Biomedical subjects

Yoshihiro Nishimura

Publications and source records attributed to Yoshihiro Nishimura.

At least 19 recordsLinked to original sources

PubMed2006

His239Arg SNP of HRAD9 is associated with lung adenocarcinoma.

BACKGROUND: It was previously reported that a functional human (h) Rad9 protein accumulated in the nuclei of non-small cell lung carcinoma (NSCLC) cells. Those experiments, however, did not examine whether the hRad9 gene was mutated in those cells. The sequence of the HRAD9 gene in NSCLC cells was investigated. METHODS: The sequence of the HRAD9 was examined in tumor and peripheral normal lung tissues obtained from 50 lung adenocarcinoma patients during surgery. The expression of its mRNA using reverse transcription polymerase chain reaction (RT-PCR) was also examined. RESULTS: No sequence alterations were detected in the HRAD9 gene, which was found to be normally transcribed in surgically resected lung carcinoma cells. However, in eight (16.0%) cases a single nucleotide polymorphism (SNP) was observed at the second position of codon 239 (His/Arg heterozygous variant) of the gene. This frequency was significantly higher than that found in the normal population. CONCLUSIONS: Whereas the capacity to produce a functional hRad9 protein was intact in lung adenocarcinoma cells, a nonsynonymous SNP of HRAD9 was detected that might be associated with the development of lung adenocarcinoma.

Adenocarcinoma↗

PubMed2006

[Usefulness of attenuation correction with transmission source in myocardial SPECT].

Attenuation correction in SPECT has been used for uniformly absorptive objects like the head. On the other hand, it has seldom been applied to nonuniform absorptive objects like the heart and surrounding lungs because of the difficulty and inaccuracy of data processing. However, since attenuation correction using a transmission source recently became practical, we were able to apply this method to a nonuniform absorptive object. Therefore, we evaluated the usefulness of this attenuation correction system with a transmission source in myocardial SPECT. The dose linearity, defect/normal ratio using a myocardial phantom, and myocardial count distribution in clinical cases was examined with and without the attenuation correction system. We found that all data processed with attenuation correction were better than those without attenuation correction. For example, in myocardial count distribution, while there was a difference between men and women without attenuation correction, which was considered to be caused by differences in body shape, after processing with attenuation correction, myocardial count distribution was almost the same in all cases. In conclusion, these results suggested that attenuation correction with a transmission source was useful in myocardial SPECT.

Aged↗

PubMed2006

Ventilator-induced lung injury is reduced in transgenic mice that overexpress endothelial nitric oxide synthase.

Although mechanical ventilation (MV) is an important supportive strategy for patients with acute respiratory distress syndrome, MV itself can cause a type of acute lung damage termed ventilator-induced lung injury (VILI). Because nitric oxide (NO) has been reported to play roles in the pathogenesis of acute lung injury, the present study explores the effects on VILI of NO derived from chronically overexpressed endothelial nitric oxide synthase (eNOS). Anesthetized eNOS-transgenic (Tg) and wild-type (WT) C57BL/6 mice were ventilated at high or low tidal volume (Vt; 20 or 7 ml/kg, respectively) for 4 h. After MV, lung damage, including neutrophil infiltration, water leakage, and cytokine concentration in bronchoalveolar lavage fluid (BALF) and plasma, was evaluated. Some mice were given N(omega)-nitro-L-arginine methyl ester (L-NAME), a potent NOS inhibitor, via drinking water (1 mg/ml) for 1 wk before MV. Histological analysis revealed that high Vt ventilation caused severe VILI, whereas low Vt ventilation caused minimal VILI. Under high Vt conditions, neutrophil infiltration and lung water content were significantly attenuated in eNOS-Tg mice compared with WT animals. The concentrations of macrophage inflammatory protein-2 in BALF and plasma, as well as plasma tumor necrosis factor-alpha and monocyte chemoattractant protein-1, also were decreased in eNOS-Tg mice. L-NAME abrogated the beneficial effect of eNOS overexpression. In conclusion, chronic eNOS overexpression may protect the lung from VILI by inhibiting the production of inflammatory chemokines and cytokines that are associated with neutrophil infiltration into the air space.

Animals↗

PubMed2006

Usefulness of the oximetry test for the diagnosis of sleep apnea syndrome in Japan.

We evaluated the usefulness of oximetry tests that are frequently used as screening tools for sleep apnea syndrome (SAS) by determining the level of agreement between oximetry test results and polysomnography test (PSG) results. We retrospectively examined 135 patients suspected of having SAS. Although the oximetry desaturation index (DSI) seemed better than the oximetry apnea index in the agreement with the polysomnography respiratory disturbance index (RDI), the criteria of DSI greater than or equal to 15 was not sensitive enough to screen for moderate SAS (PSG-RDI >or= 20). Multivariate analyses revealing that body mass index (BMI) as well as DSI correlated well with PSG-RDI, we established a new criterion by adding the BMI score (DSI >or= 15 or BMI >or= 25), which remarkably improved the sensitivity. This criterion may be useful not only in clinical practice but also in medical checkups for asymptomatic patients, and also suggests that obese patients with sleep disturbance should undergo PSGs, irrespective of the DSI score.

Adult↗

PubMed2006

Lung carcinosarcoma with liposarcoma element: autopsy case.

Pulmonary carcinosarcoma, consisting of both carcinoma and sarcoma with a heterologous element, is a rare subtype, comprising approximately 0.3% of primary lung neoplasia. A 57-year-old man was admitted because of severe dyspnea. A tumor wholly occupying the right thorax was biopsied and diagnosed as pleomorphic sarcoma. The tumor did not respond to chemotherapy, and the patient died of respiratory failure and sepsis. At autopsy, pleomorphic sarcoma was histologically dominant and contained a liposarcoma element confirmed by histocytological and electron microscopic analysis. Adenocarcinoma component with papillary and tubular patterns was confined to the medial lesion of the right lower lobe (3x8 cm), which was found in the chest X-ray 3 years before admission, and had continuously merged with the sarcomatous lesion through the histological transition of both components. Aggressive and rapid growth of the sarcoma derived from the earlier adenocarcinoma became prevalent and contributed to the severe clinical outcome. This is the first documented case of primary lung carcinosarcoma with a liposarcoma element.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Overexpression of nitric oxide synthase by the endothelium attenuates bleomycin-induced lung fibrosis and impairs MMP-9/TIMP-1 balance.

BACKGROUND: Nitric oxide (NO) produced by endothelial NO synthase (eNOS) is thought to effect an anti-inflammatory response, but its mechanism is still unknown. METHODS: eNOS transgenic (eNOS-TG) mice and their littermate controls (C57/BL6) were used to clarify the role of NO derived from eNOS. Bleomycin hydrochloride (1 U/body/day) or PBS was injected intraperitoneally. RESULTS: Subpleural fibrotic changes and hydroxyproline content in the eNOS-TG mice were significantly reduced compared with those of the wild-type (WT) mice by day 56. Administration of N(omega)-nitro-L-arginine methyl ester, a potent inhibitor of NO synthase, worsened the fibrotic response in bleomycin-treated eNOS-TG mice. Gelatinolytic activity in lung homogenates, corresponding to metalloproteinase-9 (MMP-9), was significantly increased in bleomycin-injured WT mice on day 14. In contrast, the level of tissue inhibitor of metalloproteinases-1 (TIMP-1), an endogenous MMP-9 inhibitor, was increased in the bleomycin-treated eNOS-TG mice compared with WT. Immunohistochemical analysis demonstrated that MMP-9 and TIMP-1 were strongly expressed in inflammatory cells, including subpleural fibrotic lesions. CONCLUSION: These data suggested that eNOS overexpression attenuates bleomycin-induced lung injury by ameliorating the MMP-9/TIMP-1 balance.

Animals↗

PubMed2006

Effect of continuous positive airway pressure on soluble CD40 ligand in patients with obstructive sleep apnea syndrome.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for atherosclerosis. CD40-CD40 ligand interaction promotes several proinflammatory mediators and plays a pivotal role in the various stages of atherosclerotic diseases. The present study examines whether CD40 ligation contributes to outcomes in patients with OSAS. METHODS: The study population comprised OSAS patients with an apnea hypopnea index (AHI) > or = 30 (n = 35) and control subjects (AHI < 5; n = 16). We measured serum levels of soluble CD40 ligand (sCD40L), tumor necrosis factor (TNF)-alpha, and hypersensitive C-reactive protein (hsCRP) before and after nasal continuous positive airway pressure (nCPAP) therapy for 3 months. RESULTS: Baseline levels of sCD40L were significantly higher in patients with OSAS (6.93 +/- 4.64 ng/mL) [mean +/- SD] than in control subjects (3.43 +/- 2.11 ng/mL, p < 0.01). Baseline levels of sCD40L positively correlated with TNF-alpha but not with hsCRP. The elevation of sCD40L was improved for 1 night after nCPAP therapy (3.83 +/- 2.78 ng/mL, p < 0.001). Even though patients with severe OSAS did not receive any other medication to control atherosclerotic risk factors for 3 months, nCPAP was continued to reduce the levels of sCD40L. CONCLUSION: The present study suggested that sCD40L is a key factor that links OSAS and atherosclerotic progression.

Adult↗

PubMed2006

Cough sensitivity in pure cough variant asthma elicited using continuous capsaicin inhalation.

BACKGROUND: Cough variant asthma has recently been described, mainly as airway inflammation in relation to bronchial asthma, but the relationship between the two types of asthma remains unclear. Further studies of cough receptor sensitivity are necessary to fully characterize cough variant asthma. METHODS: We assessed the relevance of testing cough sensitivity using an Astograph with continuous capsaicin inhalation, and compared the results with those obtained using intermittent inhalation. We showed the clinical applicability of testing cough sensitivity (0.156-80 microM capsaicin; five or more coughs, 1 minute of continuous inhalation at each concentration) using this method. We compared cough sensitivity among patients with pure cough variant asthma who did not develop bronchial asthma after an observation period of at least 1 year, patients with bronchial asthma and healthy individuals. RESULTS: The continuous cough sensitivity test using the Astograph was reproducible and reliable. Cough sensitivity in patients with pure cough variant asthma was significantly higher than that in healthy individuals. CONCLUSIONS: The cough sensitivity of patients with cough variant asthma is not necessarily identical to that of healthy individuals.

Administration, Inhalation↗

PubMed2005

The effect of overexpression of endothelial nitric oxide synthase on eosinophilic lung inflammation in a murine model.

The effects of nitric oxide (NO) on allergic inflammation are controversial. In particular, the role of endothelial nitric oxide synthase (eNOS) in asthma remains uncertain. In the present study, we examined the effects of overexpression of eNOS on allergic inflammation using eNOS transgenic (eNOS-Tg) mice, in which eNOS protein is overexpressed in the vascular endothelium and airway epithelium. We found that eNOS-Tg mice showed a reduction of the asthmatic response to allergen challenge. Eosinophilic accumulation in the airspaces, eosinophilic activity, and bronchial responsiveness to acetylcholine were significantly attenuated in eNOS-Tg mice, as compared with wild-type mice following ovalbumin sensitization/challenge, even though the levels of circulating eosinophils were comparable in the wild-type and eNOS-Tg mice. The concentrations of eotaxin in the bronchoalveolar lavage fluid were significantly less in eNOS-Tg mice than in the wild-type mice. In addition, immunohistochemical analysis showed that the expressions of both intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 on the pulmonary endothelium of eNOS-Tg mice was decreased compared with the controls. These results suggest that chronic eNOS overexpression contributes to the suppression of allergic inflammation by reducing the production of eotaxin in the airspaces and/or the expression of adhesion molecules in the vascular endothelium.

Acetylcholine↗

PubMed2005

EGFR mRNA is upregulated, but somatic mutations of the gene are hardly found in renal cell carcinoma in Japanese patients.

PURPOSE: Heterozygous somatic mutations of epidermal growth factor receptor (EGFR) in exons 18, 19, and 21 were recently reported to be associated with response to gefitinib in patients having nonsmall cell lung cancer. Such mutations are more frequently found among Japanese than Europeans. In this work, the frequency of mutations was investigated in renal cell carcinoma (RCC) samples obtained from Japanese subjects to examine the potential of gefitinib as a therapeutic agent for RCC. METHODS: Nineteen patients with RCC, who gave written informed consent, were enrolled in this study. mRNA expression levels of EGFR were measured in RCC and its adjacent noncancerous renal tissue via the real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. Somatic mutations were determined using genomic DNA extracted from RCC by direct sequencing method. RESULTS: mRNA expression was confirmed to be about 19 times higher in RCC than in adjacent noncancerous renal tissues, but no such mutations were detected in both. CONCLUSION: Results from this study do not support the validity of further clinical trials on gefitinib for RCC with genotyping even in Japanese patients, although EGFR plays a key role in tumor progression.

Carcinoma, Renal Cell↗

PubMed2005

Characteristics of patients with chronic cough who developed classic asthma during the course of cough variant asthma: a longitudinal study.

BACKGROUND: Some patients develop asthmatic symptoms such as wheezing and dyspnea during the course of cough variant asthma (CVA), which are considered precursors of classical asthma. OBJECTIVES: To identify the characteristics of such patients, we investigated the nature of CVA patients with or without developing bronchial asthma in the longitudinal study. METHODS: In 28 CVA patients whom we could observe over 5 years, duration of coughing, physical examination findings, pulmonary function and bronchial hyperresponsiveness to inhaled methacholine were retrospectively assessed. RESULTS: Of these patients with CVA, 10 developed the asthmatic symptoms of wheezing and dyspnea (precursors of classical asthma) over 5 years. All these 10 patients showed marked bronchial hyperresponsiveness; however, there were no significant differences in the bronchial responsiveness to methacholine between patients with precursors of classical asthma and pure CVA patients who did not wheeze. The duration of coughing had a significant relationship with precursors of classical asthma. Seven patients with precursors of classical asthma developed wheezing in the first year and 1 patient each in the second, third and fourth year. CONCLUSIONS: These findings of a 5-year observation suggest that longer duration of coughing may be an important factor that develops precursors of classical asthma in patients with CVA.

Adult↗

PubMed2005

Oxygen-enhanced MR imaging: correlation with postsurgical lung function in patients with lung cancer.

PURPOSE: To prospectively determine if lung function as assessed with oxygen-enhanced magnetic resonance (MR) imaging correlates with postsurgical lung function in patients with lung cancer, as compared with quantitative and qualitative findings of computed tomography (CT) and scintigraphy. MATERIALS AND METHODS: Study received institutional review board approval, and informed patient consent was obtained. Thirty consecutive patients (16 men and 14 women, aged 44-81 years; mean age, 65 years) considered candidates for lung resection underwent oxygen-enhanced MR imaging, CT, perfusion scintigraphy, and measurement of forced expiratory volume in 1 second (FEV1). A respiratory-synchronized inversion-recovery half-Fourier single-shot turbo spin-echo MR sequence was used for data acquisition. Correlation of postsurgical lung function (postsurgical FEV1) as determined with oxygen-enhanced MR imaging (FEV1MR), quantitative assessment with CT (FEV1Quant), qualitative assessment with CT (FEV1Qual), and perfusion scintigraphy (FEV1PS) was conducted with actual postsurgical FEV1, and the limits of agreement of each were determined with Bland-Altman analysis. RESULTS: Correlation between postsurgical FEV1MR and actual postsurgical FEV1 values was excellent (r2= 0.81, P < .001); it was better than that of FEV1Qual (r2= 0.76) and FEV1PS (r2= 0.77) and similar to that of FEV1Quant (r2= 0.81) values. The limits of agreement of FEV1MR were between -9.9% and 10.9%. CONCLUSION: Oxygen-enhanced MR imaging can be used to predict posturgical lung function in patients with lung cancer, similar to quantitative CT.

Adult↗

PubMed2005

Thin-section multiplanar reformats from multidetector-row CT data: utility for assessment of regional tumor extent in non-small cell lung cancer.

PURPOSE: To determine the clinical utility of thin-section multiplanar reformats (MPRs) from multidetector-row CT (MDCT) data sets for assessing the extent of regional tumors in non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: Sixty consecutive NSCLC patients, who were considered candidates for surgical treatment, underwent contrast-enhanced MDCT examinations, surgical resection and pathological examinations. All MDCT examinations were performed with a 4-detector row computed tomography (CT). From each raw CT data set, 5mm section thickness CT images (routine CT), 1.25 mm section thickness CT images (thin-section CT) and 1.25 mm section thickness sagittal (thin-section sagittal MPR) and coronal images (thin-section coronal MPR) were reconstructed. A 4-point visual score was used to assess mediastinal, interlobar and chest wall invasions on each image set. For assessment of utility in routine clinical practice, mean reading times for each image set were compared by means of Fisher's protected least significant difference (PLSD) test. A receiver operator characteristic (ROC) analysis was performed to determine the diagnostic capability of each of the image data sets. Finally, sensitivity, specificity and accuracy of the reconstructed images were compared by McNemar test. RESULTS: Mean reading times for thin-section sagittal and coronal MPRs were significantly shorter than those for routine CT and thin-section CT (p<0.05). Areas under the curve (Azs) showing interlobar invasion on thin-section sagittal and coronal MPRs were significantly larger than that on routine CT (p=0.03), and the Az on thin-section sagittal MPR was also significantly larger than that on routine CT (p=0.02). Accuracy of chest wall invasion by thin-section sagittal MPR was significantly higher than that by routine CT (p=0.04). CONCLUSION: Thin-section multiplanar reformats from multidetector-row CT data sets are useful for assessing the extent of regional tumors in non-small cell lung cancer patients.

Adult↗

PubMed2005

Differential expression of S100A2 and S100A4 in lung adenocarcinomas: clinicopathological significance, relationship to p53 and identification of their target genes.

Previous studies suggest that some S100 proteins are involved in the progression of certain types of cancer. However, no comprehensive data is currently available on the expression of S100 family genes in lung adenocarcinomas. Oligonucleotide array, quantitative reverse transcription-polymerase chain reaction and western blot analyses of lung adenocarcinoma cell lines and bronchiolar epithelial cells (SAEC and NHBE) revealed that S100A2 and S100A4 were the most strikingly downregulated and upregulated members of the S100 family, respectively. Immunohistochemical analyses of 94 primary lung adenocarcinomas showed that positive S100A2 expression (33/94, 35.1%) was significantly associated with lymphatic invasion (P=0.0233) and positive S100A4 expression (19/94, 20.2%) with vascular invasion (P=0.0454). Interestingly, a strong inverse relationship was found between S100A4 and p53 expression (P=0.0008). Survival analyses showed that S100A4 positivity was associated with poor patient prognosis (P=0.042). S100A2 positivity was not associated with patient survival when the whole patient group was analyzed; however, S100A2 positivity was a favorable prognostic indicator in patients with p53-negative tumors (P=0.0448). Finally, we used oligonucleotide array analyses and identified potential S100A2 and S100A4 target genes involved in cancer progression: S100A2 induced RUNX3 and REPRIMO; S100A4 induced EZRIN, RUNX1 and WISP1; S100A2 repressed EGFR, NFKB2 and RELA2; and S100A4 repressed ANXA10 and IL1RN. Thus, the present study demonstrates involvement of S100A2 and S100A4 in the progression of lung adenocarcinomas and an inverse association between S100A4 and p53 expression, and provides a list of targets regulated by S100A2 and S100A4.

Adenocarcinoma↗

PubMed2005

Static suppression of tomato bacterial wilt by bacterial coagulation using a new functional polymer that coagulates bacterial cells and is highly biodegradable.

Tomato bacterial wilt by Ralstonia solanacearum was suppressed by coagulation of bacterial cells without disinfection using a copolymer of methyl methacrylate with N-benzyl-4-vinylpyridinium chloride in a molar ratio of 3:1 (PMMA-co-BVP) as a polymeric coagulant for bacterial cells. When 10 mg/kg of PMMA-co-BVP was added to soil before transplanting of tomato seedlings, and 2 mg/kg was supplemented once a week after transplanting, a 51% reduction of appearance and a 54% reduction of index of symptoms were observed. PMMA-co-BVP did not exhibit bactericidal activity against R. solanacearum, and coagulation of the bacterial cells appeared to reduce the opportunity for infectious contact of roots of tomato with cells of R. solanacearum, and resulted in disease suppression. PMMA-co-BVP was shown to be highly biodegradable, and the half-life was 5.1 d when treated with activated sludge in soil.

Biodegradation, Environmental↗

PubMed2005

Sphingosine 1-phosphate induces alpha-smooth muscle actin expression in lung fibroblasts via Rho-kinase.

Transformation of fibroblasts into myofibroblasts is an important phenomenon that contributes to airway remodeling in bronchial asthma. Although several articles have recently indicated that a bioactive lysosphingolipid sphingosine 1-phosphate (S1P) plays roles in the pathogenesis of bronchial asthma, the role of S1P in the remodeling process is poorly understood. In the present study, we examined the effects of S1P on alpha-smooth muscle actin (SMA) expression and the morphology in lung fibroblasts. S1P stimulated the expression of alpha-SMA in a human lung fibroblast cell line WI38 that expresses EDG/S1P receptors. These processes were inhibited by Y-27632, but not by pertussis toxin. These results suggest that S1P induces a phenotypic change of lung fibroblasts via Rho-kinase that may lead to airway remodeling.

Actins↗

PubMed2004

Vascular endothelial cell growth factor attenuates actions of transforming growth factor-beta in human endothelial cells.

Because vascular endothelial cell growth factor (VEGF) and transforming growth factor-beta (TGF-beta) are both involved in cellular growth and differentiation, we examined whether VEGF modifies TGF-beta signaling cascade in human umbilical cord vein endothelial cells (HUVEC). Production of plasminogen activator inhibitor-1 (PAI-1), which is under the specific control of TGF-beta, was strongly enhanced (3.5-fold) by TGF-beta treatment. Remarkably, physiological concentration of VEGF (30 nm) profoundly (by 60%) attenuated the TGF-beta stimulation of PAI-1 production without an effect on the basal PAI-1 production. In HUVECs transiently transfected with an expression construct containing a PAI-1 promoter fused to luciferase reporter gene, TGF-beta-stimulation of transcription of PAI-1 was clearly (by 60%) inhibited by VEGF. TGF-beta phosphorylation of Smad2/3, an obligatory step of intracellular TGF-beta signaling, was also suppressed by VEGF. VEGF attenuation of TGF-beta action was also demonstrated in two other endothelial cell lines. In conclusion, VEGF attenuates TGF-beta action in the human endothelial cell, specifically at the level of transcription of PAI-1 gene and Smad2/3 phosphorylation.

Androstadienes↗

PubMed2004

NMDA receptor-dependent long-term potentiation is dependent on low-voltage-activated calcium currents in the sensorimotor cortex of cats.

The role of low-voltage-activated (LVA) calcium channels in the expression of long-term potentiation (LTP) was examined by intracellular recording in slices from cat agranular cortex. In the normal solution, LTP was induced, and the potentiation of low-threshold rebound potential was evoked by negative current injection. In the cells, in which resting membrane potential was depolarized, the incidence of LTP was very low. LTP was blocked completely in the presence of NMDA receptor antagonist or 50-100 microM nickel. It was suggested that LVA calcium channels function downstream of NMDA receptor-dependent signaling.

2-Amino-5-phosphonovalerate↗