Biomedical subjects

Yasushi Sato

Publications and source records attributed to Yasushi Sato.

At least 19 recordsLinked to original sources

PubMed2006

Terbinafine increases the plasma concentration of paroxetine after a single oral administration of paroxetine in healthy subjects.

OBJECTIVE: Paroxetine is believed to be a substrate of CYP2D6. However, no information was available indicating drug interaction between paroxetine and inhibitors of CYP2D6. The aim of this study was to examine the effects of terbinafine, a potent inhibitor of CYP2D6, on pharmacokinetics of paroxetine. METHODS: Two 6-day courses of either a daily 150-mg of terbinafine or a placebo, with at least a 4-week washout period, were conducted. Twelve volunteers took a single oral 20-mg dose of paroxetine on day 6 of both courses. Plasma concentrations of paroxetine were monitored up to 48 h after dosing. RESULTS: Compared with the placebo, terbinafine treatment significantly increased the peak plasma concentration (C(max)) of paroxetine, by 1.9-fold (6.4 +/- 2.4 versus 12.1 +/- 2.9 ng/ml, p < 0.001), and the area under the plasma concentration-time curve from zero to 48 h [AUC (0-48)] of paroxetine by 2.5-fold (127 +/- 67 vs 318 +/- 102 ng/ml, p < 0.001). Elimination half-life differed significantly (15.3 +/- 2.4 vs 22.7 +/- 8.8 h, p < 0.05), although the magnitude of alteration (1.4-fold) was smaller than C(max )or AUC. CONCLUSION: The present study demonstrated that the metabolism of paroxetine after a single oral dose was inhibited by terbinafine, suggesting that inhibition of CYP2D6 activity may lead to a change in the pharmacokinetics of paroxetine. However, further study is required to confirm this phenomenon at steady state.

Administration, Oral↗

PubMed2006

Involvement of gibberellin in tracheary element differentiation and lignification in Zinnia elegans xylogenic culture.

Gibberellin (GA) is considered an important growth regulator involved in many aspects of plant development. However, little is known about the relationship between GA and lignification. In this study, we analyzed the role of GA in tracheary element (TE) differentiation and lignification using a Zinnia elegans xylogenic culture. When gibberellic acid-3 (GA3) was exogenously supplied, a slight increase in the frequency of TE differentiation and a remarkable increase in lignin content were observed. Computer image analysis of individual TEs showed that the lignification level of each TE was significantly increased in the culture treated with GA3 compared with those of the control. In contrast, suppression of TE differentiation and lignification was observed when GA biosynthesis was inhibited by ancymidol, paclobutrazol, or uniconazole. This suppression was restored by the addition of GA3. These results suggest that GA plays an important role in TE differentiation, and even more so in lignification. When conditioned medium obtained after 120 h of control culture was analyzed by high-performance liquid chromatography, many lignin precursors were detected. However, these lignin precursors were greatly reduced in the GA-treated culture. This result suggests that GA promotes lignification by activating the polymerization of lignin precursors.

Asteraceae↗

PubMed2006

Ex vivo large-scale generation of human platelets from cord blood CD34+ cells.

In the present investigation, we generated platelets (PLTs) from cord blood (CB) CD34(+) cells using a three-phase culture system. We first cultured 500 CB CD34(+) cells on telomerase gene-transduced human stromal cells (hTERT stroma) in serum-free medium supplemented with stem cell factor (SCF), Flt-3/Flk-2 ligand (FL), and thrombopoietin (TPO) for 14 days. We then transferred the cells to hTERT stroma and cultured for another 14 days with fresh medium containing interleukin-11 (IL-11) in addition to the original cytokine cocktail. Subsequently, we cultured the cells in a liquid culture medium containing SCF, FL, TPO, and IL-11 for another 5 days to recover PLT fractions from the supernatant, which were then gel-filtered to purify the PLTs. The calculated yield of PLTs from 1.0 unit of CB (5 x 10(6) CD34(+) cells) was 1.26 x 10(11) - 1.68 x 10(11) PLTs. These numbers of PLTs are equivalent to 2.5-3.4 units of random donor-derived PLTs or 2/5-6/10 of single-apheresis PLTs. The CB-derived PLTs exhibited features quite similar to those from peripheral blood in morphology, as revealed by electron micrographs, and in function, as revealed by fibrinogen/ADP aggregation, with the appearance of P-selectin and activated glycoprotein IIb-IIIa antigens. Thus, this culture system may be applicable for large-scale generation of PLTs for future clinical use.

Antigens, CD34↗

PubMed2006

Characterization of two laccases of loblolly pine (Pinus taeda) expressed in tobacco BY-2 cells.

We previously showed that eight laccase genes (Lac 1-Lac 8) are preferentially expressed in differentiating xylem and are associated with lignification in loblolly pine (Pinus taeda) [Sato et al. (2001) J Plant Res 114:147-155]. In this study we generated transgenic tobacco suspension cell cultures that express the pine Lac 1 and Lac 2 proteins, and characterized the abilities of these proteins to oxidize monolignols. Lac 1 and Lac 2 enzymatic activities were detected only in the cell walls of transgenic tobacco cells, and could be extracted with high salt. The optimum pH for laccase activity with coniferyl alcohol as substrate was 5.0 for Lac 1 and between 5.0 and 6.0 for Lac 2. The activities of Lac 1 and Lac 2 increased as the concentration of CuSO(4) in the reaction mixtures increased in the range from 1 to 100 microM. Both enzymes were able to oxidize coniferyl alcohol and to produce dimers of coniferyl alcohol. These results are consistent with the hypothesis that Lac 1 and Lac 2 are involved in lignification in differentiating xylem of loblolly pine.

Cell Line, Transformed↗

PubMed2006

Standardization of 152Eu and 154Eu by 4pibeta-4pigamma coincidence method and 4pi(beta+gamma) integral counting.

The 4pibeta-4pigamma coincidence counting and 4pi(beta+gamma) integral counting techniques were applied for the standardization of 152Eu and 154Eu. In these techniques, the beta-detector is composed of two thin plastic scintillators sandwiching the source coupled with a slender photomultiplier tube. This beta-detector was inserted into a large well-type NaI(Tl) scintillation detector for gamma-ray detection, making a 4pibeta-4pigamma detector configuration. The results obtained by the above two techniques were in good agreement and consistent with the results of international comparisons.

Algorithms↗

PubMed2006

Response calculation for standard ionization chambers in the APMP using EGS4 Monte Carlo code.

In the APMP radioactivity group (TCRI), a series of intercomparisons were conducted between member laboratories, with the aim to improve the calibration of ionization chambers used as secondary standards for radioactivity measurement. Several sources were sent to the participating institutes and the measurement results of calibration factors have been compared. Good agreement between laboratories was found for radioisotopes where the major contribution to the ionization current stems from high-energy gamma rays. It was expected in this energy region that these ratios would become unity for any type of chamber by normalizing with the same type of reference sources. However, where the dominating contribution to the measured ionization current is due to the presence of low-energy gamma rays, there were some serious discrepancies between participating institutes. In order to understand these differences, Monte Carlo simulation has been utilized by studying the effects of changing the wall thickness of the re-entrant well, the materials of the sample holder and the composition of the ionizing gas.

Algorithms↗

PubMed2006

A phase I/II study of nedaplatin and 5-fluorouracil with concurrent radiotherapy in patients with esophageal cancer.

PURPOSE: To determine the recommended dose (RD) of cis-diammine-glycolatoplatinum (nedaplatin) when given concurrently with 5-FU and high dose radiation therapy in the treatment of esophageal cancer. The purpose of the phase II trial is to determine efficacy and further define the side effect profile. METHODS: Twenty-six patients with clinical stage I to IVA squamous cell carcinoma of the esophagus were enrolled in a non-surgical treatment comprised of a fixed dose of fluorouracil (400 mg/m2 administered as continuous intravenous infusion on days 1-5 and days 8-12) plus escalating doses of nedaplatin (40 mg/m2 in level 1, 50 mg/m2 in level 2, or 60 mg/m2 in level 3 on days 1 and 8), repeated twice every 3 weeks with concurrent radiotherapy (60 Gy). RESULTS: Between July 1998 and February 2004, a total of 26 patients entered this trial, all of whom were considered evaluable for toxicity assessment. In phase I of the study, 12 patients were treated in sequential cohorts of three to six patients per dose level. The maximum tolerated dose was reached at level 3 with two grade 4 neutropenia and one grade 4 thrombocytopenia. Thus, the recommended dosing schedule is level 2. Of the 20 patients treated at the RD level 2, including 6 patients of the RD phase I portion, 8 out of 20 patients (40%) had grade 3-4 neutropenia, 5 patients (25.0%) had grade 3-4 thrombocytopenia, 4 patients (20.0%) had grade 3 anemia and 4 patients (20.0%) had grade 3-4 esophagitis. Other toxicities were relatively mild and usually of grade 2 or less. Objective responses were noted in the 26 patients (overall response rate, 88.5%) including 11 (42.3%) complete remissions. The 1- and 3-year survival rates were 65.1 and 37.2%, respectively, with a median survival time of 21.2 months. CONCLUSIONS: The combination of nedaplatin and 5-FU with radiation is a feasible regimen that shows promising antitumor activity with an acceptable safety profile in patients with esophageal cancer.

Aged↗

PubMed2006

Isolation and characterization of a novel peroxidase gene ZPO-C whose expression and function are closely associated with lignification during tracheary element differentiation.

In an attempt to elucidate the regulatory mechanism of vessel lignification, we isolated ZPO-C, a novel peroxidase gene of Zinnia elegans that is expressed specifically in differentiating tracheary elements (TEs). The ZPO-C transcript was shown to accumulate transiently at the time of secondary wall thickening of TEs in xylogenic culture of Zinnia cells. In situ hybridization indicated specific accumulation of the ZPO-C transcript in immature vessels in Zinnia seedlings. Immunohistochemical analysis using anti-ZPO-C antibody showed that the ZPO-C protein is abundant in TEs, especially at their secondary walls. For enzymatic characterization of ZPO-C, 6 x His-tagged ZPO-C was produced in tobacco cultured cells and purified. The ZPO-C:6 x His protein had a peroxidase activity preferring sinapyl alcohol as well as coniferyl alcohol as a substrate, with a narrow pH optimum around 5.25. The peroxidase activity required calcium ion and was elevated by increasing Ca2+ concentration in the range of 0-10 mM. An Arabidopsis homolog of ZPO-C, At5g51890, was examined for expression patterns with transgenic plants carrying a yellow fluorescent protein (YFP) gene under the control of the At5g51890 promoter. The YFP fluorescence localization demonstrated vessel-specific expression of At5g51890 in the Arabidopsis roots. Taken collectively, our results strongly suggest that ZPO-C and its homologs play an important role in lignification of secondary cell walls in differentiating TEs.

Amino Acid Sequence↗

PubMed2006

Colorectal cancer: genetics of development and metastasis.

It has been well documented that there are two major pathways in colorectal carcinogenesis. One is the chromosomal instability pathway (adenoma-carcinoma sequence), which is characterized by allelic losses on chromosome 5q (APC), 17p (p53), and 18q (DCC/SMAD4), and the other is a pathway that involves microsatellite instability. Recent progress in molecular biology, however, has shown that colorectal carcinogenesis is not necessarily clearly divided into these two pathways, but is in fact more complicated. Other routes, including the transforming growth factor-beta/SMAD pathway, the serrated pathway, and the epigenetic pathway, have been reported. Cross talk among these pathways has also been reported. In the invasion and metastasis steps of colorectal cancers, many more genes have now been identified as being involved in proteolysis, adhesion, angiogenesis, and cell growth. Recently accumulated evidence indicates that colorectal cancer is a genetically heterogeneous and complicated disease.

Adenocarcinoma↗

PubMed2006

Amelioration of murine dextran sulfate sodium-induced colitis by ex vivo extracellular superoxide dismutase gene transfer.

BACKGROUND: Although the etiology of inflammatory bowel disease has not been fully clarified, reactive oxygen species is speculated to be involved. Extracellular superoxide dismutase (EC-SOD), an isozyme of SODs, is known to function mainly in body fluids. We investigated the efficacy of an ex vivo EC-SOD gene transfer into dextran sulfate sodium (DSS)-induced colitis mice. MATERIALS AND METHODS: Experimental colitis was induced by providing Balb/c mice with DSS in sterile distilled water provided as desired. The syngenic fibroblasts were obtained from Balb/c mice embryos and retrovirally transduced with the hEC-SOD gene. These engineered cells were confirmed to secrete EC-SOD in culture medium by enzyme-linked immunosorbent assay and were inoculated subcutaneously in the backs of DSS-treated mice. Mucosal injury of the colon was evaluated by the disease activity index (DAI: body weight, rectal bleeding, and stool consistency), grading of histologic disease severity, and levels of cytokine (tumor necrosis factor-alpha, interleukin-1beta) production. 8-Hydroxydeoxyguanosine (8-OHdG) levels in the mucosal tissue were assessed by immunohistochemical staining. Malondialdehyde (MDA) was measured using a colorimetric assay. RESULTS: A significant improvement was observed in DAI score and histologic severity as well as in mucosal tissue levels of inflammatory cytokines, 8-OHdG, and MDA of mice treated with the EC-SOD gene as compared with those without gene therapy, not only in a mild colitis model but also in a severe colitis model. Survival of treated mice in these models was significantly prolonged. CONCLUSIONS: Ex vivo transfer of the EC-SOD gene was feasible for treatment of DSS-induced colitis.

Animals↗

PubMed2006

[Enteropathy-type T-cell lymphoma with CD8 and CD56 expression].

A 54-year-old male presented at a previous hospital with abdominal pain, where the patient was diagnosed as having abdominal and retroperitoneal lymphadenopathies by CT scan, then, he was referred to our hospital for further examination. Upper gastrointestinal endoscopy showed a tumor formation in the second portion of the duodenum, and there were medium sized atypical lymphocytes in biopsy specimens of the tumor. Since the atypical lymphocytes in the biopsy specimens were positive for CD3, CD8, CD56 and CD103 by immunostain, and had a rearrangement of the T-cell receptor 7-chain, the patient was diagnosed as having enteropathy-type T-cell lymphoma (ETL). Although ETL usually occurs as a complication of celiac disease, malabsorption and anti-gliadin antibodies, which are normally present in celiac disease, were not observed in this patient.

CD3 Complex↗

PubMed2006

[A case of recurrent biliary cystadenocarcinoma successfully treated with 5FU/CDDP systemic chemotherapy].

We report a case of biliary cystadenocarcinoma which recurred 41 months postoperatively. A 60-year-old woman was admitted for further examination of multiple metastatic tumors and a large amount of ascites. Systemic administration of 5FU and CDDP caused her CEA level to decrease gradually and abdominal computed tomography revealed considerable reduction of the metastatic tumors and ascites. Since her general condition had improved, chemotherapy was continued in the outpatient clinic.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

[Peripheral T-cell lymphoma presenting with eosinophilia due to interleukin-5 produced by lymphoma cells].

A 72-year-old male was admitted to our hospital to determine the cause of neck lymphadenopathies. He was diagnosed pathologically by a lymph node biopsy as having peripheral T-cell lymphoma (PTCL). He also had developed eosinophilia and his serum concentration of Interleukin-5 (IL-5) was extremely high. Immunostaining of a resected lymph node revealed that there were lymphoma cells which were stained with anti-IL-5 antibody. After 2 courses of CHOP therapy, the lymphadenopathies and eosinophilia disappeared and the concentration of serum IL-5 was normalized. It was suggested that IL-5 produced by lymphoma cells had induced his eosinophilia.

Aged↗

PubMed2006

[Anaphylactic reaction to oxaliplatin--a case of colon cancer].

Oxaliplatin (L-OHP) is a new third-generation platinum which is efficacious in treating advanced unresectable recurrent colorectal cancer as a first-line regimen. The marketing authorization was given in Japan in March, 2005. Its increased use has resulted in rare serious adverse effects, including anaphylactic shock. We experienced a case that developed anaphylactic shock by L-OHP. We report a 69-year-old man who was treated for recurrent colorectal cancer who underwent systemic chemotherapy with FOLFOX 4. After eight cycles he developed severe L-OHP associated neuropathy and lung metastases was a progressive tendency. The FOLFOX 4 regimen was discontinued and another modality, FOLFIRI regimen, was used. After eight cycles of FOLFIRI regimen, lung and liver metastases showed progressive disease for response assessment by RECIST criteria. Although a patient was stopped L-OHP for neurotoxicity, neuropathy was disappeared after 4 months interval. Therefore, we reintroduced L-OHP, FOLFOX 4 regimen. Anaphylactic shock occurred in the second cycle of reintroduction of the FOLFOX 4 regimen (total 10 cycles), 30 minutes after infusion of L-OHP. L-OHP infusion was immediately withdrawn and he was treated with intravenous hydroxyzine hydrochloride and methylprednisolone. The anaphylaxis symptoms resolved in 30 minutes. Chemotherapy based on L-OHP for unresectable recurrence colorectal cancer causes anaphylactic shock as a rare severe complication. The prediction factor is not proved. We should take steps for early detection of anaphylactic reaction and perform the appropriate treatment.

Adenocarcinoma↗

PubMed2005

Nucleolonema as a fundamental substructure of the nucleolus.

The nucleolus is the most obvious structure in the eukaryotic nucleus. It is known to be a ribosome-producing apparatus where ribosomal (r) DNA is transcribed and the primary rRNA transcripts are processed to produce three of the four rRNA species. Electron microscopy has shown that the nucleolus consists of three major components, a dense fibrillar component (DFC), a granular component (GC) and a fibrillar center (FC). The DFC and FCs are integrated into a fundamental nucleolar substructure called the nucleolonema. The DFC corresponds to the matrix of the nucleolonema, and the FC is an electron microscopic counterpart of argyrophobic lacunae localized in the nucleolonema. The spherical FCs are intermittently arranged along the length of the nucleolonema in actively growing cells but are fused with each other to form tubular FCs when rDNA transcription is hampered. The RNase-gold complex does not bind to the FC but to the DFC and the GC, suggesting that rDNA transcription does not occur in the FC although both fluorescence in situ hybridization (FISH) and electron microscopic in situ hybridization reveal that the rDNA is specifically localized in the FCs. Immunogold-labeling after bromo-UTP (BrUTP) incorporation shows that rDNA transcription takes place in the boundary region between the FC and the DFC, and primary rRNA transcripts are expected to be processed outward within the DFC. Data have accumulated suggesting that the nucleolonema is a fundamental substructure of the nucleolus, and its skeleton is the tandem arrangement of the FCs, which are resting harbors or storages of rDNA. This paper proposes that the transversal structural organization of the nucleolonema is centrifugally built up by several structural and functional domains: condensed and/or loosened rDNA, rDNA transcription zone, and transcript processing and ribosome assembly zones.

Cell Nucleolus↗

PubMed2005

Augmentation of antitumor effects of p53 gene therapy by combination with HDAC inhibitor.

We have previously shown that the HDAC inhibitors (HDACI) activate the p53 molecule through acetylation of 320 and 373 lysine residues, upregulate PIG3 and NOXA and induce apoptosis in cancer cells expressing wild and pseudo-wild type p53 genes (Terui T, et al. Cancer Res 2003; 63:8948-54). It has also been reported that expression of the Coxsackie adenovirus receptor and subsequent transfection efficiency of the adenovirus in cancer cells were enhanced by HDACI treatment. In this study, we extended these observations to explore the combination effect of adenoviral vector carrying wild type p53 (Ad-p53) gene therapy with a HDACI, sodium butyrate (SB), on xenografted human gastric cancer cells (KATO-III) and hepatocellular carcinoma cells (HuH7) in nude mice. We first confirmed an increased expression of Coxsackie adenovirus receptors with an associated increment of transgene (X-gal) expression by SB treatment in KATO-III cells. We then injected Ad-p53 into subcutaneous tumors of KATO-III and HuH7 combined with intraperitoneal administration of SB and found a significantly higher growth suppressive effect than single treatments of each. Even a complete regression of tumors was observed in three of five mice treated with this combination while with single treatment no tumor regression was observed. Tumors treated with the combination showed higher numbers of TUNEL positive cells than those treated with a single modality. Moreover, necrotic changes were more evident in tumors treated with the combination than separately, a compatible finding to the observation that vascularity revealed by CD34 staining was poorer in tumors treated with the combination than those treated with p53 gene or SB alone. This was further supported by the finding that BAI-1 (brain specific angiogenesis inhibitor-1), an inhibitor of vascularization, was induced by SB treatment in KATO-III and HuH7 cells transfected with Ad-p53. Thus SB was shown to be an efficient potentiator of p53 gene therapy for cancer.

Adenoviridae↗

PubMed2005

Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion.

Hepatic transdifferentiation of bone marrow cells has been previously demonstrated by intravenous administration of donor cells, which may recirculate to the liver after undergoing proliferation and differentiation in the recipient's bone marrow. In the present study, to elucidate which cellular components of human bone marrow more potently differentiate into hepatocytes, we fractionated human bone marrow cells into mesenchymal stem cells (MSCs), CD34+ cells, and non-MSCs/CD34- cells and examined them by directly xenografting to allylalcohol (AA)-treated rat liver. Hepatocyte-like cells, as revealed by positive immunostaining for human-specific alpha-fetoprotein (AFP), albumin (Alb), cytokeratin 19 (CK19), cytokeratin 18 (CK18), and asialoglycoprotein receptor (AGPR), and by reverse transcription-polymerase chain reaction (RT-PCR) for expression of AFP and Alb mRNA, were observed only in recipient livers with MSC fractions. Cell fusion was not likely involved since both human and rat chromosomes were independently identified by fluorescence in situ hybridization (FISH). The differentiation appeared to follow the process of hepatic ontogeny, reprogramming of gene expression in the genome of MSCs, as evidenced by expression of the AFP gene at an early stage and the albumin gene at a later stage. In conclusion, we have demonstrated that MSCs are the most potent component in hepatic differentiation, as revealed by directly xenografting into rat livers.

Albumins↗

PubMed2005

Involvement of extracellular dilignols in lignification during tracheary element differentiation of isolated Zinnia mesophyll cells.

During differentiation of isolated Zinnia mesophyll cells into tracheary elements (TEs), lignification on TEs progresses by supply of monolignols not only from TEs themselves but also from surrounding xylem parenchyma-like cells through the culture medium. However, how lignin polymerizes from the secreted monolignols has not been resolved. In this study, we analyzed phenol compounds in culture medium with reversed-phase HPLC, gas chromatography-mass spectrometry and nuclear magnetic resonance spectrometry, and found 12 phenolic compounds including coniferyl alcohol and four dilignols, i.e. erythro-guaiacylglycerol-beta-coniferyl ether, threo-guaiacylglycerol-beta-coniferyl ether, dehydrodiconiferyl alcohol and pinoresinol, in the medium in which TEs were developing. Coniferyl alcohol applied to TE-inductive cultures during TE formation rapidly disappeared from the medium, and caused a sudden increase in dilignols. Addition of the dilignols promoted lignification of TEs in which monolignol biosynthesis was blocked by an inhibitor of phenylalanine anmmonia-lyase (PAL), L-alpha-aminooxy-beta-phenylpropionic acid (AOPP). These results suggested that dilignols can act as intermediates of lignin polymerization.

Asteraceae↗