PubMed Health⌕ Search

Biomedical subjects

Motoyuki Kohjima

Publications and source records attributed to Motoyuki Kohjima.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of tissue pressure and ablation time between the LeVeen and cool-tip needle methods.

BACKGROUND: Radio frequency ablation (RFA) has been accepted clinically as a useful local treatment for hepatocellular carcinoma (HCC). However, intrahepatic recurrence after RFA has been reported which might be attributable to increase in intra-tumor pressure during RFA. To reduce the pressure and ablation time, we developed a novel method of RFA, a multi-step method in which a LeVeen needle, an expansion-type electrode, is incrementally and stepwise expanded. We compared the maximal pressure during ablation and the total ablation time among the multi-step method, single-step method (a standard single-step full expansion with a LeVeen needle), and the method with a cool-tip electrode. Finally, we performed a preliminary comparison of the ablation times for these methods in HCC cases. RESULTS: A block of pig liver sealed in a rigid plastic case was used as a model of an HCC tumor with a capsule. The multi-step method with the LeVeen electrode resulted in the lowest pressure as compared with the single-step or cool-tip methods. There was no significant difference in the ablation time between the multi-step and cool-tip ablation methods, although the single-step methods had longer ablation times than the other ablation procedures. In HCC cases, the multi-step method had a significantly shorter ablation time than the single-step or cool-tip methods. CONCLUSION: We demonstrated that the multi-step method was useful to reduce the ablation time and to suppress the increase in pressure. The multi-step method using a LeVeen needle may be a clinically applicable procedure for RFA.

Journal Article↗
PubMed2006

An adult case with Hunter's syndrome presenting prominent hepatic failure: light and electron microscopic features of the liver.

We describe a 40-year-old male patient with Hunter's syndrome. His main manifestations were ascites and esophageal varices due to cirrhotic liver. We obtained hepatic biopsy samples and examined them. Ultrastructurally, the features of the hepatocytes and Kupffer cells were the same as those reported in young patients. The passage of 40 years led to gradual progression to fibrosis, and ultimately liver cirrhosis. Namely, with a longer survival time, the complications of liver cirrhosis become more remarkable. Hepatic fibrosis in Hunter's syndrome is slowly progressive and patients who are expected to have a longer life span should be continuously monitored for hepatic complications.

Adult↗
PubMed2006

Arterial steroid injection therapy can inhibit the progression of severe acute hepatic failure toward fulminant liver failure.

AIM: To utilize transcatheter arterial steroid injection therapy (TASIT) via the hepatic artery to reduce hepatic macrophage activity in patients with severe acute hepatic failure. METHODS: Thirty-four patients with severe acute hepatic failure were admitted to our hospital between June 2002 to June 2006 providing for the possibility of liver transplantation (LT). Seventeen patients were treated using traditional liver supportive procedures, and the other 17 patients additionally underwent TASIT with 1000 mg methylprednisolone per day for 3 continuous days. RESULTS: Of the 17 patients who received TASIT, 13 were cured without any complications, 2 died, and 2 underwent LT. Of the 17 patients who did not receive TASIT, 4 were self-limiting, 7 died, and 6 underwent LT. Univariate logistic analysis revealed that ascites, serum albumin, prothrombin time, platelet count, and TASIT were significant variables for predicating the prognosis. Multivariate logistic regression analysis using stepwise variable selection showed that prothrombin time, platelet count, and TASIT were independent predictive factors. CONCLUSION: TASIT might effectively prevent the progression of severe acute hepatic failure to a fatal stage of fulminant liver failure.

Adult↗
PubMed2006

Two forms of human Inscuteable-related protein that links Par3 to the Pins homologues LGN and AGS3.

In cell polarization of Drosophila neuroblasts, Inscuteable (Insc) functions via tethering Partner of Insc (Pins) to Bazooka, homologous to human cell polarity protein Par3. However, little has been known about mammalian homologues of Insc. Here we describe cloning of two distinct cDNAs from human Insc gene, which is differentially expressed from alternative first exons: one encodes 579 amino acids, whereas the other lacks the N-terminal 47 amino acids. In contrast to human homologues for Pins and Par3, human Insc exhibits a weak homology with the Drosophila counterpart. Nevertheless, human Insc proteins bind to the human Pins homologues LGN and AGS3, and also to human Par3 and its related protein Par3beta. Although LGN by itself is incapable of interacting with Par3, coexpression of human Insc leads to the interaction between LGN and Par3, indicating that human Insc plays an evolutionarily conserved role as an adaptor protein that links Pins to Par3.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Baseline characterization of patients aged 70 years and above with hepatocellular carcinoma.

AIM: To characterize the baseline profiles of patients aged 70 years and above with hepatocellular carcinoma (HCC). METHODS: A series of 127 consecutive patients with HCC were enrolled between 2000 and 2004, and none of them had been diagnosed as having HCC previously. Baseline profiles, including parameters of hepatic function such as serum transaminase and prothrombin time [PT (% activity)] were compared between patients aged > or = 70 and < 70 years. RESULTS: Patients > or = 70 years old showed significantly lower levels of aspartate aminotransferase (P = 0.04) and alanine aminotransferase (P = 0.01), and significantly higher PTs (P = 0.04) and platelet counts (P = 0.02). Concomitantly, among > or = 70-year-old patients, HCC was more common in non-cirrhotics, whereas among patients < 70 years old, HCC was more common in cirrhotics. There was no significant difference between the groups in the number or size of tumors. CONCLUSION: Older HCC patients showed less inflammation and better preservation of hepatic function, indicating that not only cirrhotic patients but also non-cirrhotic patients should be considered as a high-risk group among the elderly.

Age Factors↗
PubMed2005

Scattered and rapid intrahepatic recurrences after radio frequency ablation for hepatocellular carcinoma.

AIM: To evaluate a series of patients with hepatocellular carcinoma (HCC) treated with several different protocols and devices. METHODS: We treated 138 patients [chronic hepatitis/liver cirrhosis (Child-Pugh A/B/C), 3/135 (107/25/3)] with two different devices and protocols: cool-tip needle [initial ablation at 60 W (standard method) (n=37) or at 40 W (modified method) (n=28)] or; ablation with a LeVeen needle using a standard single-step, full expansion (single-step) method (n=39) or a multi-step, incremental expansion (multi-step) method. RESULTS: Eleven patients experienced rapid and scattered recurrences 1 to 7 mo after the ablation. Nine patients were treated by the cool-tip original protocol (60 W) (9/37=24%) and the other two by the LeVeen single-step method (2/39=5%). The location of the recurrence was surrounding and limited to the site of ablation segment in three cases, and spread over one lobule or both lobules in the other eight cases. There was no recurrence in the patients treated with the modified cool-tip modified method (40 W) or the LeVeen multi-step method. CONCLUSION: There is a risk of rapid and scattered recurrence after RFA, especially when the standard cool-tip procedure is used. Because such recurrence would worsen the prognosis, we recommend that modified protocols for the cool-tip and LeVeen needle methods should be used in clinical practice.

Adult↗
PubMed2005

Re-evaluation of antitumor effects of combination chemotherapy with interferon-alpha and 5-fluorouracil for advanced hepatocellular carcinoma.

AIM: To evaluate the efficacy of combination chemotherapy with interferon-alpha (IFNalpha) and 5-fluorouracil (5-FU) in patients with advanced hepatocellular carcinoma (HCC). METHODS: Twenty-eight HCC patients in advanced stage were enrolled in the study. They were treated with IFNalpha/5-FU combination chemotherapy. One cycle of therapy lasted for 4 wk. IFNalpha (3 x 10(6) units) was subcutaneously injected thrice weekly on days 1, 3, and 5 for 3 wk, and 5-FU (500 mg/d) was administered via the proper hepatic artery for 5 consecutive days per week for 3 wk. No drugs were administered during the 4(th) wk. The effect of combination chemotherapy was evaluated in each patient after every cycle based on the reduction of tumor volume. RESULTS: After the 1(st) cycle of therapy, 16 patients showed a partial response (PR, 57.1%) but none showed a complete response (CR, 0%). At the end of therapy, the number of patients who showed a CR, PR, or no response (NR) was 1, 10, and 17, respectively. The response rate for therapy (CR+PR) was 21.5%. Biochemical tests before therapy were compared between responsive (CR+PR) and non-responsive (NR) patients, but no significant differences were found for any of the parameters examined, indicating that no reasonable predictors could be identified in our analysis. CONCLUSION: Attempts should be made to discriminate between responders and non-responders by evaluating tumor size after the first cycle of IFNalpha/5-FU combination chemotherapy. For non-responders, therapy should not proceed to the next cycle, and instead, different combination of anticancer drugs should be explored.

Antineoplastic Agents↗
PubMed2005

Phosphorylation-dependent binding of 14-3-3 to Par3beta, a human Par3-related cell polarity protein.

Mammalian Par3alpha and Par3beta/Par3L participate in cell polarity establishment and localize to tight junctions of epithelial cells; Par3alpha acts via binding to atypical PKC (aPKC). Here we show that Par3beta as well as Par3alpha interacts with 14-3-3 proteins in a phosphorylation-dependent manner. In the interaction, Ser-746 of Par3beta and the corresponding residue of Par3alpha (Ser-814) likely play a crucial role, since replacement of these residues by unphosphorylatable alanine results in a loss of interacting activity. The mutant Par3 proteins with the replacement are correctly recruited to tight junctions of MDCK cells and to membrane ruffles induced by an active form of the small GTPase Rac in HeLa cells. Thus, the interaction with 14-3-3 appears to be dispensable to Par3 localization. Consistent with this, the Par3alpha-14-3-3 interaction does not inhibit the Par3alpha-aPKC association required for the Par3alpha localization, although the aPKC-binding site lies close to the Ser-814-containing, 14-3-3-interacting region.

14-3-3 Proteins↗
PubMed2005

Epigallocatechin-3-gallate, a green-tea polyphenol, suppresses Rho signaling in TWNT-4 human hepatic stellate cells.

Epigallocatechin-3-gallate (EGCG), a major constituent of the polyphenoids in green tea, has been reported to possess a wide range of biologic activities, including antifibrogenesis. Activated hepatic stellate cells (HSCs) are central to hepatic fibrosis, and Rho (a small GTPase)-signaling pathways have been implicated in the activation and proliferation of HSCs. In this study, we investigated the effect of EGCG on Rho-signaling pathways in activated human HSC-derived TWNT-4 cells. EGCG inhibited stress-fiber formation, an indicator of Rho activation, and changed the distribution of alpha-smooth-muscle actin. These inhibitory effects of EGCG were restored by overexpression of constitutively active Rho. A pull-down assay revealed that activated Rho (GTP-bound state) was strongly inhibited by ECGC and accompanied by suppressed phosphorylation of focal adhesion kinase, which is a regulator of Rho-signaling pathways. 5-Bromo-2'-deoxy-uridine incorporation demonstrated that ECGC (100 micromol/L suppressed cell growth by 80%, and terminal deoxynucleotidyl transferase viotin-deoxyruidine triphosphate nick end-labeling revealed that EGCG (100 micromol/L) caused apoptosis in half of the total cells. EGCG also strongly inhibited lysophoaphatidic acid (an activator of Rho) and induced phosphorylation of mitogen-activated protein kinases (Erk1/2, c-jun kinase, and p38). These findings demonstrate that EGCG regulates the structure and growth of HSCs by way of Rho-signaling pathways and suggest that EGCG has therapeutic potential in the setting of liver fibrosis.

Actins↗
PubMed2005

A multi-step, incremental expansion method for radio frequency ablation: optimization of the procedure to prevent increases in intra-tumor pressure and to reduce the ablation time.

BACKGROUND/AIMS: Radio frequency ablation (RFA) has been accepted clinically as a useful local treatment for hepatocellular carcinoma (HCC). However, intra-hepatic recurrence after RFA has been reported. We initially hypothesized that recurrence was attributable to increases in intra-tumor pressure during RFA, and we subsequently measured the pressure and optimized the procedure. METHODS: A block of pig liver sealed in a rigid plastic case was used as a model of an HCC tumor with a capsule. We compared the pressure between a single-step full expansion of the needle (single-step method) and incremental, stepwise expansion (multi-step method), and evaluated the effect of varying the electrical power. Finally, we performed a preliminary comparison of the ablation times for these methods in HCC cases. RESULTS: The multi-step method resulted in a significantly lower pressure and shorter total ablation time than the single-step method. Furthermore, incremental expansion in 10 steps resulted in a lower pressure and shorter ablation time than four steps. Seventy W-ablation resulted in a lower pressure and shorter time than 30- or 50 W-ablation. In HCC cases, the multiple-step method had a significantly shorter ablation time than the single-step method. CONCLUSION: The multi-step method can be recommended to reduce the ablation time, and suppress the increase in pressure.

Animals↗
PubMed2005

Effect of IL-4 and IL-13 on collagen production in cultured LI90 human hepatic stellate cells.

BACKGROUND: Recently, it has been reported that interleukin 4 (IL-4) and 13 (IL-13) directly activate fibroblasts and promote fibrosis. In the process of hepatic fibrosis, the effects of these cytokines on hepatic stellate cells (HSCs) are not well known. METHODS: We evaluated the effects of IL-4 and IL-13 on the collagen production and the proliferation of LI90, a hepatic stellate cell line. We also examined whether interferon (IFN) interferes with the expression of collagen, since IFN has been reported to clinically suppress hepatic fibrosis. RESULTS: The receptor complex for IL-4 and IL-13 was IL-4Ralpha/IL-13Ralpha1 on LI90 cells, and the phosphorylation of Stat6 was induced by IL-4 and IL-13. The treatment of LI90 cells with IL-4 or IL-13 increased the production of collagen I protein levels by nearly three times in comparison with untreated cells. Collagen mRNA levels were increased roughly 10-fold by IL-4 and 100-fold by IL-13. Interestingly, BrdU incorporation in LI90 cells was decreased by IL-4 or IL-13 treatment. Furthermore, induction of collagen I production by these cytokines was blocked by IFNalpha or IFNbeta treatment, although neither treatment alone suppressed collagen production. CONCLUSIONS: Our data suggested that IL-4 and IL-13 directly affected HSCs by increasing collagen production and suppressing cell proliferation. The anti-fibrogenetic effect of IFN may be due in part to the blockade of IL-4 and IL-13 stimulation of HSCs.

Base Sequence↗
PubMed2005

High glucose stimulates hepatic stellate cells to proliferate and to produce collagen through free radical production and activation of mitogen-activated protein kinase.

BACKGROUND: Nonalcoholic steatohepatitis is a clinicopathologic condition that may progress to liver fibrosis. Hyperglycemia is supposed to be one of the factors inducing hepatic fibrogenesis, but the mechanism has not been fully clarified. Oxidative stress is increasingly found in patients with diabetes/hyperglycemia in which conditions reactive oxygen species (ROS) are produced. METHODS: We performed experiments using hepatic stellate cells (HSCs) in culture in order to confirm the effect of high glucose concentrations on cell proliferation, type I collagen production, ROS production and activation of mitogen-activated protein (MAP) kinase pathway. RESULTS: High glucose stimulated cell growth of HSCs and up-regulated the levels of activated/phosphorylated extracellular signal-regulated kinase 1/2 and free radical production in HSCs. The MAP kinase phosphorylation and cell proliferation were suppressed by diphenylene iodonium chloride, an NADPH oxidase inhibitor, and by calphostin C, a protein kinase C (PKC)-specific inhibitor. Increased type I collagen mRNA and protein levels were also observed in HSCs at high glucose concentrations. CONCLUSIONS: Our findings indicate that high glucose concentrations may stimulate ROS production through PKC-dependent activation of NADPH oxidase, and induce MAP kinase phosphorylation subsequent to proliferation and type I collagen production by HSCs.

Animals↗
PubMed2005

Fasudil hydrochloride hydrate, a Rho-kinase (ROCK) inhibitor, suppresses collagen production and enhances collagenase activity in hepatic stellate cells.

BACKGROUND/AIMS: The Rho-ROCK signaling pathways play an important role in the activation of hepatic stellate cells (HSCs). We investigated the effects of fasudil hydrochloride hydrate (fasudil), a Rho-kinase (ROCK) inhibitor, on cell growth, collagen production, and collagenase activity in HSCs. METHODS: Rat HSCs and human HSC-derived TWNT-4 cells were cultured for studies on stress fiber formation and alpha-smooth muscle actin (alpha-SMA) expression. Proliferation was measured by BrdU incorporation, and apoptosis by TUNEL assay. The phosphorylation states of the MAP kinases (MAPKs), extra cellular signal -regulated kinase 1/2 (ERK1/2), c-jun kinase (JNK), and p38 were evaluated by western blot analysis. Type I collagen, matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) production and gene expression were evaluated by ELISA and real-time PCR, respectively. Collagenase activity (active MMP-1) was also evaluated. RESULTS: Fasudil (100 microM) inhibited cell spreading, the formation of stress fibers, and expression of alpha-SMA with concomitant suppression of cell growth, although it did not induce apoptosis. Fasudil inhibited phosphorylation of ERK1/2, JNK, and p38. Treatment with fasudil suppressed the production and transcription of collagen and TIMP, stimulated the production and transcription of MMP-1, and enhanced collagenase activity. CONCLUSION: These findings demonstrated that fasudil not only suppresses proliferation and collagen production but also increases collagenase activity.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2005

Beraprost sodium, a prostacyclin (PGI) analogue, ameliorates concanavalin A-induced liver injury in mice.

BACKGROUND/AIMS: Prostacyclin (PGI(2)) is a potent mediator in the inflammatory and coagulation processes. The aim of this study was to test whether beraprost sodium, a PGI(2) analogue, could prevent experimental hepatic injury induced by concanavalin A (Con A), which is a model of fulminant hepatic failure. METHODS: Beraprost (100 microg/kg) was administered intraperitoneally simultaneously with Con A (40 mg/kg) in C57B6J mice. Blood circulation in the liver was determined by laser-Doppler flowmetry. Plasma levels of alanine aminotransferase (ALT), tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-6 were determined. Levels of TNF-alpha and IFN-gamma in culture supernatant of splenocytes were also determined. RESULTS: Beraprost administration reduced the incidence of death following hepatic failure (76.5% vs. 29.4%, P<0.05). Plasma levels of ALT were significantly lower in the beraprost-treated group than in the control group, and in the former, there was concomitant suppression of the histological features of injury. Beraprost significantly increased hepatic blood flow volume in Con A-treated mice. Plasma levels of TNF-alpha and IFN-gamma were significantly reduced at 6 and 12 h after Con A injection, respectively, but the levels of IL-6 were increased at 6 h. In vitro, beraprost also suppressed Con A-induced TNF-alpha production in splenocytes, while it stimulated IFN-gamma production. CONCLUSION: These findings imply that beraprost suppresses Con A-induced liver injury. These data also suggest that beraprost, which is clinically effective in treating pulmonary hypertension, may have therapeutic potential for preventing hepatic injury.

Animals↗
PubMed2005

Evaluation of liver parenchymal pressure and portal endothelium damage during radio frequency ablation in an in vivo porcine model.

BACKGROUND/AIMS: We previously developed a multi-step, incremental expansion method (multi-step method) for radio frequency ablation (RFA) in vitro, which prevented increases in pressure and reduced the ablation time as compared with other methods. In this study, we evaluated liver parenchymal pressure and portal endothelium damage during RFA with different devices and protocols in an in vivo porcine model. METHOD: Nine healthy female pigs were anaesthetized. RFA was performed with two different devices and protocols; one involved the use of a LeVeen needle with a single-step full expansion method or a multi-step method, and the other used a cool-tip needle with 40 or 60 W power. We measured the pressure in the liver parenchyma and the gallbladder during RFA. We also evaluated portal endothelium damage by NADH staining. RESULTS: The multi-step method with the LeVeen electrode resulted in the lowest parenchymal and intra-gallbladder pressures (multi-step method<single-step method <cool-tip 40 W <cool-tip 60 W). In contrast, the ablation time was shortest with the cool-tip needle at 60 W (cool-tip 60 W <cool-tip 40 W=multi-step method <single-step method). NADH staining revealed severe endothelium damage after ablation with the cool-tip needle, but only slight damage with the LeVeen needle. CONCLUSION: Ablation with the LeVeen needle, especially when used with a multi-step protocol, produced less of an increase in liver parenchymal and intra-gallbladder pressures and less damage to portal endothelial cells than did the cool-tip electrode.

Animals↗
PubMed2005

Remote delivery and expression of soluble type II TGF-beta receptor in muscle prevents hepatic fibrosis in rats.

Transforming growth factor-beta (TGF-beta) has been implicated in the process of hepatic fibrosis, and stimulates production of extracellular matrix in hepatic stellate cells, which play a major role in the process. It has been recently reported that blockage of TGF-beta signaling prevents hepatic fibrosis. We evaluated a strategy for anti-TGF-beta gene therapy for hepatic fibrosis by transfecting plasmids expressing an entire extracellular domain of human TGF-beta type II [soluble type II TGF-beta receptor (sTGF-betaIIR)] into skeletal muscle in a rat experimental model of dimethylnitrosamine- (DMN-) induced fibrosis. sTGF-betaIIR treatment decreased significantly the occurrence of DMN-induced hepatic fibrosis, evaluated by computed image analysis and by measurement of hydroxyproline content of the liver, and reduced the expression of collagen and alpha-smooth muscle actin. The treatment also caused a significant decrease in hepatic levels of interleukin- (IL-) 12 (Th1 cytokine) and an increase in those of IL-10 (Th2 cytokine), indicating a change in the Th1/Th2 cytokine balance in the liver. In conclusion, blockade of TGF-beta after intramuscular transfer of the soluble type II TGF-beta receptor gene suppressed hepatic fibrosis, suggesting that this strategy may be useful for gene therapy of hepatic fibrosis.

Actins↗
PubMed2005

[A case of idiopathic portal hypertension complicated with sepsis caused by Aeromonas hydrophila].

A 53 year old man with idiopathic portal hypertension (IPH) was admitted because of high fever and diarrhea. Nineteen years before admission, he had received splenic hilar renal shunt operation with proximal flush ligation of splenic vein due to gastric varices. Three months before admission, he had been admitted to our hospital for evaluation of liver dysfunction. Liver biopsy examination had revealed peri-portal fibrosis consistent with IPH. Aeromonas hydrophila was isolated from blood. Although he was treated with antibiotics plus dopamine, glucose-insulin therapy, and mechanical ventilation, he had severe septic shock, and died 29 days after admission. We have to take notice of A. hydrophila infection in cases of portosystemic shunt because they fall in severe septic shock.

Aeromonas hydrophila↗