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T Yoshida

Publications and source records attributed to T Yoshida.

At least 19 recordsLinked to original sources
PubMed2007

Deficiency of tenascin-C attenuates liver fibrosis in immune-mediated chronic hepatitis in mice.

Tenascin-C (TNC), an extracellular matrix glycoprotein, is upregulated in chronic liver disease. Here, we investigated the contribution of TNC to liver fibrogenesis by comparing immune-mediated hepatitis in wild-type (WT) and TNC-null (TNKO) mice. Eight-week-old BALB/c mice received weekly intravenous injections of concanavalin A to induce hepatitis, and were sacrificed one week after the 3rd, 6th, 9th, and 12th injections. In WT livers, immunohistochemical staining revealed a gradual increase in TNC deposition. TNC mRNA levels also increased sequentially and peaked after the 9th injection. Collagen deposition, stained with picrosirius red, was significantly less intense in TNKO mice than in WT mice, and procollagen I and III transcripts were significantly upregulated in WT mice compared with TNKO mice. Inflammatory infiltrates were most prominent after the 3rd-6th injections in both groups and were less intense in TNKO mice than in WT mice. Interferon-gamma, tumour necrosis factor-alpha, and interleukin-4 mRNA levels were significantly higher in WT mice than in TNKO mice, while activated hepatic stellate cells (HSCs) and myofibroblasts, a cellular source of TNC and procollagens, were more common in WT livers. Transforming growth factor (TGF)-beta1 mRNA expression was significantly upregulated in WT mice, but not in TNKO mice. In conclusion, TNC can promote liver fibrogenesis through enhancement of inflammatory response with cytokine upregulation, HSC recruitment, and TGF-beta expression during progression of hepatitis to fibrosis.

Animals↗
PubMed2007

Extended storage of red blood cells under anaerobic conditions.

BACKGROUND: Red blood cells (RBC) are subject to oxidative stress by reactive oxygen species during refrigerated storage. Near-complete removal of oxygen from red cells during storage should eliminate this contributor to the red cell 'storage lesion'. The in vitro effects of storing red cells under oxygen-depleted conditions for extended periods were investigated, and these were correlated with the observed recoveries after reinfusion. STUDY DESIGN AND METHODS: Units of red cells, obtained after 'soft spin', were placed in a double volume of AS-3 additive solution and subdivided. Oxygen in the test units was depleted by repeated exposure to Ar gas (to O(2) saturation < 4%), and units were stored in anaerobic canisters for up to 15 weeks. Samples were taken weekly to monitor adenosine triphosphate (ATP), 2,3-diphosphoglycerate (2,3-DPG), cell-free haemoglobin, and vesicle production. In a parallel experiment, six units of red cells was depleted of oxygen in a similar manner, stored for 8, 9 and 10 weeks, and reinfused autologously to determine the 24 h post-transfusion recovery via (51)Cr/(99m)Tc radiolabelling. A similar study was also carried out using EAS61 additive solution, which by itself, had shown the ability to support 9-week storage, comparing biochemical profiles and in vivo recovery after aerobic vs. anaerobic storage. RESULTS: Oxygen-depleted AS-3 units had significantly elevated ATP levels compared to controls. They also had significantly lower cell free haemoglobin and vesicle production when RBCs were stored for more than 9 weeks. An average of over 75% post-transfusion survival was observed after 9 weeks of anaerobic storage with less than 0.43% haemolysis. However, no further extension of storage was achieved with EAS61 additive. CONCLUSION: Anaerobic conditions permit acceptable 9-week storage of RBCs using double-volume AS-3 additive solution. It did not synergize with the alkaline, 9-week additive, EAS61, to further lengthen the acceptable storage time. These studies indicate that anaerobic storage may allow reduction in the effect of the storage lesion, but suggest that other factors contribute to limitations of RBC storage as well.

Anaerobiosis↗
PubMed2007

Fat and fish intake and asthma in Japanese women: baseline data from the Osaka Maternal and Child Health Study.

OBJECTIVE: It remains controversial whether the intake of n-3 polyunsaturated fatty acids and fish is preventive against asthma. This cross-sectional study investigated the relationship between fat and fish intake and the prevalence of asthma using baseline data from a prospective study. DESIGN: The subjects were 1002 pregnant Japanese females. A diet history questionnaire was used to assess dietary habits. Current asthma and asthma after age 18 were defined as present if subjects had been treated with medications at some time in the previous 12 months and after reaching the age of 18, respectively. RESULTS: Fish consumption was independently associated with a decreased prevalence of asthma after age 18 and current asthma. A significant inverse relationship was observed between the ratio of n-3 to n-6 polyunsaturated fatty acid intake and the prevalence of current asthma, but not asthma after age 18. Intake of total fat, saturated, monounsaturated, n-3 polyunsaturated and n-6 polyunsaturated fatty acids, cholesterol, meat, eggs or dairy products was not evidently related to either outcome for asthma. CONCLUSION: Our results suggest that fish consumption and the high ratio of n-3 to n-6 polyunsaturated fatty acid intake may be associated with a reduced prevalence of asthma in young female Japanese adults.

Adult↗
PubMed2006

Telmisartan inhibits AGE-induced C-reactive protein production through downregulation of the receptor for AGE via peroxisome proliferator-activated receptor-gamma activation.

AIMS/HYPOTHESIS: C-reactive protein (CRP), an acute-phase reactant produced mainly by the liver, is elevated in diabetes, thus contributing to the development and progression of atherosclerosis. However, the molecular mechanism underlying the elevation of CRP in diabetes is not fully understood. Since a crosstalk between AGE and angiotensin II (Ang II) has been proposed in the pathogenesis of accelerated atherosclerosis in diabetes, we examined here whether and how telmisartan, a unique Ang II type 1 receptor blocker (ARB) with peroxisome proliferator-activated receptor-gamma (PPAR-gamma)-modulating activity, could inhibit AGE-induced CRP expression in a human hepatoma cell line, Hep3B cells. METHODS: Protein levels of the receptor for AGE (RAGE) were analysed by western blots. Gene expression was analysed by quantitative real-time RT-PCR. CRP released into the medium was measured with ELISA. Intracellular formation of reactive oxygen species (ROS) was measured using the fluorescent probe CM-H(2)DCFDA. RESULTS: Telmisartan, but not candesartan, another ARB, downregulated RAGE mRNA levels in a dose-dependent manner. Telmisartan decreased basal as well as AGE-induced RAGE protein expression in Hep3B cells. Furthermore, telmisartan dose-dependently inhibited AGE-induced ROS generation and subsequent CRP gene and protein induction in Hep3B cells. GW9662, an inhibitor of PPAR-gamma, blocked the inhibitory effects of telmisartan on RAGE expression and its downstream signalling in Hep3B cells. CONCLUSIONS/INTERPRETATION: Our present study indicates a unique beneficial aspect of telmisartan: it may work as an anti-inflammatory agent against AGE by suppressing RAGE expression via PPAR-gamma activation in the liver and may play a protective role in vascular injury in diabetes.

Benzimidazoles↗
PubMed2006

Photoemission from buried interfaces in SrTiO3/LaTiO3 superlattices.

We have measured photoemission spectra of SrTiO3/LaTiO3 superlattices with a topmost SrTiO3 layer of variable thickness. A finite coherent spectral weight with a clear Fermi cutoff was observed at chemically abrupt SrTiO3/LaTiO3 interfaces, indicating that an "electronic reconstruction" occurs at the interface between the Mott insulator LaTiO3 and the band insulator SrTiO3. For SrTiO3/LaTiO3 interfaces annealed at high temperatures (approximately 1000 degrees C), which leads to Sr/La atomic interdiffusion and hence to the formation of La(1-x)Sr(x)TiO3-like material, the intensity of the incoherent part was found to be dramatically reduced whereas the coherent part with a sharp Fermi cutoff was enhanced due to the spread of charge. These important experimental features are well reproduced by layer dynamical-mean-field-theory calculation.

Journal Article↗
PubMed2006

Correlation between the expression level of c-maf and glutathione peroxidase-3 in c-maf -/- mice kidney and c-maf overexpressed renal tubular cells.

Large mafs are transcriptional factors and members of the basic leucine zipper (b-Zip) superfamily. Since we previously identified expression of c-maf in mouse kidney, we presently investigated the mRNA expression profile in the kidney of c-maf gene knockout mice by using DNA microarray, and plasma glutathione peroxidase-3 (GPx3) was predominantly downregulated. We focused on the relation between the expression level of c-maf and GPx3 in vivo and in vitro. Since GPx3 is an antioxidant enzyme, oxidative stress was induced by exposing a culture cell derived from mouse renal tubules (mIMCD3) to hydrogen peroxide. Real-time PCR demonstrated that mRNA expression of both c-maf and GPx3 increased in parallel during exposure to oxidative stress in a time- and dose-dependent manner. Then, the mIMCD3 cells were transfected with c-maf-cDNA containing plasmid, which resulted in an increase in mRNA and protein expression of GPx3 compared with the control cells. Thus, c-maf may be transcriptional regulator of GPx3 expression and modulate the antioxidative pathway in the kidney.

Animals↗
PubMed2006

Cooperation of oncogenic K-ras and p53 deficiency in pleomorphic rhabdomyosarcoma development in adult mice.

Human rhabdomyosarcomas (RMSs) frequently demonstrate genetic alterations in ras and p53. To investigate their possible involvement in the tumorigenesis, we generated a knock-in mouse line with oncogenic K-ras, conditionally expressed by Cre/LoxP system on a background of p53 alteration. Electroporation of Cre expression vector in skeletal muscle tissues resulted in the generation of tumor in adults with tumor incidences of 100% at 10 weeks and 40% at 15 weeks, in p53(-/-) and p53(-/+) backgrounds, respectively. The tumor histology was pleomorphic RMS with characteristic bizarre giant cells, positive for desmin and alpha-sarcomeric actin and exhibiting remarkable increase in total and phosphorylated extracellular signal-regulated protein kinase (ERK)1 and ERK2. Loss of the wild-type p53 was detected in K-rasG12V-expressed tumors of p53(-/+) mice. Early lesions 3 weeks after electroporation consisted of proliferating populations of myogenic progenitors, including stem cells positive for ScaI antigen, immature cells positive for desmin and neural cell adhesion molecule-positive myotubes. Thus, cooperation of oncogenic K-ras and p53 deficiency resulted in the development of pleomorphic RMS in adult mice, providing a useful mouse model for further detailed studies.

Animals↗
PubMed2006

Spreds, inhibitors of the Ras/ERK signal transduction, are dysregulated in human hepatocellular carcinoma and linked to the malignant phenotype of tumors.

Aberrant activation of the Ras/Raf-1/extracellular-regulated kinase (ERK) pathway has been shown to be involved in the progression of human hepatocellular carcinoma (HCC). However, the mechanism of dysregulation of ERK activation is poorly understood. Recently, we identified Sprouty-related protein with Ena/vasodilator-stimulated phosphoprotein homology-1 domain (Spred) as a physiological inhibitor of the Ras/Raf-1/ERK pathway. In this study, we found that the expression levels of Spred-1 and -2 in human HCC tissue were frequently decreased, comparing with those in adjacent non-tumorous tissue. Moreover, Spred expression levels in HCC tissue were inversely correlated with the incidence of tumor invasion and metastasis. Forced expression of Spred-1 inhibited HCC cell proliferation in vitro and in vivo, which was associated with reduced ERK activation. Spred-1 overexpression also reduced the secretion of matrix metalloproteinase-9 (MMP-9) and MMP-2, which play important roles in tumor invasion and metastasis. In addition, Spred-1 inhibited growth factor-mediated HCC cell motility. These data indicate that the reduction of Spred expression in HCC is one of the causes of the acquisition of malignant features. Thus, Spred could be not only a novel prognostic factor but also a new therapeutic target for human HCC.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Loss of SOCS3 in the liver promotes fibrosis by enhancing STAT3-mediated TGF-beta1 production.

Recently, DNA methylation and reduced expression of the suppressor of the cytokine signaling-3 (SOCS3) gene in human hepatocellular carcinoma (HCC) patients have been reported. However, the roles of SOCS3 in HCC development in vivo have not been clarified. Using RT-PCR analysis and Western blotting, we confirmed that SOCS3 expression was reduced in HCC patients. However, reduced expression of SOCS3 occurred not only in HCC but also in nontumor regions, and this reduction was stronger as the fibrosis grade increased. Furthermore, SOCS3 levels were inversely correlated with signal transducers and activators of transcription-3 (STAT3) activation as well as transforming growth factor (TGF)-beta1 levels in the non-HCC region. To define the molecular consequences of SOCS3 silencing/STAT3 hyperactivation and liver fibrosis, we examined liver-specific SOCS3-deficient mice. We demonstrated that SOCS3 deletion in the liver resulted in hyperactivation of STAT3 and promoted ConA- and chemical-induced liver fibrosis. The expression of TGF-beta1, a mediator of fibrosis, was enhanced by SOCS3 gene deletion, but suppressed by the overexpression of a dominant-negative STAT3 or SOCS3 both in vivo and in vitro. These data suggest that TGF-beta1 is a target gene of STAT3 and could be one of the mechanisms for enhanced fibrosis in SOCS3-deficient mice. Thus, our present study provides a novel role of SOCS3 and STAT3 in HCC development: in addition to the previously characterized oncogenic potentials, STAT3 enhances hepatic fibrosis through the upregulation of TGF-beta1 expression, and SOCS3 prevents this process.

Animals↗
PubMed2006

Biological function of the pld gene product that degrades epsilon-poly-L-lysine in Streptomyces albulus.

Epsilon-poly-L-lysine (epsilon-PL) is one of the few naturally occurring biopolymers and is characterized by a peptide bond between the alpha-carboxyl and epsilon-amino groups. Previously, we purified and characterized the epsilon-PL-degrading enzyme (Pld) from Streptomyces albulus, which is an epsilon-PL producer, and this enzyme was expected to confer self-resistance to the epsilon-PL produced by the organism itself. The gene encoding Pld was cloned based on the N-terminal amino acid sequence determined in this study, and a sequencing analysis revealed eight open reading frames (ORFs), i.e., ORF1 to ORF8 in the flanking region surrounding the pld gene (present in ORF5). To investigate the biological function of Pld, we constructed a knockout mutant in which the pld gene is inactivated. Studies on epsilon-PL susceptibility, epsilon-PL-degrading activity, and epsilon-PL productivity demonstrated that the pld gene does play a partial role in self-resistance and that S. albulus was found to produce other epsilon-PL-degrading enzyme(s) in addition to Pld. To the best of our knowledge, this is the first report on a self-resistance gene for a biopolymer possessing antibacterial activity.

Amino Acid Sequence↗
PubMed2006

LPP expression during in vitro smooth muscle differentiation and stent-induced vascular injury.

Lipoma preferred partner (LPP) has been identified as a protein highly expressed in smooth muscle (SM) tissues. The aim of the present study was to determine mechanisms that regulate LPP expression in an in vitro model of SM cell (SMC) differentiation and in stent-induced pig coronary vessel injury. All trans-retinoic acid treatment of A404 cells induced a strong increase in LPP, as well as SM alpha-actin, SM myosin heavy chain, and smoothelin mRNA levels, in a Rho kinase (ROK)-dependent manner. Adenovirus mediated overexpression of myocardin in A404 cells significantly increased LPP mRNA expression. Interestingly, inactivation of RhoA with C3-exoenzyme or treatment with ROK inhibitors strongly inhibited myocardin mRNA expression in retinoic acid-treated A404 cells or human iliac vein SMCs. LPP silencing with short interfering RNA significantly decreased SMC migration. LPP expression was also markedly decreased in focal adhesion kinase (FAK)-null cells known to have impaired migration but rescued with inducible expression of FAK. LPP expression in FAK-null fibroblasts enhanced cell spreading. In stented pig coronary vessels, LPP was expressed in the neointima of cells lacking smoothelin and showed expression patterns identical to those of SM alpha-actin. In conclusion, LPP appears to be a myocardin-, RhoA/ROK-dependent SMC differentiation marker that plays a role in regulating SMC migration.

Animals↗
PubMed2006

Validation of the quality of histological images obtained of fresh and formalin-fixed specimens of esophageal and gastric mucosa by laser-scanning confocal microscopy.

BACKGROUND AND STUDY AIMS: We have previously reported the success of a method of virtual histology using laser-scanning confocal microscopy (LCM) in vitro on untreated fresh specimens obtained from the gastrointestinal mucosa. In the present study, we aimed to apply LCM to both fresh and formalin-fixed specimens, without additional treatment, in order to validate and compare the quality of the images obtained. METHODS: We obtained 18 specimens from 11 patients, either by endoscopic biopsy or following surgical resection. First, we observed the fresh, saline-immersed specimen with LCM using the Fluroview microscope (Olympus Co. Ltd., Tokyo, Japan). We then fixed the specimen with formalin and obtained further LCM images 1 hour, 3 hours, and 24 hours after fixation. Three independent observers observed the images and were asked to assess the origin of the samples, the treatment of the samples, the time after formalin fixation, and whether they showed benign or malignant lesions. We used kappa statistics to compare the agreement among the three observers in each of these four areas of interest. RESULTS: Between January and March 2003, we obtained 191 LCM images from 18 specimens. Thirty images were randomly selected for observation. The overall accuracy for differentiating between esophagus and stomach specimens was 96.6 %. The accuracy of differentiating normal from cancerous lesions was 92.2 %. The differentiation between saline-immersed and formalin-fixed specimens was 59.7 % accurate and the assessment of the time interval after formalin fixation was only 37.3 % accurate. The kappa statistics showed that there was strong interobserver agreement on the differentiation of specimen origin and of cancerous from benign lesions. However, there was no agreement among the observers on the method of specimen preparation or on the estimated time interval after formalin fixation. CONCLUSIONS: We concluded that images obtained from fresh specimens using LCM were of a quality good enough to make an accurate diagnosis of upper gastrointestinal carcinoma.

Biopsy↗
PubMed2006

Preliminary study on the effects of bar placement on the thorax after the nuss procedure for pectus excavatum using bone scintigraphy.

AIM: Bone scintigraphy was performed to elucidate the effects of the Nuss procedure for pectus excavatum on the bony thorax. METHODS: Eight boys and 6 girls (5 - 24 years of age) underwent bone scintigraphy, using (99m)Tc-HMDP. Eleven patients were studied 5 to 21 days after the Nuss procedure; 6 were studied 20 to 24 months after the operation before bar removal. Three of 14 were studied twice after the Nuss procedure and before bar removal. RESULTS: In the early postoperative phase, RI accumulation was found at the sternum and ribs in only 1 of 6 patients under 9 years of age, whereas in all 5 older patients, RI had accumulated at the sternum. Scintigrams before bar removal revealed, regardless of age, hot spots at the lateral ribs in contact with the bar and at the costochondral junctions where the bar passed through the intercostal spaces. Furthermore, chest roentgenograms showed the deformed lateral ribs in contact with the bar. CONCLUSIONS: The Nuss procedure creates minute fractures at the sternum and the ribs, especially in older patients. The bar deforms the ribs and restrains the growth of the thorax. Furthermore, it constantly rubs against the ribs and can therefore cause late complications. Bone scintigraphy may determine the appropriate timing for bar removal.

Adolescent↗
PubMed2006

Differences between Lactococcus garvieae isolated from the genus Seriola in Japan and those isolated from other animals (trout, terrestrial animals from Europe) with regard to pathogenicity, phage susceptibility and genetic characterization.

AIMS: To clarify the epidemiological relationship between Lactococcus garvieae isolates from the Seriola in Japan and isolates from other animals. METHODS AND RESULTS: A total of 32 isolates obtained from aquatic (the genus Seriola and trout) and terrestrial animals (cow, pig, cat, dog and horse) was used to evaluate its pathogenicity to yellowtail and mouse, phenotype (KG+ and KG-), its susceptibility to three bacteriophages and the pattern of pulsed field gel electrophoresis (PFGE). Lactococcus garvieae isolated from Seriola showed strong pathogenicity to yellowtail, while isolates from trout showed weak pathogenicity and those obtained from terrestrial animals showed no distinct pathogenicity. Only, the isolates from the genus Seriola in Japan showed susceptibility to the bacteriophages. The results of PFGE pattern indicate that the isolates obtained from the Seriola predict homogeneity, while there is no similarity among the isolates obtained from different animals. CONCLUSION: This experiment indicates that L. garvieae isolated from Seriola in Japan appears to be very different from the isolates obtained from other animals, and the isolates prevalent among the genus Seriola in Japan might be homogeneous. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that a particular genetic group that has specially adapted and acquired virulence toward yellowtail were prevalent among the genus Seriola in Japan.

Animals↗
PubMed2006

Characterization of Lancefield group C Streptococcus dysgalactiae isolated from farmed fish.

A Lancefield group C streptococcal (GCS) infection caused by Streptococcus dysgalactiae that is characterized by severe necrotic lesions of the caudal peduncle has been an increasing cause of mortality in farmed fish such as amberjack, Seriola dumerili, and yellowtail, Seriola quinqueradiata, in the southern part of Kyushu, Japan. In this study, enzymatic profiles of GCS strains from fish and mammals were investigated using the API ZYM system, and genotypic characterization of GCS strains was performed using biased sinusoidal field gel electrophoresis (BSFGE). The partial sequence of the 16S-23S rDNA intergenic spacer region of the GCS strain isolates from fish and mammals was also compared. The API ZYM test indicated that it is difficult to differentiate isolates of S. dysgalactiae from fish and animals based on enzymological variations. In the BSFGE analysis, the macrorestriction profiles, which were obtained using SmaI or ApaI as a restriction enzyme, revealed variations between the fish and animal isolates. The partial sequence of the 16S-23S rDNA intergenic spacer region of all the tested fish isolates differed from all mammalian isolates in one or two nucleotides. The possibility of a clonal expansion of S. dysgalactiae strains in farmed fish was also suggested by the BSFGE profiles of fish isolates.

Animals↗
PubMed2006

Genetic variations and haplotype structures of the ABCB1 gene in a Japanese population: an expanded haplotype block covering the distal promoter region, and associated ethnic differences.

As functional ABCB1 haplotypes were recently reported in the promoter region of the gene, we resequenced the ABCB1 distal promoter region, along with other regions (the enhancer and proximal promoter regions, and all 28 exons), in a total of 533 Japanese subjects. Linkage disequilibrium (LD) analysis based on 92 genetic variations revealed 4 LD blocks with the same make up as previously described (Blocks -1, 1, 2 and 3), except that Block 1 was expanded to include the distal promoter region, and that a new linkage between polymorphisms -1,789G>A in the distal promoter region and IVS5 + 123A>G in intron 5 was identified. We re-assigned Block 1 haplotypes, and added novel haplotypes to the other 3 blocks. The reported promoter haplotypes were further classified into several types according to tagging variations within Block 1 coding or intronic regions. Our current data reconfirm the haplotype profiles of the other three blocks, add more detailed information on functionally-important haplotypes in Block 1 and 2 in the Japanese population, and identified differences in haplotype profiles between ethnic groups. Our updated analysis of ABCB1 haplotype blocks will assist pharmacogenetic and disease-association studies carried out using Asian subjects.

ATP Binding Cassette Transporter, Subfamily B↗