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Biomedical subjects

S Yanagisawa

Publications and source records attributed to S Yanagisawa.

At least 19 recordsLinked to original sources
PubMed2006

Improvement of pulmonary function and dyspnea by tiotropium in COPD patients using a transdermal beta(2)-agonist.

BACKGROUND: A combination of bronchodilators may be effective in the treatment of chronic obstructive pulmonary disease (COPD). We examined the effect of adding a long-acting anti-cholinergic agent (tiotropium) to a transdermal-type beta(2)-agonist (tulobuterol) on dyspnea as well as pulmonary function. METHODS: In a multicentre, randomized, parallel design study, 60 COPD patients treated with the transdermal beta(2)-agonist tulobuterol were divided into a tiotropium added group (Tulo+Tio group, n=40) or transdermal beta(2)-agonist tulobuterol alone group (Tulo group, n=20), and then treated for 4 weeks after a 2 week run-in period. Pulmonary function and a dyspnea (Medical Research Council (MRC)) scale were assessed before and after the treatment. Daily peak expiratory flow (PEF) monitoring was also performed. RESULTS: After 4 weeks, the Tulo+Tio group showed a significant increase in pulmonary function compared with the Tulo group; DeltaFVC (0.31+/-0.06 L vs. 0.06+/-0.05 L, p< 0.01), DeltaFEV(1) (0.15+/-0.03 L vs. -0.02+/-0.02 L, p<0.0001), and DeltaPEF (41.0+/-5.1 L/min vs. 0.5+/-3.5 L/min, p<0.0001). The MRC dyspnea scale was also significantly improved in Tulo+Tio, but not in Tulo group. CONCLUSION: These results suggest that tiotropium caused a significant improvement in both pulmonary function and dyspnea in COPD patients already treated with the transdermal beta(2)-agonist tulobuterol.

Administration, Cutaneous↗
PubMed2006

Inhibition of reactive nitrogen species production in COPD airways: comparison of inhaled corticosteroid and oral theophylline.

BACKGROUND: Reactive nitrogen species (RNS) are thought to be one of the important factors in the pathogenesis of chronic obstructive pulmonary disease (COPD). A study was undertaken to examine the effects of theophylline and fluticasone propionate (FP) on RNS production in subjects with COPD. METHODS: Sixteen COPD subjects participated in the study. Theophylline (400 mg/day orally) or FP (400 mug/day inhalation) were administered for 4 weeks in a randomised crossover manner with a washout period of 4 weeks. Induced sputum was collected at the beginning and end of each treatment period. 3-nitrotyrosine (3-NT), which is a footprint of RNS, was quantified by high performance liquid chromatography with an electrochemical detection method as well as by immunohistochemical staining. RESULTS: Theophylline significantly reduced the level of 3-NT in the sputum supernatant as well as the number of 3-NT positive cells (both p<0.01). FP also reduced 3-NT formation, but the effect was smaller than that of theophylline. Theophylline also significantly reduced the neutrophil cell counts in the sputum (p<0.01), while FP treatment had no effect on the number of inflammatory cells in the sputum, except eosinophils. CONCLUSIONS: Theophylline reduces nitrative stress and neutrophil infiltration in COPD airways to a larger extent than inhaled corticosteroid.

Administration, Inhalation↗
PubMed2006

Primary chondrosarcoma in the liver of a dog.

Primary chondrosarcoma was found in the quadrate lobe of the liver of a 6-year-old, intact, male Golden Retriever. At 6 months after partial hepatectomy, recurrence in the liver occurred. The dog died of its systemic metastases 10 months thereafter. Histologically, the hepatic mass revealed neoplastic chondrocytes with abundant chondroid matrix, and there were few myxoid areas where the cellularity and pleomorphism of the neoplastic cells were more prominent. The neoplastic cells were positive for periodic acid-Schiff and were immunohistochemically positive for vimentin and S-100 protein; the matrix was deeply stained for alcian blue and was metachromatic for toluidine blue stain. This tumor might be derived from pluripotent mesenchymal cells in the connective tissue of the liver. To the best of our knowledge, in all mammalians, including humans, this is the first report of extraskeletal chondrosarcoma primarily arising in the liver.

Animals↗
PubMed2005

Intratumoural expression of thymidylate synthase is an independent predictor of prognosis in patients with squamous cell carcinoma of the tongue: results from a retrospective study.

The aim of this study was to assess the importance of immunohistochemical thymidylate synthase (TS) expression level as a prognostic marker in tongue cancer patients. In 140 patients with primary squamous cell carcinoma (SCC) of the tongue, intratumoural TS expression was evaluated by immunohistochemistry. The level of TS expression was determined by a semiquantitative scoring system, ranging from 1+ to 3+ according to the ratio of TS-positive cells. Of 140 patients, 64 (45.7%), 49 (35.0%) and 27 (19.3%) were assessed as 1+, 2+ and 3+, respectively. Univariate analyses demonstrated that both disease-free survival (DFS) and overall survival (OS) were significantly lower in patients with a TS 3+ tumour than in those with a TS 1+/2+ tumour (DFS: P = 0.0082, OS: P = 0.0100). In a multivariate analysis using the Cox regression model, cervical lymph-node status and TS expression level were selected as independent factors for DFS and OS. Maintenance adjuvant chemotherapy by oral 5-fluorouracil (5-FU) significantly improved DFS and OS in patients with a TS 1+/2+ tumour (DFS: P = 0.0027, OS: P = 0.0398). These data suggest that the level of immunohistochemical TS expression is an independent prognosticator in patients with tongue SCC, and may be useful in the selection of patients who would benefit from oral 5-FU adjuvant chemotherapy.

Adult↗
PubMed2004

Comparison of health-seeking behaviour between poor and better-off people after health sector reform in Cambodia.

This study compared health-seeking behaviour between poor and better-off people after health sector reform in Cambodia. The survey was conducted in the Prek Dach Health Centre coverage area, which is located in South-east Cambodia. The study population consisted of 257 housewives of reproductive age, selected at random. Data were collected through household surveys with a structured questionnaire. Data collected included socio-demographic information on the housewives, as well as episodes of illness of family members within 30 days prior to the survey. Two indicators, the floor area of living space and a rating scale on asset ownership, were used to identify poor and very poor people. When a family member became ill, subjects most often used home remedies as a first step, followed by self-medication. Subsequently, people used self-medication or the private health sector. Very poor people used the health centre more often than better-off people as a first step. For the second step, use of the health centre was also high among the poor compared with better-off people, although the difference was not statistically significant. Keeping the treatment fees low and abolishing informal fees maintained the affordability of health-centre services for the poor. However, this benefit diminished quickly with distance from the health centre. The significant difference between poor and better-off people disappeared for villages situated more than 2 km from the health centre. Thus, the health centre in the studied area was shown to be effective in providing primary health care to the economically disadvantaged, but only within a limited geographic area.

Adolescent↗
PubMed2003

Predictive value of immunohistochemical thymidylate synthase expression for histological response to Tegafur/Uracil (UFT) in oral squamous cell carcinoma.

Thymidylate synthase (TS), an enzyme involved in the DNA synthesis, is a critical target for fluoropyrimidines. We investigated the relationship between the level of tumoural TS expression and response to tegafur/uracil (UFT) in 26 patients with oral squamous cell carcinoma. The patients received peroral administration of UFT alone preoperatively. In biopsy specimens, TS expression level was assessed by the immunohistochemical staining and graded as 1+, 2+ or 3+ according to the frequency of strongly-stained tumour cells. Out of 26 tumours, 10 (38.5%), 10 (38.5%) and 6 (23.1%) cases were categorized as 1+, 2+ and 3+, respectively. The response to UFT was histologically evaluated by a grading system according to the extent of degenerative or necrotic cancer cells in surgical specimens. Results showed patients with the lower TS expression had the higher response and there was a statistically significant association between TS expression and response to UFT (P=0.031). This finding suggests that TS expression is a predictor of chemosensitivity to UFT in oral squamous cell carcinomas.

Aged↗
PubMed2002

Expression of cyclin D1 and GSK-3beta and their predictive value of prognosis in squamous cell carcinomas of the tongue.

The status of cyclin D1 and glycogen synthase kinase 3beta (GSK-3beta) was investigated in 41 patients with T1 and T2 squamous cell carcinomas (SCCs) of the tongue. Out of the 41 SCCs, 27 (65.9%) showed overexpression of cyclin D1 in comparison with normal lingual epithelia by an immunohistochemical method. Cyclin D1 gene amplification was detected in only two (9.1%) of 22 informative cases of the SCCs by differential PCR. Expression of GSK-3beta, which was found to regulate proteosomal degradation of cyclin D1 protein, was reduced in 16 cases (39.0%) of the SCCs relative to normal epithelia, and the intensity of GSK-3beta staining showed an inverse association with cyclin D1. These findings suggest that overexpression of cyclin D1 primarily results from stabilization due to reduction of GSK-3beta, but not cyclin D1 gene amplification, in lingual SCCs. Kaplan-Meier analysis demonstrated that the patients with high cyclin D1 and reduced GSK-3beta expression had a significantly lower 5-year survival than the patients with low cyclin D1 and non-reduced GSK-3beta expression (P=0.014). The cyclin D1 and GSK-3beta coupled assessment was more valuable for the prediction of prognosis than assessment based on cyclin D1.

Adult↗
PubMed2001

Angiogenesis in pancreatic carcinoma: thymidine phosphorylase expression in stromal cells and intratumoral microvessel density as independent predictors of overall and relapse-free survival.

BACKGROUND: Recently, the usefulness of intratumoral microvessel density (IMD) and expression of several angiogenic factors as prognostic indicators have been demonstrated in several human solid tumors. METHODS: One hundred four patients with pancreatic ductal adenocarcinoma were examined retrospectively. The investigated clinicopathologic and immunohistologic data included staining for vascular endothelial growth factor (VEGF), thymidine phosphorylase (TP), basic fibroblast growth factor (bFGF), CD34 (for calculating IMD), p53, and Ki-67. RESULTS: Multivariate analysis for both overall and relapse-free survival revealed two independent variables, IMD and TP staining in stromal cells (TPs, P < 0.02). Whereas the frequency of hepatic metastasis was correlated significantly with cytoplasmic expression of TP or bFGF in tumor cells (TPc, bFGFc), IMD, and p53 status, local recurrence was significantly more common in patients with positive staining for TPs, bFGF in stromal cells (bFGFs), and for the pM category (P < 0.05). TPc, bFGFc, VEGF, and p53 expression correlated with IMD (P < 0.01), although TPs and bFGFs expression did not. VEGF and IMD status correlated with p53 expression (P < 0.001), although TP, bFGF, and Ki-67 status did not. CONCLUSIONS: TPs expression and IMD were revealed to be valuable tools for predicting overall and relapse-free survival in patients with pancreatic adenocarcinoma. Whereas TPc and bFGFc are likely to participate in hepatic metastasis by means of their angiogenic properties, TPs and bFGFs may be related to local tumor progression. Angiogenesis in human pancreatic carcinoma may be dependent on VEGF, TP, and bFGF. p53 abnormality is likely to take part in VEGF-related angiogenesis.

Adenocarcinoma↗
PubMed2001

The transcriptional activation domain of the plant-specific Dof1 factor functions in plant, animal, and yeast cells.

Maize Dof1, one of the plant-specific Dof transcription factors, is involved in light-regulated gene expression. To elucidate the molecular mechanism underlying the activity of Dof1, in vivo functional analyses were carried out using transient expression assays with maize mesophyll protoplasts. The results suggest that the Dof domain alone, the region conserved among Dof factors, can mediate interaction with DNA in vivo and distinct Dof1 activities in greening and etiolated protoplasts. A region rich in basic amino acids was identified as a nuclear localization signal. Deletion analysis defined the transcriptional activation domain of 48 amino acids located in the C-terminus of Dof1. This activation domain was also found to be functional in both human cells and yeast, implying that Dof1 may stimulate transcription through a mechanism evolutionarily conserved among eukaryotes. A computer homology search with known transcription factors revealed that the activation domain of Dof1 displayed only a limited similarity to Activation domain II of animal transcription factor GATA-4. Mutational analysis revealed the critical role of a tryptophan residue within the activation domain of Dof1, as had been shown in Activation domain II of GATA-4.

Amino Acid Sequence↗
PubMed2001

Hepatectomy using the coagulating shears type of ultrasonically activated scalpel.

Since the ultrasonically activated scalpel (UAS) incorporates multiple functions, we have used it for hepatectomies. The present study discusses the noteworthy points and problems of use, and shows initial results. Intraoperative ultrasonography is an important tool for comprehending the positional relationship between the plane of division and the main blood vessels. It allows initial adjustment of coagulation and cutting effects according to the rigidity of the liver parenchyma by means of variable ultrasound levels and exchangeable blade tips, and offers good visibility of the cut surface in deep sites as long as adequate tension on the tissue and an upper position for the blade are maintained. 30 patients underwent hepatectomies using the UAS. The amount of blood loss for lobectomy was significantly less than that for partial lobectomy in normal livers in addition to a significant difference between normal and damaged livers in each group according to the extent of resection. There were no serious complications seen in all cases during the operation. The incidence of positive bile leakage was high. It is recommended that bile leakage testing be carried out as thoroughly as possible. There were 3 postoperative bile fistulas and 1 postoperative hemorrhage. In conclusion, although a dramatic improvement in blood loss and shortened operating time could not be obtained in all procedures, the safety and usefulness were demonstrated in lobectomy. The UAS can be considered as a surgical device that can contribute to the efficiency of hepatectomy, depending on the indications selected.

Blood Loss, Surgical↗
PubMed2000

Heterogeneous Sp1 mRNAs in human HepG2 cells include a product of homotypic trans-splicing.

Sp1 is one of the well documented transcription factors, but the whole structure of human Sp1 has not been determined yet. In the present study, we isolated several cDNAs representing two forms of human Sp1 mRNA with different 5'-terminal structures in HepG2 cells. Isolation of a genomic clone established that one of the cDNAs represents the mRNA having consecutive alignment of exons, which allowed deducing the complete amino acid sequence for human Sp1. Another cDNA clone had a surprising structure that possessed an alignment of exons 3-2-3. Both reverse transcriptase-polymerase chain reaction and RNase protection assays confirmed accumulation of the two forms of Sp1 mRNA in HepG2 cells. Because Southern blot analysis suggested that exon 3 is of a single copy in the genome, the cDNA clone having the duplicated sequences for exon 3 appeared to reflect the trans-splicing between pre-mRNAs of human Sp1.

Amino Acid Sequence↗
PubMed2000

Asymmetric synthesis of the core structure of (-)-CP-263,114.

The enantioselective construction of a fully functionalized core structure of (-)-CP-263,114 (1), containing most of the required functionality for total synthesis, was conducted through sequential radical fragmentation-reductive olefination.

Enzyme Inhibitors↗
PubMed2000

Identification and characterization of a novel cAMP receptor protein in the cyanobacterium Synechocystis sp. PCC 6803.

Three open reading frames of Synechocystis sp. PCC 6803 encoding a domain homologous with the cAMP binding domain of bacterial cAMP receptor protein were analyzed. These three open reading frames, sll1371, sll1924, and slr0593, which were named sycrp1, sycrp2, and sypk, respectively, were expressed in Escherichia coli as His-tagged or glutathione S-transferase fusion proteins and purified, and their biochemical properties were investigated. The results obtained for equilibrium dialysis measurements using these recombinant proteins suggest that SYCRP1 and SYPK show a binding affinity for cAMP while SYCRP2 does not. The dissociation constant of His-tagged SYCRP1 for cAMP is approximately 3 microM. A cross-linking experiment using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide revealed that His-tagged SYCRP1 forms a homodimer, and the presence or absence of cAMP does not affect the formation of the homodimer. The amino acid sequence reveals that SYCRP1 has a domain similar to the DNA binding domain of bacterial cAMP receptor protein in the COOH-terminal region. Consistent with this, His-tagged SYCRP1 forms a complex with DNA that contains the consensus sequence for E. coli cAMP receptor protein in the presence of cAMP. These results strongly suggest that SYCRP1 is a novel cAMP receptor protein.

Amino Acid Sequence↗
PubMed2000

Inactivation of N-terminal signaling domain of Sonic hedgehog by forming a disulfide bond.

The N-terminal domain of mouse Sonic hedgehog (Shh-N) expressed in mammalian cells showed four-fold bands on non-reduced SDS-PAGE, though it was homogeneous under reduced conditions. It contains three cysteine residues, Cys-25, Cys-103, and Cys-184, which may be concerned with this heterogeneity. Therefore, we examined the formation of a disulfide bond in the recombinant Shh-N and identified three kinds of disulfides with a combination of peptide mapping and NH(2)-terminal amino acid sequencing analysis. Among them, one type of the Shh-N containing a disulfide bond of Cys-103/Cys-184 could be separated from the other Shh-Ns using reverse phase HPLC and had no activity of alkaline phosphatase induction in C3H10T1/2 cells. This molecule could also be made by denaturation of the purified Shh-N with guanidine-HCl under non-reduced conditions. On the other hand, the reduced Shh-N and the reduced S-methylated Shh-N at cysteine residues showed approximately 10-fold higher activity compared to the originally purified Shh-N. These results suggested that Shh-N was synthesized as an active form whose three cysteine residues did not form disulfide and inactivated finally by forming a disulfide bond between Cys-103 and Cys-184.

Animals↗
PubMed2000

Immunohistochemical study of the distribution of endogenous biotin and biotin-binding enzymes in ductal structures of salivary gland tumours.

To clarify the pathologic value of endogenous biotin in the salivary gland, we examined in a series of neoplasms of the salivary gland by immunohistochemical staining the distribution of endogenous biotin and of biotin-binding enzymes, namely, acetyl CoA carboxylase (AC), which is a cytosolic enzyme, and pyruvate carboxylase (PC), which is a mitochondrial enzyme. In pleomorphic adenoma, we found biotin and PC in ductal epithelial elements, while AC was found mainly in myoepithelial elements. Carcinoma ex pleomorphic adenoma, adenocarcinoma and mucoepidermoid carcinoma were frequently immunopositive for biotin, PC and AC, while adenoid cystic carcinoma was rarely immunopositive for biotin, PC or AC. These results indicate that endogenous biotin might be associated with the mitochondrial enzyme, which is present at high levels in ductal cells of the salivary gland. However, the neoplastic cells in adenoid cystic carcinoma seemed to have an unusual expression of biotin and related enzymes.

Acetyl-CoA Carboxylase↗
PubMed2000

Dof1 and Dof2 transcription factors are associated with expression of multiple genes involved in carbon metabolism in maize.

Dof proteins are transcription factors that appear to be unique to plants. Maize Dof1 has been suggested to be a regulator for C4 photosynthetic phosphoenolpyruvate carboxylase (C4PEPC) gene expression. The present study demonstrates that Dof1 also enhances transcription from the promoters of both cytosolic orthophosphate dikinase (cyPPDK) genes and a non-photosynthetic PEPC gene, which are not present in animals. Expression of Dof1-specific antisense RNA or the DNA-binding domain of Dof1 alone reduced the activities of these promoters in maize leaf protoplasts. Electrophoretic mobility shift assays revealed several Dof1-binding sites in these promoters. The cyppdk1 promoter contained two Dof1-binding sites, one of which was linked to the binding site of a plant bZIP protein. By using deleted or mutated cyppdk1 promoters, both Dof1-binding sites were shown to be functional. Furthermore, Dof1 elevated the activities of the cyppdk and pepc promoters more strongly in greening protoplasts than in etiolated protoplasts, in accordance with the different activities of these promoters in two types of protoplasts. Another Dof protein of maize, Dof2, suppressed the activity of the C4pepc promoter but was able to activate certain other promoters. These results suggest that Dof proteins may play regulatory roles in multiple gene expressions associated with the plant-specific pathway for carbon metabolism in maize. In addition, the primary characteristic of Dof proteins, i.e. different activities in distinct types of cells and opposite actions on promoters in different contexts, suggests the potential of Dof proteins to differentially regulate diverse promoters in a variety of plant tissues. Speculation raised by these results concerning the evolution of the C4pepc gene is also discussed.

Arabidopsis Proteins↗