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Etsuro Hatano

Publications and source records attributed to Etsuro Hatano.

14 recordsLinked to original sources
PubMed2004

Effectiveness of endoscopic nasobiliary drainage for postoperative bile leakage after hepatic resection.

The effectiveness of endoscopic nasobiliary drainage (ENBD) for postoperative bile leakage after hepatic resection was investigated retrospectively. Between 1997 and 2002 a series of 486 hepatectomies without biliary reconstruction were performed. Bile leakage was divided into two categories. Type A was defined as bile leakage communicating with the main bile tree fistulographically or endoscopic cholangiographically, and type B was bile leakage without such a patency of bile flow. Bile leakage developed in 31 patients (6.4%) (types A/B = 16/15). Type A frequently occurred at the major Glisson's sheath. In contrast, most type B cases occurred at the peripheral bile duct at the cut surface of the liver. Among the type A patients, 10 of 11 were effectively treated with ENBD. For the type B patients, 12 of 15 patients were successfully treated with intraabdominal drainage via surgical drains inserted during the operation or percutaneous tubes newly inserted for biliary fluid collection. ENBD was effective in two of three type B patients. The duration of bile leakage significantly shortened after initiation of ENBD in type A patients (15.3 +/- 6.9 vs. 25.8 +/- 13.2 days, p < 0.05). The classification based on communication with the main bile tree is useful for determining therapeutic strategy. Type A leakage has a good indication for ENBD, whereas type B can be treated with intraabdominal drainage in most cases, although ENBD may be effective in some intractable type B cases. It is preferable to initiate ENBD as early as possible to shorten the duration of bile leakage and the subsequent hospital stay.

Bile Duct Neoplasms↗
PubMed2004

Impact of novel histone deacetylase inhibitors, CHAP31 and FR901228 (FK228), on adenovirus-mediated transgene expression.

BACKGROUND: Histone deacetylase inhibitors (HDIs) are known to enhance adenovirus (Ad)-mediated transgene expression. Recently, novel HDIs, including cyclic hydroxamic-acid-containing peptide 31 (CHAP31) and FR901228 (FK228), have been developed. METHODS: The effects of these two novel HDIs on Ad-transduced or endogenous gene expression were investigated. Acetylation of core histones and the expression of the coxsackie and adenovirus receptor (CAR) in HDI-treated cells were examined using Western blot and a quantitative reverse transcription polymerase chain reaction (TaqMan RT-PCR), respectively. Their in vivo effect on adenoviral gene expression was investigated in BALB/c mice. RESULTS: Both compounds enhanced and prolonged Ad-mediated beta-galactosidase expression more effectively than did trichostatin A, a classic HDI. The same effect was observed in Ad-transduced heat shock protein 72 (HSP72), but not in hyperthermia-induced endogenous expression of HSP72, suggesting that the effect is specific for transduced gene expression. Hyperacetylation of core histones induced by HDIs was considered responsible for the augmentative effects of gene expression. Intravenous administration of either CHAP31 or FR901228 enhanced beta-galactosidase expression in mice infected with AdLacZ. CONCLUSIONS: CHAP31 and FR901228 amplified Ad-mediated transgene expression. The enhancement of transgene expression by HDIs may result in fewer vector doses for necessary gene expression, helping to alleviate disadvantages caused by Ad vectors. This could be a useful tool in overcoming current limitations of gene therapy using adenovirus vectors.

Acetylation↗
PubMed2004

Akt activation protects rat liver from ischemia/reperfusion injury.

BACKGROUND: Apoptosis as well as necrosis may play an important role in hepatic ischemia/reperfusion (I/R) injury. Akt, a serine-threonine protein kinase, is known to promote cell survival. We investigated whether gene transfer of constitutively active or dominant negative Akt could affect hepatic I/R injury. MATERIALS AND METHODS: Hepatic I/R injury was induced in rats by Pringle's maneuver for 20 min followed by reperfusion. Adenoviruses encoding a constitutively active form of Akt (myrAkt), a dominant negative form of Akt (dnAkt), or beta-galactosidase (LacZ) were injected through the tail vein 72 h before hepatic I/R. RESULTS: Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining demonstrated a significant increase in the positive cells 240 min after reperfusion. Immunoblotting with phospho-Akt antibody showed phosphorylation of Akt from 90 to 180 min after reperfusion. The expression of myrAkt reduced the number of TUNEL-positive cells and hepatic necrosis around the central veins in the liver after reperfusion. This expression also significantly inhibited the increase in serum alanine aminotransferase (297 +/- 131 IU/L, P < 0.05) 120 min after I/R, compared with increases in uninfected (1761 +/- 671 IU/L), LacZ adenovirus (1528 +/- 671 IU/L)-, and dnAkt adenovirus (1342 +/- 485 IU/L)-infected rats. MyrAkt expression phosphorylated Bad and inhibited the release of cytochrome-c after reperfusion. No difference in nuclear translocation of nuclear factor (NF)-kappaB, p65 was seen among the three groups of rats, however. CONCLUSION: Adenoviral gene transfer of myrAkt could inhibit apoptotic cell death and subsequent hepatic I/R injury in the rat, through Bad, not NF-kappaB.

Adenoviridae↗
PubMed2004

TNF alpha-induced hepatocyte apoptosis is associated with alterations of the cell cycle and decreased stem loop binding protein.

BACKGROUND: Inhibition of nuclear factor kappa B (NF kappa B) during liver regeneration induces hepatocyte apoptosis associated with normal DNA synthesis but decreased mitosis, suggesting that inhibition of NF kappa B impairs progression from S-phase through the G(2)/M phase of the cell cycle. Our aim was to determine if inhibition of NF kappa B alters cell cycle characteristics in hepatocytes treated with tumor necrosis factor alpha (TNF alpha). METHODS: Primary hepatocytes from BALB/c mice were infected with adenoviruses expressing luciferase (control; AdLuc) or the I kappa B super-repressor (AdI kappa B) and treated with or without TNF alpha (30 ng/ml). Flow cytometry was performed (0 to 40 hours) to determine apoptosis and cell cycle progression. Reverse transcriptase-polymerase chain reaction and immunoblots assessed changes in cell cycle mediators and antiapoptotic factors. RESULTS: Primary hepatocytes treated with AdI kappa B and TNF alpha demonstrated significantly more S-phase cells (14% +/- 3% vs 6% +/- 2%, P<.05) at 14 hours compared with controls. Inhibition of NF kappa B with or without TNFalpha was associated with decreased expression of stem loop bind protein, a marker of cell cycle progression through S-phase. The NF kappa B-induced antiapoptotic proteins, iNOS and TRAF2, had decreased message at 9 and 12 hours, respectively, in TNF alpha- and AdI kappa B-treated cells. CONCLUSION: Inhibition of NF kappa B in TNF alpha-treated primary mouse hepatocytes is associated with increased S-phase cell cycle retention and decreased stem loop bind protein.

Animals↗
PubMed2004

Inhibition of tumor necrosis factor-induced apoptosis in transgenic mouse liver expressing creatine kinase.

BACKGROUND: The mitochondrion acts as a pivotal decision center in many types of apoptotic responses. To clarify the effects of the enhanced mitochondrial function on tumor necrosis factoralpha (TNFalpha)-induced apoptosis, we studied hepatic injuries in transgenic mice whose livers express creatine kinase (CK). METHODS: Mice fed a diet containing 10% creatine, came to accumulate phosphocreatine and to enhance hepatic ATP levels and mitochondrial oxidative phosphorylation activities. TNFalpha-mediated hepatic apoptosis in normally fed and Cr-feeding CK transgenic mice were assessed. RESULTS: TNFalpha and actinomycin D cause severe liver failure in normally fed transgenic mice, and in the wild-type mice. In contrast, no significant elevations in transaminase levels after injection were observed in Cr feeding transgenic mice. The disruption of the mitochondrial transmembrane potential at 2 h after TNFalpha injection, prior to ATP depletion, activation of caspase 3 like protease, and DNA fragmentation at 4-6 h after injection, were observed in normally fed transgenic mice. These were fully suppressed in Cr feeding transgenic mice. However, anti-Fas antibody-induced apoptosis was not inhibited in both groups. CONCLUSIONS: The results indicate that TNFalpha-induced apoptosis was inhibited in CK transgenic mice livers by maintaining mitochondrial function.

Adenine↗
PubMed2003

Myoglobin gene expression attenuates hepatic ischemia reperfusion injury.

BACKGROUND: Cellular functions are maintained by a continuous supply of ATP, which is supplied efficiently by mitochondrial oxidative phosphorylation. Since myoglobin, found in cardiac myocytes and red skeletal muscle, but not in the liver, facilitates oxygen diffusion under low oxygen conditions and enhances oxidative phosphorylation, this study seeks to enhance hepatic ATP levels and attenuate ischemia-reperfusion injury in rodent livers by adenovirus-mediated myoglobin expression. MATERIAL AND METHODS: After infecting Hep3B and rodent livers with adenovirus carrying CMV promoter sequences linked to the human myoglobin gene (AdCMVMyo), reverse transcriptase-PCR and immunodetection for myoglobin, and cellular and hepatic ATP levels were examined. The effect of myoglobin was evaluated in a hepatic ischemia-reperfusion model in the rat. RESULTS: Myoglobin expression was confirmed in Hep3B and rat livers after AdCMVMyo infection. The ATP levels in Hep3B cells and C57BL/6 mice livers 72 h after AdCMVMyo transfection were significantly higher than control levels and those after adenovirus-mediated beta-galactosidase transfection. Finally, expression of myoglobin attenuated ischemia-reperfusion injury in the rat liver. CONCLUSION: These results indicate that myoglobin gene transfer to the liver enhanced ATP levels both in vitro and in vivo and might be a novel strategy to reduce ischemia-reperfusion injury.

Adenosine Triphosphate↗
PubMed2003

Results of hepatic resection for hepatocellular carcinoma invading major portal and/or hepatic veins.

Nonsurgical therapy for patients with advanced hepatocellular carcinoma (HCC) has yielded poor long-term survival. This study evaluates the effects of surgical treatments for patients with HCC invading major portal and/or hepatic veins. The surgical results of 112 patients with HCC invading major portal and/or hepatic veins who underwent hepatic resection between 1985 and 2001 were studied to evaluate the feasibility of hepatic resection as a local treatment.

Adult↗
PubMed2003

c-Jun-N-terminal kinase drives cyclin D1 expression and proliferation during liver regeneration.

The c-Jun-N-terminal kinase (JNK) pathway is strongly activated after partial hepatectomy (PH), but its role in hepatocyte proliferation is not known. In this study, JNK activity was blocked with the small molecule inhibitor JNK SP600125 in vivo and in vitro as shown by a reduction of c-Jun phosphorylation, AP-1 DNA binding activity, and c-jun messenger RNA (mRNA) expression. SP600125 inhibited proliferating cell nuclear antigen (PCNA) expression, cyclin D1 mRNA and protein expression and reduced mitotic figures after PH. Survival was reduced significantly 3 days after PH in SP600125-treated versus vehicle-treated rats (3 of 11 vs. 8 of 9, P <.01). In epidermal growth factor (EGF)-treated primary cultures of rat hepatocytes, SP600125 decreased (3)H-thymidine uptake, cyclin D1 mRNA and protein expression, and inhibited the EGF-induced transcription of a cyclin D1 promoter-driven reporter gene. The defective regeneration and the decreased survival in SP600125-treated rats did not result from a major increase in apoptosis as shown by normal levels of caspase 3 activity and only slight increases in apoptotic figures. In conclusion, our data show that JNK drives G0 to G1 transition in hepatocytes and that cyclin D1 is a downstream target of the JNK pathway during liver regeneration.

Animals↗
PubMed2003

Inactivation of the small GTPase Rac1 protects the liver from ischemia/reperfusion injury in the rat.

BACKGROUND: In ischemia/reperfusion (I/R) injury, a massive generation of reactive oxygen species (ROS) after reperfusion is a critical factor. Rac, a member of the Rho GTPase superfamily, plays important roles in the production of ROS and activation of nuclear factor-kappaB (NF-kappaB) in vitro. However, the exact role of Rac in the ROS production and NF-kappaB activation in vivo after I/R is still obscure. METHODS: We blocked Rac1 activity in the rat liver using adenovirus encoding a dominant negative rac1 mutant (Ad5N17Rac1) and examined whether inactivation of Rac1 could prevent ROS generation in the hepatic I/R injury. Seventy-two hours after the adenoviral infection, hepatic I/R was induced by Pringle's maneuver for 20 minutes, followed by reperfusion in the rats. RESULTS: Ad5N17Rac1 infection significantly attenuated ROS production after reperfusion and suppressed the hepatic injury. Furthermore, N17Rac1 suppressed NF-kappaB activation and messenger RNA expression of tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthetase (iNOS). Ad5LacZ, a control adenovirus, had no effect on the induced hepatic I/R injury, nor did it affect NF-kappaB activation. Immunohistochemical analysis of NF-kappaB (p65) revealed that translocation of p65 to the nucleus after reperfusion was blocked in many of non-parenchymal cells (NPCs) and in hepatocytes in the Ad5N17Rac1-infected liver. CONCLUSION: We conclude that Rac1 is required in ROS generation and NF-kappaB activation after hepatic I/R in vivo, and that inactivation of NF-kappaB in NPCs and suppression of ROS generation in NPCs and hepatocytes possibly account for the protective effect of N17Rac1 in this study.

Active Transport, Cell Nucleus↗
PubMed2003

Cholangitis and liver abscess after percutaneous ablation therapy for liver tumors: incidence and risk factors.

PURPOSE: To determine the risk factors of cholangitis and liver abscess occurring after percutaneous ablation therapy for liver tumors. MATERIALS AND METHODS: Between October 1995 and September 2002, 358 patients with 455 liver tumors underwent a total of 683 ablation procedures, such as percutaneous ethanol injection (PEI), percutaneous microwave coagulation (PMC), and radiofrequency (RF) ablation therapy. With a retrospective review of medical records, the rates and outcomes of cholangitis and/or liver abscess occurring after ablation therapy were evaluated. The relationship between cholangitis and/or liver abscess and multiple variables (age, disease, Child-Pugh class, size of nodules, multiplicity of nodules, history of transcatheter arterial embolization, presence of bilioenteric anastomosis, and lack of prophylactic antibiotics administration) were statistically analyzed. RESULTS: Cholangitis and/or liver abscess occurred in 10 sessions (1.5%) in 10 patients: six sessions after PEI, three sessions after PMC, and one session after RF ablation. Both cholangitis and liver abscess were noted in seven sessions, cholangitis was noted in two, and liver abscess was noted in one. Six patients recovered, but two developed recurrent cholangitis and liver abscess, one developed lung abscess complicated with liver abscess, and one died of septic shock associated with cholangitis. On stepwise regression analysis, bilioenteric anastomosis was the sole significant predictor of cholangitis and/or liver abscess formation (P <.001; odds ratio = 36.4; 95% CI = 9.67-136.9). CONCLUSION: Bilioenteric anastomosis strongly correlated with the development of cholangitis and/or liver abscess after percutaneous ablation therapy. Close posttreatment attention should be paid to this subgroup of patients.

Adolescent↗
PubMed2002

Suppression of proliferative cholangitis by E2F decoy oligodeoxynucleotide.

BACKGROUND: Proliferative cholangitis (PC) associated with hepatolithiasis results in stricture of the main bile ducts and is a major cause of residual and/or recurrent stones after repeated treatment for hepatolithiasis. The transcription factor E2F controls the expression of several genes involved in cell proliferation. The aim of this study was to inhibit PC using cytostatic gene therapy by transferring fusigenic anionic liposome-hemagglutinating virus of Japan (HVJ-anionic liposome) complexes containing a synthetic double-stranded oligodeoxynucleotide with high affinity for E2F (E2F decoy). MATERIALS AND METHODS: PC was induced by introducing a fine nylon thread into the bile duct in a rat model. HVJ-anionic liposomes containing the E2F decoy were administered directly into the biliary tract. HVJ-anionic liposomes containing a missense oligodeoxynucleotide (scramble decoy) were also given as a control. The count of peribiliary glands in the bile duct, 5'-bromodeoxyuridine (BrdU) labeling index, and immunohistochemical staining for proliferating cell nuclear antigen (PCNA) in the bile duct were compared among untransfected, scramble decoy-transfected, and E2F decoy-transfected rats. RESULTS: E2F decoy-transfected bile ducts showed inhibition of the papillary proliferation of the biliary epithelium and peribiliary gland hyperplasia. BrdU incorporation and PCNA expression in the bile ducts were inhibited in E2F decoy-transfected rats. CONCLUSION: Our cytostatic gene therapy approach using direct E2F decoy transfer into the biliary tract suppressed PC in a rat model and may offer an effective therapeutic option for reducing recurrence following treatment for hepatolithiasis.

Animals↗
PubMed2002

Percutaneous radiofrequency ablation therapy after intrathoracic saline solution infusion for liver tumor in the hepatic dome.

Two liver tumors undetected by ultrasonography (US) because they were located in the hepatic dome were treated with radiofrequency (RF) ablation therapy after intrathoracic saline solution infusion. After administration of local anesthesia, artificial pneumothorax was produced by needle thoracentesis and a drainage catheter was inserted into the right thoracic cavity. After saline solution (450-500 mL) was injected into the thoracic cavity via the catheter, US-guided RF ablation was performed. No severe complications occurred and complete therapeutic effects were obtained. Percutaneous RF ablation therapy with intrathoracic saline solution injection seems to be a feasible alternative to other ablation therapies.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

Resection for hepatocellular carcinoma with duodenal invasion: report of a case.

A 73-year-old man was admitted to our hospital on emergency for severe anemia. Upper gastrointestinal endoscopic study revealed a hemorrhagic ulcer in the duodenal bulb. He underwent endoscopic hemostasis. Abdominal ultrasonography and computed tomography showed a huge mass in segment 4 of the liver, growing into the extrahepatic space with direct invasion to the duodenal bulb. Extended left lobectomy and partial gastroduodenectomy was performed, because the endoscopic management of hemostasis was incomplete. He was discharged on the 30th postoperative day. Histopathologically, the tumor cells were moderately differentiated hepatocellular carcinoma with direct invasion to the duodenal mucosa. This report demonstrated the first case with a hepatocellular carcinoma with duodenal invasion, for which hepatic resection was performed successfully.

Aged↗