[Show abstract][Hide abstract] ABSTRACT: Yaks have adapted to high altitude and they do not develop hypoxic pulmonary hypertension. Although we previously identified the important role of augmented nitric oxide synthase activity in the yak pulmonary circulatory system, evidence of the direct involvement of Rho-kinase as a basal vascular tone regulator is lacking. Four domesticated male pure-bred yaks and four bulls that were born and raised at an altitude of 3000 m in the Tien-Shan mountains were studied at an altitude of 3,100 m. Mean pulmonary artery pressure (mPAP) was measured before and after fasudil (60 mg in 20 mL of saline) was intravenously administered using a Swan-Ganz catheter at a rate of 3.3 mL/min for 30 min. Fasudil decreased mPAP in bulls from 67.8±14.9 to 32.3±5.3 mmHg (P < 0.05) after 15 min and the level was maintained for 30 min, but it merely blunted mPAP in yaks from 28.2±4.5 to 25.1±11.1 and 23.2±2.7 mmHg after 5 and 30 min, respectively. These findings comprise the first evidence of a modest role of Rho-kinase in the maintenance of pulmonary artery pressure in the yak.
BioMed Research International 12/2014; 2015. · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives
Recent advances in endobronchial ultrasonography with a guide sheath (EBUS-GS) have enabled better visualization of distal airways, while virtual bronchoscopic navigation (VBN) has been shown useful as a guide to navigate the bronchoscope. However, indications for utilizing VBN and EBUS-GS are not always clear. To clarify indications for a bronchoscopic examination using VBN and EBUS-GS, we evaluated factors that predict the diagnostic yield of a transbronchial biopsy (TBB) procedure for peripheral lung cancer (PLC) lesions.
We retrospectively reviewed the charts of 194 patients with 201 PLC lesions (≤3 cm mean diameter), and analyzed the association of diagnostic yield of TBB with [18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography and chest computed tomography (CT) findings.
The diagnostic yield of TBB using VBN and EBUS-GS was 66.7%. High maximum standardized uptake value (SUVmax), positive bronchus sign, and ground-glass opacity component shown on CT were all significant predictors of diagnostic yield, while multivariate analysis showed only high 18F-FDG uptake (SUVmax ≥2.8) and positive bronchus sign as significant predictors. Diagnostic yield was higher for PLC lesions with high 18F-FDG uptake (SUVmax ≥2.8) and positive bronchus sign (84.6%) than for those with SUVmax <2.8 and negative bronchus sign (33.3%). High 18F-FDG uptake was also correlated with tumor invasiveness.
High 18F-FDG uptake predicted the diagnostic yield of TBB using VBN and EBUS-GS for PLC lesions. 18F-FDG uptake and bronchus sign may indicate for the accurate application of bronchoscopy with those modalities for diagnosing PLC.
Lung cancer (Amsterdam, Netherlands) 07/2014; · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Losing the sense of smell, which suggests eosinophilic rhinosinusitis, is a subjective symptom, sometimes reported in asthmatic patients taking controller medication. Upper abdominal symptoms, suggesting gastroesophageal reflux disease (GERD) or functional dyspepsia, occur also in these patients. However, the relationship between these symptoms, concomitant with asthma, and the intensity of eosinophilic airway inflammation remains obscure.
[Show abstract][Hide abstract] ABSTRACT: Abstract Kojonazarov, Baktybek, Jainagul Isakova, Baktybek Imanov, Nurmira Sovkhozova, Talantbek Sooronbaev, Takeshi Ishizaki, and Almaz A. Aldashev. Bosentan reduces pulmonary artery pressure in high altitude residents. High Alt Med Biol. 13:217-223, 2012.-Endothelin-1 (ET-1) plays a critical role in the regulation of pulmonary vascular tone. The aim of this study was to investigate the role of ET-1 in the pathogenesis of high altitude pulmonary arterial hypertension (HAPH). Methods: Pulmonary artery pressure (PAP) was measured by echocardiography in permanent residents of the Kyrgyz Republic (3200-4000 m above sea level) both before and 3 h after a single oral dose of ET receptor antagonist, bosentan (125 mg). Plasma ET-1 levels were measured by ELISA assay. Genomic DNA was extracted from peripheral blood samples and the frequency of -3a and -4a alleles of the ET-1 gene determined by PCR. Results: Plasma ET-1 in HAPH highlanders was significantly higher than in healthy subjects (7.05±2.35 vs. 4.65±1.65 pg/ml, p<0.002). After the treatment with 125 mg bosentan, systolic PAP decreased from 46±1.9 to 37±2.2 mm Hg (p<0.01), and pulmonary artery acceleration time (PAAT) increased from 0.086±0.001 to 0.098±0.001 sec (p<0.001). The frequency of the -4a allele was significantly higher in HAPH patients compared to healthy highlanders (0.43 vs. 0.3, χ(2)=4.3, p=0.03). Conclusion: Increased ET-1 levels play an important role in development of HAPH.
High altitude medicine & biology 09/2012; 13(3):217-23. · 1.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Relationships among clinical, physiological, imaging and pathological findings of small airway disease associated with Sjögren's syndrome have remained unclear. Subjects and methods: We retrospectively studied 14 patients who underwent surgical lung biopsy and who were diagnosed with small airway disease associated with primary or secondary Sjögren's syndrome. We compared clinical, bronchoalveolar lavage, physiological, imaging and pathological findings between primary and secondary Sjögren's syndrome. We scored HRCT and pathological abnormalities and investigated correlations among physiological, HRCT and pathological data, changes in physiological parameters and in HRCT scores after two years of treatment, as well as correlations between these values and pathological scores.
Bronchoalveolar lavage fluid, physiological, imaging and pathological findings of the airways did not significantly differ between primary and secondary Sjögren's syndrome. Air trapping on HRCT negatively correlated with MEF50 and MEF25. Although lymphoid cell infiltration and peribronchiolar fibrosis were the most common pathologies, constrictive change scores correlated negatively with MEF50 and MEF25, positively with air trapping scores and negatively with improvements after therapy in MEF(50), MEF(25) and air trapping.
Constrictive change was the most significant determinant of physiological and imaging presentations and of changes in these factors after therapy for small airway disease associated with Sjögren's syndrome.
Respiratory medicine 09/2011; 105(12):1931-8. · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The value of dual-time- point (18) F-FDG PET was investigated to predict the prognosis of patients with pulmonary sarcoidosis.
Twenty-one patients with pulmonary sarcoidosis underwent (18) F-FDG PET examinations at two time points: an early scan at 60min and a delayed scan at 180min after injection of (18) F-FDG. Standardized uptake values (SUVs) at the two time points and the retention index (RI-SUV) calculated from these were evaluated. To evaluate disease progression, all patients underwent chest CT 1year after (18) F-FDG PET. Using these results, the accuracy of (18) F-FDG PET parameters and (67) Ga uptake for predicting disease persistence were compared, and the correlations between those parameters and serum markers were assessed. Results: RI-SUV was significantly higher in patients with increased or unchanged pulmonary lesions at follow-up CT (persistent group; 21.3±9.6%) than in patients with improved pulmonary lesions (improved group; -9.2±28.6%, P=0.0075). The diagnostic accuracy of RI-SUV in the persistent group was significantly greater than that of early SUV or (67) Ga uptake, and serum soluble IL-2 receptor showed a significant correlation with RI-SUV.
RI-SUV showed better diagnostic accuracy compared with early SUV or (67) Ga uptake, in patients with persistent lung involvement at 1year. It may be a useful measure of persistent inflammation in patients with pulmonary sarcoidosis.
[Show abstract][Hide abstract] ABSTRACT: In humans, aromatase (CYP19) gene expression is regulated via alternative promoters. Activation of each promoter gives rise to a CYP19 mRNA species with a unique 5'-untranslated region. Inhibition of aromatase has been reported to downregulate lung tumor growth. The genetic basis for CYP19 gene expression and aromatase activity in lung cancer remains poorly understood. We analyzed tissues from 15 patients with non-small cell lung cancer (NSCLC) to evaluate CYP19 promoter usage and promoter-specific aromatase mRNA levels in NSCLC tumor tissues and adjacent non-malignant tissues. CYP19 promoter usage was determined by multiplex RT-PCR and aromatase mRNA levels were measured with real-time RT-PCR. In non-malignant tissues, aromatase mRNA was primarily derived from activation of CYP19 promoter I.4. Although promoter I.4 usage was also dominant in tumor tissues, I.4 activation was significantly lower compared with adjacent non-malignant tissues. Activity of promoters I.3, I.1 and I.7 was significantly higher in tumor tissues compared with non-malignant tissues. In 4 of 15 cases of non-small cell lung cancer, switching from CYP19 promoter I.4 to the alternative promoters II, I.1 or I.7 was observed. In 9 cases, there were significantly higher levels of aromatase mRNA in lung tumor tissues compared with adjacent non-malignant tissues. These findings suggest aberrant activation of alternative CYP19 promoters that may lead to upregulation of local aromatase expression in some cases of NSCLC. Further studies are needed to examine the impact of alternative CYP19 promoter usage on local estrogen levels and lung tumor growth.
Lung cancer (Amsterdam, Netherlands) 02/2011; 73(3):289-93. · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic hypoxia induces pulmonary arterial remodeling, resulting in pulmonary hypertension and right ventricular hypertrophy. Hypoxia has been implicated as a physiological stimulus for p53 induction and hypoxia-inducible factor-1α (HIF-1α). However, the subcellular interactions between hypoxic exposure and expression of p53 and HIF-1α remain unclear. To examine the role of p53 and HIF-1α expression on hypoxia-induced pulmonary arterial remodeling, wild-type (WT) and p53 knockout (p53KO) mice were exposed to either normoxia or hypoxia for 8 wk. Following chronic hypoxia, both genotypes demonstrated elevated right ventricular pressures, right ventricular hypertrophy as measured by the ratio of the right ventricle to the left ventricle plus septum weights, and vascular remodeling. However, the right ventricular systolic pressures, the ratio of the right ventricle to the left ventricle plus septum weights, and the medial wall thickness of small vessels were significantly greater in the p53KO mice than in the WT mice. The p53KO mice had lower levels of p21 and miR34a expression, and higher levels of HIF-1α, VEGF, and PDGF expression than WT mice following chronic hypoxic exposure. This was associated with a higher proliferating cell nuclear antigen expression of pulmonary artery in p53KO mice. We conclude that p53 plays a critical role in the mitigation of hypoxia-induced small pulmonary arterial remodeling. By interacting with p21 and HIF-1α, p53 may suppress hypoxic pulmonary arterial remodeling and pulmonary arterial smooth muscle cell proliferation under hypoxia.
[Show abstract][Hide abstract] ABSTRACT: We attempted to develop a new specific antibody detection method for discriminating infection state from colonization state in hospitalized immunocompromised patients with a positive sputum culture for Pseudomonas aeruginosa. Serum samples from 65 patients with P. aeruginosa in sputum culture (total PA patients), including 24 patients with P. aeruginosa-related pulmonary infections (PA infection group) and 21 patients without pulmonary infections (PA colonization group), as well as samples from 20 patients positive for other bacteria in blood culture (non-PA infection group) and 38 healthy controls were examined and compared for IgG and IgA anti-P. aeruginosa antibodies by a newly developed enzyme-linked immunosorbent assay (ELISA). Both IgG and IgA antibody ELISA showed satisfactory reproducibility with low coefficient of variation (CV) percent, and western blotting analysis showed two protein bands as the corresponding antigens common to both antibodies. The serum levels of both antibodies in all the PA patients were higher than those in the healthy controls with high significance (p<0.0001). The PA infection group showed significantly higher mean levels of both IgG and IgA class antibodies than the PA colonization group, non-PA infection group and healthy controls (each, p<0.0001). In receiver operating characteristic (ROC) curves analysis to differentiate between total PA infections and the PA colonization group, the area under curve (AUC) of the IgA antibody (0.848) was significantly larger than the AUC of the IgG antibody (0.677) (p=0.019). At the optimal IgA antibody cutoff value for differentiation of 1.37 units/mL, the sensitivity and specificity of IgA anti-P. aeruginosa ELISA were 83.3% and 85.7%, respectively. These findings suggest that IgA antibody ELISA, rather than IgG antibody ELISA, may be useful for differentiating P. aeruginosa-related pneumonia from latent colonization in immunocompromised patients with a positive sputum culture.
Journal of microbiological methods 09/2010; 82(3):198-204. · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a case of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) after pandemic influenza (H1N1) vaccination. A 57-year-old man, who had been diagnosed with IPF in September 2008, was admitted to our hospital in December 2009 because of aggravation of dyspnea and fever two days after H1N1 vaccination. Chest computed tomography showed diffuse bilateral ground-glass opacities superimposed on preceding reticular opacities. We diagnosed AE-IPF. Corticosteroid and cyclophosphamide were effective. Although the efficacy of influenza vaccination in patients with chronic lung diseases is well established, physicians should keep in mind that influenza vaccination has the potential to cause AE-IPF.
Internal Medicine 01/2010; 49(21):2333-6. · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 69-year-old male non-smoker with a history of atopic asthma presented with symptoms suggestive of chronic obstructive pulmonary disease and this appeared to be corroborated by lung function testing and a chest radiograph. However, a chest CT showed no evidence of pulmonary emphysema and instead demonstrated free air along the bronchovascular sheaths indicative of pulmonary interstistial emphysema, possibly caused by repeated prior exacerbations of asthma. His lung function tests and symptoms improved within months of being treated for his airways disease but the CT findings were unchanged after 2 years.