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1.  Prevention of Allogeneic Cardiac Graft Rejection by Transfer of Ex Vivo Expanded Antigen-Specific Regulatory T-Cells 
PLoS ONE  2014;9(2):e87722.
The rate of graft survival has dramatically increased using calcineurin inhibitors, however chronic graft rejection and risk of infection are difficult to manage. Induction of allograft-specific regulatory T-cells (Tregs) is considered an ideal way to achieve long-term tolerance for allografts. However, efficient in vitro methods for developing allograft-specific Tregs which is applicable to MHC full-mismatched cardiac transplant models have not been established. We compared antigen-nonspecific polyclonal-induced Tregs (iTregs) as well as antigen-specific iTregs and thymus-derived Tregs (nTregs) that were expanded via direct and indirect pathways. We found that iTregs induced via the indirect pathway had the greatest ability to prolong graft survival and suppress angiitis. Antigen-specific iTregs generated ex vivo via both direct and indirect pathways using dendritic cells from F1 mice also induced long-term engraftment without using MHC peptides. In antigen-specific Treg transferred models, activation of dendritic cells and allograft-specific CTL generation were suppressed. The present study demonstrated the potential of ex vivo antigen-specific Treg expansion for clinical cell-based therapeutic approaches to induce lifelong immunological tolerance for allogeneic cardiac transplants.
PMCID: PMC3912059  PMID: 24498362
2.  Discontinuation of Living Donor Liver Transplantation due to Donor's Intraoperative Latex-Induced Anaphylactic Shock 
International Surgery  2012;97(4):356-359.
We report on a 33-year-old female liver donor candidate who developed intraoperative latex-induced anaphylactic shock during surgery for living donor transplantation. She was the mother of the organ recipient, who was a 9-year-old boy with biliary atresia. We planned extended lateral segmentectomy for her. Although we dissected the ligament around the left lobe, the systolic blood pressure suddenly dropped and her body became flushed and warm. We administered transfusion and an ephedrine injection to recover the blood pressure. Because she recovered after the treatment, we restarted the procedure. However, she went into shock again within a few minutes. We decided to discontinue the operation. Postoperative blood tests revealed an increase in IgE-RAST and basophil activation, suggesting that the anaphylactic shock was induced by latex. Because latex allergy has become a public health problem, this allergy should be kept in mind as a potential donor operation risk.
PMCID: PMC3727268  PMID: 23294079
Latex allergy; Living donor liver transplantation; Anaphylactic reaction; Shock
3.  Li-Fraumeni syndrome with simultaneous osteosarcoma and liver cancer: Increased expression of a CD44 variant isoform after chemotherapy 
BMC Cancer  2012;12:444.
Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome that is commonly associated with a germline mutation in the tumor suppressor gene p53. Loss of p53 results in increased expression of CD44, a cancer stem cell (CSC) marker, which is involved in the scavenging of reactive oxygen species (ROS). Here, we report a change in the expression of a CD44 variant isoform (CD44v8-10) in an 8-year-old female LFS patient with osteosarcoma and atypical liver cancer after chemotherapy.
Case presentation
The patient visited a clinic with a chief complaint of chronic pain in a bruise on her right knee. Magnetic resonance imaging (MRI) raised the possibility of a bone malignancy. Biochemical testing also revealed significantly elevated levels of AFP, which strongly suggested the existence of a primary malignancy in the liver. MRI imaging showed the simultaneous development of osteosarcoma and liver cancer, both of which were confirmed upon biopsy. Combined therapy with surgical resection after chemotherapy was successful in this patient. Regardless of the absence of a familial history of hereditary cancer, a germline mutation in p53 was identified (a missense mutation defined as c.722 C>T, p.Ser241Phe). To better understand the cancer progression and response to treatment, immunohistochemical (IHC) analysis of biopsy specimens obtained before and after chemotherapy was performed using a specific antibody against CD44v8-10.
This case demonstrates the ectopic up-regulation of CD44v8-10 in a biopsy sample obtained after cytotoxic chemotherapy, which confers high levels of oxidative stress on cancer cells. Because the alternative splicing of CD44 is tightly regulated epigenetically, it is possible that micro-environmental stress resulting from chemotherapy caused the ectopic induction of CD44v8-10 in vivo.
PMCID: PMC3488581  PMID: 23031740
Li-Fraumeni syndrome (LFS); cancer stem cells (CSCs); CD44 variant isoforms
4.  Effect of an omega-3 lipid emulsion in reducing oxidative stress in a rat model of intestinal ischemia−reperfusion injury 
Pediatric Surgery International  2012;28(9):913-918.
The usefulness of omega-3 lipid emulsions has been extensively studied. The objectives of the present study were to examine the effect of an omega-3 lipid emulsion in reducing oxidative stress in a rat model of intestinal ischemia−reperfusion injury and the underlying mechanism.
A total of 66 rats were divided into three dietary groups (lipid-free, soybean oil, and fish oil groups). Each animal was administered total parenteral nutrition for 3 days, followed by induction of intestinal ischemia for 100 min. Animals subjected to sham surgery served as the controls. Intestinal tissue and blood were harvested 6 and 12 h after the surgery, then, assessment of the histological damage score, plasma-related parameters, and statistical evaluation were performed.
The histological damage score in the intestinal tissues was significantly lower in the fish oil group than in the soybean oil group (P = 0.0121). The late-phase urinary level of 8-hydroxy-2-deoxyguanosine was also significantly lower in the fish oil group as compared with that in the other groups (P = 0.0267). Furthermore, the plasma level of high-mobility group box 1 protein was also significantly lower in the fish oil group as compared with that in the lipid-free group (P = 0.0398).
It appeared that intravenous administration of an omega-3 lipid emulsion prior to ischemia−reperfusion injury reduced the oxidative stress and severity of tissue damage. Modification of membrane fatty acids may serve as the mechanism underlying this reduction of tissue damage.
PMCID: PMC3433667  PMID: 22907722
Ischemia–reperfusion injury; Omega-3; Oxidative stress; HMGB1

Results 1-4 (4)