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Biomedical subjects

T Tsunoda

Publications and source records attributed to T Tsunoda.

At least 19 recordsLinked to original sources
PubMed2006

Risk factors for de novo acute cardiac events in patients initiating hemodialysis with no previous cardiac symptom.

An initial major adverse cardiac event (MACE) is an important predictor of future cardiovascular events in patients with chronic kidney disease (CKD). We sought to identify factors influencing occurrence of initial MACE in new maintenance hemodialysis patients without previous cardiac symptoms during the predialysis phase of CKD. Among 112 participating patients with no predialysis cardiac history, 57 underwent coronary angiography, whereas the other 55 underwent stress thallium-201 single-photon emission computed tomography within 1 month of beginning hemodialysis to detect asymptomatic coronary artery disease (CAD). In subsequent follow-up for a median of 24 months, subjects experiencing an initial MACE were compared with those who did not have such an event based on several clinical parameters at the end of predialysis phase. Asymptomatic CAD was present in 47 patients (42%), who had a higher cumulative MACE rate, than subjects without CAD (49 vs 3%, P<0.001). Multivariate Cox's regression analysis showed that three variables independently predicted initial MACE: asymptomatic CAD (hazard ratio or HR, 611.31; 95% confidence interval or CI, 14.07-26549.23; P<0.001), diabetes (HR, 20.41; 95% CI, 2.07-200.00; P=0.010), and each 1 mg/l increment in C-reactive protein (CRP) (HR, 1.94; 95% CI, 1.27-2.94; P=0.002). In conclusion, detection of asymptomatic CAD, presence of diabetes, or elevated CRP at the end of the predialysis phase were significantly associated with occurrence of an initial MACE in CKD patients starting hemodialysis who had no CAD symptoms.

Aged↗
PubMed2005

Single nucleotide polymorphisms in the gene encoding Krüppel-like factor 7 are associated with type 2 diabetes.

AIMS/HYPOTHESIS: Although genetic susceptibility plays an important role in the pathogenesis of type 2 diabetes, most of the genes that influence susceptibility to type 2 diabetes have yet to be identified. Krüppel-like transcription factors are known to play important roles in development and cell differentiation, and have recently been implicated in the pathogenesis of type 2 diabetes. The present study aimed to examine the associations of single nucleotide polymorphisms (SNPs) in genes encoding members of the Krüppel-like-factor (KLF) family with type 2 diabetes in a large cohort of Japanese subjects. METHODS: We genotyped 33 SNP loci found in 12 KLF genes in subjects with type 2 diabetes and in subjects from the general population using the PCR-Invader assay. We also examined the effects of the overexpression of KLF7 on adipogenesis in 3T3-L1 cells. RESULTS: We identified a significant association between an SNP in KLF7 and type 2 diabetes (A vs C: p=0.004 after Bonferroni's correction, odds ratio=1.59, 95% CI 1.27-2.00). The expression of Klf7 decreased in response to the differentiation of 3T3-L1 adipocytes, and the overexpression of KLF7 resulted in significant inhibition of adipogenesis in 3T3-L1 cells. CONCLUSIONS/INTERPRETATION: These results indicate that the gene encoding KLF7 is a novel candidate for conferring genetic susceptibility to type 2 diabetes.

3T3 Cells↗
PubMed2005

CUL1, a component of E3 ubiquitin ligase, alters lymphocyte signal transduction with possible effect on rheumatoid arthritis.

Ubiquitination affects various immune processes and E3 ubiquitin ligases (E3) play an important role in determining substrate specificity. We identified 11 human E3 ligase genes of potential importance in pathogenesis of autoimmune diseases by search of public databases and screened them for candidacy of biological investigation with case-control linkage disequilibrium tests on multiple SNPs in the genes using rheumatoid arthritis (RA) as a model of autoimmune diseases. Significant association with RA was observed in an SNP in intron 3 of Cullin 1 (CUL1) that affected transcriptional efficiency of the promoter activity in lymphocytic cell lines. Quantitative expression analysis revealed that CUL1 mRNA was highly detected in lymphoid tissues including spleen and tonsil, and was specifically expressed in T and B lymphocytes in fractionated peripheral leukocytes. Histological evaluation of tonsils indicated that CUL1 protein expression was relatively specific for maturing germinal centers. Suppression of CUL1 expression had influence on the phenotype of T-cell line, that is, it inhibited IL-8 induction, which is known to play an important role in the migration of inflammatory cells into the affected area seen in RA. Our data suggest that the regulation of CUL1 expression in immunological tissues may affect the susceptibility of RA via altering lymphocyte signal transduction.

Arthritis, Rheumatoid↗
PubMed2005

The expression of platelet-derived growth factor and connective tissue growth factor in different types of abdominal aortic aneurysms.

AIM: An atherosclerotic abdominal aortic aneurysms (AAAA) differ from inflammatory abdominal aortic aneurysms (IAAA), which are characterized by a non specific inflammatory reaction leading to considerable aneurysmal wall thickness from the media to adventitia and retroperitoneal fibrosis in the surrounding tissue. Platelet-derived growth factor (PDGF) and its receptor have been localized to specific cell types within atherosclerotic plaques. Human connective tissue growth factor (CTGF) is a cysteine rich polypeptide that has similar structures to PDGF and has been implicated in connective tissue formation. PDGF and CTGF may play a role in the development of aneurysmal walls in both AAAA and IAAA. METHODS: Using in situ hybridization technique with DIG-labeled RNA probes and immunostaining, we investigated CTGF gene expression, and expression of PDGF and its receptor protein, in human aneurysmal walls. RESULTS: Expression of CTGF mRNA was found on vascular smooth muscle cells (VSMC) in specimens from AAAA and IAAA. Strong CTGF expression was localized in VSMC around calcification in AAAA. In IAAA, strong expression of CTGF was observed around inflammatory cells. In the aneurysmal walls of AAAA, PDGF A and B chains were strongly stained on small vessels, and the PDGF beta receptor was also strongly stained on VSMC around calcification. In the aneurysmal wall of IAAA, weak expressions of PDGF A and B chains were observed in endothelial cells of vessel walls around the inflammatory cells, but the intensity of expression was much weaker than that on the vessel walls in AAAA. CONCLUSIONS: Such differences in fibrogenic cytokine expression may be involved in characteristic aneurysmal formation.

Adult↗
PubMed2004

Kernohan's phenomenon associated with left ruptured occipital arteriovenous malformation.

A 23-year-old woman presented with ipsilateral hemiparesia due to rupture of a left occipital arteriovenous malformation (AVM). Emergency decompression (the onset-operation interval was 46 minutes,) was carried out and the patient could leave the hospital upon recovery without neurological deficits. In general, Kernohan's phenomenon is caused by the gradual displacement of the cerebral peduncle against the tentorial edge caused by compression by the contralateral mass. This phenomenon is very rare among the cases with spontaneous intracranial hemorrhage and only three cases including the present one have been reported in the literature. In all cases the onset-operation intervals of were very short. Kernohan's phenomenon associated with a ruptured AVM is a rare condition and emergency decompression is required.

Adult↗
PubMed2004

Questing height of nymphs of the bush tick, Haemaphysalis longicornis, and its closely related species, H. mageshimaensis: correlation with body size of the host.

The questing height (i.e. ambush height) of ticks on a plant plays an important role in host selection. To test the hypothesis that the questing height of ticks in a locality had adapted to the body size of the host in that locality, we examined the questing height of nymphs of the ticks, Haemaphysalis longicornis and H. mageshimaensis, at 7 locations in Japan. Sika deer, Cervus nippon, is the primary host of these ticks and there is considerable geographical variation in the body size of sika deer. Multiple regression analysis revealed that the questing height in the field was influenced by the height of the plants and by the body size of deer at a location. However, the questing height of ticks at some locations may have been constrained by the height of the plants and might not be the same as their intrinsic questing height. When ticks were placed in vertical glass tubes in the laboratory, the questing height of ticks from a locality was correlated with the mean body size of deer at that locality. Therefore, the prominent cue determining the questing height of H. longicornis and H. mageshimaensis seems to be the body size of the host deer.

Adaptation, Psychological↗
PubMed2004

Present characteristics of symptomatic Entamoeba histolytica infection in the big cities of Japan.

Medical records, for 2000 and 2001, of symptomatic amoebic patients who were treated at our hospitals in Tokyo, Yokohama and Osaka were studied retrospectively for the purpose of gathering epidemiological data on symptomatic Entamoeba histolytica infection. A total of 58 patients were treated. Fifty-five of them were male, and 96% of the male patients were Japanese. The mean age of patients was 44.9 years old, and 91% of patients contracted the disease in Japan. Fifty-six per cent of the male patients indicated that they were practising homosexuals, and 44% of the male patients denied these practices or left the question unanswered. The serum Treponema pallidum haemagglutination test was positive in 45% of the patients, and antibody to human immunodeficiency virus (HIV) was positive in 45%. Our study revealed that recent symptomatic E. histolytica infection almost exclusively afflicted middle-aged males in the big cities of Japan, that a majority of the patients were probably exposed to the causative organism during homosexual activity, and that an increasing number of patients will be co-infected with HIV.

AIDS Serodiagnosis↗
PubMed2004

Estimation of the density of nymphs of the bush tick, Haemaphysalis longicornis (Acari: Ixodidae), by the catch effort method.

The density of nymphs of the bush tick, Haemaphysalis longicornis, was investigated by the catch effort method with flagging. The spatial distribution of H. longicornis nymphs fit the model of contagiously distributed colonies by Iwao's m*-m analysis (Iwao 1968). A sequential sampling method was used to predict the theoretical point at which to stop sampling. Our analysis showed that five quadrats (4 m x 4 m) were sufficient to estimate the density of H. longicornis nymphs with a mean density of 5.39 per quadrat. We estimated the tick density by two methods with respect to the sampling interval. The estimated density of ticks based on ticks collected during short sampling intervals (within a half hour) was 511.34 in the 18 quadrats with the extrapolation of the linear regression equation. On the other hand, for the long interval sampling, the total number of ticks estimated by the linear regression equation was 635.47 in six quadrats in which ticks had been collected by long interval sampling. There was a significant difference between the slopes of the two linear regression equations, suggesting that the rate of reduction in the number of H. longicornis nymphs in the study area by the catch effort method differed between the two sampling methods.

Animals↗
PubMed2004

Comprehensive gene expression profiling of anaplastic thyroid cancers with cDNA microarray of 25 344 genes.

Little is known about the genetic mechanisms of anaplastic thyroid cancer (ATC). This is the most virulent of all human malignancies, and it is believed to result from transformation of differentiated thyroid cancers. To identify a set of genes involved in the development of ATC, we investigated expression profiles of 11 cell lines derived from ATC using a cDNA microarray representing 25 344 genes. Semi-quantitative RT-PCR experiments carried out for some genes that had shown altered expression on the microarray verified frequent over-expression of destrin, HSPA8, stathmin, LDH-A, ATP5A1, PSMB6, B23, HDP-1 and LDH-B, and frequent under-expression of thyroglobulin, PBP and c-FES/FPS genes among the cell lines and also among ten primary ATCs. In addition to mRNA expression studies, up-regulation of GDI2, destrin and stathmin were confirmed with immunohistochemical analysis. The extensive list of genes identified provides valuable information towards understanding the development of ATC, and provides a source of possible biomarkers for diagnosis and/or molecular targets for the development of novel drugs to treat ATC.

Biomarkers, Tumor↗
PubMed2003

Specific T-cell immunity against Ki-ras peptides in patients with pancreatic and colorectal cancers.

Mutations of codon 12 in the Ki-ras gene are frequently found in pancreatic and colorectal cancers. It has been demonstrated that human T-cells have the potential to recognise tumours expressing mutated ras-derived peptides. However, it remains unclear whether T-cells from a given individual can recognise the mutant peptides, which are expressed in that individual's tumour tissues. Mutations of the Ki-ras oncogene were analysed by the mutant-allele-specific amplification (MASA) method in pancreatic and colorectal tumour tissues, and T-cell responses against mutated Ki-ras-derived peptides were measured by [(3)H]thymidine incorporation and IFN-gamma production assays. Specific T-cell responses against Ki-ras-products were found in cancer patients, whereas no immune response was observed in normal individuals (P<0.01). Six of the eight pancreatic cancer patients (75%) and nine of 26 colorectal cancer patients (35%) had T-cell responses to mutated Ki-ras-derived-peptides. T-cell response in a given individual cannot recognise the same mutated ras peptide, which is expressed in that individual's tumour tissues. However, pancreatic and colorectal cancer patients have T-cell immunity against Ki-ras-peptides, and this provides potential target for cancer immunotherapy.

Cell Division↗
PubMed2003

Treatment for ovarian hyperstimulation syndrome using an oral dopamine prodrug, docarpamine.

Dopamine treatment constitutes a major advance towards the management of severe ovarian hyperstimulation syndrome (OHSS) by causing renal and mesenteric vasodilatation as well as diuretic and positive inotropic actions. Docarpamine, an oral dopamine prodrug, is converted into dopamine after enteral administration, and the generated dopamine causes renal vasodilatation and diuresis. The purpose of this study was to assess whether docarpamine had beneficial effects in patients with OHSS. Twenty-seven patients, hospitalized because of OHSS and refractory to the initial therapy with intravenous albumin, were treated by docarpamine, after informed consent had been obtained. A 750-mg tablet of docarpamine was taken every 8 h. In some cases, the plasma levels of free dopamine were measured. The daily urinary outputs before and 1, 2, 3 and 4 days after the docarpamine treatment were 839 +/- 424 ml, 1121 +/- 608 ml, 1168 +/- 504 ml, 1325 +/- 815 ml and 1133 +/- 509 ml, respectively. There were significant differences between the first and each of the others (p < 0.05). In 19 (86.4%) of 22 patients treated, clinical symptoms associated with ascites were gradually improved after administrating docarpamine. The plasma free dopamine concentration rose to as high as 55.9 +/- 33.2 mg/ml during the first hour, which corresponded to the usual intravenous drip infusion treatment with dopamine. Moreover, there were no major adverse effects of docarpamine in this study. This was the first demonstration of docarpamine treatment in patients with intravenous albumin-resistant OHSS. Although no effect was seen in pregnant women, diuresis was increased in some women, and ascites decreased. These findings indicate that oral docarpamine administration could be one of the options in the management of patients with OHSS using dopamine therapy.

Adult↗
PubMed2002

Effects of an eosinophil chemotaxis inhibitor, TAK-661, on antigen-induced asthmatic responses in allergic sheep.

Eosinophils have been shown to play a role in allergen-induced airway responses. The aim in this study was to examine the effects of TAK-661, a newly developed product as a specific inhibitory agent of eosinophil chemotaxis, on antigen-induced asthmatic responses in allergic sheep model. Seven Ascaris-sensitive, "dual-respondent" allergic sheep were provocated by an Ascaris suum antigen or phosphate-buffered saline 2 hrs after intra-stomach administration of TAK-661 or a placebo. Pulmonary resistances were measured throughout the experiment, and airway responsiveness to methacholine, bronchoalveolar lavage (BAL), and histological examination were performed 8 hrs after the antigen challenge. Antigen provocation induced dual-phase bronchoconstriction, eosinophilia in BAL and eosinophil infiltration into the airway wall, and an increase in airway responsiveness in placebo-treated sheep. The administration of TAK-661 significantly reduced the bronchoconstriction during the late phase, along with the inhibition of eosinophilia in BAL and the eosinophil infiltration into the airway wall. TAK-661 had a tendency to reduce early-phase bronchoconstriction and airway hyperresponsiveness, but there were no significant differences. These findings suggest that the eosinophil accumulation into the airway induced by antigen provocation may contribute to the development of late-phase bronchoconstriction, however, the development of airway hyperresponsiveness during late asthmatic response may not always be due to only eosinophilic inflammation in the airway.

Animals↗
PubMed2001

Up-regulation of the ectodermal-neural cortex 1 (ENC1) gene, a downstream target of the beta-catenin/T-cell factor complex, in colorectal carcinomas.

To clarify the molecular mechanisms of human carcinogenesis associated with abnormal Wnt/wingless signaling, we searched for genes the expression of which was significantly altered by introduction of wild-type AXIN1 into LoVo colon cancer cells. By means of a cDNA microarray, we compared expression profiles of LoVo cells infected with either adenoviruses expressing wild-type AXIN1 (Ad-Axin) or those expressing a control gene (Ad-LacZ). Among the genes showing altered expression, the ectodermal-neural cortex 1 (ENC1) gene was down-regulated in response to Ad-Axin. The promoter activity of ENC1 was elevated approximately 3-fold by transfection of an activated form of beta-catenin together with wild-type T-cell factor (Tcf)4 in HeLa cells. Semiquantitative reverse transcription-PCR experiments revealed that expression of ENC1 was increased in more than two-thirds of 24 primary colon cancer tissues that we examined compared with corresponding noncancerous mucosae. Introduction of exogenous ENC1 increased the growth rate of HCT116 colon cancer cells in serum-depleted medium. In other experiments, overexpression of ENC1 in HT-29 colon cancer cells suppressed the usual increase of two differentiation markers, in response to treatment with sodium butyrate, a differentiation-inducible agent. These data suggest that ENC1 is regulated by the beta-catenin/Tcf pathway and that its altered expression may contribute to colorectal carcinogenesis by suppressing differentiation of colonic cells.

Axin Protein↗
PubMed2001

Identification of AF17 as a downstream gene of the beta-catenin/T-cell factor pathway and its involvement in colorectal carcinogenesis.

To elucidate the molecular mechanism of colorectal carcinogenesis, we have been attempting to isolate genes involved in the beta-catenin/T-cell factor pathway. In the experiments reported here, analysis by cDNA microarray indicated that AF17, a fusion partner of the MLL gene in acute leukemias with t(11;17)(q23;q21), was transactivated according to accumulation of beta-catenin. Expression of AF17 was significantly enhanced in 8 of the 12 colorectal cancer tissues examined. Introduction of a plasmid designed to express AF17 stimulated growth of NIH3T3 cells, and fluorescence-activated cell sorter analysis indicated that the AF17 regulation of cell-cycle progression was occurring mainly at the G(2)-M transition. Our results suggest that the AF17 gene product is likely to be involved in the beta-catenin-T-cell factor/lymphoid enhancer factor signaling pathway and to function as a growth-promoting, oncogenic protein. These findings should aid development of new strategies for diagnosis, treatment, and prevention of colon cancers and acute leukemias by clarifying the pathogenesis of these conditions.

3T3 Cells↗
PubMed2001

Prediction of sensitivity of esophageal tumors to adjuvant chemotherapy by cDNA microarray analysis of gene-expression profiles.

We applied cDNA microarray analyses of 9216 genes to establish a genetic method for predicting the outcome of adjuvant chemotherapy to esophageal cancers. We analyzed expression profiles of 20 esophageal cancer tissues from patients who were treated with the same adjuvant chemotherapy after removal of tumor by operation, and we attempted to find genes associated with the duration of survival after surgery. By comparing expression profiles of those cancer tissues, we identified by statistical analysis 52 genes that were likely to be correlated with prognosis and possibly with sensitivity/resistance to the anticancer drugs. We also developed a drug response score based on the differential expression of these genes, and we found a significant correlation between the drug response score and individual patients' prognoses. Our results indicated that this scoring system, based on microarray analysis of selected genes, is likely to have great potential for predicting the prognosis of individual cancer patients with the adjuvant chemotherapy.

Aged↗
PubMed2001

Identification of AXUD1, a novel human gene induced by AXIN1 and its reduced expression in human carcinomas of the lung, liver, colon and kidney.

Axin, an important regulator of beta-catenin, is frequently mutated in human hepatocellular carcinomas (HCCs), and transduction of the wild-type Axin gene (AXIN1) induces apoptosis in HCC cells as well as in colon cancer cells. To investigate the detailed biological function of Axin, we searched on a cDNA microarray for genes whose expression was altered by transfer of wild-type AXIN1 into colon-cancer cell line LoVo. Among the genes showing altered expression, we focused on one, termed AXUD1 (AXIN1 up-regulated), that revealed enhanced expression in response to exogenously expressed AXIN1 but not to LacZ, a control gene. The AXUD1 gene consists of five exons and encodes a transcript with an open reading frame of 1767 bp. A 3.2-kb transcript of AXUD1 was expressed in all human tissues examined, most abundantly in lung, placenta, skeletal muscle, pancreas and leukocyte. By radiation-hybrid mapping we assigned its chromosomal location at 3p22, a region where frequent loss of heterozygosity has been reported in lung, renal, prostate, breast and cervical cancers. AXUD1 was frequently down-regulated in lung, kidney, liver and colon cancers compared with their corresponding normal tissues, suggesting that AXUD1 may have a tumor-suppressor function in those organs.

Animals↗
PubMed2001

Absence of beta-catenin gene mutations in pancreatic duct lesions induced by N-nitrosobis(2-oxopropyl)amine in hamsters.

The involvement of beta-catenin gene alterations in pancreatic duct carcinogenesis induced by N-nitrosobis(2-oxopropyl)amine (BOP) in hamsters was examined by polymerase chain reaction-single strand conformation polymorphism analysis and the expression of beta-catenin protein was examined by immunohistochemistry. No mutations of the beta-catenin gene were detected in 20 pancreatic duct adenocarcinomas (PDAs). Immunohistochemical staining showed the beta-catenin protein to be ubiquitously localized in the cell membranes. beta-Catenin accumulation was not identified in the cytoplasm and/or nucleus in any of 102 hyperplasias, 35 atypical hyperplasias, and 73 PDAs, as well as normal pancreatic duct cells. These results suggest that the Wnt/beta-catenin signaling pathway may not play an important role in pancreatic duct carcinogenesis induced by BOP in hamsters.

Animals↗