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Takahito Yagi

Publications and source records attributed to Takahito Yagi.

At least 19 recordsLinked to original sources
PubMed2006

The immunosuppressive effects of ciprofloxacin during human mixed lymphocyte reaction.

Interleukin (IL)-18, which is elevated in the plasma during acute rejection after organ transplantation, is known to induce the expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40 and CD40 ligand (CD40L) on monocytes, the production of interferon (IFN)-gamma and IL-12 and the proliferation of lymphocytes during the human mixed lymphocyte reaction (MLR). Ciprofloxacin (CIP), which is useful for the clinical treatment of infections due to its antibacterial properties after transplantation, was shown to suppress the IFN-gamma and IL-12 production, the lymphocyte proliferation and the ICAM-1, B7.1, B7.2 and CD40 expression on monocytes during MLR in the presence of IL-18. CIP also induced the production of prostaglandin (PG) E2. In order to determine whether the effects of CIP on the expression of the activation markers were due to CIP-dependent production of PGE2, we examined the effect of cyclooxygenase (COX)-2 and protein kinase A (PKA) inhibitors on the actions of CIP. Thereby, the inhibitors were found to abolish the actions of CIP. These results therefore suggest that CIP might exert its immune modulatory effects via the production of PGE2.

B7-1 Antigen↗
PubMed2006

Complications of arterial reconstruction in living donor liver transplantation: a single-center experience.

PURPOSE: Microsurgical reconstruction of the fine hepatic arteries (HA) reduces the chance of complications in living donor liver transplantation (LDLT). We reviewed HA reconstructions and analyzed their complications and treatment in a single center. METHODS: Between August 1996 and September 2004, we performed LDLT on 71 adults and 19 children. Patients received a lateral segment graft (n = 16), a left lobe graft (n = 11), an extended left lobe graft (n = 12), or a right lobe graft (n = 51). RESULTS: Hepatic artery reconstruction was performed by end-to-end anastomosis under an operating microscope in all except five adults who received right lobe grafts with loupe magnification. Arterial complications developed in 5 (5.6%) of the 90 patients. Three patients required reanastomosis during their primary operation because of HA thrombosis, anastomotic kinking, and stenosis, respectively. There were three postoperative complications: an anastomotic stenosis, revised by percutaneous transluminal angioplasty; rupture of an HA pseudoaneurysm, treated by embolization; and anastomotic kinking, revised by reanastomosis. The patient with the pseudoaneurysm died of arterial complications. Multivariate analysis of cases before (4/13, 30.8%) and after 2000 (1/77, 1.3%) revealed that surgical experience was the only significant factor in reducing the incidence of HA complications (P = 0.007). CONCLUSION: Case number-dependent anastomotic reliability using microsurgical techniques is important for safer arterial reconstruction.

Adolescent↗
PubMed2006

Percutaneous radiofrequency ablation combined with previous bronchial arterial chemoembolization and followed by radiation therapy for pulmonary metastasis from hepatocellular carcinoma.

A 56-year-old man had a lung metastasis from hepatocellular carcinoma 4.7 cm x 3.4 cm in size located directly adjacent to the pulmonary hilar vessels. The tumor was treated with radiofrequency ablation combined with earlier bronchial arterial chemoembolization and subsequent radiation therapy. A complete remission of the tumor has been observed for 6 months since completion of therapy. Considering that complete treatment of such an intermediate-sized tumor adjacent to the large vessels is usually difficult with radiofrequency ablation alone, this result suggests a possible role for combined therapy for pulmonary neoplasms.

Carcinoma, Hepatocellular↗
PubMed2006

Ex vivo adenoviral gene transfer of constitutively activated STAT3 reduces post-transplant liver injury and promotes regeneration in a 20% rat partial liver transplant model.

Signal transducer and activator of transcription-3 (STAT3) is one of the most important transcription factors for liver regeneration. This study was designed to examine the effects of constitutively activated STAT3 (STAT3-C) on post-transplant liver injury and regeneration in a rat 20% partial liver transplant (PLTx) model by ex vivo adenoviral gene transfer. Adenovirus encoding the STAT3-C gene was introduced intraportally into liver grafts and clamped for 30 min during cold preservation. After orthotopic PLTx, liver graft/body weights and serum biochemistry were monitored, and both a histological study and DNA binding assay were performed. STAT3-C protein expression and its binding to DNA in the liver graft were confirmed by Western blotting and electrophoretic mobility shift assay (EMSA), respectively. This treatment modality promoted post-Tx liver regeneration effectively and rapidly. The serum levels of alanine aminotransferase/aspartate aminotransferase (AST/ALT) and bilirubin decreased in rats with STAT3-C. However, albumin (a marker of liver function) did not. Ex vivo gene transfer of STAT3-C to liver grafts reduced post-Tx injury and promoted liver regeneration. Thus, the activation of STAT3 in the liver graft may be a potentially effective clinical strategy for improving the outcome of small-for-size liver transplantation.

Adenoviridae↗
PubMed2005

Effect of antibodies against intercellular adhesion molecule-1, B7, and CD40 on interleukin-18-treated human mixed lymphocyte reaction.

The interleukin (IL)-18 level in plasma is elevated during the acute rejection after organ transplantation. IL-18 elicits adhesion molecule expression as well as interferon-gamma/IL-12 production and T-cell proliferation in the human mixed lymphocyte reaction, an in vitro model of acute rejection. We examined whether antibodies (Abs) against intercellular adhesion molecule (ICAM)-1, B7, CD40, and CD40, ligand (CD40L) affect the cytokine production and T-cell proliferation. Anti-ICAM-1 and B7 Abs suppressed the cytokine production, while all Abs inhibited T-cell proliferation. ICAM-1 and B7 as well as CD40 may play different roles in the acute rejection.

Antibodies↗
PubMed2005

Involvement of prostaglandin receptors (EPR2-4) in in vivo immunosuppression of PGE2 in rat skin transplant model.

BACKGROUND: Prostaglandin E2 (PGE2) is known to modulate immune responses and is widely viewed as a general immunosuppressant. There have been recognized four receptors for PGE2 (EP1-EP4 receptor) so far, and EP2 and EP4 receptors are mainly involved in the immunosuppressive effect of PGE2 in vitro. In the present study we examined the in vivo immunosuppressive effects of selective EP receptor agonists using a high-responder rat skin transplantation model. MATERIALS AND METHODS: Skin allografts from ACI donors were transplanted onto LEW recipients. Agents were injected everyday between day 0 and day 5 after skin transplantation at the dose of 300 microg/kg subcutaneously. Survival of the skin allograft, histological changes and changes of the intragraft cytokine expressions were analyzed using the reverse transcription polymerase chain reaction (RT-PCR). We also assessed the mixed lymphocyte reaction (MLR) assay using splenocytes. RESULTS: PGE2 significantly prolonged allograft survival (18.8+/-1.5 days) compared with untreated control (14.8+/-0.8 days). EP2R+EP3R+EP4R agonists also prolonged allograft survival (18.0+/-1.0 days) although EP3R agonist or EP2R+EP4R agonists alone failed (15.5+/-0.7, 15.4+/-1.3 days, respectively). RT-PCR analysis in the skin grafts demonstrated IL-10 up-regulation and IFN-gamma down-regulation in all groups except untreated control and EP2R agonist-treated groups. MLR was significantly reduced in groups of EP2R+EP4R agonists, EP2R+EP3R+EP4R agonists and PGE2, compared with untreated control. CONCLUSIONS: The effect of PGE2 to prolong the survival of skin transplant requires the action of a combination of three receptors, i.e., EP2+EP3+EP4.

Animals↗
PubMed2005

Prolonged survival of donor-specific rat intestinal allograft by administration of bone-marrow-derived immature dendritic cells.

It has been reported that intraportal administration of donor antigens induced donor-specific hyporesponsiveness. We studied here the effects of transplantation of BM-derived immature dendritic cells (imDCs) and mature DCs (mDCs) via portal vein on rat small intestinal allograft survival. This study comprised four treatment groups: 1) untreated controls; 2) FK506 alone; 3) intraportal donor-specific BM-derived imDCs transplantation+FK506; 4) mDCs/Tx+FK506. Allograft survival was minimal in control group (5.2+/-0.8 days) and maximal in imDC+FK506 group (28.4+/-3.0 days). The rats in mDC+FK506 group showed systemic inflammatory reaction due to GVHR, and died within 10 days after transplantation. The in vitro MLR reaction using imDCs was also strongly inhibited both in direct and indirect recognition pathways. The impact of imDCs for the specific induction of transplant tolerance may suggest that immunization with donor-specific imDCs has therapeutic potential in organ transplantation.

Animals↗
PubMed2005

Intraductal oncocytic papillary neoplasm of the pancreas with celiac artery compression syndrome and a jejunal artery aneurysm: report of a case.

A 79-year-old woman presented with epigastralgia, and computed tomography showed a 3-cm multiloculated mass with a mural nodule in the head of the pancreas. Arteriography showed stenosis of the celiac artery and a saccular aneurysm, arising from the first jejunal artery. We made a preoperative diagnosis of intraductal papillary adenocarcinoma of the pancreatic head and performed a laparotomy. Transection of the median arcuate ligament failed to restore adequate hepatic blood flow, necessitating construction of celiac vascularization, achieved by a gastroduodenal to jejunal artery anastomosis. After ligation of the jejunal artery aneurysm, we performed a pylorus-preserving pancreaticoduodenectomy. Microscopically, the tumor had papillary intracystic growth, and was lined by plump cells with abundant eosinophilic cytoplasm, consistent with a diagnosis of intraductal oncocytic papillary neoplasm. We discuss this recently recognized entity of papillary neoplasm of the pancreas, and the importance of managing hepatic blood flow during pancreaticoduodenectomy in celiac artery compression syndrome.

Abdominal Pain↗
PubMed2005

Prostaglandin E1-initiated immune regulation during human mixed lymphocyte reaction.

Prostaglandin E1 (PGE1) has therapeutic value for transplantations due to its microvascular activity. Interleukin (IL)-18, which is elevated in plasma during the acute rejection after organ transplantation, elicits the expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40, and CD40 ligand (CD40L) on monocytes as well as the production of interferon (IFN)-gamma and IL-12 and proliferation of T-cells during the human mixed lymphocyte reaction (MLR) in an in vitro model of acute rejection. In contrast, PGE1 inhibits all the adhesion molecule expression, cytokine production and T-cell proliferation in the presence of IL-18. The effects of PGE1 depend on stimulation of the IP/EP2/EP4-receptor, and thus, PGE1 might have therapeutic potential for treating acute rejection due to its immune regulatory effect.

Alprostadil↗
PubMed2004

Effect of beta2-adrenergic receptor agonists on intercellular adhesion molecule (ICAM)-1, B7, and CD40 expression in mixed lymphocyte reaction.

BACKGROUND: The plasma interleukin (IL)-18 level is elevated in acute rejection after organ transplantation. Although beta2-adrenergic receptor (AR) agonists suppress the rejection of organ and tissue transplants, little is known about their action mechanisms. We examined the effects of endogenous catecholamines and beta2-AR agonists on the expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40, and CD40 ligand (CD40L) in human mixed lymphocyte reaction (MLR) and in an in vitro model of acute rejection in the presence or absence of IL-18. METHODS: ICAM-1, B7.1 B7.2, CD40, and CD40L expression on monocytes was measured by flow cytometry, and the production of interferon (IFN)-gamma and IL-12 was determined by enzyme-linked immunosorbent assay. Lymphocytes proliferation in MLR was measured by [3H]-thymidine uptake. The relevant AR subtypes were characterized using subtype-selective agonists and antagonists. RESULTS: beta2-AR agonists inhibited the expression of ICAM-1 and CD40 during MLR in the absence of IL-18. Among IL-18-induced expression of ICAM-1, B7.1, B7.2, CD40, and CD40L, beta2-AR agonists inhibited ICAM-1 and CD40 expression. beta2-AR agonists prevented the production of IFN-gamma and IL-12 in the presence of IL-18 but had no effect in the absence of IL-18. beta2-AR agonists inhibited lymphocyte proliferation in IL-18-treated MLR. CONCLUSIONS: We found that beta2-AR agonists strongly inhibited the expression of ICAM-1 and CD40, irrespective of the presence or absence of IL-18, which is different from that of histamine and prostaglandin E2.

Adrenergic beta-Agonists↗
PubMed2004

The impact of portal infusion with donor-derived bone marrow cells and intracellular cytokine expression of graft-infiltrating lymphocytes on the graft survival in rat small bowel transplant model.

BACKGROUND: Intraportal administration of alloantigen is reported to reduce antigen-specific immune responses, although the underlying mechanisms for the reduced immunological reactions, especially those of the graft, are poorly understood. We examined intracellular cytokine production by graft-infiltrating lymphocytes (GILs) and peripheral blood lymphocytes (PBLs) to elucidate the underlying mechanisms of beneficial effects on intraportal infusion of donor cells in rat small bowel transplantation (SBT). METHODS: Recipient rats (Lewis) were transplanted with small bowel from ACI rats. Tacrolimus (Tac) was injected daily from days 0 to 4. Bone marrow cells of ACI rats were infused via the portal or tail vein on the day of surgery. On day 5, both GILs and PBLs collected from SBT graft and peripheral blood, respectively, were analyzed for intracellular cytokine production of recipient-derived alphabeta-T cells. The Th1/Th2 balance in each group was designated as the ratio of the percentage of GILs or PBLs staining positive for intracellular IL-4 or IFN-gamma, respectively. The total cell numbers of GILs from SBT graft were also counted. RESULTS: Survival of recipients was markedly prolonged by the combination of Tac and donor-specific bone marrow infusion via the portal vein (DSBMI-PV-Tac) compared with the untreated control, Tac alone, or DSBMI tail vein plus Tac. DSBMI-PV-Tac significantly decreased the total cell numbers of GILs and also induced remarkable Th2-type response in GILs. CONCLUSIONS: Our results indicate that DSBMI-PV-Tac decreased GILs and enhanced Th2-type response in SBT graft, both of which are associated with a significant prolongation of graft survival in SBT.

Animals↗
PubMed2004

Failure of the gut barrier system enhances liver injury in rats: protection of hepatocytes by gut-derived hepatocyte growth factor.

OBJECTIVE: Clinical and experimental studies suggest that impairment of the mucosal barrier system increases gut-derived endotoxin in the portal blood, which causes liver injury. The aim of this study was to elucidate the mechanism of liver injury caused by gut defence failure. DESIGN: Wistar rats were administered either enteral lipopolysaccharide (LPS) or LPS via the portal vein. METHODS: Blood samples were collected via the inferior vena cava at necropsy. Serum aspartate transaminase (AST) and alanine transaminase (ALT) were analysed by standard enzymatic procedures and cytokines [tumour necrosis factor-alpha, interleukin (IL)-1beta, interferon-gamma, IL-6 and hepatocyte growth factor (HGF)] were measured by enzyme-linked immunosorbent assay. Livers were removed and snap-frozen in liquid nitrogen. CD14, CD68, Toll-like receptor (TLR) 2, TLR4 and Fas ligand (FasL) were analysed immunohistochemically. Expression of TLR2, TLR4 and CD14 mRNA was determined by reverse transcriptase-polymerase chain reaction. RESULTS: In enterally-treated rats, AST and ALT were not increased and cytokine levels were under the limits of detection in the absence of a rise in HGF. Enteral administration of LPS increased HGF dose-dependently. Injection of LPS in the portal vein resulted in significant increases in AST, ALT, tumour necrosis factor-alpha, IL-1beta, interferon-gamma and IL-6 levels, but no change in HGF levels. Immunohistochemical analysis revealed that intraportal LPS administration increased CD14, TLR4, CD68 and FasL. Reverse transcriptase-polymerase chain reaction analysis demonstrated that TLR4 mRNA expression was upregulated 0.5 h after intraportal LPS administration. CONCLUSION: s Our data suggest that Kupffer cell activation mediated by intraportal LPS via TLR4 is involved in liver injury, possibly through both tumour necrosis factor-alpha/IL-1beta and FasL, and that lack of HGF activity in the impaired gut could not counteract liver injury.

Alanine Transaminase↗
PubMed2004

Hepatic infarction following abdominal interventional procedures.

To clarify the incidence, background, and progress of hepatic infarction following interventional procedures, cases of hepatic infarction following interventional procedures at our department during the last decade were identified by reviewing the clinical records of 1982 abdominal angiography and interventional procedures and records of abdominal CT. Nine episodes (0.5%) in 8 patients were identified as hepatic infarction following an interventional procedure. Five episodes were preceded by embolization of the hepatic or celiac artery at emergency angiography for postoperative bleeding with hemorrhagic shock. Three episodes followed the elected interventional procedure for hepatocellular carcinoma, and the remaining episode occurred after 12 months of chemoinfusion through an indwelling catheter in the hepatic artery and portal vein. Hepatic arterial occlusion in all episodes and portal venous flow abnormality in 5 episodes were observed on angiography. Four patients whose liver function was initially impaired died of hepatic infarction, although the extent of the disease on CT did not appear to be related to the mortality. Multiple risk factors, including arterial insufficiency, were observed in each patient. The incidence of hepatic infarction following interventional procedures in this series was low but sometimes fatal, and occurred most frequently in emergency embolization in hemorrhagic shock.

Abdomen↗
PubMed2004

Increased heme oxygenase-1 and decreased delta-aminolevulinate synthase expression in the liver of patients with acute liver failure.

Acute liver failure (ALF) remains a serious problem in critical care with a high rate of mortality. Although the pathophysiology of ALF has not been fully elucidated, oxidative stress has been in part implicated in its pathogenesis. Heme oxygenase-1 (HO-1) is known to be induced not only by its substrate, heme, but also by various oxidative stresses, and thought to play an important role in the protection of the host from oxidative tissue injuries. In the present study, we examined expression of HO-1 as well as the non-specific delta-aminolevulinate synthase (ALAS-N, or ALAS1), the rate-limiting enzyme in heme catabolism and biosynthesis, respectively, in the livers of patients with ALF. Compared with livers from control subjects who had various disorders, but normal hepatic function, HO-1 in the liver of ALF patients was highly up-regulated at both transcriptional and protein levels. Immunohistochemical studies demonstrated that HO-1 expression occurred predominantly in hepatocytes, but not in non-parenchymal cells. In contrast to HO-1, ALAS1 gene expression was markedly down-regulated in ALF patients compared with controls. These findings suggest that, in the liver of ALF patients, there may be an increase in free heme concentration which up-regulates HO-1 gene expression, while down-regulating ALAS1 gene expression, resulting in markedly altered heme metabolism and liver function.

5-Aminolevulinate Synthetase↗
PubMed2003

Effect of prostaglandin E2 on intercellular adhesion molecule-1 and B7 expression in mixed lymphocyte reaction.

BACKGROUND: The elevation of plasma interleukin (IL)-18 levels and the expression of intercellular adhesion molecule (ICAM)-1 and B7 on monocytes are involved in acute rejection. Prostaglandin (PG) E2 suppresses the rejection in animal transplantation models; however, little is known about its action mechanism. We examined the effect of PGE2 on the expression of ICAM-1 and B7 in the human mixed leukocyte reaction (MLR) in the presence or absence of IL-18. METHODS: We measured the expression of ICAM-1, B7.1, and B7.2 on human monocytes by flow cytometry and determined the associated production of interferon-gamma and IL-12 by enzyme-linked immunosorbent assay. The modulatory effects of PGE2 and the relevant PGE2 receptor subtypes were characterized pharmacologically. RESULTS: PGE2 inhibited the expression of ICAM-1, B7.1, and B7.2 on monocytes in MLR in a concentration-dependent manner. Whereas IL-18 significantly induced the expression of ICAM-1, B7.1, and B7.2 on monocytes in MLR and the production of interferon-gamma and IL-12, PGE2 inhibited these IL-18-initiated enhancements. The effects of PGE2 were mimicked by selective EP2 and EP4 agonists, but not by EP1 and EP3 agonists. CONCLUSION: PGE2 strongly inhibited MLR with respect to the expression of ICAM-1, B7.1, and B7.2 via the EP2 and EP4 receptors, irrespective of the presence or absence of IL-18. In the previous study, histamine inhibited ICAM-1 expression in the presence of IL-18 but had no effect in the absence of IL-18. These results indicate that the inhibitory effect of PGE2 may be more general and stronger than that of histamine and may play an important role in future immunosuppressive strategies.

B7-1 Antigen↗
PubMed2003

Induction of indirect donor-specific hyporesponsiveness by transportal RT1-peptide pulse in rat skin transplantation.

In the present study, we examined whether transportal pulse of class I major histocompatibility complex (MHC) allopeptides can induce indirect (non-chimeric) donor-specific hyporesponsiveness, using a high-responder rat skin transplantation model. Two donor-specific 8-amino acid peptides corresponding to residues 58-65 and 70-77 in the alpha(1) helical region of RT1.A(a) were synthesized. In order to test immunogenicity of these peptides, mixed lymphocyte reaction (MLR) was performed. Then, 100-microg portions of peptides were injected into recipient Lewis (LEW, RT1.A(l)) rats via the portal vein 14 days before skin transplantation. Skin allografts from August Copenhagen Irish (ACI, RT1(a)) or Wistar King A (WKA, RT1(k), third-party) donors were transplanted to LEW (RT1(l)) recipients. Transportal pulse of residues 58-65 and 70-77 prolonged graft survival significantly in ACI-to-LEW skin transplantation (17.6+/-0.40 and 18.0+/-0.45 days) compared with control (14.2+/-0.37 days). However, pulse of residues 106-113, a non-donor-specific control, did not prolong graft survival time (14.6+/-0.40 days) in the same combination. Regarding the third-party donor, residues 58-65 injected into LEW recipients had no effect on survival time of skin grafts (19.0+/-0.84 days) derived from WKA donors compared with the untreated WKA-to-LEW control (19.4+/-0.93 days). Transportal pulse of RT1.A(a) peptides induced donor-specific hyporesponsiveness even in a high-responder rat skin transplantation model. Our results suggest that graft enhancement by transportal exposure to donor cells may not be induced by a chimeric process but, instead, by an indirect mechanism not involving intervention of viable donor cells.

Amino Acid Sequence↗
PubMed2003

Annexin V assay-proven anti-apoptotic effect of ascorbic acid 2-glucoside after cold ischemia/reperfusion injury in rat liver transplantation.

Controversy exists over whether the predominant cell death of hepatocytes is due to apoptosis or necrosis after ischemia/reperfusion injury. In this study we investigated the predominant cell death of hepatocytes after cold ischemia/reperfusion injury using the Annexin V-based assay, and evaluated the anti-apoptotic effect of ascorbic acid 2-glucoside (AA-2G) added to the University of Wisconsin solution (UW solution) in rat liver transplantation. The retrieved liver was preserved in 4 UW solution for 24 h, and then transplanted orthotopically to the syngeneic Wistar recipient. The animals were divided into 2 groups, a control group (n=10), in which liver grafts were preserved in UW solution (4), and an AA-2G group (n=10), in which liver grafts were preserved in UW solution (4) with AA-2G (100 ug/ml). The serum AST level 4 h after reperfusion in the control group was significantly suppressed in the AA-2G group, and the bile production of the liver graft in the AA-2G group was well recovered. The mean survival time in the AA-2G group was significantly improved compared with that in the control group. Annexin-V and Propidium iodide staining 4 h after reperfusion showed a significantly higher percentage of viable hepatocytes in the AA-2G group compared with the control group (93.4 +/- 2.0 vs. 80.3 +- 2.1%, P<0.05). In the control group, the main cell death of hepatocytes was apoptosis (early apoptosis: 10.0 +- 4.7%, late apoptosis: 6.4 +/- 1.7%). The addition of AA-2G to the UW solution significantly inhibited both early and late apoptotic cell death 4 h after reperfusion (early apoptosis: 0.98 +/- 0.88%, late apoptosis: 2.2 +/- 1.1%). The expression of caspase 9 in the immunostaining of the liver graft was suppressed in the AA-2G group compared with in the control group. Our study using the Annexin V-based assay provided evidence that the predominant cell death of hepatocytes was apoptosis after 24 h cold ischemia/reperfusion injury in rat liver transplantation. The addition of AA-2G to the UW solution attenuated 24 h cold ischemia/reperfusion injury by inhibiting the apoptosis of hepatocytes.

Animals↗