Search PubMed⌕ Search

Biomedical subjects

Mitsuo Shimada

Publications and source records attributed to Mitsuo Shimada.

At least 73 records · Page 4Linked to original sources
PubMed2003

Accurate preoperative estimation of liver-graft volumetry using three-dimensional computed tomography.

BACKGROUND: The aim of this study was to clarify the value of three-dimensional computed-tomography (3D-CT) volumetry for size matching in living-donor liver transplantation (LDLT). METHODS: 3D-CT volumetry was applied to 25 donors who underwent hepatectomy for a living relative needing an orthotopic liver transplantation. Fifteen patients underwent extended left lobectomy, one patient an extended left lateral lobectomy, and nine patients right lobectomy. 3D-CT imaging was performed with the workstation ZIO M900 (Zio Software Inc., Tokyo, Japan). The estimated volume of the grafts in two-dimensional (2D) and 3D images were compared, and an error ratio was calculated. RESULTS: 3D-CT imaging revealed the anatomy of the hepatic vein bifurcation and the shape of the graft. The error ratio was 12.8+/-2.3% in 3D, compared with 19.4+/-2.5% in 2D. As such, 3D-CT volumetry appears to be more exact than conventional 2D-CT volumetry, but volumetry by 3D-CT still produces an error ratio of approximately 13%. The weight transition of the rats' livers under preservation in University of Wisconsin (UW) solution indicated that the graft volume seems to decrease during perfusion with UW solution. Mismatch of the cutting line and volume reduction by dehydration (approximately 5% reduction 1 hour after perfusion) seems to cause the error in 3D-CT volumetry. CONCLUSIONS: Three-dimensional CT volumetry is useful for size matching in cases of living-related orthotopic liver transplantation.

Adult↗
PubMed2003

Feasibility of duct-to-duct biliary reconstruction in left-lobe adult-living-donor liver transplantation.

A Roux-en-Y choledochojejunostomy (CDJ) has been the sole method of choice for the reconstruction of the bile duct in living-donor liver transplantation (LDLT) using left-lobe grafts. In this study, we evaluated the feasibility of duct-to-duct (DD) biliary reconstruction in adult-to-adult LDLT using left-lobe grafts. Between October 1996 and October 2001, 46 adult-to-adult LDLTs using the left lobe were performed at our institution. The DD biliary reconstruction (hepaticocholedochostomy) over a T-tube was performed for seven of the last nine recipients (DD group, n=7), whereas the conventional Roux-en-Y CDJ was used for the remaining cases (CDJ group, n=39). The technical problems and the incidence of biliary complications were compared between the groups. Bile leakage developed in only 1 of 7 (14%) in the DD group (leakage from a T-tube exit site), whereas it occurred in 8 of 39 (20%) in the CDJ group. Up to now, no patients from the DD group developed anastomotic stricture, whereas twelve (30.7%) patients from the CDJ group did. Other complications included bleeding from the Roux-en-Y jejunojejunostomy (n=1) and anastomotic occlusion caused by an internal stent (n=1), and both complications were associated with CDJ. In conclusion, DD anastomosis is a simple and viable option for biliary reconstruction in left-lobe LDLTs. A long-term follow-up, especially regarding the incidence of biliary stricture, is thus warranted in such patients.

Adult↗
PubMed2003

Histone deacetylase inhibitor trichostatin A induces cell-cycle arrest/apoptosis and hepatocyte differentiation in human hepatoma cells.

Remodeling of the chromatin template by inhibition of HDAC activities represents a potential transcriptional therapy for neoplastic disease. A number of HDAC inhibitors that modulate in vitro cell growth and differentiation have been developed. We analyzed the effects of TSA, a specific and potent HDAC inhibitor, on the human hepatoma cell lines HepG2 and Huh-7. TSA increased levels of acetylated histones H3 and H4 in both HepG2 and Huh-7. It inhibited cell proliferation in vitro and induced G(0)/G(1) arrest in HepG2 and apoptosis in Huh-7. Gene expression of liver-specific functions and liver-enriched transcription factors was upregulated by TSA. TSA upregulated the ammonia removal rate and the albumin synthesis rate of HepG2 and Huh-7. Our results indicate that TSA can induce cell-cycle arrest/apoptosis and hepatocyte differentiation in human liver cancer cell lines.

Albumins↗
PubMed2003

Renal tubular acidosis secondary to FK506 in living donor liver transplantation: a case report.

FK506 is an immunosuppressant that is thought to be less nephrotoxic than cyclosporine A. However, complications due to renal tubular acidosis (RTA) have recently been reported. We report a case of RTA secondary to FK506 administration in liver transplantation. A 6-month-old girl was treated with FK506 after undergoing living donor liver transplantation for fulminant hepatitis. On postoperative day 17, she demonstrated hyperkalaemia and metabolic acidosis; she was diagnosed to have hyperkalaemic distal RTA with aldosterone deficiency (type IV). Intravenous sodium bicarbonate and furosemide, and intrarectal calcium polystyrenesulfonate were administered to correct the acidosis and promote potassium secretion. Thereafter, the FK506 concentration in whole blood gradually decreased, and the hyperkalaemia and metabolic acidosis following RTA improved. RTA is one type of nephrotoxicity induced by FK506, and it is reversible in mild cases when appropriately treated. The mechanism of RTA induced by FK506 has not yet been clearly elucidated. Surgeons and physicians should therefore be aware of the potential for RTA to occur with FK506 after any organ transplantation. The treatment for acidosis and hyperkalaemia should be started as soon as RTA is diagnosed, and the dosage of FK506 should also be reduced if possible.

Acidosis, Renal Tubular↗
PubMed2003

Human WISP1v, a member of the CCN family, is associated with invasive cholangiocarcinoma.

Family members of the connective tissue growth factor, cysteine-rich 61, nephroblastoma over-expressed gene (CCN) encode cysteine-rich secreted proteins with roles in human fibrotic disorders and tumor progression. In this study, we identified a CCN family member, WISP1v, as over-expressed in human cholangiocarcinomas. Genetic analysis of WISP1v was performed on surgically resected specimens of cholangiocarcinoma. The WISP1v biological effects were analyzed using the HuCCT1 human cholangiocarcinoma cell line. The WISP1v gene was expressed in 19 of 39 cholangiocarcinoma tissues (49%) but not in normal livers. Expression of WISP1v was significantly associated with lymphatic and perineural invasion of tumor cells (P <.05), as well as a poor clinical prognosis (P <.01). In the intraductal papillary cholangiocarcinomas, WISP1v was detected only in the cases with duct wall invasion but not in the cases without duct wall invasion (P <.05). No mutation of WISP1v gene was detected in the examined samples. In vitro analysis revealed that WISP1v stimulated the invasive phenotype of cholangiocarcinoma cells with activation of both p38 and p42/p44 mitogen-activated protein kinases (MAPKs). Furthermore, WISP1v-induced cholangiocarcinoma invasion was significantly suppressed by the p38 MAPK inhibitor SB203580 but not by the p42/p44 MAPK kinase (MEK) inhibitor PD98059. Our findings suggest that WISP1v-mediated signaling is involved in the generation of invasive cellular properties and leads to progression of cholangiocarcinoma.

3T3 Cells↗
PubMed2003

Outcome analysis in adult-to-adult living donor liver transplantation using the left lobe.

Graft size problems remain the greatest limiting factor for expansion of living donor liver transplantation (LDLT) to the adult population. The result of adult-to-adult LDLT using the left lobe with special reference to graft size has not been fully evaluated to date. In this study, we evaluated the outcome of adult-to-adult LDLT using the left lobe and also analyze the impact of using small-for-size grafts on outcome. Thirty-six recipients who underwent adult-to-adult LDLT using the left lobe (n = 14) or left lobe plus caudate lobe (n = 22) were included in the study. Variables including preoperative and operative data, patient and graft survival, complications, and causes of graft loss were studied. Furthermore, the incidence of small-for-size syndrome and its impact on graft survival were studied. Mean graft volume (GV) was 420 +/- 85 g (range, 260 to 620 g), which resulted in 38.2% +/- 8.1% (range, 22.8% to 53.8%) of the recipient standard liver volume (SLV). Overall 1-year patient and graft survival rates were 85.7% and 82.9%, respectively. Seven grafts were lost. Small-for-size syndrome occurred in 7 of 16 patients (43.8%) with cirrhosis and only 1 of 20 patients (5.0%) without cirrhosis (P =.005). Recipients who developed small-for-size syndrome had inferior graft survival to those who did not (P =.07). In conclusion, adult-to-adult LDLTs were found to be feasible without affecting patient or graft survival. Small-for-size syndrome developed more frequently in patients with cirrhosis. Minimum GV in adult-to-adult LDLT should be 30% less than the recipient's SLV in patients without cirrhosis, whereas 45% less was required in patients with cirrhosis.

Adult↗
PubMed2003

Tenascin expression at the invasive front is associated with poor prognosis in intrahepatic cholangiocarcinoma.

Tenascin and decorin are components of the extracellular matrix (ECM) that are implicated in cell proliferation in tumors. Here, we propose that abnormal expression of stromal ECM may play an important role in the progression of intrahepatic cholangiocarcinoma, which is characterized by desmoplastic reaction. To explore this hypothesis, we performed immunohistochemical analysis in order to examine the expression and distribution of tenascin and decorin in 75 cases of intrahepatic cholangiocarcinoma. In the intratumoral stroma, positive staining for tenascin was observed in 51 (68%) cases, and positive staining for decorin was observed in 61 (81%) cases. However, at the invasive front, positive staining for tenascin was found in 23 (31%) cases, and positive staining for decorin was found in 6 (8%) cases. Decorin staining was not correlated with aggressive behavior of intrahepatic cholangiocarcinoma, whereas intratumoral tenascin staining was correlated with lymphatic permeation and proliferative activity measured by Ki67. Tenascin staining at the invasive front was associated with tumor size, lymphatic permeation, lymph node metastasis, and proliferative activity and appeared to be a useful prognostic factor by univariate analysis, although it was not an independent prognostic factor. These results indicate that tenascin plays a role in tumor progression in cases of intrahepatic cholangiocarcinoma and that tenascin expression, especially at the invasive front, may be a useful marker in evaluating an unfavorable prognosis in patients with intrahepatic cholangiocarcinoma.

Adult↗
PubMed2003

Antisense RNAs transcribed from the upstream region of the precore/core promoter of hepatitis B virus.

The bidirectional activity of the precore/core promoter of hepatitis B virus (HBV) has been demonstrated in cultured cell lines. However, HBV antisense transcripts (asRNAs) have not been demonstrated in vivo. In the present study using liver tissue from patients with chronic hepatitis, an anchored 5'RACE mapping the 5' ends at position 1680/1681, 1655 or 1609/1602 was carried out. In limited cases, RLM-3'RACE detected asRNAs to terminate at four or five consecutive dT residues in the 0.7 kb downstream region. PCR of oligo(dT)-primed cDNA did not amplify a typical polyadenylated asRNA. RT-PCR using various primers did not detect any spliced forms. Competitive RT-PCR estimated the copy numbers of the asRNAs to be 0.05-0.4 % of total sense RNAs. All sequenced asRNAs had ORF6 but, in one patient, the asRNA initiating at position 1680/1681 had additional initiation and termination codons in front of ORF6. Therefore, asRNAs are transcribed by RNA polymerase III at a low level, encompass a dispensable ORF6 gene and might be retained in the nucleus. The endogenous asRNAs complementary to the common ends of all sense RNAs suggest antisense-mediated self-regulation of hepadnavirus.

Base Sequence↗
PubMed2003

Efficacy of a larger version of the hybrid artificial liver support system using a polyurethane foam/spheroid packed-bed module in a warm ischemic liver failure pig model for preclinical experiments.

We have reported the usefulness of a polyurethane foam packed-bed culture system of hepatocyte spheroids as a hybrid artificial liver support system (PUF-HALSS). The aim of this study was to evaluate in detail the efficacy in serum parameters regarding the liver function of a larger version of the PUF-HALSS containing 2 x 10(10) porcine hepatocytes for clinical use in warm ischemic liver failure pigs. Warm ischemic liver failure pigs weighing 25 kg were divided into two groups: (1) a control group (n = 3), in which each pig was attached to a PUF-HALSS without hepatocytes, and (2) a HALSS group (n = 3), in which each pig was attached to a PUF-HALSS. In the HALSS group, the increase of blood ammonia was completely suppressed and blood lactate levels were significantly suppressed. The Fisher's ratio was better maintained, and the increase of total bile acid, glycochenodeoxycholic acid, and taurochenodeoxycholic acid was significantly suppressed in the HALSS group. Serum creatinine levels were significantly lower, and blood glucose levels were significantly higher in the HALSS group. Serum levels of tumor necrosis factor- a were not elevated in either group. In conclusion, the larger version of the PUF-HALSS demonstrated many advantages as a liver support system in warm ischemic liver failure pigs.

Amino Acids↗
PubMed2003

Angiogenic switch as a molecular target of malignant tumors.

In vivo progression to malignancy is characterized by the switch to an angiogenic phenotype. The angiogenic switch is a critical control point for tumor expansion. The ability of a tumor to become neovascularized permits rapid expansion of tumor growth and increases the likelihood of metastases. The genetic alterations that accompany the switch to the angiogenic phenotype are unknown. Discoveries of such genes lead to comprehension of molecular mechanisms of the tumor progression, as well as development of novel therapeutic tools. We have isolated a novel "angiogenic switch molecule," angiopoietin-2, upregulated specifically in hypervascular hepatocellular carcinoma (HCC). Angiopoietin family proteins have been originally identified as ligands of the vascular endothelial receptor of tyrosine kinase Tie2. Ectopic expression of angiopoietin-2 promotes the rapid development of human HCCs and produces hemorrhage within tumors in nude mice. These results suggest a role for angiopoietin-2 in the neovascularization of HCC. In vitro expression of a dominant-negative construct, containing a soluble Tie2 ectodomain (sTie2), led to Angiopoietin protein interaction, inhibition of endogenous Tie2 phosphorylation in vascular endothelial cells. Tumorigenicity with angiogenesis was suppressed by in vivo gene transfer and sTie2 expression in a murine HCC model, suggesting a possible role for angiopoietin/Tie2 signaling in the induction of HCC neovascularization and disease progression. More important, inhibition of the angiopoietin/Tie2 signal transduction cascade is a promising approach for HCC treatment.

Angiogenesis Inducing Agents↗
PubMed2003

Transcriptional repressor snail and progression of human hepatocellular carcinoma.

PURPOSE: Snail protein is a suppressive transcriptional factor of E-cadherin that mediates cell-to-cell adhesion, tumor progression, and metastases. We explored the expression and function of Snail and its family member Slug in human hepatocellular carcinoma (HCC) to identify its role in tumor progression. EXPERIMENTAL DESIGN AND RESULTS: Transfection of Snail cDNA in Li-7, endogenous E-cadherin-positive human HCC cells, selectively induced the loss of E-cadherin protein expression. We then investigated the expression of Snail and Slug mRNA in 43 human tissue samples of HCC. Using in situ hybridization, Snail mRNA was determined to dominantly express in HCC cells, but not in bile duct cells, blood vessels or infiltrating leukocytes. The mRNA of Snail and Slug were quantified using real-time reverse transcriptase-PCR, and correlations with E-cadherin expression and clinicopathological factors were investigated. Snail mRNA was overexpressed in 7 cases (16%) of HCC compared with adjacent noncancerous liver tissue. E-Cadherin protein expression determined in the same 43 cases by immunohistochemistry was significantly down-regulated in those cases with Snail mRNA overexpression (P = 0.04). The tumor and nontumor ratio of Snail mRNA independently correlated with tumor invasiveness (P = 0.04). However, Slug mRNA correlated with neither E-cadherin expression nor tumor invasiveness. CONCLUSIONS: The data indicate that Snail both down-regulates E-cadherin expression and promotes the invasion in human HCC.

Aged↗
PubMed2003

Genetic polymorphism at the 5' regulatory region of multidrug resistance 1 (MDR1) and its association with interindividual variation of expression level in the colon.

The multidrug resistance 1 (MDR1) is a key molecule in determining not only the resistance of cancer cells to anticancer agents but also the disposition of a variety of drugs in intestinal and other tissues. However, the mechanism underlying interindividual variations in levels of MDR1 activity and expression in various tissues remains unclear. We analyzed the nucleotide sequence polymorphisms in the 5' upstream regulatory region of the gene spanning 4 kb from the transcriptional start site of MDR1 and tried to identify any associations between polymorphisms and MDR1 expression. Within that region, we identified eight single nucleotide polymorphisms (SNPs) in the region in the Japanese population. Of the SNPs identified, -2410T>C, -1910T>C, and 692T>C were in perfect linkage disequilibrium. In normal colorectal mucosa, diplotypes at the region showed more significant association with the expression level of MDR1 mRNA than each SNP did. In an in vitro reporter assay, transcription activity of the minor-type construct carrying haplotypes 2 and 3 was significantly lower than that of the major-type construct carrying haplotype 1. We next identified two DNA binding proteins: one protein bound to the nucleotide sequence carrying -692T but not to that carrying -692C and another bound to the nucleotide sequence carrying -2352G but three times weaker than that carrying -2352A. This suggested the significance of SNP at -692 and -2352 of MDR1 in variable expression in the colon interindividually. This is the first report connecting SNPs and interindividual variety of MDR1 expression rationally.

Alleles↗
PubMed2003

A robotic surgery system (da Vinci) with image guided function--system architecture and cholecystectomy application.

We have developed a data fusion system for the robotics surgery system "da Vinci". The data fusion system is composed of an optical 3D location sensor and a digital video processing system. The 3D location sensor is attached to the da Vinci's laparoscope and measures its location and direction. The digital video processing system captures the laparoscope's view and superimposes 3D patient's organ models onto the captured view in real-time. We applied the system to "da Vinci" and examined this system during a cholecystectomy. In this experiment, the surgeon was able to observe the inner conditions of the organs with a stereo view.

Cholecystectomy↗
PubMed2002

Potent cytotoxic effect of the trans10, cis12 isomer of conjugated linoleic acid on rat hepatoma dRLh-84 cells.

We evaluated the cytotoxic effect of conjugated linoleic acid (CLA) on rat hepatoma dRLh-84 cells in vitro. When cells were cultured in the presence of CLA, strong cytotoxic effect on dRLh-84 cells was recognized at 1 microM level compared to the control vehicle group, and trans10, cis12-CLA but not cis9, trans11-CLA was shown to be an active isomer for inducing this effect. Increase of the sub-G1 population and activation of caspase-3 and 9 accompanied with a time-dependent cleavage of poly(ADP-ribose) polymerase were recognized in dRLh-84 cells treated with trans10, cis12-CLA. In addition, we could see nuclear fragmentation in dRLh-84 cells treated with trans10, cis12-CLA by laser scanning confocal microscopy observation. Cytotoxic effect of trans10, cis12-CLA on normal hepatocytes was weaker than on dRLh-84 cells. These data indicate trans10, cis12-CLA has a potent cytotoxic effect on dRLh-84 cells through at least in part by an apoptotic pathway.

Animals↗
PubMed2002

Beneficial effect of MCI-186 on hepatic warm ischemia-reperfusion in the rat.

Despite growing evidence that reactive oxygen species are responsible for deleterious effects of ischemia-reperfusion (I/R) injury of the liver, there exists, until now, no reliable antioxidant therapeutics applicable in the clinical setting. We investigated the effects of free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), using an isolated liver perfusion model to elucidate its possible therapeutic effects on hepatic warm I/R injury. Isolated livers from Wistar rats were reperfused for 120 min with an oxygenated Krebs-Henseleit bicarbonate buffer after 1 hr of warm ischemia. Addition of MCI-186 (1 mg/L) into the perfusate significantly improved portal flow, hepatic enzyme release into the perfusate, total bile production, histologic alteration, and malondialdehyde concentration but not sinusoidal endothelial cell function as assessed by the clearance of hyaluronic acid. MCI-186 seems to have protective effects against hepatic warm I/R injury by attenuating the damage of the hepatocyte, which is the major target of oxidative damage in this model.

Animals↗
PubMed2002

In vivo gene transfer into muscle via electro-sonoporation.

Among the nonviral techniques for gene transfer in vivo, electroporation is simple, potent, inexpensive, and safe. To upregulate the expression levels of the transferred gene, we investigated the applicability of in vivo electro-sonoporation, which consists of a combination of electric pulse and ultrasound, for gene transfer using plasmid DNA encoding luciferase and mouse interleukin-12 (mIL-12). The quadriceps muscles of mice were injected with plasmid DNA, then sonoporated for 5 min, and electroporated by a pair of electrode plates at the middle of the duration of sonoporation. Three days later, mice that had undergone electro-sonoporation demonstrated twofold higher luciferase activity and low tissue damage in quadriceps muscle compared to mice having undergone electroporation alone. Serum mIL-12 levels in mice that had undergone electro-sonoporation (peaking at 25.5 ng/ml) were twofold higher after gene transfer than were those in mice having undergone electroporation alone (peaking at 14.3 ng/ml), and maintained high serum level of 13.9 ng/ml at 28 days after gene transfer. The efficacy of gene transfer via electro-sonoporation was superior when the plasmid DNA solution was 0.85% NaCl compared to albumin microbubble echo-contrast material. These results demonstrated that gene transfer into muscle via electro-sonoporation could provide a new potent nonviral technique for gene transfer in vivo.

Animals↗