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Biomedical subjects

Tetsuya Ueda

Publications and source records attributed to Tetsuya Ueda.

At least 19 recordsLinked to original sources
PubMed2007

Prevalence and clinical manifestations of gastro-oesophageal reflux-associated chronic cough in the Japanese population.

Gastro-oesophageal reflux (GOR) is one of the most common causes of chronic cough in Western countries, responsible for 10 to 40% of cases. In Japan, however, GOR-associated chronic cough (GOR-CC) has been rarely reported and its clinical manifestation including frequency of concomitant reflux laryngitis is poorly known. We have analyzed prevalence and clinical characteristics of patients who were diagnosed as having GOR-CC among adult patients with chronic cough (>or= 8 weeks) who visited our asthma and cough clinic over a period of 19 months. Diagnosis of GOR-CC was based on the response of coughing to a proton-pump inhibitor (lansoprazole) and/or positive results of 24 h ambulatory esophageal pH monitoring. Laryngeal involvement was based on symptoms or objective diagnosis by specialists.GOR-associated chronic cough was diagnosed in 7.1% (8 of 112) of chronic cough patients. In addition to the demographic data which were consistent with the characteristics of patients with GOR-CC in the Western populations, including gender (6 females), age (mean +/- SE, 56.9 +/- 5.8 years), duration of cough (9.9 +/- 3.3 months), lack of gastrointestinal symptoms (3 of 8) and complication with other causes of cough (5 of 8), we found the standard range of body mass index (23.9 +/- 1.5 kg/m2) and high incidence of concomitant reflux laryngitis (5 of 8) in the present 8 patients. Among 4 patients who could stop treatment with temporal resolution of cough, cough recurred in 3 patients, 1 week to 8 months after the discontinuation. In conclusion, GOR-CC is a less frequent cause of chronic cough in Japan than in Western countries. Signs or symptoms of laryngitis may be important as clues to suspicion of GOR-CC.

Journal Article↗
PubMed2006

HMG chromosomal proteins in development and disease.

The high mobility group (HMG) proteins are a superfamily of abundant and ubiquitous nuclear proteins that bind to DNA and nucleosomes and induce structural changes in the chromatin fiber. They are important in chromatin dynamics and influence DNA processing in the context of chromatin. Results emerging from studies of human disease, genetically modified mice and cells with altered HMG expression indicate that the expression of the HMG proteins is developmentally regulated and that changes in HMG protein levels alter the cellular phenotype and can lead to developmental abnormalities and disease. Here, we focus on the biological function of HMG proteins and highlight their possible roles in cellular differentiation and in the etiology of various diseases.

Animals↗
PubMed2006

Role of small airways in asthma: investigation using high-resolution computed tomography.

BACKGROUND: Small airways may have an important role in asthma but are more difficult to assess pathologically than central airways. Computed tomographic indices of lung density are assumed to reflect air trapping and may be a useful noninvasive measure of small airways disease, but their pathophysiological relevance remains undetermined. OBJECTIVE: To evaluate lung density on high-resolution computed tomography and examine its correlations with clinical and physiologic variables in 29 patients with stable asthma. METHODS: Both lungs were scanned at full-inspiratory and full-expiratory phases to quantify percentage of lung field occupied by low attenuation area (LAA%; < -960 Hounsfield units) and mean lung density. Asthma severity, pulmonary function, methacholine airway sensitivity and reactivity, and sputum eosinophil counts were evaluated. RESULTS: The mean lung density increased and LAA% decreased in all patients at expiratory phase compared with inspiratory phase. The inspiratory density indices and expiratory mean lung density correlated only with FEV(1)/forced vital capacity (FVC). Expiratory LAA% correlated more strongly than other variables with FEV(1)/FVC and with indices of peripheral airflow obstruction. Expiratory/inspiratory ratios of LAA% and mean lung density correlated, the former more strongly, with disease severity, residual volume/total lung capacity, and airway sensitivity, as well as with indices of global (FEV(1) and FEV(1)/FVC) and peripheral airflow obstruction. CONCLUSION: Expiratory/inspiratory high-resolution computed tomography is useful for assessing small airways disease in asthma. Small airways involvement is associated with airflow obstruction, airway hypersensitivity, and more severe disease. CLINICAL IMPLICATIONS: Small airways are an important therapeutic target in asthma.

Adult↗
PubMed2006

Distinct domains in high mobility group N variants modulate specific chromatin modifications.

We have demonstrated that levels of specific modification in histone H3 are modulated by members of the nucleosome-binding high mobility group N (HMGN) protein family in a variant-specific manner. HMGN1 (but not HMGN2) inhibits the phosphorylation of both H3S10 and H3S28, whereas HMGN2 enhances H3K14 acetylation more robustly than HMGN1. Two HMGN domains are necessary for modulating chromatin modifications, a non-modification-specific domain necessary for chromatin binding and a modification-specific domain localized in the C terminus of the HMGNs. Thus, chromatin-binding structural proteins such as HMGNs affect the levels of specific chromatin modifications and therefore may play a role in epigenetic regulation.

Acetylation↗
PubMed2006

Determinants of histone H1 mobility and chromatin binding in living cells.

The dynamic interaction of chromatin-binding proteins with their nucleosome binding sites is an important element in regulating the structure and function of chromatin in living cells. Here we review the major factors regulating the intranuclear mobility and chromatin binding of the linker histone H1, the most abundant family of nucleosome-binding proteins. The information available reveals that multiple and diverse factors modulate the interaction of H1 with chromatin at both a local and global level. This multifaceted mode of modulating the interaction of H1 with nucleosomes is part of the mechanism that regulates the dynamics of the chromatin fiber in living cells.

Animals↗
PubMed2006

Prognosis of cough variant asthma: a retrospective analysis.

Patients with cough variant asthma, a common cause of chronic cough, may develop wheezing. We examined the determinants of this phenomenon and achievement of remission in 42 patients. During 4 years after diagnosis, wheezing developed in 13 of the patients. Early inhaled corticosteroid treatment was inhibitory against the development of wheezing by univariate analysis and by multivariate analysis with an odds ratio of 0.12 (95% confidence interval, 0.02 to 0.87, p = 0.037). Remission was achieved in 7 patients, who were younger than those without remission by univariate analysis (p = 0.048). Early treatment with inhaled corticosteroid may prevent the progression of cough variant asthma to classic asthma.

Adult↗
PubMed2005

Efficacy of triple therapy plus cetraxate for the Helicobacter pylori eradication in partial gastrectomy patients.

In the present study, we aimed to establish an additional standardized protocol with a higher H. pylori eradication rate in the remnant stomach. Fifty-five H. pylori-positive patients were randomly allocated to one of three regimens: LAC--lansoprazole, amoxicillin, and clarithromycin b.i.d. for 7 days (n = 17); LAC+CET--LAC b.i.d. plus cetraxate q.i.d. for 7 days (n = 20); and LEFT--LAC for 7 days in a horizontal body position on the left side for 30 min (n = 18). Patient compliance and side effects were checked via interviews. H. pylori eradication was successful in 75, 72, and 41% in LAC+CET, LEFT, and LAC, respectively. The eradication rate was significantly higher in LAC+CET than in LAC (P = 0.024) but not in LEFT (P = 0.058). Adverse events that occurred in each group were almost all mild ones. Cetraxate plus LAC for 1 week is a safe and effective regime for the eradication of H. pylori in patients after partial gastrectomy.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

Prediction of functional improvement of ischemic myocardium with (123I-BMIPP SPECT and 99mTc-tetrofosmin SPECT imaging: a study of patients with large acute myocardial infarction and receiving revascularization therapy.

BACKGROUND: (18)F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) is assumed to be the most useful method of evaluating the viability of the myocardium, but its use is limited by the need for a cyclotron. In the present study, the ability of a combination of (99m)Tc-tetrofosmin (TF) and (123)I-beta-methyliodophenyl pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT), a combination of (18)F-FDG PET and (123)I-BMIPP SPECT, and a combination of (18)F-FDG PET and (99m)Tc-TF SPECT were compared to predict functional improvement of ischemic myocardium after a large acute myocardial infarction (AMI). METHODS AND RESULTS: Ten patients with large AMI were studied by (99m)Tc-TF SPECT, (123)I-BMIPP SPECT and (18)F-FDG PET within 3 weeks. Six months later, (99m)Tc-TF imaging was performed. All patients underwent successful revascularization, and had no restenosis. Regional tracer uptake was scored using a 4-point scale in 20 segments of the SPECT and PET images. When the defect score of (123)I-BMIPP SPECT exceeded the defect score of (99m)Tc-TF SPECT or (18)F-FDG PET by 1 point or more, and when the defect score of (99m)Tc-TF SPECT exceeded the defect score of (18)F-FDG PET by 1 point or more, the segment was considered to show mismatching. When the defect score was the same in 2 tracers, the segment was considered to show matching. (99m)Tc-TF imaging at 3 weeks and 6 months used quantitative gated SPECT (QGS) to score wall motion using a 6-point scale (-1= dyskinesis, 0= akinesis, 1= severe hypokinesis, 2= moderate hypokinesis, 3= mild hypokinesis, and 4= normokinesis). The sensitivity of the combination of (123)I-BMIPP and (99m)Tc-TF imaging in predicting functional improvement was 61%, that of (18)F-FDG PET and (123)I-BMIPP SPECT was 94%, and that of (18)F-FDG PET and (99m)Tc-TF SPECT was 76%. The specificity of the combination of (123)I-BMIPP and (99m)Tc-TF imaging in predicting functional improvement was 83%, that of (18)F-FDG PET and (123)I-BMIPP SPECT was 40%, and that of (18)F-FDG PET and (99m)Tc-TF SPECT was 49%. The accuracy of the combination of (123)I-BMIPP and (99m)Tc-TF imaging in predicting functional improvement was 70%, that of (18)F-FDG PET and (123)I-BMIPP SPECT was 71%, and that of (18)F-FDG PET and (99m)Tc-TF SPECT was 63%. CONCLUSION: The combination of (123)I-BMIPP and (99m)Tc-TF imaging is a practical modality for predicting the functional improvement of ischemic myocardium after a large AMI.

Aged↗
PubMed2004

Acidic C-tail of HMGB1 is required for its target binding to nucleosome linker DNA and transcription stimulation.

HMGB1, a nonhistone chromosomal protein in higher eukaryotic nuclei, consists of two DNA binding motifs called HMG boxes and an acidic C-tail comprising a continuous array of 30 acidic amino acid residues. In the preceding study, we showed that the acidic C-tail of HMGB1 is required for transcription stimulation accompanied by chromatin decondensation in cultured cells. However, details of the involvement of the acidic C-tail in transcription stimulation were not clear. To clarify the mechanism of transcription stimulation by the acidic C-tail, we assessed the effect of the acidic C-tail on the transcription stimulation and nucleosome binding. Transcription stimulation assays using acidic C-tail deletion mutants showed that the five amino acid residues at the C-terminal end of HMGB1, a DDDDE sequence, are essential for the stimulation. The DDDDE sequence was also required for the preferential binding of HMGB1 to nucleosome linker DNA, which is a cognate HMGB1 binding site in chromatin. Cross-linking and far-Western experiments demonstrated that the DDDDE sequence interacts with the core histone H3 N-tail. These results strongly suggest that the interaction between the DDDDE sequence of HMGB1 and the H3 N-tail is a key factor for the transcription stimulation by HMGB1 as well as the preferential binding of HMGB1 to chromatin.

Animals↗
PubMed2004

Bezafibrate stimulates canalicular localization of NBD-labeled PC in HepG2 cells by PPARalpha-mediated redistribution of ABCB4.

Fibrates, including bezafibrate (BF), upregulate the expression of ATP binding cassette protein B4 (ABCB4) through gene transcription in mice. To determine the effects of BF on the expression levels of ABCB4 and on the stimulation of biliary phosphatidylcholine (PC) transport in human HepG2 hepatoblastoma cells, mRNA and protein levels as well as subcellular localization were investigated in the cells treated with BF. The canalicular accumulation of a fluorescent PC was assessed by confocal laser scanning microscopy. Treatment with 300 micromol/l BF for 24 h increased levels of ABCB4 mRNA but not protein by up to 151%. BF caused redistribution of ABCB4 into pseudocanaliculi formed between cells. In association with this redistribution, BF accelerated the accumulation of fluorescent PC in bile canaliculi (up to 163% of that in nontreated cells). Suppression of peroxisome proliferator-activated receptor alpha (PPARalpha) expression by either a small interfering RNA duplex or morpholino antisense oligonucleotide attenuated the BF-induced redistribution of ABCB4. These findings suggest that BF may enhance the capacity of human hepatocytes to direct PC into bile canaliculi via PPARalpha-mediated redistribution of ABCB4 to the canalicular membrane. This provides a rationale for the use of BF to improve cholestasis and/or cholangitis that is attributable to hypofunction of ABCB4.

4-Chloro-7-nitrobenzofurazan↗
PubMed2004

Effect of short-term treatment with inhaled corticosteroid on airway wall thickening in asthma.

PURPOSE: Computed tomography studies demonstrate thickening of the asthmatic airway wall and its relation to disease severity. We evaluated the effect of inhaled corticosteroid on this phenomenon. METHODS: Cross-sectional images of the right upper lobe apical segmental bronchus were obtained by helical computed tomography in 45 corticosteroid-naïve patients with persistent asthma and 28 healthy controls. Airway wall thickness was measured as airway wall area normalized to body surface area. Computed tomography, pulmonary function, and serum levels of eosinophil cationic protein were examined before and after treatment with beclomethasone (800 microg/d for 12 weeks). RESULTS: Before treatment, airway wall thickness was greater in asthma patients than in controls (P <0.0001). After treatment, it decreased by 11% (P <0.001) but remained high (P <0.0001 vs. control); the serum level of eosinophil cationic protein decreased, and airflow obstruction was reduced, but not to the level in controls. The decrease in wall thickness was associated with a decrease in the serum level of eosinophil cationic protein (r = 0.39, P = 0.009) and an increase in the forced expiratory volume in 1 second (r = 0.45, P = 0.003) and was inversely related to disease duration at entry (r = -0.38, P = 0.009). Post-treatment wall thickness was related to disease duration (r = 0.45, P = 0.003) and remaining airflow obstruction. CONCLUSION: Wall thickening of asthmatic central airways responds partially to inhaled corticosteroid therapy and may reflect an overall reduction in airway inflammation. "Unresponsive components," possibly involving structural changes, may increase in the absence of inhaled corticosteroid treatment, potentially leading to chronic airflow obstruction.

Administration, Inhalation↗
PubMed2004

Expression of UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase isozyme 3 in the subserosal layer correlates with postsurgical survival of pathological tumor stage 2 carcinoma of the gallbladder.

PURPOSE AND EXPERIMENTAL DESIGN: Little is known about the molecular events leading to the development and progression of pathological tumor stage 2 (pT(2)) gallbladder carcinoma. An alteration in the site of O-glycosylation may be associated with malignant behavior of carcinoma cells by modulation of the biological properties of the target mucin. The UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase isozyme 3 (GalNAc-T3) has the epithelial gland-specific expression and catalyzes mucin-type O-glycosylation. In this study, immunohistochemistry was performed to determine the expression level of GalNAc-T3 in 34 cases of pT(2) gallbladder carcinoma to determine the correlation of the GalNAc-T3 expression level with mode of recurrence and postsurgical survival. RESULTS: The expression levels of GalNAc-T3 protein and mRNA were increased in gallbladder carcinomas compared with the levels in adjacent noncancerous tissues and in intact gallbladders. Immunostaining of GalNAc-T3 was recognized in the cancerous epithelia, and the subcellular localization was classified into granular and diffuse types. In the 34 cases of pT(2) carcinoma, the localization of GalNAc-T3 was granular type in 50% and diffuse type in 50% of the cases at the deepest invading sites in the subserosal layer. Postsurgical recurrence was significantly more frequent in cases showing diffuse-type localization of GalNAc-T3 at the deepest invading sites (65%) than in those showing granular-type localization (23%; P < 0.05). Postsurgical survival was significantly poorer in cases showing diffuse-type localization than in those showing granular-type localization (P = 0.033) CONCLUSIONS: In pT(2) gallbladder carcinoma, the presence of diffuse-type localization of GalNAc-T3 in the subserosal layer is correlated with aggressiveness of the disease. This phenotype may serve as a unique biological feature associated with the malignant behavior.

Biomarkers↗
PubMed2004

Highly specific marker genes for detecting minimal gastric cancer cells in cytology negative peritoneal washings.

Peritoneal wash cytology plays a pivotal role in the decision for gastric cancer treatment because advanced gastric cancer often turns out incurable with peritoneal metastasis. Molecular detection of minimal cancer cells from peritoneal washings may overcome the sensitivity boundary of conventional cytology and contribute to the prediction of the disease outcome. To select marker candidates out of ten thousands of genes, we performed microarray analyses in 12 gastric cell lines and 8 peritoneal washings of early stage cases. With 40 candidates selected by the above expression profiling, RT-PCR in 16 representative peritoneal wash samples was performed to identify genes specific to cytology positive samples. The finally selected five genes, CK20, FABP1, MUC2, TFF1, and TFF2, were then evaluated for their utility as a marker for minimal residual disease in 99 peritoneal wash samples. Nested RT-PCR using the five genes showed positive results highly specific to incurable cases (91-100%). With a high specificity, the combination of these five genes succeeded in identifying 6 out of 20 (30%) additional patients with all types of early recurrence that could not be predicted by the conventional method. The six newly identified recurrences included four non-peritoneal ones, showing that RT-PCR using the five genes without a real-time quantitative PCR technique contributes to the detection of minimal residual disease.

Ascitic Fluid↗
PubMed2004

Roles of systemic nitric oxide metabolites for human coronary circulation.

Several previous studies have suggested decreased bioactivity of nitric oxide (NO) in coronary artery diseases using NO synthase inhibitors. Nitrite is delivered as bioactive NO in the forearm circulation. However, the role(s) of NO metabolites in the systemic and coronary circulation are still unknown. The aim of this study was to investigate the role(s) of systemic NO metabolites for human coronary circulation in patients with and without coronary spastic angina (CSA). Twenty-nine patients with chest symptoms were enrolled to perform the acetylcholine (Ach) provocative test. Blood was sampled from the aorta at baseline, and from the great cardiac vein at baseline and after Ach to measure plasma levels of nitrate and nitrite (NOx). The epicardial left anterior descending artery was examined by quantitative angiography. The patients were divided into the two groups according to the Ach provocative test. In the non-CSA group, the NOx uptake across the coronary circulation correlated with the endothelium-dependent vasoresponse to Ach (r = -0.61, p < 0.05) and NOx levels of the aorta also correlated (r = -0.72, p < 0.005), which suggested the compensatory increase of systemic NOx levels for impaired endothelial function. In the CSA group, the NOx uptake across the coronary circulation did not correlate with the vasoresponse to Ach (r = 0.29, p = 0.28). However, NOx levels of the aorta correlated with vasosensitivity to Ach (r = 0.61, p < 0.005). The higher systemic NOx levels correlated well with the vasodilator responsiveness to Ach. These results suggest that systemic NOx is delivered into the coronary circulation as bioactive NO to preserve endothelial function in the non-CSA patients, and to attenuate Ach-induced vasoconstriction in the CSA patients. There is a possibility that systemic NOx plays a complementary role on impaired coronary vasoregulation.

Acetylcholine↗
PubMed2004

ATP-dependent chromatin structural modulation by multiprotein complex including HMGB1.

High mobility group box protein 1, HMGB1, is a major nonhistone chromatin component in higher eukaryotic cells. HMGB1 is thought to be involved in the processes of global nuclear events such as transcription, recombination and repair, but the mechanism of these processes is unclear. Here, we show a concrete example of chromatin structural modulation by HMGB1 in HeLa S3 cells. A co-immunopurification experiment with Flag-tagged HMGB1 revealed that a portion of HMGB1 in HeLa S3 cells is included in a large-molecular-weight multiprotein complex. The multiprotein complex including HMGB1 showed ATP hydrolysis and ATP-dependent chromatin structural modulation activities that increased the susceptibility of chromatin to MNase digestion, while HMGB1 alone had no such activity. Thus, HMGB1 in the multiprotein complex is critical for expressing the chromatin structural modulation activity. These results suggest that HMGB1 is involved in chromatin structural modulation in global nuclear events through its interaction with a multiprotein complex in mammalian cells.

Adenosine Triphosphate↗
PubMed2004

Bronchial dilatation in asthma: relation to clinical and sputum indices.

BACKGROUND: Investigations using high-resolution CT (HRCT) show that bronchial dilatation (BD) is found in many patients with asthma. However, the pathogenesis and pathophysiologic relevance of BD in asthma are poorly understood. A balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may control the remodeling of extracellular matrix, and excess MMPs have been associated with destruction or dilatation of airways in patients with bronchiectasis. OBJECTIVES: To study the prevalence of BD as assessed by HRCT according to standard subjective criteria in 37 patients with stable asthma and 10 healthy control subjects, and to examine the relation of BD in asthmatic patients to clinical characteristics and sputum indices, including MMP-9 and TIMP-1 levels. DESIGN: A prospective cohort study. RESULTS: At least one dilated bronchus was present in 23 asthmatic subjects (62%) and 2 control subjects (20%) [p = 0.030]. The ratio of dilated bronchi to all eligible bronchi in each subject (individual BD%) was higher in the asthmatic patients than in the control subjects (11.4 +/- 16.1% vs 1.3 +/- 3.0%, p = 0.011) [mean +/- SD]. Asthmatic patients with (n = 23) and those without BD (n = 14) were similar with regard to age, duration and severity of asthma, atopy, pulmonary function, sputum eosinophil or neutrophil count, and sputum levels of MMP-9 or TIMP-1 and their molar ratio. Individual BD% of asthmatic patients was also unrelated to these clinical and sputum variables. When analysis was confined to the 23 patients with BD, however, individual BD% correlated with the severity score of asthma (r = 0.49, p = 0.023). The results of follow-up HRCT obtained from 19 patients suggested that BD was a fixed rather than transient phenomenon. CONCLUSION: BD is more prevalent in asthmatic patients than in normal subjects and might be associated with the severity of asthma. Cellular inflammation or possible imbalance between MMP-9 and TIMP-1 was not demonstrated in this study to be related to BD in asthma.

Asthma↗
PubMed2004

Clinical assessment of airway remodeling in asthma: utility of computed tomography.

Airway remodeling is an established feature of asthma. Histologic examination is essential in the assessment of remodeling that is a pathologic concept. Examinations of autopsied or resected lung have enabled detailed morphologic and morphometric studies and have provided fundamental knowledge of airway remodeling in asthma. However, such materials are only accidentally available, and clinical information may often be insufficient in autopsied cases. Bronchoscopic mucosal biopsy has been widely used since the 1980s, and has contributed substantially to basic investigations of inflammation and remodeling. However such specimens are limited in size and depth, limited to central airways, and the procedure might be too invasive to be repeated. Remodeling can also be assessed indirectly. Pulmonary function tests to evaluate chronic airflow obstruction are available in clinical settings and suitable for screening or mass studies, but they may be affected by concomitant diseases or short-term asthma control. Computed tomography (CT) has recently been utilized to assess remodeling. It cannot discern pathologic details but provides a broader range of airway/lung morphology and may be less invasive compared to biopsy. In addition to classic subjective evaluations,quantitative assessment has been reported for central airway dimensions, such as airway wall area, luminal area and wall thickness, and for peripheral airway abnormality or air trapping as measured by decreased lung attenuation or increased mosaic perfusion. This article summarizes the merits and limitations of various methods to assess airway remodeling, and describes the details of methodologies, interpretations, pathophysiologic relevance, and future directions of asthmatic airway remodeling assessed by CT.

Adult↗