Biomedical subjects

Masahiro Ohira

Publications and source records attributed to Masahiro Ohira.

6 recordsLinked to original sources

PubMed2006

Adoptive transfer of TRAIL-expressing natural killer cells prevents recurrence of hepatocellular carcinoma after partial hepatectomy.

BACKGROUND: Antitumor activity of the liver natural killer (NK) cells reportedly decreases after partial hepatectomy, suggesting that patients with such depressed immune status are susceptible to the recurrence of hepatocellular carcinoma (HCC). We hypothesize that adoptive immunotherapy using activated NK cells can be a novel strategy to improve the depressed immune status in patients with HCC after hepatectomy or partial liver transplantation. In the present study, we have tested this hypothesis by using a mouse model. METHODS: Intraportal injection of 1-5 x 10(6) Hepa1-6 cells (hepatoma cell line) did not result in liver metastases in untreated B6 mice, but led to the growth of liver metastases after extensive partial hepatectomy. Utilizing this murine HCC metastasis model, we investigated the antitumor activity of both remnant liver and exogenously transferred NK cells. RESULTS: The anti-HCC activity of liver NK cells significantly decreased after partial hepatectomy. The expression of CD69 and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on liver NK cells was temporarily downregulated. The adoptive transfer of NK cells, including a TRAIL-expressing fraction, extracted from the liver perfusates of poly I:C-stimulated B6 mice inhibited the growth of liver metastasis in B6 or (B6xBALB/c) F1 (B6CF1) mice that underwent hepatectomy and received intraportal Hepa1-6 injection. CONCLUSIONS: These findings indicate that adoptive immunotherapy using activated NK cells extracted from normal liver perfusates may be a novel technique for reconstituting the depressed immune status in cases of living donor liver transplantation involving HCC patients, recipients of a partial liver graft.

Adoptive Transfer↗

PubMed2006

Preheparin serum lipoprotein lipase mass might be a biomarker of metabolic syndrome.

Lipoprotein lipase mass in preheparin serum (preheparin LPL mass) is assumed to reflect some of the LPL production in the whole body and insulin sensitivity. While metabolic syndrome is a common underlying condition for cardiovascular diseases, biological marker of this syndrome has not been fully established. To clarify the characteristics of preheparin LPL mass in metabolic syndrome, 362 Japanese subjects were studied to examine the relationship between symptoms of metabolic syndrome and preheparin LPL mass and compare with plasma adiponectin. Furthermore the relation with urinary 8-hydroxydeoxyguanosine (8-OHdG) that reflects oxidative stress to DNA was also studied. Both preheparin LPL mass and plasma adiponectin correlated positively with HDL-cholesterol and negatively with body weight and triglyceride. Only preheparin LPL mass showed a negative correlation with fasting blood glucose and HbA1c. Both mean preheparin LPL mass and plasma adiponectin decreased with an increase in severity of the metabolic syndrome with/without obesity and with/without diabetes. The correlation coefficient between preheparin LPL mass and plasma adiponectin was r=0.562. A negative correlation between preheparin LPL mass and urinary 8-OHdG was observed. These results suggest that low preheparin LPL mass may reflect systemic oxidative stress and also a biomarker of the severity of metabolic syndrome.

Adiponectin↗

PubMed2006

The angiotensin II receptor antagonist valsartan enhances lipoprotein lipase mass in preheparin serum in type 2 diabetes with hypertension.

Recent studies suggest that blockade of angiotensin type 1 (AT1) receptor may have some effect on glucose and lipoprotein metabolism. Serum level of preheparin lipoprotein lipase (LPL) reflects LPL production mainly in adipocytes and is believed to be related to insulin sensitivity. We studied the effect of a selective AT1 antagonist, valsartan, on glucose, lipid metabolism and the preheparin LPL mass in 55 patients with type 2 diabetes and hypertension. Patients were randomized into a group administered valsartan 80 mg/day for 12 weeks or a group not administered valsartan (control). Blood pressure decreased significantly. HbA1c and TG levels decreased and HDL-C level increased, but these changes tended to be significantly different. TC and LDL-C levels were not significant changes. Preheparin LPL mass increased after valsartan administration compared with control (P = 0.0307), and migration ratio of LDL (LDL-Rm), which correlated negatively with LDL particle size, decreased compared with control (P < 0.0001). DeltaLDL-Rm correlated inversely with Delta preheparin LPL mass (r = -0.459). Among subjects treated with valsartan, greater improvement in preheparin LPL mass and blood pressure was observed in the subgroup with preheparin LPL mass <40 ng/ml. The results of this study suggest that valsartan may enhance LPL production in adipocytes, resulting in enlarged LDL particle size.

Aged↗

PubMed2006

Difference in cytotoxicity against hepatocellular carcinoma between liver and periphery natural killer cells in humans.

In rodents, liver natural killer (NK) cells have been shown to mediate higher cytotoxic activity against tumor cells than do peripheral blood (PB) NK cells. However, such differences between liver and PB NK cells have not been extensively investigated in humans. The phenotypical and functional properties of NK cells extracted from liver perfusates at the time of living donor liver transplantation were investigated. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a critical molecule for NK cell-mediated anti-tumor cell killing, was not expressed by freshly isolated PB NK cells or by liver NK cells. Stimulation with interleukin (IL)-2, significantly up-regulated the expression of TRAIL on liver NK cells, but this effect was barely observed on PB NK cells. Donor liver NK cells showed the most vigorous cytotoxicity against HepG2, a hepatocellular carcinoma (HCC) cell line, after IL-2 stimulation (90.5% +/- 2.2% at E: T = 10:1), compared with donor and recipient PB NK cells and recipient liver NK cells (64.8% +/- 8.2%, 56.1% +/- 8.9%, and 34.6% +/- 7.5%, respectively). IL-2 stimulation resulted in an increased expression of killing inhibitory receptors on liver NK cells in parallel with TRAIL expression. Consistently, the cytotoxicities of IL-2-stimulated donor liver NK cells against self and recipient lymphoblasts were negligible. In conclusion, adoptive transfer of IL-2-stimulated NK cells extracted from donor liver graft perfusate could mount an anti-tumor response without causing toxicity against 1-haplotype identical recipient intact tissues. These findings present a concept to prevent recurrence of HCC after liver transplantation.

Adult↗

PubMed2006

Probucol and atorvastatin decrease urinary 8-hydroxy-2'-deoxyguanosine in patients with diabetes and hypercholesterolemia.

To clarify whether probucol and statins suppress oxidative stress in diabetic patients, we studied the effects of probucol and the statin atorvastatin on urinary 8-hydroxy-2'deoxyguanosine (8-OHdG) levels in diabetics with hypercholesterolemia. A randomized, open study was performed on a total of 36 patients with type 2 diabetes and hypercholesterolemia. The patients were randomly assigned to a probucol group (500 mg/day, n = 18) or an atorvastatin group (10 mg/day, n = 18). During three months, total- and LDL-cholesterol decreased significantly in both groups. LDL-cholesterol was significantly lower in the atorvastatin group than probucol group. HDL-C decreased significantly in the probucol group and did not change in the atorvastatin group. 8-OHdG decreased significantly in both groups after 3 months; 12.4 +/- 7.5 to 8.1 +/- 4.2 ng/mg/Cr in the atorvastatin group (p < 0.05) and 12.3 +/- 8.8 to 6.8 +/- 2.6 ng/mg/Cr in the probucol group (p < 0.05), and these changes did not differ significantly between the two groups. But, in patients with high 8-OHdG levels (more than 10 ng/mg/Cr) before administration, urinary 8-OHdG decreased significantly from 19.5 +/- 4.9 to 9.2 +/- 3.4 ng/mg Cr (p < 0.01) in the atorvastatin group, and from 19.7 +/- 8.2 to 6.67 +/- 2.2 ng/mg Cr (p < 0.01) in the probucol group. Urinary 8-OHdG was significantly lower in the probucol group than in the atorvastatin group after the second and third months of administration (p < 0.05). These results suggest that while probucol and atorvastatin both reduce systemic oxidative stress, probucol might be the more useful in patients with strong oxidative stress.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2005

Probucol delays progression of diabetic nephropathy.

Probucol has antioxidant and cholesterol-lowering effects. This study examined the effect of probucol on progression of diabetic nephropathy. We performed a randomized, open trial on 102 type 2 diabetes patients with clinical albuminuria (urinary albumin excretion >300 mg/g Cr). Fifty-one patients were assigned to probucol treatment (500 mg/day) and 51 to no probucol treatment. Among all patients, 40 who had serum creatinine >or=2mg/dl at baseline were defined as advanced cases. All patients were followed for a maximum 3 years. HbA1c levels were not different between two groups. High-density lipoprotein cholesterol decreased significantly in probucol group. Increase in urinary protein (g/day/month) was significantly greater in non-probucol than in probucol group. Hemodialysis was initiated in 23 patients (10 in probucol group and 13 in non-probucol group). The mean interval to initiation of hemodialysis was significantly longer in probucol group (20.7+/-8.2 months) than in non-probucol group (11.3+/-7.4 months). In advanced cases, increases of both serum creatinine and urinary protein were significantly suppressed in probucol group. In advanced cases, the hemodialysis-free rate was significantly higher in probucol group than in non-probucol group. These results suggest that probucol may suppress the progression of diabetic nephropathy.

Aged↗