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Yutaka Shimada

Publications and source records attributed to Yutaka Shimada.

At least 73 records · Page 4Linked to original sources
PubMed2004

Suppressive effects of Stephania tetrandra on the neutrophil function in patients with rheumatoid arthritis.

Crude preparations of Stephania tetrandra (ST), a traditional herbal medicine, have been used safely for arthritis and silicosis in China. The concentration of granulocyte elastase - alpha 1 protease inhibitor complex in plasma is enhanced in inflammatory processes, e.g. in septicaemia and rheumatoid arthritis (RA), being an expression of granulocyte activation during inflammatory response. It has previously been reported that ST showed beneficial and immunomodulatory effects in the treatment of relatively mild RA. After the administration of ST for 12 weeks, the proportion of granulocytes and the granulocyte count in peripheral blood decreased significantly. The lipid peroxide and human granulocyte elastase levels of stored plasma declined significantly. Furthermore, both the leukocyte/elastase ratio and granulocyte/elastase ratio increased significantly. The findings of this study suggest that the suppressive effect of ST administration on excessive granulocyte activation resulted in the improvement of inflammation with rheumatoid arthritis.

Adjuvants, Immunologic↗
PubMed2004

Effects of Choto-san and hooks and stems of Uncaria sinensis on antioxidant enzyme activities in the gerbil brain after transient forebrain ischemia.

Previously, we revealed that oral administrations of Choto-san, a Kampo formula, and the hooks and stems of Uncaria sinensis Haviland (Rubiaceae), a medicinal plant comprising Choto-san, enhanced superoxide anion and hydroxyl radical scavenging activities in the hippocampus, and prevented delayed neuronal death of pyramidal cells in the hippocampal CA1 region in a transient forebrain ischemia gerbil model. In the present study, for the purpose of clarifying whether the endogenous antioxidant enzymes contribute to these mechanisms, we investigated the effects of Choto-san extract (CSE) and Uncaria sinensis extract (USE) on superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities in the brain by using the same experimental model. 1.0% CSE or 3.0% USE were dissolved in water and provided to gerbils ad libitum from 7 days prior to ischemia/reperfusion (i/rp). Seven days of continuous administrations of CSE or USE without i/rp procedure enhanced CAT activity but not SOD and GSH-Px activities in both the hippocampus and cortex. CSE elevated CAT activity in the hippocampus at 7 days and in the cortex at 3h after i/rp. USE raised CAT activity in both the hippocampus and cortex at 3 h and 7 days after i/rp. These results suggest that one of the mechanisms of the protective effects of CSE and USE against transient brain ischemia-induced neuronal damage may be their enhancing effect on CAT activity in the brain.

Animals↗
PubMed2004

Protective effects of Choto-san and hooks and stems of Uncaria sinensis against delayed neuronal death after transient forebrain ischemia in gerbil.

Previously, we revealed that Choto-san (Diao-teng-san in Chinese), a Kampo formula, is effective on vascular dementia clinically, and the hooks and stems of Uncaria sinensis (Oliv.) Havil., a medicinal plant comprising Chotosan, has a neuroprotective effect in vitro. In the present study, for the purpose of clarifying their effects in vivo, we investigated whether the oral administration of Choto-san extract (CSE) or U. sinensis extract (USE) reduces delayed neuronal death following ischemia/reperfusion (i/rp) in gerbils. Transient forebrain ischemia was induced by bilateral carotid artery occlusion for 4 min, and two doses (1.0% and 3.0%) of CSE or USE were dissolved in drinking water and provided to the gerbils ad libitum from 7 days prior to i/rp until 7 days after i/rp. It was found that 1.0% and 3.0% CSE treatments significantly reduced pyramidal cell death in the hippocampal CA1 region at 7 days post i/rp. Three percent USE treatment also inhibited pyramidal cell death significantly at 7 days after i/rp. Superoxide anion and hydroxyl radical scavenging activities of the homogenized hippocampus at 7 days after i/rp in the 1.0% CSE- and 3.0% USE-treated groups were significantly enhanced compared to those of control. Further, lipid peroxide and NO2-/NO3- levels of the homogenized hippocampus at 48h after i/rp in the 1.0% CSE- and 3.0% USE-treated groups were significantly lower than those of control. These results suggest that the oral administration of CSE or USE provides a protective effect against transient ischemia-induced delayed neuronal death by reducing oxidative damage to neurons.

Animals↗
PubMed2004

Enteric excretion of baicalein, a flavone of Scutellariae Radix, via glucuronidation in rat: involvement of multidrug resistance-associated protein 2.

PURPOSE: Baicalin (BG) and its aglycone, baicalein (B), are strong antioxidants and have various pharmacological actions. The purpose of this study was to evaluate efflux of BG from rat intestinal mucosal cell following glucuronidation of B absorbed after oral administration of B. METHODS: The absorption and excretion of BG and B were evaluated in rats using the in situ jejunal loop technique and in vitro jejunal everted sac experiments. BG and B levels were determined by high-performance liquid chromatography with electro-chemical detection to ensure selectivity and high sensitivity. RESULTS: A large amount (30.4% recovery) of BG, but no B, was detected in the intestinal lumens of germ-free rats 4 h after oral administration of B (12.1 mg/kg), in comparison with a substantial recovery (55.1%) of unabsorbed BG 4 h after its administration. During the in situ rat jejunal loop absorption experiment, B disappeared rapidly, and 8% of the lost B was excreted into the loop as BG 20 min after infusing 0.1 mM B. In an in vitro absorption experiment using everted rat jejunal sac, BG also appeared outside the sac, accompanied by the disappearance of B from the outer (mucosal) side. However, very little of B was transferred to the inner (serosal) side of the sac, and only a trace of BG was detected inside the sac. Thus, in both the loop and the everted sac systems, the efflux of BG from the mucosal surface was saturated with the concentration of B added. Moreover, the efflux rate of BG in the everted jejunal sac from Eisai hyperbilirubinemic rat (EHBR) was significantly lower by 56.4% than that from Sprague-Dawley rat. CONCLUSIONS: These results indicate that, in rat, a large proportion of any B absorbed is retained, transformed into BG within the intestinal mucosal cells, and coordinately excreted through multidrug resistance-associated protein 2 (MRP2) into the intestinal lumen.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2004

Caspase-3 expression in human gastric carcinoma and its clinical significance.

OBJECTIVES: Caspase-3 is one of the most important molecules in the apoptosis cascade, and the relationship between caspase-3 expression and prognosis has been reported in many types of malignancies. However, the involvement of caspase-3 in human gastric carcinoma is not fully understood. We evaluated caspase-3 expression in human gastric carcinoma to clarify the clinicopathological importance and investigated the apoptosis avoidance mechanism by an immunohistological method. METHODS: Specimens from 151 patients who underwent gastrectomy at the Department of Surgery and Surgical Basic Science of Kyoto University Hospital were investigated. Caspase-3 expression in cancer cells was evaluated by comparing its expression in the germinal center of the lymphoid follicle, and was quantified as the caspase-3 expression index (C3EI). C3EI was compared with the expression of Bcl-2 and the TdT-mediated dUTP biotin nick-end labeling (TUNEL) in 80 randomly selected cases. Actual activation of caspase-3 was determined by immunohistochemistry using monoclonal antibody that recognizes only activated caspase-3. RESULTS: C3EI correlated significantly with lymph node metastasis (negative 105.5-78.7, positive 153.8 +/- 66.1 p = 0.001) and the lower C3EI group had a better prognosis than the higher group (log-rank test, p = 0.0001). Cox multivariate analysis showed that age, operation curability, tumor invasion and C3EI were significant independent determinants of overall survival. Bcl-2 and TUNEL staining had no significant correlations with C3EI. Immunohistochemistry of activated caspase-3 revealed that most caspase-3 in gastric cancer cells was not activated, in accordance with TUNEL assay. CONCLUSIONS: Our results show that C3EI is a novel, independent prognostic factor in gastric cancer patients and cancer cells may avoid apoptosis by inhibiting caspase-3 activation.

Aged↗
PubMed2004

Prognostic significance of dysadherin expression in esophageal squamous cell carcinoma.

OBJECTIVE: Dysadherin is a cancer-associated cell membrane glycoprotein that has been reported to downregulate E-cadherin expression and promote metastasis. To evaluate the role of dysadherin in metastasis of esophageal squamous cell carcinoma (ESCC), we examined dysadherin and E-cadherin expression in patients with this cancer. METHODS: Dysadherin and E-cadherin expression was evaluated in 117 ESCC patients (pT1, 31; pT2, 30; pT3, 39; pT4, 17) by immunohistochemistry. The findings were compared with the clinicopathological data of the patients. RESULTS: Both dysadherin and E-cadherin were localized to the cell membrane. Thirty patients (29.1%) had tumors positive for dysadherin and 41 patients (35.0%) had tumors positive for E-cadherin. Tumors showing dysadherin positivity and negative E-cadherin expression had a significantly worse prognosis than other tumors. When the patients with dysadherin- positive tumors were combined with E-cadherin-negative patients, this group had a worse prognosis (p < 0.0001). Cox multivariate analysis revealed that dysadherin expression was an independent prognostic factor for ESCC (p = 0.003), but E-cadherin expression was not. CONCLUSION: Combined analysis of dysadherin and E-cadherin expression may help to predict the prognosis of patients with ESCC. Our results suggested that expression of dysadherin by this cancer may partly explain the poor prognosis of patients with preservation of E-cadherin expression.

Aged↗
PubMed2004

The prognostic relevance of fascin expression in human gastric carcinoma.

OBJECTIVE: Fascin, an actin-bundling protein that is found in membrane ruffles, microspikes, and stress fibers, induces membrane protrusions and increases cell motility in various transformed cells. The expression of fascin in epithelial neoplasms has been described only recently, and its role in gastric cancer is still unknown. METHODS: Paraffin sections of gastric carcinoma from 214 patients were immunohistochemically investigated using monoclonal antifascin antibody. Staining more than 5% of tumor cells was recorded as positive immunoreactivity. RESULTS: Overall, fascin immunoreactivity was detected in 54 out of a total of 214 patients (25%). 26 patients were classified as 1+ (5-25% immunoreactive tumor cells) and 28 were 2+ (>25%). In these patients, 7 tumors showed high (>75%) fascin immunoreactivity. Increased immunoreactivity of fascin was sometimes seen at the edge of the tumor. Fascin immunoreactivity was increased according to the extent of primary tumor (p = 0.026). Fascin expression was correlated with age (p = 0.005), serosal invasion (p = 0.013), positive lymph node metastasis (p = 0.006), histopathological grading (p = 0.019), TNM stage (p = 0.003) and recurrence (p = 0.006); however, it was not correlated with distant metastasis (p = 0.108), Lauren's type (p = 0.205), or R classification (p = 0.056). Among 166 patients with T1, T2, T3 or T4, those with fascin-positive tumors had a significantly poorer prognosis than those with fascin-negative tumors (p = 0.029). Multivariate analysis showed that fascin expression was not an independent poor prognostic factor. CONCLUSION: Our findings suggest that the immunohistochemical detection of fascin could provide useful information as one of the prognostic factors in gastric cancer patients.

Actins↗
PubMed2003

Surgery plus chemotherapy compared with surgery alone for localized squamous cell carcinoma of the thoracic esophagus: a Japan Clinical Oncology Group Study--JCOG9204.

PURPOSE: We performed a multicenter randomized controlled trial to determine whether postoperative adjuvant chemotherapy improves outcome in patients with esophageal squamous cell carcinoma undergoing radical surgery. PATIENTS AND METHODS: Patients undergoing transthoracic esophagectomy with lymphadenectomy between July 1992 and January 1997 at 17 institutions were randomly assigned to receive surgery alone or surgery plus chemotherapy including two courses of cisplatin (80 mg/m2 of body-surface area x 1 day) and fluorouracil (800 mg/m2 x 5 days) within 2 months after surgery. Adaptive stratification factors were institution and lymph node status (pN0 versus pN1). The primary end point was disease-free survival. RESULTS: Of the 242 patients, 122 were assigned to surgery alone, and 120 to surgery plus chemotherapy. In the surgery plus chemotherapy group, 91 patients (75%) received both full courses of chemotherapy; grade 3 or 4 hematologic or nonhematologic toxicities were limited. The 5-year disease-free survival rate was 45% with surgery alone, and 55% with surgery plus chemotherapy (one-sided log-rank, P =.037). The 5-year overall survival rate was 52% and 61%, respectively (P =.13). Risk reduction by postoperative chemotherapy was remarkable in the subgroup with lymph node metastasis. CONCLUSION: Postoperative adjuvant chemotherapy with cisplatin and fluorouracil is better able to prevent relapse in patients with esophageal cancer than surgery alone.

Adult↗
PubMed2003

Involvement of TSLC1 in progression of esophageal squamous cell carcinoma.

Frequent allelic losses of 11q23 in esophageal squamous cell carcinoma (ESCC) have been reported previously, but no tumor suppressor genes in this region have been identified in ESCC. TSLC1 was identified on chromosome 11q23.2 as a tumor suppressor gene in non-small cell lung cancer by functional complementation of a lung adenocarcinoma cell line. The purpose of this study is to evaluate the role of TSLC1 in ESCC. Loss of TSLC1 expression was observed by reverse transcription-PCR in 75% of the cell lines (27 of 36) and 50% of the primary tumors from ESCC patients (28 of 56). In a clinicopathological analysis, loss of TSLC1 expression correlated significantly with depth of invasion (pT) and status of metastasis (pM; P = 0.012 and 0.036, respectively). Patients with tumors lacking TSLC1 expression tended to have a poorer prognosis than those with tumors expressing TSLC1. (P = 0.079). Moreover, TSLC1 expression was an independent prognostic factor in a multivariate analysis (P = 0.049). Methylation analyses revealed that TSLC1 expression or loss correlated with the promoter methylation status, as determined by bisulfite sequencing, and that TSLC1 expression could be restored by a demethylating agent in certain cell lines. The growth of TSLC1-transfected ESCC cells was significantly suppressed both in vitro and in vivo (P < 0.01), possibly by a G(1) cell cycle arrest. TSLC1 expression also suppressed motility and invasion of ESCC cells in vitro significantly (P < 0.01). These findings suggest that loss of TSLC1 expression has an important role in tumor growth, cell motility, and invasion and is associated with aggressive tumor behavior in ESCC.

Aged↗
PubMed2003

Identification of ZASC1 encoding a Krüppel-like zinc finger protein as a novel target for 3q26 amplification in esophageal squamous cell carcinomas.

Among the transcription factors that direct proliferation, differentiation, and death of cells, several Krüppel-like zinc finger molecules such as GLI1 and ZNF147 can become oncogenic when the genes encoding them are overexpressed by the DNA amplification mechanism. Here, we report the discovery of a novel member of this class, ZASC1, from a recently reported critical region of 3q26 amplification frequently observed in various squamous cell carcinomas, including esophageal squamous cell carcinomas (ESCs). The deduced 485-amino acid protein product of ZASC1 contained a putative nuclear localization signal; the exogenously transfected ZASC1 was translocated into cell nuclei. ZASC1 was frequently coamplified and subsequently overexpressed with PIK3CA in our panel of ESC cell lines and primary tumors. In patients with ESC, a higher mRNA expression level of ZASC1 appeared to be associated with shorter overall survival, and a multivariate analysis demonstrated that ZASC1 mRNA expression was an independent prognosticator. In addition, exogenous expression of ZASC1 promoted the growth of ESC cells, whereas down-regulation of ZASC1 expression by means of an antisense oligonucleotide suppressed the growth of ESC cells. Taken together, our results suggest that ZASC1 might be involved in the pathogenesis of ESC as one of the targets for 3q26 amplification, alone or in concert with other targets.

Aged↗
PubMed2003

Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours.

Activation of the Hedgehog (Hh) signalling pathway by sporadic mutations or in familial conditions such as Gorlin's syndrome is associated with tumorigenesis in skin, the cerebellum and skeletal muscle. Here we show that a wide range of digestive tract tumours, including most of those originating in the oesophagus, stomach, biliary tract and pancreas, but not in the colon, display increased Hh pathway activity, which is suppressible by cyclopamine, a Hh pathway antagonist. Cyclopamine also suppresses cell growth in vitro and causes durable regression of xenograft tumours in vivo. Unlike in Gorlin's syndrome tumours, pathway activity and cell growth in these digestive tract tumours are driven by endogenous expression of Hh ligands, as indicated by the presence of Sonic hedgehog and Indian hedgehog transcripts, by the pathway- and growth-inhibitory activity of a Hh-neutralizing antibody, and by the dramatic growth-stimulatory activity of exogenously added Hh ligand. Our results identify a group of common lethal malignancies in which Hh pathway activity, essential for tumour growth, is activated not by mutation but by ligand expression.

Animals↗
PubMed2003

Association of CC chemokine receptor 7 with lymph node metastasis of esophageal squamous cell carcinoma.

PURPOSE: CC chemokine receptor 7 (CCR7) plays a critical role in the migration of activated dendritic cells to regional lymph nodes. Recent studies have shown that CCR7 is involved in metastasis in some malignant diseases. The role of CCR7 in esophageal squamous cell carcinoma (SCC) has not yet been clarified. EXPERIMENTAL DESIGN: We performed reverse transcription-PCR analysis for CCR7 in 20 esophageal SCC cell lines and immunohistochemical analysis of 96 esophageal SCC samples. We then performed a cell migration assay, F-actin polymerization, and a phagokinetic assay on esophageal SCC cell lines in the presence of CCL21, a ligand of CCR7. RESULTS: CCR7 mRNA was detected in 9 of 20 esophageal SCC cell lines. Immunoreactive CCR7 was found mainly in esophageal cancer cells. High CCR7 expression was significantly correlated with esophageal SCC lymphatic permeation, lymph node metastasis, tumor depth, and tumor-node-metastasis stage and was associated with poor survival. In vitro studies demonstrated that CCL21 significantly increased the cell migration ability of esophageal SCC cell lines, and pseudopodia formation was induced by CCL21 stimulation. Furthermore, CCL21 markedly enhanced the motility of esophageal carcinoma cell lines by the phagokinetic assay. CONCLUSIONS: The results suggested that the CCR7/CCL21 receptor ligand system may play a role in the lymph node metastasis of esophageal SCC.

Aged↗
PubMed2003

Neurotrophin receptor p75(NTR) characterizes human esophageal keratinocyte stem cells in vitro.

We report here that human esophageal keratinocyte stem cells are characterized by the expression of the low-affinity neurotrophin receptor p75(NTR) and differentially expressed cell adhesion molecules, the beta1 and beta4 integrins. The candidate stem cells could be fractionated from keratinocytes as a minor cell subset by means of immunocytochemical cell sorting based on the different levels of expression of these cell surface molecules. Flow cytometric analysis revealed that this minor cell subset retained a relatively slow-cycling phenotype in vitro. These cells expressed low levels of involucrin and cytokeratin 13, indicating that the p75(NTR)-positive cell subset is immature relative to the other predominant subpopulations coexpressing beta1 integrin at higher levels. The p75(NTR)-positive cell subset was crucial for achieving longevity and the greatest output of keratinocytes comprising all distinguishable subpopulations in vitro. This process was associated with self-renewal and self-amplification of the p75(NTR)-positive cell subset. These findings strongly implicate p75(NTR) as a stem cell marker, which will be valuable for prospectively investigating stem cell regulation in association with different biological processes including neoplastic transformation of regenerative epithelia.

Blotting, Western↗
PubMed2003

Identification of benzo(a)pyrene diol epoxide-binding DNA fragments using DNA immunoprecipitation technique.

Benzo(a)pyrene diol epoxide (BPDE), an active metabolite of the tobacco carcinogen benzo(a)pyrene, can induce p53 gene mutation, down-regulate retinoic acid receptor beta, and increase cyclooxygenase-2 expression in human epithelial cells. However, it remains unknown whether these effects are direct or indirect. To investigate the direct effects of BPDE on gene expression, we used our newly developed DNA immunoprecipitation technique to identify and clone BPDE-binding DNA fragments. A total of 67 fragments were sequenced and grouped into four categories after their sequences were blasted in the GenBank database: (a). 15 fragments matched known gene sequences; (b). 24 matched expressed sequence tag clones; (c). 22 matched genomic DNA of unknown genes; and (d). 6 clones did not show any homology with GenBank sequences known to date. The 67 fragments include DNA repair and apoptosis-related genes, zinc finger protein, cellular enzymes, expressed sequence tag clones, and CpG islands. These data further demonstrate that BPDE-induced gene alterations are important events in carcinogenesis and that the identification of the resulting clones may help us to better understand the mechanisms of BPDE-induced carcinogenesis.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed2003

Variations in the number and position of human lumbar sympathetic ganglia and rami communicantes.

The purpose of this study is to provide precise anatomical and statistical information about the number and location of lumbar sympathetic ganglia and the number and length of the related rami communicantes, and to consider the neurological pathway for nociception from the low back. Three-hundred ninety-three ganglia and 719 rami communicantes from 50 human cadavers were identified by gross dissection. The number of ganglia in a single lumbar chain ranged from 2 to 6, the mean being 3.9. The mean lengths of rami connected to the 1st and 5th lumbar spinal nerves, respectively, were significantly longer and shorter than those connected to the 2nd, 3rd, and 4th nerves. The lumbar sympathetic ganglia and rami communicantes were not distributed segmentally. The present results may assist in understanding the nociceptive pathway from the low back.

Aged↗
PubMed2003

Inhibitory effects of triterpenes isolated from Hoelen on free radical-induced lysis of red blood cells.

Hoelen, sclederma of Poria cocos Wolf, has long been used as a sedative and diuretic in traditional medicine. Formerly, we demonstrated that Hoelen in vitro protects red blood cells from AAPH-induced hemolysis. In this study, tests were carried out to identify the main ingredient of Hoelen that has the scavenging effect on free-radicals. Triterpene carboxylic acids isolated from the methanol extract of Hoelen, i.e. pachymic acid, polyporenic acid, 3-epidehydrotumulosic acid, 3beta-hydroxylanosta-7,9(11), 24-trien-21-oic acid and 3-o-acetyl-16 alpha -hydroxytrametenolic acid, were found to have inhibitory activities against AAPH-induced lysis of red blood cells.

Amidines↗
PubMed2003

Natural killer cytolytic activity is associated with the expression of killer cell immunoglobulin-like receptors on peripheral lymphocytes in human.

Although it has been shown that killer cell immunoglobulin-like receptors (KIRs) on peripheral lymphocytes are upregulated by interleukin-2 (IL-2), which activates natural killer (NK) activity, it has not been demonstrated whether the expression of KIRs is related to NK activity. Therefore, we investigated the association between the KIR expression on lymphocytes and NK activity. CD158a/b expression on lymphocytes obtained from 37 subjects was analyzed using flow cytometry. Simultaneously, NK activity was measured each sample using a 51Cr-release assay. Additionally, lymphocytes were cultured in RPMI 1640 medium with or without IL-2 for 48 h, and then their CD158a/b expression and NK activity was analyzed. CD158a/b expression was significantly correlated with NK activity. Especially, the percentage of CD16+CD158a+ and CD8+CD158a/b+ cells in lymphocytes showed a highly significant correlation with NK activity. However, analysis of CD8+ and CD16+ cells revealed that there was only a significant correlation between the percentage of CD8+CD158a+ cells among only CD8+ cells and NK activity. The upregulation of CD16+CD158a+/b+ cells in response to IL-2 tended to be related to the increase of NK activity, but the relationship was not significant. In conclusion, the level of KIR expression was correlated with NK activity, and IL-2 treatment resulted in an increase of NK activity as well as KIR expression, suggesting that upregulation of KIRs enhances the ability to sort target cells, such as virus-infected cells from uninfected cells, according to major histocompatibility complex class I expression.

Adult↗