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Ken Sato

Publications and source records attributed to Ken Sato.

69 records · Page 4Linked to original sources
PubMed2003

Cloning and characterization of a novel RING-B-box-coiled-coil protein with apoptotic function.

We have identified a novel RING-B-box-coiled-coil (RBCC) protein (MAIR for macrophage-derived apoptosis-inducing RBCC protein) that consists of an N-terminal RING finger, followed by a B-box zinc finger, a coiled-coil domain, and a B30.2 domain. MAIR mRNA was expressed widely in mouse tissues and was induced by macrophage colony-stimulating factor in murine peritoneal and bone marrow macrophages. MAIR protein initially showed a granular distribution predominantly in the cytoplasm. The addition of zinc to transfectants containing MAIR cDNA as part of a heavy metal-inducible vector caused apoptosis of the cells characterized by cell fragmentation; a reduction in mitochondrial membrane potential; activation of caspase-7, -8, and -9, but not caspase-3; and DNA degradation. We also found that the RING finger and coiled-coil domains were required for MAIR activity by analysis with deletion mutants.

Amino Acid Sequence↗
PubMed2003

Usefulness of urinary NMP22 to detect tumor recurrence of superficial bladder cancer after transurethral resection.

BACKGROUND: In a prospective study we compared the usefulness of urinary nuclear matrix protein 22 (NMP22) with that of urine cytology and other urinary markers in the monitoring of superficial bladder cancer after transurethral resection (TURBT). METHODS: The subjects were 156 patients, comprising 99 patients with superficial bladder cancer in whom TURBT was planned (untreated group) and 57 patients without tumors in the bladder who had been followed up after TURBT (follow-up group). RESULTS: Among the 156 patients, who were monitored for 11-26 months (median, 21 months), recurrence was observed in 51 patients (33.0%). At the time of recurrence, the sensitivities of NMP22, basic fetoprotein (BFP), and bladder tumor antigen (BTA) tests, and urine cytology were 18.6%, 23.3%, 9.3%, and 7.0%, respectively. The factors affecting the sensitivity of NMP22 were tumor size and urinary WBC. The size of recurrent tumors was significantly smaller (P<0.05) than that of the initial tumors. Based on receiver operating characteristic (ROC) curves calculated from the data of patients with recurrence, the ideal cutoff values at recurrence were recommended to be 5.0 U/ml for NMP22 and 6.0 ng/ml for BFP. Using these cutoff values, the sensitivities of NMP22 and BFP were 48.8% and 44.2%, respectively. CONCLUSIONS: Because the size of recurrent bladder tumors is usually smaller than that of the initial tumors, the cutoff values of urinary markers should be reduced to detect these tumors. We recommend 5.0 U/ml as a cutoff value of NMP22 for detection of recurrence of bladder tumor.

Adult↗
PubMed2003

Pilot clinical trial of the use of alpha-tocopherol for the prevention of hepatocellular carcinoma in patients with liver cirrhosis.

Patients with chronic hepatitis C virus (HCV) infection often develop liver cirrhosis and hepatocellular carcinoma (HCC). The purpose of this study was to test the chemopreventive effect of alpha-tocopherol on hepatocarcinogenesis in patients with liver cirrhosis and a history of HCV infection. Eighty-three patients with liver cirrhosis and with positive history of HCV infection were divided at random into two groups. Forty-four patients were treated with alpha-tocopherol (Vit E group) while the other 39 were followed as controls. The clinical background (gender, age, and laboratory data) was similar in the two groups. Serum levels of alpha-tocopherol, albumin, alanine aminotransferase (ALT), and total cholesterol and platelet count were measured serially over a period of five years. The mean serum concentration of alpha-tocopherol was low in both groups at entry and was significantly higher in the Vit E group than in the control group one month after treatment. Platelet count, serum albumin, ALT, and total cholesterol were not different between the two groups during the five-year period. Cumulative tumor-free survival and cumulative survival rate tended to be higher in the Vit E group than in controls, albeit statistically insignificant. The serum level of alpha-tocopherol was low in patients with liver cirrhosis and positive for HCV. Although the administration of alpha-tocopherol normalized the level one month later, it could neither improve liver function, suppress hepatocarcinogenesis, nor improve cumulative survival. Patients treated with alpha-tocopherol tended to live longer without development of HCC but the difference was not statistically significant.

Alanine Transaminase↗
PubMed2003

Mechanisms of increased insulin resistance in non-cirrhotic patients with chronic hepatitis C virus infection.

BACKGROUND AND AIM: Evidence showing a higher prevalence of diabetes mellitus (DM) in patients with chronic hepatitis C virus (HCV) infection has been accumulating. However, the reason why chronic HCV infection promotes DM remains unknown. In the present study, the authors focused on non-cirrhotic and non-diabetic patients with chronic HCV infection and evaluated the factors responsible for increases in insulin resistance. METHODS: Fifty-six patients diagnosed with HCV-related chronic liver disease were included. Biochemical information including body mass index (BMI), aspartate aminotransferase (AST), alanine aminotransferase, cholinesterase, triglyceride, total cholesterol, hemoglobin, platelet count, glycosylated hemoglobin, immunoreactive insulin (IRI), and serum levels of tumor necrosis factor (TNF)-alpha and HCV-RNA were determined using venous blood samples obtained from each patient after overnight fasting. Homeostasis model assessment of insulin resistance (HOMA-IR), a simple and convenient measure of insulin resistance, was also calculated. The relationship between the stage of liver fibrosis and HOMA-IR, and the clinical factors responsible for the increase in HOMA-IR in non-diabetic patients was investigated. RESULTS: Homeostasis model assessment of insulin resistance and IRI levels increased parallel with the progression of fibrosis. Among the non-diabetic patients with mild to moderate liver fibrosis, BMI, serum levels of AST and TNF-alpha were related with HOMA-IR (BMI: r = 0.395, P = 0.041; AST: r = 0.465, P = 0.014; TNF-alpha: r = 0.396, P = 0.040). In contrast, HOMA-IR related to TNF-alpha (r = 0.526, P = 0.013) in non-diabetic patients with advanced liver fibrosis. CONCLUSION: Collectively, hepatic fibrosis and inflammation appear to play key roles in the increase in insulin resistance in patients with chronic HCV infection.

Aged↗
PubMed2003

[Atresia hymenalis with acute urinary retention under the anti-histamine drug: a case report].

A case of atresia hymenalis with acute urinary retention under the administration of the anti-histamine drug for pollinosis was reported. The patient was an 11 year-old female, who complained with acute urinary retention under the administration of the anti-histamine drug. Ultrasonography and magnetic resonance imaging revealed an expansive urinary bladder and an intravaginal hematoma. Subsequently examination of the external genitalia revealed atresia hymenalis and hematocolpos. The symptoms disappeared completely after a hymenal incision and drainage. To our knowledge, approximately fifty cases of atresia hymenalis have been previously reported in Japan. For the urologists, atresia hymenalis may not be experienced because of the rarely gynecological disease. However, we believe it should be considered as one causative disease in pubescent girls who complaining of difficulty in urination. Subsequently an examination of the external genitalia should be performed.

Child↗
PubMed2002

CCl4-induced acute liver injury in mice is inhibited by hepatocyte growth factor overexpression but stimulated by NK2 overexpression.

Hepatocyte growth factor (HGF) inhibits acute liver injury. NK2 acts as an antagonist to HGF in vitro, but its in vivo function has reached no consensus conclusions. We have investigated in vivo effects of HGF and NK2 on CCl4-induced acute liver injury. Elevation of the serum alanine aminotransferase level and extension of centrilobular necrosis were inhibited in HGF transgenic mice but were promoted in NK2 transgenic mice. Hepatocyte proliferation after liver injury was not inhibited in NK2 transgenic mice. Thus, this study indicates that HGF inhibits liver injury, and NK2 antagonizes HGF on liver injury, however, NK2 may not antagonize HGF on hepatocyte proliferation.

Alanine Transaminase↗
PubMed2002

Evidence for the intimate relationship between vesicle budding from the ER and the unfolded protein response.

Yeast Saccharomyces cerevisiae Sec12p, an ER membrane protein, carries out an essential function as the guanine nucleotide exchange factor of the small GTPase Sar1p. Sar1p-GTP is pivotal for the assembly of a coat protein complex, COPII, on the ER membrane, and thus Sec12p can be regarded as the initiator of vesicle budding from the ER. In an effort to identify genes that positively regulate Sec12p, we isolated IRE1 as a novel multicopy suppressor of the temperature-sensitive sec12-4 mutant. IRE1 encodes a transmembrane kinase/nuclease, which controls the unfolded protein response (UPR) to induce transcription of ER chaperones under stress conditions. The constitutive activation of the UPR by overexpression of either IRE1 or active mutant HAC1, a transcription factor responsible for the UPR, suppresses sec12-4. Interestingly, overproduction of some cargo proteins also results in suppression of sec12-4 through the activation of the UPR. The overexpression of IRE1 suppresses the sec mutants defective in vesicle budding from the ER but not others, highlighting a close relationship between the ER exit and the UPR.

Biological Transport↗
PubMed2002

Severe manifestation of acute hepatitis A recently found in Gunma, Japan.

BACKGROUND: The incidence of acute hepatitis A infection in Japan peaked 10 years ago and has been decreasing since then. However, an increase in severe cases of the disease has been documented recently. We experienced an outbreak in 1998-1999, and compared the clinical features of the disease in 1998-1999 (recent outbreak) and in 1987-1988 (past outbreak) in our prefecture (Gunma). METHODS: Forty patients with acute hepatitis A were admitted to nine Gunma hospitals from October 1998 to September 1999. Their clinical features were compared with those of 100 patients with acute hepatitis A admitted to the same hospitals in 1987-1988. RESULTS: Both outbreaks occurred mostly during the winter-spring season. Secondary familial infection was significantly decreased in the recent outbreak. Patients in the recent outbreak were 7 years older than those in the past outbreak. Laboratory findings, such as serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and prothrombin time, were worse in the recent than in the past outbreak. Severe-type hepatitis and fulminant hepatitis occurred in 5 patients (12.5%) in the recent outbreak but in only 2 patients (2.0%) in the past outbreak. CONCLUSIONS: Clinical data and manifestations were more severe in the recent outbreak than in the past outbreak of acute hepatitis A. It is important to be aware of hepatitis A virus infection and to take into account the available vaccination against hepatitis A virus in Japan.

Acute Disease↗
PubMed2002

Emp47p and its close homolog Emp46p have a tyrosine-containing endoplasmic reticulum exit signal and function in glycoprotein secretion in Saccharomyces cerevisiae.

The yeast open reading frame YLR080w/EMP46 encodes a homolog of the Golgi protein Emp47p. These two proteins are 45% identical and have a single transmembrane domain in their C-terminal regions and a carbohydrate recognition domain signature in the N-terminal region. The C-terminal tail of Emp46p includes a dilysine signal. This protein is localized to Golgi membranes at steady state by subcellular fractionation and green fluorescent protein labeling. On block of forward transport in sec12-4 cells, redistribution of Emp46p from the Golgi to the endoplasmic reticulum is observed. These localization features are similar to those previously reported for Emp47p. In addition, mutagenesis of the C-terminal region identified a tyrosine-containing motif as a critical determinant of the Golgi-localization and interaction with both COPI and COPII components. Similar motifs are also observed in the C-terminal tail of Emp47p and other mammalian homologs. Disruption of Emp47p displays a growth defect at a high temperature or on Ca(2+)-containing medium, which is rescued by overexpression of Emp46p, suggesting a partially overlapping function between Emp46p and Emp47p. In addition, we found that the disruption of both Emp46p and Emp47p show a marked defect in the secretion of a subset of glycoproteins. Analysis of the C-terminal mutants for Ca(2+) sensitivity revealed that the forward transport of Emp46/47p is essential for their function, whereas the retrograde transport is not. We propose that Emp46p and Emp47p are required for the export of specific glycoprotein cargo from the endoplasmic reticulum.

Amino Acid Sequence↗
PubMed2002

Interleukin-10 differently regulates monocyte chemoattractant protein-1 gene expression depending on the environment in a human monoblastic cell line, UG3.

Interleukin (IL)-4, IL-10, and IL-13 affect monocyte/macrophage functions including regulation of cytokine production. We analyzed the regulatory effects of these cytokines on cytokine production using a human monoblastic cell line, UG3. It is interesting that IL-10 up-regulated, whereas IL-4 and IL-13 down-regulated monocyte chemoattractant protein-1 (MCP-1) production by unstimulated UG3 cells. IL-10-induced expression of MCP-1 mRNA occurred without de novo protein synthesis at transcriptional and post-transcriptional levels. The enhancement of binding activity of nuclear factor Sp1 (Sp-1) and signal transducer and activators of transcription (STAT)1 and 3 but not nuclear factor kappaB (NF-kappaB) was associated with this IL-10-induced MCP-1 expression. Furthermore, IL-10 suppressed lipopolysaccharide (LPS)-induced NF-kappaB binding but not Sp-1. The present results suggest IL-10 has two contrasting actions on the MCP-1 production of monocytes/macrophages, between the resting and activated conditions. The combination of activated Sp-1 and STATs is important for IL-10-induced MCP-1 expression in resting monocytes/macrophages, and the inhibition of LPS-induced NF-kappaB binding is crucial for down-regulation of MCP-1 by IL-10 in stimulated monocytes/macrophages.

Cell Line↗
PubMedDate not supplied

Advanced dynamic flow imaging with contrast-enhanced ultrasonography for the evaluation of tumor vascularity in liver tumors.

To examine the usefulness of advanced dynamic flow imaging in diagnosing hepatic tumor and in assessing therapeutic effects in patients with hepatocellular carcinoma (HCC) and metastatic hepatic tumor, we performed contrast-enhanced ultrasonography (US) with Levovist, a microbubble contrast agent. Twenty-two patients of 35 HCC nodules infected with hepatitis C virus (HCV) and six patients with metastatic liver nodules were studied. They were diagnosed as having HCC or metastasis with helical dynamic computed tomography (CT) and/or celiac angiography. Tumor vascularities in the early arterial and postvascular phases were assessed by real-time scanning of advanced dynamic flow imaging and intermittent interval-delay scanning of contrast pulse subtraction imaging with a wide-band power Doppler technology. All patients showed hypervascular enhancement of HCC on contrast-enhanced US and/or dynamic CT. The advanced dynamic flow could be obtained as vascular and perfusion images of hepatic tumors. Tumor vascularities, including tumor vessels and parenchymal flow, were able to demonstrate in 27 of 29 nodules including 17 patients with 27 HCC nodules and 2 patients with 2 metastatic nodules before radiofrequency ablation (RFA) treatment by the advanced dynamic flow on contrast-enhanced harmonic US. Two nodules gave insufficient dynamic flow which were located approximately 12 cm in depth from the body surface. The advanced dynamic flow, which was done 7-10 days after RFA, indicated disappearance of the tumor vessels in 27 of visible 27 nodules. The study on early phase of helical dynamic CT revealed the same results as noted in early vascular phase of dynamic flow US. No major complication of RFA procedure was noted. The results indicated that contrast-enhanced advanced dynamic flow imaging on US clearly depicted intratumoral vascularity in real time and thus it is useful to diagnose and assess therapeutic efficacy in patients with HCC and metastatic liver tumor.

Aged↗
PubMedDate not supplied

A case of hepatocellular carcinoma (HCC) treated with radiofrequency ablation (RFA) using 4D real-time ultrasound system.

The patient was a 62-year-old man. The anamnesis revealed an alcoholic liver disease. The patient was admitted to the department of otolaryngology in our hospital with sudden deafness in March 2003. The liver damage was pointed out due to the laboratory data on admission. A liver tumor was identified on the subsequently performed CT scan and the patient was referred to another department at another ward for detailed examinations. Based on the results of contrast echography, CT findings and angiography a HCC was diagnosed and RFA was performed. The conventional B-mode ultrasound examination sometimes presented unclear cross-sectional images of the tumor at the target area, and so additional treatment had to be given from time to time. Simultaneously with the puncturing multi-slice imaging could be obtained, allowing exact and definite performance of the RFA using a 4D real-time ultrasound system. Additionally, ultrasound examination with contrast media was conducted to help determine the efficacy of treatment.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

The effect of o6-methylguanine-DNA methyltransferase (MGMT) and mismatch repair gene (hMLH1) status on the sensitivity to alkylating agent 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea(ACNU) in gallbladder carcinoma cells.

The aim of this study was to correlate O6-methylguanine-DNA methyltransferase (MGMT) and mismatch repair gene (hMLH1) expression in gallbladder carcinoma cells with drug sensitivity to the bifunctional alkylating agent 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU). Using 5 gallbladder carcinoma cell lines and 1 colon carcinoma cell line (SW48), the MGMT and hMLH1 status was assessed both by RT-PCR and Western blot analyses. Sensitivity to ACNU was estimated by the MTT assay. MGMT+/hMLH1+ status was revealed in 2 gallbladder carcinoma cells, MGMT-/hMLH1+ in another 3 gallbladder carcinomas and MGMT-/hMLH1- in SW48. MGMT-/hMLH1+ and MGMT-/hMLH1- cells were more sensitive to ACNU compared with MGMT+/hMLH1+ cells. These results indicate that MGMT, but not hMLH1, expression is an important determinant for drug sensitivity to ACNU in gallbladder carcinoma cells. The drug effect of ACNU, which depends on the MGMT status, was verified using xenograft tumors grown in nude mice. Furthermore, the apoptotic index of MGMT- GB-dl xenografts was significantly increased by ACNU treatment, compared with that of MGMT+ KMG-C. In conclusion, the sensitivity to ACNU was not associated with hMLH1 status, but was found to depend only on the MGMT status. ACNU might be a useful chemotherapeutic agent for MGMT- gallbladder carcinoma, which is associated with poor patient outcome.

Adaptor Proteins, Signal Transducing↗
PubMedDate not supplied

Four-dimensional ultrasonography for therapeutic radiofrequency ablation for hepatocellular carcinoma.

BACKGROUND/AIMS: We examined whether four-dimensional real-time flow imaging on ultrasonography (US) is valuable to display the accurate position of percutaneous radiofrequency ablation (RFA) needle in the nodule of hepatocellular carcinoma (HCC). METHODOLOGY: Ten patients with 12 HCC nodules were studied; nine were infected with hepatitis C virus (HCV) and one was diagnosed as non-B non-C. Diagnosis was done by helical dynamic CT and/or celiac angiography. Tumor vascularities in the early arterial and post-vascular phases after injection of a microbubble contrast agent were assessed by real-time US scanning of coded harmonic imaging and intermittent interval-delay scanning with a wide-band power Doppler technology. Percutaneous RFA was performed with four-dimensional real-time flow imaging under US to display the accurate position of cool-tip needle. RESULTS: It was possible to obtain accurate position of the needle during RFA procedure in all 12 nodules. The needle was confirmed to be inserted into the center of the tumor nodule by various angles. The simultaneous study before RFA therapy showed the inflow of arterial blood and tumor staining in all nodules at early arterial phase of coded harmonic angio on contrast-enhanced US scan. Posttreatment study to evaluate the therapeutic efficacy showed no blood flow at both early vascular and post-vascular phases. No residual blood flow was noted on early phase of CT scan with adequate safety margin. There was no discrepancy in the finding at early phase between contrast-enhanced US and dynamic CT. CONCLUSIONS: It appeared that four-dimensional real-time US provided more perceptible information on the spatial relationship between RFA needle and the target lesion, and resulted in accurate therapeutic efficacy for percutaneous RFA procedure.

Adult↗