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Takahito Yagi

Publications and source records attributed to Takahito Yagi.

25 records · Page 2Linked to original sources
PubMed2003

Suppression of allogeneic response by viral IL-10 gene transfer.

Th1 cell activation and cytokine production shift the balance between Th1 and Th2, favoring the upregulation of proinflammatory activity that leads to destruction of allogeneic hepatocytes following transplantation. Th2-type cytokines. such as IL-10, have immune regulatory function. The aim of this study was to determine the antirejection efficacy of allogeneic hepatocytes with spheroidal shape (spheroids) genetically modified with viral IL-10 (vIL-10). Allogeneic hepatocyte spheroids, transferred vIL-10 gene by using adenovirus as the vector, were transplanted into the spleen of Nagase's analbuminemic rats (NAR). NAR transplanted with vIL-10-transfected hepatocytes showed an abrupt rise in serum albumin levels that peaked on day 7 and remained at high levels up to day 21 after transplantation. The peak level of albumin on day 7 in vIL-10-transfected NAR was eminently higher than that in nontransfected NAR. Histopathological analysis revealed that in nontransfected NAR hepatocyte spheroids were more or less rejected on day 4, and, in contrast, vIL-10-transfected spheroids were still not rejected on day 14. This protective effect correlated with sustained high vIL-10 level in the splenic vein in NAR transplanted with vIL-10-transfected hepatocyte spheroids, suggesting that vIL-10 secreted from the transplanted hepatocytes induced an active suppression of allogeneic response. This study provides evidence to support the possibility of using vIL-10 gene therapy to prevent allogeneic response in hepatocyte transplantation.

Adenoviridae↗
PubMed2002

Effect of histamine on intercellular adhesion molecule-1 expression and production of interferon-gamma and interleukin-12 in mixed lymphocyte reaction stimulated with interleukin-18.

BACKGROUND: Interleukin (IL)-18 was identified as an interferon (IFN)-gamma-inducing factor and was demonstrated to up-regulate the expression of intercellular adhesion molecule (ICAM)-1 on human monocytes. In organ transplantation, elevation of plasma IL-18 levels has been reported during acute rejection. In the present study, we examined the effect of IL-18 on human mixed lymphocyte reaction (MLR), an in vitro model of acute rejection after organ transplantation. We also investigated the modulatory effects of histamine on IL-18 action because histamine has been demonstrated to be a modulator of IL-18 effect and a mediator of inflammation. METHODS: We measured the expression of ICAM-1 on human monocytes in MLR in the presence or absence of IL-18 by flow cytometer and determined the associated production of IFN-gamma and IL-12 by ELISA. The modulatory effects of histamine and the relevant histamine receptor subtypes were characterized pharmacologically. RESULTS: The expression of ICAM-1 on monocytes in MLR was markedly enhanced by the addition of IL-18 in a concentration- and time-dependent manner. In parallel to ICAM-1 up-regulation, IL-18 significantly enhanced the production of IFN-gamma and IL-12 in MLR. Histamine concentration-dependently inhibited ICAM-1 expression and cytokine production in MLR stimulated with IL-18, whereas histamine alone did not show any effects on these responses in the absence of IL-18. The effects of histamine on both ICAM-1 expression and cytokine production were mimicked by the selective H2-receptor agonists 4-methylhistamine and dimaprit and were antagonized by the H2-receptor antagonist famotidine but not by H1- and H3-receptor antagonists. CONCLUSION: IL-18 strongly enhanced human MLR with respect to ICAM-1 expression and cytokine production. The fact that histamine could inhibit the IL-18-stimulated MLR implies that immunomodulation by histamine and selective H2-receptor agonists may have an important role in future immunosuppressive strategies.

Histamine↗
PubMed2002

High-flow-rate haemodiafiltration as a brain-support therapy proceeding to liver transplantation for hyperacute fulminant hepatic failure.

In fulminant hepatic failure (FHF), rapidly progressive cerebral oedema remains the main fatal complication and an obstacle in liver transplantation. A 29-year-old Japanese woman presented with sudden-onset hepatic encephalopathy and jaundice. Hepatic encephalopathy deteriorated within 2 days of the onset of jaundice. She manifested extensory sustained clonus and was responsive only to pain. Diffuse cerebral oedema was noted on brain computerized tomography (CT) scan. Urgent living-donor liver transplantation (LDLT) at the time of admission was abandoned because of deterioration of neurological status and radiologically evident diffuse cerebral oedema. Instead, a high-flow-rate (7.2-9.0 l/h) haemodiafiltration with a high-performance membrane was commenced, combined with plasma exchange. This treatment regimen resulted in a gradual improvement of hepatic encephalopathy and complete disappearance of cerebral oedema within 7 days. Liver regeneration did not occur during this period, as evident by CT scan volumetry and serological tests. LDLT was subsequently performed using the right liver lobe of the patient's brother. Our case suggests that high-flow-rate haemodiafiltration with a high-performance membrane, combined with plasma exchange, could potentially be brain-support therapy for patients with FHF, and may contribute, when combined with liver transplantation, to the improvement of prognosis in hyperacute FHF.

Adult↗
PubMed2002

[Infection and rejection].

Forty-one living donor liver transplantations (LDLT), including 11 pediatric and 30 adult recipients, were performed in Okayama University Hospital. Thirty-seven patients survive (overall survival rate 90.2%). Postoperative infection and rejection were analyzed. The incidence of bacterial and cytomegalovirus infection was 26.8% and 22%, respectively, but no patient developed lethal infection. Posttransplant lymphoproliferative disease occurred in 3 recipients who received additional pre- or postoperative intensive immunosuppressive therapy. Even though all recipients were administered a tacrolimus-based double or triple regimen including prophylactic programmed pulse therapy (methylpredonisone 10 mg/kg, days 5 to 7), 30 rejection episodes were observed in 19 patients(46.3%). Two recipients died of both steroid- and OKT-3-resistant rejection. Routine daily Doppler ultrasonography (US) revealed the presence of early severe rejection with hepatic hemodynamic changes in 7 patients. Patients exhibiting rejection with hemodynamic changes had a significantly shorter incubation period (8.8 +/- 2.2 vs 38.7 +/- 29.6 days, p < 0.01), more severe histological features(rejection activity index, 6.1 +/- 1.2 vs 3.0 +/- 0.5, p < 0.001), and higher peak alanine aminotransferase value (883 +/- 354 IU/L vs 198 +/- 115 IU/L, p < 0.01) than in those exhibiting rejection without hemodynamic changes. Diagnostic programmed pulse therapy plus frequent routine Doppler US may be useful in the diagnosis of and therapy for earlier and more severe acute rejection in LDLT.

Adult↗
PubMed2002

[Radiofrequency ablation for hepatocellular carcinoma].

We performed radiofrequency ablation (RFA) for 14 patients with hepatocellular carcinoma (HCC) between May 2001 and March 2002. The underlying hepatic disease was type C liver cirrhosis in all patients. Seven patients had a solitary lesion, and 7 patients had multiple lesions. RFA was chosen for the primary tumor in 5 cases and for a recurrent tumor in 9 cases. Three cases of well differentiated HCC were included. Transcatheter arterial embolization (TAE) was performed in 10 cases simultaneously. Nine patients received RFA under general anesthesia (open laparotomy: 5 cases, transthoracic: 1 case, CT guided: 2 cases, US guided: 1 case) and 5 patients under local anesthesia (CT guided: 2 cases, US guided: 3 cases). RFA was performed for 12 minutes in each session and the mean number of sessions per patient was 3.2. Excellent ablation was achieved in all cases according CT evaluation, and no additional therapy was needed. No recurrences have been found in any cases so far. RFA for HCC achieved excellent therapeutic effect in combination with other therapies as multimodal therapy.

Aged↗
PubMedDate not supplied

The role of a protease inhibitor against hepatectomy.

BACKGROUND/AIMS: Nafamostat Mesilate (NM) is a synthetic serine protease inhibitor that is capable of inhibiting the various coagulation factors. To determine whether NM may also be useful in attenuating operative invasiveness, we investigated the effects of perioperative administration of NM on postoperative serum levels of proinflammatory cytokine IL-6 and hepatocyte growth factor (HGF). METHODOLOGY: Thirty patients undergoing hepatectomy with hepatocellular carcinoma, biliary carcinoma and metastatic colorectal cancer were enrolled in this study. These patients were separated into two groups; high invasive group (resected liver volume: 1000cm3 <) and less invasive group (resected liver volume: 1000cm3 >). The high invasive group of 11 patients received perioperative administration of NM (Group NM), while the less invasive group of 19 patients did not (Group C). Serum levels of IL-6, HGF and soluble IL-6 receptor (sIL-6R) were simultaneously measured on preoperative and postoperative day ('day 0', 'day 7'). RESULTS: Serum IL-6 levels on day 0 were significantly elevated and returned to preoperative levels on day 7 in both groups, and the serum IL-6 level in Group NM on day 0 was significantly lower than that in Group C on day 0. Serum HGF levels on day 0 and day 7 were significantly higher in Group NM than those in Group C. Compared with healthy control subjects, the higher serum level of HGF on the preoperative day in all patients was attributable to tumor-burden. The sIL-6R levels on day 0 decreased in both groups, and their levels in Group NM were significantly lower than those in Group C, suggesting that increased synthesis of IL-6/sIL-6R complex which could accelerate liver regeneration. CONCLUSIONS: These results suggested that perioperative administration of NM may attenuate surgical stress by decreasing production of proinflammatory cytokine IL-6, and may accelerate liver regeneration through stimulation with the IL-6/sIL-6R complex and possible involvement of increased production of HGF.

Aged↗