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Biomedical subjects

Satoshi Fujii

Publications and source records attributed to Satoshi Fujii.

At least 19 recordsLinked to original sources
PubMed2025

2,3-Pyridinedicarboxylate Is Associated with Shorter Recurrence-Free Survival in Patients with Hypopharyngeal Squamous Cell Carcinoma.

UNLABELLED: Introduction: Metabolites are associated with the biology of cancer; however, no metabolites related to prognosis have been identified in head and neck cancer. This study aimed to identify metabolites associated with prognosis in patients with hypopharyngeal squamous cell carcinoma (HPSCC). METHODS: Fifty-two patients who underwent surgery for HPSCC were included and randomly divided into test and validation cohorts of 26 patients each for further metabolome analysis using capillary electrophoresis/mass spectrometry on tumor and non-tumor tissues of the hypopharynx. Twenty-two patients who received adjuvant therapy after surgery were included. The receiver operating characteristic (ROC) and univariate and multivariate analyses were used to explore the relationship between recurrence-free survival (RFS), clinicopathological factors, and differentiated metabolites. RESULTS: ROC analysis revealed six metabolites significantly associated with RFS in both cohorts, and multivariate analysis indicated that 2,3-pyridinedicarboxylate was a significantly independent poorer prognostic factor in the cohorts including patients with HPSCC without any adjuvant therapies (p = 0.017). CONCLUSION: 2,3-Pyridinedicarboxylate, involved in NAD+ metabolism and genomic stability, suggests the possibility of developing molecular-targeted drugs for the production of metabolites related to prognosis. This study identifies novel prognostic metabolites and their associated metabolic pathways in HPSCC, highlighting potential therapeutic targets for treatment. .

Humans↗
PubMed2007

Efficient synthesis of phenanthridinone derivatives via a palladium-catalyzed coupling process.

A palladium-mediated domino reaction was developed to conveniently synthesize phenanthridinone derivatives. Phosphine ligand 1 strongly promotes the domino process, which includes aryl-aryl coupling and C-N bond formations concomitant with a deamidation reaction. The versatility and applicability to a broad range of substrates make this reaction useful for the development of bioactive derivatives. [reaction: see text].

Acetates↗
PubMed2006

Influence of cationic molecules on the hairpin to duplex equilibria of self-complementary DNA and RNA oligonucleotides.

A self-complementary nucleotide sequence can form both a unimolecular hairpin and a bimolecular duplex. In this study, the secondary structures of the self-complementary DNA and RNA oligonucleotides with different sequences and lengths were investigated under various solution conditions by gel electrophoresis, circular dichroism (CD) and electron paramagnetic resonance (EPR) spectroscopy and a ultraviolet (UV) melting analysis. The DNA sequences tended to adopt a hairpin conformation at low cation concentrations, but a bimolecular duplex was preferentially formed at an elevated cationic strength. On the other hand, fully matched RNA sequences adopted a bimolecular duplex regardless of the cation concentration. The thermal melting experiments indicated a greater change in the melting temperature of the bimolecular duplexes (by approximately 20 degrees C) than that of the hairpin (by approximately 10 degrees C) by increasing the NaCl concentration from 10 mM to 1 M. Hairpin formations were also observed for the palindrome DNA sequences derived from Escherichia coli, but association of the complementary palindrome sequences was observed when spermine, one of the major cationic molecules in a cell, existed at the physiological concentration. The results indicate the role of cations for shifting the structural equilibrium toward a nucleotide assembly and implicate nucleotide structures in cells.

Cations↗
PubMed2006

Selective cognitive dysfunction in mice lacking histamine H1 and H2 receptors.

Previous pharmacological experiments provide conflicting findings that describe both facilitatory and inhibitory effects of neuronal histamine on learning and memory. Here, we examined learning and memory and synaptic plasticity in mice with a null mutation of gene coding histamine H1 or H2 receptor in order to clarify the role of these receptors in learning and memory processes. Learning and memory were evaluated by several behavioral tasks including object recognition, Barnes maze and fear conditioning. These behavioral tasks are highly dependent on the function of prefrontal cortex, hippocampus or amygdala. Object recognition and Barnes maze performance were significantly impaired in both H1 receptor gene knockout (H1KO) and H2 receptor gene knockout (H2KO) mice when compared to the respective wild-type (WT) mice. Conversely, both H1KO and H2KO mice showed better auditory and contextual freezing acquisition than their respective WT mice. Furthermore, we also examined long-term potentiation (LTP) in the CA1 area of hippocampus in H1KO and H2KO mice and their respective WT mice. LTP in the CA1 area of hippocampus was significantly reduced in both H1KO and H2KO mice when compared with their respective WT mice. In conclusion, our results demonstrate that both H1 and H2 receptors are involved in learning and memory processes for which the frontal cortex, amygdala and hippocampus interact.

Analysis of Variance↗
PubMed2006

IL-1 and IL-6 induce hepatocyte plasminogen activator inhibitor-1 expression through independent signaling pathways converging on C/EBPdelta.

To elucidate signaling pathways activated by IL-1 and IL-6 that contribute to increased expression of plasminogen activator inhibitor-1 (PAI-1), we studied human hepatoma (HepG2) cells and primary mouse hepatocytes. HepG2 cell PAI-1 mRNA increased in response to IL-1beta, IL-6, and IL-1beta plus IL-6 as shown by real-time PCR. Activity of the transiently transfected PAI-1 promoter (-829 to +36 bp) increased as well. Systematic promoter deletion assays showed that the region from -239 to -210 bp containing a putative CCAAT-enhancer binding protein (C/EBP) binding site was critical. Point mutations in this region abolished the IL-1beta and IL-6 responses. Antibody interference electrophoretic mobility shift assays showed that C/EBPdelta (but not C/EBPalpha or C/EBPbeta) binding and protein were increased by IL-1beta, IL-6, and IL-1beta plus IL-6 in HepG2 cells. IL-1beta and IL-6 increased expression of both PAI-1 mRNA and C/EBPdelta mRNA in mouse primary hepatocytes as well. Downregulation of C/EBPdelta induced with small interfering RNA (siRNA) decreased secretion of PAI-1. As judged from results obtained with inhibitors, signal transduction in all three of the mitogen-activated protein kinase pathways was involved in IL-1-inducible PAI-1 expression. By contrast, JAK signaling was responsible for the IL-6-induced inducible expression. Thus IL-1 and IL-6 exert directionally similar effects on PAI-1 expression, but the induction involves distinct signaling pathways with a final common mediator, C/EBPdelta.

Animals↗
PubMed2006

Hepatocyte growth factor regulates E box-dependent plasminogen activator inhibitor type 1 gene expression in HepG2 liver cells.

OBJECTIVE: We sought to determine the etiologic mechanism of pleiotropic growth factor, hepatocyte growth factor (HGF), as a regulator of hepatic synthesis of plasminogen activator inhibitor (PAI)-1, the physiological inhibitor of fibrinolysis and a potential inducer of atherothrombosis. METHODS AND RESULTS: HGF increased PAI-1 mRNA expression and PAI-1 protein accumulation in the conditioned media of human liver-derived HepG2 cells, and increased hepatic PAI-1 mRNA expression in vivo in mice. HGF-inducible PAI-1 mRNA was attenuated by U0126, a specific inhibitor of mitogen-activated protein kinase (MAPK) kinase, and genistein, an inhibitor of tyrosine kinase. HGF increased the human PAI-1 promoter (-829 to +36 bp) activity, and deletion and mutation analysis uncovered a functional E box (5'-CACATG-3') at positions -158 to -153 bp. Electrophoretic mobility shift assays demonstrated that this E box binds upstream stimulatory factors (USFs). HGF phosphorylated USFs through MAPK and tyrosine kinase pathways. Co-transfection of USF1 expression vector increased PAI-1 promoter activity. Sterol regulatory element-binding protein-1 attenuated HGF-inducible PAI-1 promoter activity. CONCLUSIONS: Because USFs are involved in the regulation of carbohydrates and lipid metabolism, HGF-mediated PAI-1 production may provide a novel link between atherothrombosis and metabolic derangements. Targeting HGF signaling pathway may modulate the thrombotic risk in high-risk patients.

Animals↗
PubMed2006

Domino Heck-C-H activation reaction of unsymmetrically substituted [3]cumulene.

The Heck reaction of an unsymmetrically substituted [3]cumulene has been investigated. Although a carbonyl conjugated alkene is present, the arylpalladium species selectively inserts into the C3-4 double bond, and a subsequent C-H activation reaction with a neighboring phenyl group gives the indene derivatives with a tetrasubstituted olefin moiety.

Journal Article↗
PubMed2006

Usability of BioCon2 for nucleic acid structures in database.

With the specific three-dimensional structure, DNA/RNA molecules express the specific structural and catalytic functions. The knowledge integration based on three dimensional structures can be used to explain biochemical observations, to predict biological functions and to design drugs specific to a given complex system. In the large RNAs, the helical stems close to each other with specific arrangement. The polymorphic nature of multiple stranded helical structure of nucleic acid relates a promising technique of achieving base sequence specific recognition and hence artificial gene regulation. The database cataloging the interaction motifs of nucleic acid moieties has been developed. Skew matrix, a kind of kink parameter, affords the structural description between the adjacent moieties. The program BioCon2 for estimating these skew matrix and cataloguing for multiple stranded helices has been developed. New version allows for the good properties, i.e., impregnable and flexible presentation of multiple helices. The tentative database including these parameters with the species and physical properties of the surrounding nucleic acid components and amino acids has been constructed.

Databases, Nucleic Acid↗
PubMed2006

Increased plasma concentrations of N-terminal pro-brain natriuretic peptide reflect the presence of mildly reduced left ventricular diastolic function in hypertension.

BACKGROUND: The potential use of assays of N-terminal pro-brain natriuretic peptide for detection of diastolic abnormalities associated with alterations in blood pressure has not been elucidated. This study was designed to determine whether increased plasma concentrations of N-terminal pro-brain natriuretic peptide sensitively reflect abnormal diastolic function associated with hypertension. METHODS: Concentrations of N-terminal pro-brain natriuretic peptide in plasma were assayed in 40 previously untreated hypertensive patients without overt congestive heart failure and in 20 age and sex-matched controls. Hypertensive patients were studied with the use of pulsed Doppler and color M-mode Doppler echocardiography for the evaluation of left ventricular diastolic function. RESULTS: Concentrations of N-terminal pro-brain natriuretic peptide were elevated in hypertensive patients [75.1+/-75.2 (SD) pg/ml compared with 37.9+/-38.5 in controls, P<0.05]. In hypertensive patients, concentrations of N-terminal pro-brain natriuretic peptide were negatively correlated with the ratio of color M-mode flow propagation velocity to transmitral E velocity consistent with the view that increased concentrations of N-terminal pro-brain natriuretic peptide are indicative of alterations in diastolic function. Hypertensive patients with N-terminal pro-brain natriuretic peptide values above the mean value in the control group exhibited significantly increased brachial intimal-medial thickness and reduced wall stress, consistent with the view that increased N-terminal pro-brain natriuretic peptide was associated with favorable peripheral arterial remodeling. CONCLUSIONS: Elevated concentrations of N-terminal pro-brain natriuretic peptide in plasma reflect the presence of left ventricular diastolic abnormalities and peripheral arterial remodeling in asymptomatic patients with hypertension.

Biomarkers↗
PubMed2006

Lower prevalence of circulating natural killer T cells in patients with angina: a potential novel marker for coronary artery disease.

OBJECTIVE: Atherosclerosis is an inflammatory disease. Natural killer T cells are a unique lymphocyte subset that can recognize lipid antigens presented by CD1d and secrete copious amounts of pro-atherogenic cytokines such as interferon-gamma. We have previously shown that natural killer T cells accelerate atherosclerosis in mice and macrophages incubated with oxidized low-density lipoproteins induce natural killer T cells to produce interferon-gamma. Thus, whether the prevalence of natural killer T cells in peripheral blood is altered in patients with angina pectoris and its correlation with coronary risk factors was determined. METHOD: Cell profiling was performed using flow cytometry in patients with stable angina, unstable angina (Braunwald IIIB), and healthy controls. Natural killer T cells in peripheral blood were identified by the expression of natural killer T specific invariant T cell receptor alpha-chain (Valpha24) and T cell receptor beta-chain (Vbeta11). RESULTS: Prevalence of natural killer T (Valpha24-Vbeta11 double positive) cells was significantly decreased in patients with unstable angina and stable angina compared with that in controls. No significant differences were observed in the prevalence between unstable and stable angina. Reduction of natural killer T cells was independently associated with the presence of angina. CONCLUSIONS: Lower prevalence of circulating natural killer T cells is related to the presence of coronary artery disease. As T cell receptor down-regulation or apoptosis after natural killer T cell activation and subsequent interferon-gamma release may contribute to atherogenesis, natural killer T cells can become a novel therapeutic target for the prevention and treatment of atherosclerotic vascular diseases.

Angina Pectoris↗
PubMed2006

Nicotine withdrawal suppresses nicotinic modulation of long-term potentiation induction in the hippocampal CA1 region.

We have previously reported that acute and chronic nicotine exposure lower the threshold for long-term potentiation (LTP) induction in the rat hippocampal CA1 region, and acute application of nicotine in the chronic-nicotine-treated hippocampus further reduces the threshold. However, it is unknown how withdrawal from chronic nicotine exposure affects the induction of LTP. Here, we show that, following nicotine withdrawal, the threshold for LTP induction fluctuates before returning to the basal level and acute nicotine is no longer effective in lowering the threshold at 4 days after withdrawal. Chronic nicotine-induced enhancement of N-methyl-d-aspartate receptor responses slowly diminishes and returns to the control level by 8 days of withdrawal. In 4-day-withdrawn hippocampi, there is functional up-regulation of postsynaptic alpha7 nicotinic acetylcholine receptors (nAChRs) on interneurons in the stratum radiatum, whereas the release of gamma-aminobutyric acid from their terminals is reduced. In both control and chronic nicotine-exposed hippocampi, acute nicotine depresses monosynaptic inhibitory postsynaptic currents recorded in pyramidal cells but has almost no effect at 4 days of withdrawal. The lack of effect is due, at least in part, to the loss of a presynaptic nicotine effect. These withdrawal-induced changes are accompanied by decreases in normal nicotine-induced enhancement of N-methyl-d-aspartate receptor responses, which may be responsible for the lack of acute nicotine-mediated facilitation of LTP induction in 4-day-withdrawn hippocampi. These withdrawal-induced changes may contribute to the cellular basis of unpleasant withdrawal symptoms and, thus, nicotine dependence.

Animals↗
PubMed2006

Phytoestrogens from Aspalathus linearis.

From the leaves of Aspalathus linearis, 24 known compounds and a new one, aspalalinin (25), were isolated. The structures of the compounds were determined mainly based on spectral evidence. The absolute configuration of aspalalinin was presented on the basis of X-ray analysis. Each isolate was assessed for its estrogenic activity by an estrogen ELISA assay. Compounds 12, 15, and 24 showed the estrogenic activity.

Aspalathus↗
PubMed2006

[Dilation of the brachial artery in response to sublingual nitroglycerin can predict the antihypertensive effects of valsartan: a study using novel high-frequency high-frame-rate ultrasound imaging].

OBJECTIVES: The efficacy of antihypertensive agents can vary in patients. Four to 8 weeks may be required before antihypertensive agents become fully effective. Predicting the efficacy can help agent selection and dose setting. This study determined whether nitroglycerin-induced vasodilation of brachial arteries can predict the antihypertensive action of angiotensin II receptor antagonist. METHODS: Untreated uncomplicated patients with essential hypertension, who gave informed consent, were studied (n = 20, mean age 55 years). Before antihypertensive treatment, nitroglycerin-induced vasodilation of the brachial arteries was measured using a novel method of 15 MHz high-frequency high-frame-rate ultrasound imaging (Hitachi EUB8000). Diameter of the brachial artery at the end-systolic phase was measured before and after 0.3 mg nitroglycerin sublingual spray and percentage vasodilation (%D-N) was calculated. The reduction of mean blood pressure after nitroglycerin (%BP-N) was calculated. Valsartan monotherapy (40-80 mg/day)was administered for 3-6 months (mean 132 days). Reduction of mean blood pressure after valsartan monotherapy (%BP-V) was calculated. RESULTS: Valsartan decreased systolic blood pressure from 138 +/- 13 to 130 +/- 17 mmHg, and diastolic blood pressure from 83 +/- 11 to 78 +/- 11 mmHg (p < 0.05). %D-N was correlated closely with %BP-V (r = - 0.70, p < 0.001). %BP-N had no correlation with %BP-V (r = 0.13, p = 0.58). CONCLUSIONS: Direct vasodilatory action of nitroglycerin on vascular smooth muscle cells may predict the chronic antihypertensive effect of angiotensin II receptor antagonist.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

Sequence-dependent conformational energy of DNA derived from molecular dynamics simulations: toward understanding the indirect readout mechanism in protein-DNA recognition.

Sequence dependence of DNA conformation plays a crucial role in its recognition by proteins and ligands. To clarify the relationship between sequence and conformation, it is necessary to quantify the conformational energy and specificity of DNA. Here, we make a systematic analysis of dodecamer DNA structures including all the 136 unique tetranucleotide sequences at the center by molecular dynamics simulations. Using a simplified conformational model with six parameters to describe the geometry of adjacent base pairs and harmonic potentials along these coordinates, we estimated the equilibrium conformational parameters and the harmonic potentials of mean force for the central base-pair steps from many trajectories of the simulations. This enabled us to estimate the conformational energy and the specificity for any given DNA sequence and structure. We tested our method by using sequence-structure threading to estimate the conformational energy and the Z-score as a measure of specificity for many B-DNA and A-DNA crystal structures. The average Z-scores were negative for both kinds of structures, indicating that the potential of mean force from the simulation is capable of predicting sequence specificity for the crystal structures and that it may be used to study the sequence specificity of both types of DNA. We also estimated the positional distribution of conformational energy and Z-score within DNA and showed that they are strongly position dependent. This analysis enabled us to identify particular conformations responsible for the specificity. The presented results will provide an insight into the mechanisms of DNA sequence recognition by proteins and ligands.

Base Sequence↗
PubMed2005

Involvement of IP3 receptors in LTP and LTD induction in guinea pig hippocampal CA1 neurons.

The role of inositol 1, 4, 5-trisphosphate receptors (IP3Rs) in long-term potentiation (LTP) and long-term depression (LTD) was studied in CA1 neurons in guinea pig hippocampal slices. In standard solution, short tetanic stimulation consisting of 15 pulses at 100 Hz induced LTP, while three short trains of low-frequency stimulation (LFS; 200 pulses at 1 Hz) at 18-min intervals or one long train of LFS (1000 pulses at 1 Hz) induced stable LTD in both the slope of the field EPSP (S-EPSP) and the amplitude of the population spike (A-PS). Bath application of 2-aminoethoxydiphenyl borate (2-APB), an IP3R antagonist, or of alpha-methyl-4-carboxyphenylglycine (MCPG), a wide-spectrum metabotropic glutamate receptor antagonist, during weak tetanic stimulation significantly increased the magnitude of the LTP in both the S-EPSP and A-PS. Three short trains of LFS or one long train of LFS delivered in the presence of 2-APB or MCPG did not induce LTD, but elicited LTP. Based on these results, we conclude that, in hippocampal CA1 neurons, IP3Rs play an important role in synaptic plasticity by attenuating LTP and facilitating LTD.

Animals↗
PubMed2005

Amino acid ester salt recognition by ferrocene-based ditopic receptor bearing oligoethylene glycol with pendant bipy subunits: CV, UV-vis and ESR studies.

The novel ferrocene-based ditopic receptor 1 was synthesized. This receptor bears two oligoethylene glycol arms with pendant 2,2'-bipyridine unit at the identical cyclopentadienyl rings, Cu(I) cation binds to 1 to form the 1 : 1 complex (1.Cu(I)) with the cavity consisting of polyether, and the resulting complex acts as a receptor for amino acid ester salts to give the ditopic complex (1.Cu(I).AAOMe-HCl). The 1H NMR spectrum of 1.Cu(I).LeuOMe-HCl exhibits strong broadening at the bipyridine region, and the ESR spectrum of the same sample gives the signals assigned as Cu(II) species. With these data, the binding of 1.Cu(I) towards AAOMe.HCl leads to the conformational change, and the Cu(I) complex is simultaneously oxidized to the Cu(II) complex.

Amino Acids↗