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Biomedical subjects

Seiji Suzuki

Publications and source records attributed to Seiji Suzuki.

At least 19 recordsLinked to original sources
PubMed2006

Variations in the viral NS5B region in Japanese patients with chronic hepatitis C virus genotype 1b infection. No specific amino acid substitution was identified as determinants of treatment response to interferon/ribavirin combination therapy.

OBJECTIVE: A recent study suggested that the substitution of amino acid 415 of HCV NS5B from phenylalanine to tyrosine in patients with HCV genotype 1a infection is induced by ribavirin and responsible for resistance to ribavirin therapy. The aim of this study was to evaluate whether specific variations in the HCV NS5B sequence in Japanese patients with HCV genotype 1b (HCV/1b) infection are associated with treatment response or selected by treatment with interferon-alpha/ribavirin combination therapy. METHODS: Eighteen Japanese patients with HCV/1b infection receiving interferon-alpha/ribavirin combination therapy for 24 weeks were studied. Five patients treated with interferon-alpha monotherapy for 24 weeks were also studied as controls. The entire HCV NS5B sequence before and after therapy was determined. RESULTS: All HCV isolates had tyrosine at position 415 of NS5B before and after therapy. Further analysis showed that no specific amino acid substitutions were identified to associate with clinical response and no specific amino acid substitutions were induced/selected by the clinical treatment. CONCLUSION: No specific HCV NS5B nucleotide/amino acid sequence variations, including amino acid 415 of NS5B, were identified as being associated with clinical treatment response or selected by the combination therapy in Japanese patients with HCV/1b infection.

Adult↗
PubMed2006

Relationship between the adiponectin-leptin ratio and parameters of insulin resistance in subjects without hyperglycemia.

We previously reported that the adiponectin-leptin (A/L) ratio was more efficacious as a parameter of insulin resistance than adiponectin or leptin alone, and a more sensitive and reliable marker of insulin resistance than homeostasis model assessment (HOMA-R) as the fasting plasma glucose (FPG) level elevated in type 2 diabetes mellitus. In this study, we examined the usefulness of the A/L ratio as compared to HOMA-R for assessing insulin resistance in Japanese subjects without hyperglycemia. A total of 411 Japanese adults without hyperglycemia (205 men, aged 49 +/- 10 years; 206 women, aged 48 +/- 10 years) were enrolled. We investigated the correlation between fasting serum insulin level, FPG, leptin or adiponectin, and body mass index (BMI), fat mass (FM), triglycerides (TGs), high-density lipoprotein (HDL) cholesterol, or preheparin serum lipoprotein lipase (LPL) as parameters of insulin resistance. Next, we examined the relationships between parameters of insulin resistance and the A/L ratio or HOMA-R. By simple regression of the correlation between serum insulin level, FPG, leptin or adiponectin, and each parameter of insulin resistance, the best correlation coefficients were seen in leptin (men, r = 0.501; women, r = 0.667) as compared with BMI, in leptin (men, r = 0.658; women, r = 0.747) as compared with FM, in adiponectin (r = -0.285) in men and leptin (r = 0.299) in women as compared with TGs, in adiponectin (men, r = 0.405; women; r = 0.442) as compared with HDL cholesterol, and in adiponectin (men, r = 0.228; women, r = 0.452) as compared with LPL. By simple regression of the correlation between A/L ratio or HOMA-R and each parameter of insulin resistance, the highest correlation coefficients were seen with the A/L ratio except HDL cholesterol in men. Next, we carried out multiple linear regression to analyze the association between A/L ratio or HOMA-R and FM, TGs, HDL cholesterol, and LPL, excluding BMI, simultaneously. In men, the A/L ratio was significantly correlated with FM and TGs, and HOMA-R was significantly correlated with FM. This model explained 34% of the variance in the A/L ratio and 17% of the variance in HOMA-R. In women, the A/L ratio was significantly correlated with FM and LPL, and HOMA-R was significantly correlated with FM and LPL. This model explained 39% of the variance in A/L ratio and 14% of the variance in HOMA-R. In conclusion, the present study suggested that the A/L ratio might be more useful than HOMA-R to accurately assess insulin resistance in subjects without hyperglycemia.

Adiponectin↗
PubMed2006

[Practical procedure of totally implanted venous access system for outpatient cancer therapy].

Some outpatient cancer chemotherapy has been replacing inpatient chemotherapy. A totally implanted venous access system is now available for patients who undergo cancer chemotherapy on an outpatient basis. All eleven outpatients who underwent cancer chemotherapy with this system underwent placement of the port and administration of chemotherapy. Complications were observed in two of these eleven patients (18%). Because a subcutaneous abscess occurred in one patient between the placement of the port and her first chemotherapy session, we had to remove the port system once. Another patient developed fungemia, so we discontinued the system after 95 outpatient chemotherapy sessions. When the infection healed, we set up the system again, and no trouble was observed later in these two cases. According to the patients' survey, all patients were satisfied with outpatient chemotherapy using this system. Therefore, we concluded that this system contributes to enhanced quality of life among outpatients who undergo cancer chemotherapy.

Abscess↗
PubMed2006

[A case of non-curatively resected colon cancer with liver and lymph node metastases treated by TS-1/CPT-11 combination therapy].

The patient was a 66-year-old male who had descending colon cancer with multiple liver metastases and paraaortic lymph node metastases. He underwent a left colectomy with lymph node dissection, but the operation resulted in curability C. The serum CEA level before the operation was 205.5 ng/ml. After 2 courses of 5-FU/LV as first-line chemotherapy, this treatment could not be continued due to grade 3 anorexia. As second-line chemotherapy, the patient was treated with daily oral administration of TS-1 (100 mg/day) for 3 weeks. Due to grade 3 anorexia, this treatment could not be continued. Tailored TS-1/CPT-11 (TS-1 80 mg/day from day 1 to day 21, CPT-11 65 mg/m(2) day 1, 15) combination therapy was then chosen as third-line chemotherapy. After 6 courses of combination therapy, the tumor marker (CEA) was decreased and para-aortic lymph nodes could not be detected by computed tomography (CT). Only grade 1 fatigue was noted as an adverse reaction to the treatment. The patient's good QOL was achieved during follow-up over 24 months with the cancer controlled. This case suggests that patients with non-curative resected colon cancer could benefit from TS-1/CPT-11 combination therapy as a second-line or third-line treatment.

Adenocarcinoma↗
PubMed2005

Plasma chloride concentration as a new diagnostic indicator of insulin insufficiency.

The medical criteria for initiating insulin therapy, based on clinical profiles of type 2 diabetic patients, have not yet been clearly established. We explored various parameters with 48 type 2 diabetic patients who were taking oral hypoglycemic medication. Among parameters, body mass index (BMI), the fasting plasma glucose level (FPG), and plasma chloride concentration were identified by forward-stepwise discriminant analysis as parameters that can discriminate between patients who were and those who were not undergoing insulin therapy. In combination, these parameters correctly diagnosed 86.4% of the patients who were undergoing insulin therapy, and 84.6% of those who were not undergoing insulin therapy. Further, we observed significant correlations between plasma chloride concentrations and either plasma sodium or organic acid concentrations, suggesting that impaired insulin action may reduce plasma chloride concentrations through changes in plasma sodium and organic acid metabolism. Our results suggest that plasma chloride concentration is a possible new indicator of insulin insufficiency.

Aged↗
PubMed2005

Correlation between the adiponectin-leptin ratio and parameters of insulin resistance in patients with type 2 diabetes.

We studied the correlation between the adiponectin-leptin (A/L) ratio and parameters of insulin resistance in 220 Japanese patients with type 2 diabetes (138 men and 82 women). Body mass index (BMI), triglycerides (TGs), HDL cholesterol (HDL), and preheparin serum lipoprotein lipase (LPL mass) were examined as laboratory parameters of the insulin resistance. The correlations between these laboratory parameters and adiponectin, leptin, or A/L ratio were studied. Adiponectin levels correlated significantly with BMI (r = -0.298, P = .0003), TGs (r = -0.221, P = .0092), HDL (r = 0.31, P = .0002), and LPL mass (r = 0.26, P = .0021) in men, and with TGs (r = -0.29, P = .0093), HDL (r = 0.239, P = .0338), and LPL mass (r = 0.499, P < .0001) in women. Leptin levels correlated significantly with only BMI (r = 0.31, P = .0002) in men, and with BMI (r = 0.71, P < .0001) and TGs (r = 0.26, P = .0201) in women. Adiponectin and leptin levels tended to correlate with these parameters in an opposite manner. On the other hand, A/L ratio significantly correlated with BMI (r = -0.4, P < .0001), TG (r = -0.199, P = .0192), HDL (r = 0.235, P = .0054), and LPL mass (r = 0.244, P = .0390) in men, and with BMI (r = -0.482, P < .0001), TG (r = -0.402, P = .0002), HDL (r = 0.358, P = .0011), and LPL mass (r = 0.487, P < .0001) in women. Next, the patients were divided into 3 groups classified by their fasting plasma glucose (FPG) level, and the correlations between the parameters and A/L ratio or homeostasis model assessment (HOMA-R), and the correlation between A/L ratio and HOMA-R were investigated in each group. Significant correlations between the parameters and A/L ratio were tended to be observed as the FPG level rose; however, the significant correlations between the parameters and HOMA-R were no longer seen as FPG level elevated. The results suggested that the A/L ratio was effective in relevance as a parameter of insulin resistance to adiponectin or leptin alone, and a more sensitive and reliable marker of insulin resistance than HOMA-R as the FPG level elevated, in patients with type 2 diabetes.

Adiponectin↗
PubMed2005

Impact of occult hepatitis B virus infection on efficacy and prognosis of interferon-alpha therapy for patients with chronic hepatitis C.

BACKGROUND/AIMS: It is reported that some patients with undetectable hepatitis B surface antigen (HBsAg) have serum hepatitis B virus (HBV) DNA in patients with chronic hepatitis C (HCV). The aim of this study was to elucidate the impact of occult HBV infection on the efficacy and prognosis of interferon-alpha (IFN) therapy in HCV patients. METHODS: One hundred and forty HCV patients without HBsAg who received IFN therapy were studied. Serum HBV DNA was quantified by real-time detection polymerase chain reaction. RESULTS: Of 140 patients, 11 (7.9%) were HBV DNA-positive before IFN therapy. The serum HBV DNA levels ranged from 106 to 884 copies/ml. Four of these 11 patients showed a sustained virologic response by IFN, compared with 39 of 129 without HBV DNA (P = NS). Interestingly, two of the 11 patients developed hepatocellular carcinoma (HCC) after therapy, compared with 16 of 129 without HBV DNA (P = NS). In the serial study, serum HBV DNA was transiently undetectable during and after IFN; however, most became positive during follow-up. CONCLUSIONS: Occult HBV infection may not have a significant impact on response to IFN therapy for chronic HCV and development of HCC after therapy. Occult HBV may be sensitive to IFN although HBV is not completely eradicated.

Adult↗
PubMed2005

Hepatitis B virus genotype C prevails among chronic carriers of the virus in Korea.

Hepatitis B virus (HBV) is one of the major causative agents of chronic liver diseases in Korea. HBV has been classified into 8 genotypes by a divergence of >8% in the entire genomic sequence, and have distinct geographic distributions. There are limited data on the relevance between HBV genotypes and clinical outcomes in Korea. To investigate the clinical feature relating to HBV genotype in Korea, a total 120 serum samples with HBsAg (65 from Seoul and 55 from the other city in Korea) were obtained from each 30 chronic HBV carriers with asymptomatic carrier (ASC), chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). HBV genotype was determined by either enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies against genotype-specific epitopes in the preS2-region or the direct sequencing of small S gene. HBV genotypes were determined in 105 (87.5%) of 120 samples. HBV genotype C was identified in all HBV carriers with ASC, CH, LC, and HCC. Genotypes A, B, D, E, F and G were not detected in any of them. Genotype C HBV prevails predominantly among chronic carriers of the virus in Korea, irrespective of their clinical stages of liver disease and geographic origin.

Carrier State↗
PubMed2005

Induction of apoptosis in human salivary gland tumor cells by anti-NCAM antibody.

Neural cell adhesion molecule (NCAM) is a type of cell surface glycoprotein and a member of the immunoglobulin superfamily. It has been reported that NCAM may be associated with perineural invasion by malignant salivary gland tumors such as adenoid cystic carcinoma. We have previously demonstrated that NCAM is constitutively expressed in the human salivary gland tumor cell line HSG, in vitro. In the present study, we have aimed to clarify the hypothesis that NCAM-mediated inhibition of salivary gland tumor proliferation is caused by homophilic binding and involves the prevention of signal transduction for perineural invasion using HSG cells. NCAM mRNA and protein expression was found to decrease in a dose-dependent manner upon treatment with the anti-NCAM antibody (MAb NCAM) for 24 h. The MTT assay showed a significant reduction in the number of viable HSG cells. Confocal laser microscopy showed that HSG cells underwent apoptosis after treatment with MAb NCAM. The activation of caspases 3, 7 and 9 was observed in HSG cells after treatment with MAb NCAM, thus confirming that apoptosis was induced by the activated caspases. Apaf-1 activity was also detected in HSG cells in a dose-dependent manner after treatment with MAb NCAM. The up-regulation of TGF-beta1-mediated NCAM expression appeared to lead to the activation of homophilic NCAM binding, further accelerating HSG cell proliferation. In addition, the localization of NCAM in adenoid cystic carcinomas (ACCs) was examined using an immunohistochemical method. NCAM was slightly to moderately positive in 9 of 13 cases (69.2%) of ACC. These findings suggest that NCAM is associated not only with a cell-to-cell adhesion mechanism, but also with tumorigenesis, including growth, development and perineural invasion in human salivary gland tumors.

Antibodies↗
PubMed2004

Genotype and phylogenetic characterization of hepatitis B virus among multi-ethnic cohort in Hawaii.

AIM: Hepatitis B virus (HBV) genomes in carriers from Hawaii have not been evaluated previously. The aim of the present study was to evaluate the distribution of HBV genotypes and their clinical relevance in Hawaii. METHODS: Genotyping of HBV among 61 multi-ethnic carriers in Hawaii was performed by genetic methods. Three complete genomes and 61 core promoter/precore regions of HBV were sequenced directly. RESULTS: HBV genotype distribution among the 61 carriers was 23.0% for genotype A, 14.7% for genotype B and 62.3% for genotype C. Genotypes A, B and C were obtained from the carriers whose ethnicities were Filipino and Caucasian, Southeast Asian, and various Asian and Micronesian, respectively. All cases of genotype B were composed of recombinant strains with genotype C in the precore plus core region named genotype Ba. HBeAg was detected more frequently in genotype C than in genotype B (68.4% vs 33.3%, P<0.05) and basal core promoter (BCP) mutation (T1762/A1764) was more frequently found in genotype C than in genotype B. Twelve of the 38 genotype C strains possessed C at nucleotide (nt) position 1858 (C-1858). However there was no significant difference in clinical characteristics between C-1858 and T-1858 variants. Based on complete genome sequences, phylogenetic analysis revealed one patient of Micronesian ethnicity as having C-1858 clustered with two isolates from Polynesia with T-1858. In addition, two strains from Asian ethnicities were clustered with known isolates in carriers from Southeast Asia. CONCLUSION: Genotypes A, B and C are predominant types among multi-ethnic HBV carriers in Hawaii, and distribution of HBV genotypes is dependent on the ethnic background of the carriers in Hawaii.

Adult↗
PubMed2004

Comparative study between DNA copy number aberrations determined by quantitative microsatellite analysis and clinical outcome in patients with stomach cancer.

PURPOSE: We detected the relative DNA copy numbers (RCNs) at target loci in patients with stomach cancer with quantitative microsatellite analysis. We additionally clarified the relationship between DNA copy number aberrations and the clinical outcome of the patients. EXPERIMENTAL DESIGN: Fresh frozen samples were obtained from 30 patients who had undergone surgery for stomach cancer. Seven microsatellite loci in chromosomes 8q, 16q, and 20q and one gene-specific locus (ZNF217) were selected as the target loci. The DNA copy number was obtained relatively to a pooled reference consisting of six microsatellite primer sets selected from the regions where few aberrations have been reported in comparative genomic hybridization analysis. On the basis of the TaqMan PCR system, the internal probes used were carrying donor (6-carboxyfluorescein) and acceptor (6-carboxytetramethylrhodamine) fluorescent molecules complementary to CA repeats in the microsatellite markers and to one gene-specific oligomer in the gene-specific marker. RESULTS: Chromosome 8q gain, 20q gain, and 16q loss were detected in 18 (60.0%), 8 (26.7%), and 13 (43.3%) cases, respectively. Gains in the RCNs of D8S1801 and D8S1724 were most frequently found (36.7%). There was a significant correlation between the loss of D16S3026 and reduced survival duration (P = 0.0158), and the simultaneous aberrations of D8S1801 gain and D16S3026 loss (double marker positive) was significantly associated with reduced survival duration (P = 0.0008). According to Cox proportional hazards model, the double marker positive was a significant and independent factor indicating an unfavorable prognostic factor (relative risk, 17.176; 95% confidence interval, 2.782-106.026; P = 0.0022). CONCLUSION: RCN aberrations in tumor tissues determined by quantitative microsatellite analysis enable identification of the prognostic factors that correlate with clinical outcome of the patients with stomach cancer.

Aged↗
PubMed2004

Increased electronegative charge of serum low-density lipoprotein in patients with diabetes mellitus.

BACKGROUND: Patients with diabetes mellitus have been reported to show increased serum levels of modified low-density lipoprotein (LDL), including glycosylated, oxidized and small, dense LDL. This change has been suggested to represent an important risk factor for diabetic macroangiopathy. A common characteristic shared by these modified LDL species is the increase in electronegative charge on particle surfaces, which can be detected by agarose gel electrophoresis as "LDL charge modified frequency" (LDL-CMF) determined from the relative mobility of LDL fraction. METHODS: LDL-CMF was measured in the sera from 129 outpatients with type 2 diabetes mellitus and compared with the data from 34 normal subjects. RESULTS: The LDL fraction from diabetics migrates more closely to the anode side as compared with that from normal subjects. The LDL-CMF measured in diabetics, 5.5+/-8.1%, was significantly (p<0.0001) higher than 0.6+/-3.4% in normal subjects. Serum LDL-CMF showed significant positive correlations with triglyceride at r=0.552 (p<0.0001) and malondialdehyde modified LDL at r=0.390 (p<0.0001), as well as systolic blood pressure, body mass index, fasting plasma glucose, hemoglobin A(1c), total cholesterol, free fatty acid (FFA) and homeostasis model assessment ratio. It showed negative correlations with high-density lipoprotein and total superoxide dismutase activity. CONCLUSION: The results indicate that LDL-CMF reflects the degree of serum LDL modification in diabetics and can be regarded as an important risk factor for diabetic macroangiopathy.

Cholesterol, HDL↗
PubMed2004

Regeneration of mandibular condyle following unilateral condylectomy in canines.

PURPOSE: The purpose of this experimental study was to investigate regeneration of the mandibular condyle after unilateral condylectomy in canines. MATERIAL AND METHODS: Five 2-year-old beagle dogs underwent unilateral mandibular condylectomy and were sacrificed either immediately postoperatively (n=1) or 3 months later (n=4). Temporomandibular joints were examined radiologically and histologically, and sides were compared. RESULTS: All joints showed postoperative regeneration of the condylar head. Maximum regeneration of the condyle occurred medially, where most bone of the glenoid fossa was present, rather than laterally. From an anteroposterior perspective, regeneration of the condylar head was more favourable anteriorly, facing the inferior slope of the glenoid fossa. Regenerated articular cartilage was irregular. Articular discs displayed central thickening compared with unoperated joints. The bone of the glenoid fossa was normal. CONCLUSION: Unilateral mandibular condylectomy in canines resulted in a certain degree of condylar regeneration during a 3-month postoperative period, with some irregular articular cartilage formation.

Animals↗
PubMed2004

Lack of association between occult hepatitis B virus DNA viral load and aminotransferase levels in patients with hepatitis C virus-related chronic liver disease.

BACKGROUND AND AIM: Occult hepatitis B virus (HBV) infection in hepatitis C virus (HCV)-infected patients might enhance the severity of chronic liver disease (CLD). To elucidate the correlation between occult HBV infection and the clinical course of HCV-related CLD, we evaluated whether the fluctuation of occult HBV-DNA directly affects the serum alanine aminotransferase (ALT) level. METHODS: Forty-one patients with HCV-related CLD who received regular outpatient treatment and 42 age-, sex-, and antibody to hepatitis B core antigen positivity-matched healthy volunteers were enrolled. Serum HBV-DNA was quantitatively detected using real-time detection polymerase chain reaction (RTD-PCR). Serial serum samples in three patients were measured for HBV-DNA, ALT and HCV core antigen. RESULTS: Hepatitis B virus DNA was amplified in eight of the HCV-related CLD patients (19.5%), which was significantly higher than that of healthy volunteers (2.4%). No significant difference between the genotype 1 HCV-related CLD group and the genotype 2 group was found. Based on the analyses using serial serum samples, the elevation of HBV-DNA did not occur before the ALT flares, but occurred at the same time or after the ALT flares. CONCLUSIONS: The prevalence of occult HBV infection of HCV-related CLD is significantly higher than that of control. Occult HBV infection has no influence on ALT flares among patients with HCV-related CLD.

Adult↗
PubMed2004

Effects of PPARgamma ligands and C/EBPbeta enhancer on expression of extracellular-superoxide dismutase.

Extracellular-superoxide dismutase (EC-SOD) is the major SOD isozyme in the blood vessel walls and may be important for antioxidant capability of the vascular walls. Expression of EC-SOD is known to be regulated by numerous substances such as cytokines and vasoactive factors. Recently, we found that the plasma EC-SOD levels in type 2 diabetic patients were significantly and inversely related to indices of insulin resistance, whereas they were strongly and positively related to adiponectin. Administration of pioglitazone significantly increased the plasma level of EC-SOD and adiponectin. Transcription factors such as CCAAT/enhancer-binding proteins (C/EBPs) and peroxisome proliferator-activated receptors (PPARs) are known to regulate genes associated with insulin resistance. The aim of this study was to assess the contribution of these transcription factors on the EC-SOD level. We found that a C/EBPbeta enhancer, prolactin, significantly induced the EC-SOD mRNA and protein levels in cultured fibroblast cell lines, but PPARgamma ligands, pioglitazone and other thiazolidinedione agents did not. Deletion analysis of the EC-SOD promoter-luciferase construct showed that an important element responsible for prolactin is located between -242 and -178 in the promoter region of the EC-SOD gene in which a known C/EBPbeta-binding site is located. Increasing the EC-SOD expression by treatment with ligands of transcription factors might be one approach to ameliorate the pathological conditions of insulin resistance.

CCAAT-Enhancer-Binding Protein-beta↗