Biomedical subjects

T Takayama

Publications and source records attributed to T Takayama.

At least 109 records · Page 6Linked to original sources

PubMed2000

Microchimerism, donor dendritic cells, and alloimmune reactivity in recipients of Flt3 ligand-mobilized hemopoietic cells: modulation by tacrolimus.

Flt3 ligand (FL) is a potent hemopoietic growth factor that strikingly enhances stem cells and dendritic cells (DC) in vivo. We examined the impact of infusing FL-mobilized bone marrow (BM) cells on microchimerism and anti-donor reactivity in normal and tacrolimus-immunosuppressed, noncytoablated allogeneic recipients. BM from B10 (H2b) mice given FL (10 microg/day; days 0-8; FL-BM) contained a 7-fold higher incidence of potentially tolerogenic immature CD11c+ DC (CD40low, CD80low, CD86low, MHC IIlow) that induced alloantigen-specific T cell hyporesponsiveness in vitro. C3H (H2k) mice received 50 x 106 normal or FL-BM cells (day 0) and tacrolimus (2 mg/kg/day; days 0-12). On day 15, enhanced numbers of donor (IAb+) cells were detected in the thymi and spleens of FL-BM recipients. Tacrolimus markedly enhanced microchimerism, which declined as a function of time. Ex vivo splenocyte proliferative and CTL responses and Th1 cytokine (IFN-gamma) production in response to donor alloantigens were augmented by FL-BM infusion, but reduced by tacrolimus. Systemic infusion of purified FL-BM immature DC, equivalent in number to that in corresponding whole BM, confirmed their capacity to sensitize, rather than tolerize, recipient T cells in vivo. In vitro, tacrolimus suppressed GM-CSF-stimulated growth of myeloid DC from normal BM much more effectively than from FL-BM without affecting MHC class II or costimulatory molecule expression. Infusion of normal B10 BM cells at the time of transplant prolonged C3H heart allograft survival, whereas FL-BM cells did not. A therapeutic effect of tacrolimus on graft survival was observed in combination with normal, but not FL-BM cells. These findings suggest the need for alternative immunosuppressive strategies to calcineurin inhibition to enable the engraftment, survival, and immunomodulatory function of FL-enhanced, immature donor DC.

Adjuvants, Immunologic↗

PubMed2000

Altered p21(WAF1/CIP1) expression is associated with poor prognosis in extrahepatic bile duct carcinoma.

This study was designed to determine the clinical implications of p21(WAF1/CIP1) expression and the relationship between p21(WAF1/CIP1) expression and p53 status in extrahepatic bile duct carcinoma (EBDC). Low p21(WAF1/CIP1) expression was immunohistochemically detected in 23 (67.6%) of 34 EBDCs, moderate in six (17.7%), and high in five (14.7%). Kaplan-Meier curves showed that low and high p21(WAF1/CIP1) expressions were significantly associated with shortened disease-free survival (low vs. moderate, P=0.02; high vs. moderate, P=0.01). There was no correlation between p21(WAF1/CIP1) and p53 expression. These findings suggest that altered p21(WAF1/CIP1) expression exerts an adverse influence on the prognosis of EBDC.

Adenocarcinoma↗

PubMed2000

Loss of p16(INK4) protein, alone and together with loss of retinoblastoma protein, correlate with hepatocellular carcinoma progression.

To investigate the role of p16(INK4) protein absence in hepatocellular carcinoma progression, we examined p16(INK4) expression immunohistochemically in 81 primary and 23 metastatic lesions of hepatocellular carcinoma, in which retinoblastoma protein status had been determined. p16(INK4) protein was absent from 44% of the total of 104 tumors. The rate of p16(INK4) absence was twice as high in metastatic lesions (74%) compared with primary lesions (36%) (P=0.001). Loss of p16(INK4) and/or retinoblastoma protein was significantly associated with decreased tumor differentiation, vascular invasion and metastasis. In conclusion, p16(INK4) protein absence, alone and together with loss of retinoblastoma protein, contributes to hepatocellular carcinoma progression.

Carcinoma, Hepatocellular↗

PubMed2000

The significance of hepatitis B virus DNA detected in hepatocellular carcinoma of patients with hepatitis C.

BACKGROUND: Recently, it has been reported that hepatitis B virus (HBV) DNA is detected in cancerous liver tissues in some hepatitis B surface antigen negative chronic hepatitis C patients with hepatocellular carcinoma (HCC). However, the significance of HBV DNA detected in such cases remains unclear. METHODS: The authors determined the presence or absence and the titers of HBV DNA in the liver tissue of anti-hepatitis C virus (HCV) positive/HBs antigen negative patients with HCC by polymerase chain reaction (PCR) and Southern hybridization, and correlated them with clinicopathologic parameters. RESULTS: HBV DNA was found in cancerous liver tissues from 12 (50.0%) of the 24 patients studied. However, Southern hybridization of genomic DNA in the cancerous liver tissues led to detection of HBV DNA in only 3 (12.5%) of the 24 patients, suggesting that the copy number of HBV DNA may be very low in most cases. Indeed, the titration of HBV DNA in cancerous liver tissues performed by the end point dilution method revealed that most contained less than one copy of HBV DNA per cell, although cells of monoclonal origin carrying integrated HBV DNA should have at least one copy of it. There was no significant difference in HBV DNA positivity between the HCC patients with and without underlying cirrhosis. CONCLUSIONS: The results of this study corroborate previous reports of frequent detection of HBV DNA in the liver tissue of anti-HCV positive/HBs antigen negative patients with HCC, but do not support an essential role of HBV in hepatocarcinogenesis in patients with chronic hepatitis C and occult HBV infection.

Aged↗

PubMed2000

Virologic analysis of non-B, non-C hepatocellular carcinoma in Japan: frequent involvement of hepatitis B virus.

Serum and liver tissues from hepatitis B surface antigen-negative/anti-hepatitis C virus (HCV)-negative (non-B, non-C) hepatocellular carcinoma (HCC) patients in Japan were examined for the presence of hepatitis B virus (HBV), HCV, and TT virus (TTV) by polymerase chain reaction. The studies evaluated the contribution of these viruses to pathogenesis of HCC. HBV DNA was detected in the sera of 20 (47.6%) of 42 non-B, non-C HCC patients, which was significantly higher than in age-matched controls without liver disease (P<.001). In 8 of 12 patients with liver tissues available, HBV DNA was detected in cancerous and adjacent noncancerous liver tissues. No HCV RNA was detected. The positivity for TTV DNA was not significantly different between HCC patients and controls. These results indicate that HBV is associated with a substantial proportion of non-B, non-C HCC cases in Japan. The role of HBV in hepatocarcinogenesis in such patients needs to be clarified.

Adult↗

PubMed2000

Peri-operative blood lactate levels in recipients of living-related liver transplantation.

BACKGROUND: The role of changes in peri-operative blood lactate levels in recipients of living-related liver transplants has not yet been clarified. METHODS: Forty-three recipients were included in this study. Blood lactate, plasma total bilirubin, aminotransferase, body temperature, and gastric mucosal PCO2 levels were measured at six time points during surgery: just before the initiation of surgery, just after dissection of the hepatic vasculature, at the end of the anhepatic phase, and 30, 60, and 120 min after reperfusion. We calculated the rate of lactate accumulation during the pre-anhepatic and anhepatic phases and the elimination rate during reperfusion (neohepatic phase), and examined the correlation between these results and the clinical findings. RESULTS: The rate of lactate elimination during the neohepatic phase was correlated with the ratio of graft weight to standard liver volume (P<0.0001). There was also a significant correlation between the rate of lactate accumulation during the pre-anhepatic phase and the preoperative total bilirubin levels (P=0.0008). CONCLUSIONS: Each pre-anhepatic, anhepatic, and neohepatic phase had a characteristic blood lactate profile. The graft size strongly affected lactate levels during the early neohepatic phase.

Adult↗

PubMed2000

Left hemihepatectomy in living donors with a thick middle hepatic vein draining the caudal half of the right liver.

Donor safety is the first consideration in living related liver transplantation. Left hemihepatectomy including the middle hepatic vein is a reasonable donor procedure for obtaining a large graft for living related liver transplantation. This procedure, however, needs to be modified in donors with hepatic venous variation. While carrying out donor hepatectomy, we encountered two cases showing a variant form of hepatic venous drainage comprising a thick middle hepatic vein draining segment 6 of the liver. This variation made it necessary to preserve the middle hepatic vein in the donor liver remnant. Failure to recognize such a variant would result in congestion in the remaining right liver of the donor. To guarantee donor safety, evaluation of the drainage area of the corresponding hepatic vein is a matter of great importance in donor hepatectomy.

Adolescent↗

PubMed2000

Intraoperative Doppler color flow imaging combined with regulation of arterial inflow during surgery for intrahepatic arterioportal fistula.

Large fistulas associated with impaired liver function should be treated by direct obliteration or removal of the shunt orifice. In a large shunt with the portal branch lying on the arterial branch, identification of the exact site of the fistula can be a challenge. We report a case of impaired liver function due to a large intrahepatic arterioportal fistula. The site of the shunt orifice could not be located accurately by preoperative imaging. However, intraoperative color Doppler ultrasonography and the simple regulation of arterial inflow clearly demonstrated the shunt orifice. This original technique has allowed the precise definition of the problem and has optimized the surgical treatment for this critical condition. Consequently, it should be considered a new option for the definition and management of large intrahepatic arterioportal fistulas.

Aged↗

PubMed2000

Effects of liver-derived dendritic cell progenitors on Th1- and Th2-like cytokine responses in vitro and in vivo.

There is evidence that donor-derived dendritic cells (DC), particularly those at a precursor/immature stage, may play a role in the immune privilege of liver allografts. Underlying mechanisms are poorly understood. We have examined the influence of in vitro generated mouse liver-derived DC progenitors (DCp) on proliferative, cytotoxic, and Th1/Th2 cytokine responses induced in allogeneic T cells. Liver DCp, propagated in GM-CSF from C57B10 mice (H2b), induced only minimal proliferation, and weak cytotoxic responses in allogeneic (C3H; H2k) T cells compared with mature bone marrow (BM)-derived DC. Flow-cytometric analysis of intracellular cytokine staining revealed that mature BM DC, but not liver DCp, elicited CD4+ T cell production of IFN-gamma. Intracellular expression of IL-10 was very low in both BM DC- and liver DCp-stimulated CD4+ T cells. Only stimulation by liver DCp was associated with IL-10 secretion in primary MLR. Notably, these liver DCp cocultured with allogeneic T cells stained strongly for IL-10. Following local (s.c. ) injection in allogeneic recipients, both BM DC and liver DCp homed to T cell areas of draining lymph nodes and spleen, where they were readily detected by immunohistochemistry up to 2 wk postinjection. Liver DCp induced clusters of IL-10- and IL-4-secreting mononuclear cells, whereas Th2 cytokine-secreting cells were not detected in mice injected with mature BM DC. By contrast, comparatively high numbers of IFN-gamma+ cells were induced by BM DC. Modulation of Th2 cytokine production by donor-derived DCp may contribute to the comparative immune privilege of hepatic allografts.

Animals↗

PubMed2000

Randomized trial of the usefulness of a bile leakage test during hepatic resection.

HYPOTHESIS: An intraoperative bile leakage test will assist in decreasing postoperative bile leakage in patients undergoing hepatic resection. DESIGN: Randomized controlled trial. SETTING: University hospital. PATIENTS: One hundred three consecutive patients who were scheduled for hepatic resection without biliary reconstruction. Associated cirrhosis was present in 49 patients (48%), and only 24 (23%) had normal livers. Patients were randomized to undergo (n = 51) or to not undergo (n = 52) a bile leakage test, according to age, liver function, and hepatectomy method. The 2 groups were similar in baseline demographics. INTERVENTION: A bile leakage test was carried out by injecting isotonic sodium chloride solution through the cystic duct, and interrupted suturing was taken for a bile leak on the transected liver surface. MAIN OUTCOME MEASURES: The incidence of postoperative bile leakage and the length of the postoperative hospital stay. Bile leakage was defined as continuous drainage, with a bilirubin level of 86 micromol/L or more (> or =5 mg/dL), beyond 1 week. RESULTS: Twenty-one patients (41%) in the test group showed a bile leak, and a median of 1 site (range, 1-6 sites) was closed during the test. Postoperative bile leakage was observed in 3 patients (6%) in the test group and in 2 (4%) in the control group (P = .99). The odds ratio of the event was 1.53 (95% confidence interval, 0.25-9.44). The median postoperative hospital stay lasted 17 (range, 13-47) and 18 (range, 12-41) days for the test and control groups, respectively (P =.98). CONCLUSION: This randomized trial suggested no advantage in using a bile leakage test during hepatic resection.

Adult↗

PubMed2000

Reconstruction of small and fragile bile ducts without mucosa-to-mucosa anastomosis.

We describe a simple and easy technique for performing choledochojejunostomy without the need to suture the full thickness of the ductal and intestinal walls for patients in whom standard choledochojejunostomy is difficult because the stumps of the residual bile ducts are small and fragile. This technique is useful in partial liver transplantation or after hepatectomy that includes removal of the extrahepatic bile ducts. The procedure involves the placing of external biliary drainage tubes through a Roux-en-Y jejunal loop, positioned transanastomotically, and the use of an external jejunostomy to decompress the loop. The tubes are fixed to the jejunal loop by a purse-string suture and to the duct by simple ligation or a purse-string suture. Anastomosis is performed by suturing the connective tissue and liver parenchyma around the ductal stump to the seromuscular layer of the intestine. Choledochojejunostomy according to this method was performed in 5 cases; the biliary drainage tubes were removed 1 to 4 months after surgery. The only complications were cerebellar infarction and cholangitis, both of which resolved with conservative treatment. We consider that this technique will be helpful as a last-ditch measure when standard choledochojejunostomy, with suturing of the full thickness of the walls of the duct and intestine to secure mucosa-to-mucosa apposition, is impossible because of small and fragile bile ducts.

Anastomosis, Surgical↗

PubMed2000

Increased uptake of 99mTc-HL91 in tumor cells exposed to X-ray radiation.

99mTc-HL91, a hypoxic marker, may be a predictor of tumor response to radiotherapy and an indicator of tumor oxygenation in the course of treatment. In this study, serial changes in 99mTc-HL91 uptake were observed in the normoxic condition in a human bladder cancer cell line exposed to a single dose or a fractionated dose of 10 Gy with an x-ray beam. The uptake per cell increased during cell growth retardation induced by the irradiation. This finding indicates that 99mTc-HL91 uptake is affected by injury to cells due to radiation; it may therefore be difficult to correctly assess the tissue oxygenation status during radiotherapy with 99mTc-HL91.

Cell Division↗

PubMed2000

Anatomical keys and pitfalls in living donor liver transplantation.

The surgery of living donor liver transplantation is more technically challenging than cadaveric whole liver transplantation and liver resection for the treatment of various pathological conditions. It requires a thorough understanding of the intra- and extra-hepatic anatomical relationships between the portal vein, hepatic artery, biliary tract, and hepatic vein, and also their respective contributions to liver physiology. Although a precise understanding of general anatomical principles is the key to correctly performing living donor liver transplantation procedures, anatomic anomalies are often present, and the means of detecting them and the surgical methods of coping with them represent technical challenges. In this monograph, we describe the anatomical keys and pitfalls of living donor liver transplantation surgery based on our own experience with more than 1800 hepatectomies, and 150 living donor liver transplantations. We also elaborate on techniques of selective intermittent vascular occlusion and their teleological and practical background.

Bile Ducts↗

PubMed2000