surgery
      Houston, Texas, United States