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Toshinori Ueno,
Ayumu Nakashima,
Shigehiro Doi,
Takeshi Kawamoto,
Kiyomasa Honda,
Yukio Yokoyama,
Toshiki Doi,
Yukihito Higashi,
Noriaki Yorioka,
Yukio Kato, Nobuoki Kohno,
Takao Masaki
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ABSTRACT: Mesenchymal stem cells (MSCs) are multipotent adult stem cells that have regenerative capability and exert paracrine actions on damaged tissues. Since peritoneal fibrosis is a serious complication of peritoneal dialysis, we tested whether MSCs suppress this using a chlorhexidine gluconate model in rats. Although MSCs isolated from green fluorescent protein-positive rats were detected for only 3 days following their injection, immunohistochemical staining showed that MSCs suppressed the expression of mesenchymal cells, their effects on the deposition of extracellular matrix proteins, and the infiltration of macrophages for 14 days. Moreover, MSCs reduced the functional impairment of the peritoneal membrane. Cocultures of MSCs and human peritoneal mesothelial cells using a Transwell system indicated that the beneficial effects of MSCs on the glucose-induced upregulation of transforming growth factor-β1(TGF-β1) and fibronectin mRNA expression in the human cells were likely due to paracrine actions. Preincubation in MSC-conditioned medium suppressed TGF-β1-induced epithelial-to-mesenchymal transition, α-smooth muscle actin, and the decrease in zonula occludens-1 in cultured human peritoneal mesothelial cells. Although bone morphogenic protein 7 was not detected, MSCs secreted hepatocyte growth factor and a neutralizing antibody to this inhibited TGF-β1 signaling. Thus, our findings imply that MSCs ameliorate experimental peritoneal fibrosis by suppressing inflammation and TGF-β1 signaling in a paracrine manner.Kidney International advance online publication, 13 March 2013; doi:10.1038/ki.2013.81.
Kidney International 03/2013; · 6.61 Impact Factor
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ABSTRACT: OBJECTIVE: Absence of a late-night cortisol nadir is a consistent biochemical abnormality in patients with cortisol-producing adenoma. We evaluated the abnormality of late-night urinary free cortisol to creatinine ratio (late-night UFCCR) in patients with subclinical Cushing's syndrome (SCS). METHODS: Fifty-eight patients with incidentally detected adrenocortical adenomas (SCS: 9; non-functioning adenoma [NF]: 49) were enrolled as subjects. Values measured in all patients were urinary free cortisol accumulated between 9:00 p.m. and 11:00 p.m. (late-night UFCCR), serum cortisol at 11:00 p.m. (midnight serum cortisol: MSC), serum cortisol after 1 mg overnight dexamethasone suppression test (1mg-DST) and 24-h urinary free cortisol (UFC). RESULTS: Median late-night UFCCR value in SCS was significantly higher than that in NF (P<0.001). Significant correlations were observed between late-night UFCCR and each of serum cortisol after 1mg-DST and MSC (r=0.537, P<0.001 and r=0.556, P<0.001, respectively). There was no significant correlation between serum cortisol after 1mg-DST and 24-h UFC (r=0.211, P=0.112). In receiver operating characteristic analysis for diagnosis of SCS, the areas under the curves of late-night UFCCR and 24-h UFC were 0.937 (95% confidence interval 0.865-1.008) and 0.726 (0.874-0.999), respectively. Late-night UFCCR cut-off value of 4.9 nmol/μmol･Cre showed a sensitivity of 100% and a specificity of 76.6%. CONCLUSION: Patients with SCS showed higher late-night UFCCR values than those with NF. Late-night UFCCR was significantly correlated with autonomous cortisol production findings. Diagnostic performance of late-night UFCCR was superior to 24-h UFC. These results suggest that late-night UFCCR might represent one of simple and reliable tests for SCS diagnosis. © 2013 Blackwell Publishing Ltd.
Clinical Endocrinology 03/2013; · 3.17 Impact Factor
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ABSTRACT: A growing body of evidence suggests that there is a relationship between impaired lung function and the risk of developing diabetes mellitus (DM). However, it is not known if this reflects a causal effect of lung function on glucose metabolism. To clarify the relationship between lung function and the development of DM, we examined the incidence of newly diagnosed prediabetes (a precursor of DM) among subjects with normal glucose tolerance (NGT) at baseline.
Primary analysis of an occupational cohort with both cross-sectional and longitudinal data (follow-up duration mean±SD: 28.4±6.1 months).
Data were analysed from 1058 men in a cross-sectional study and from 560 men with NGT in a longitudinal study. OUTCOMES AND METHODS: Impaired lung function (per cent predicted value of forced vital capacity (%FVC) or per cent value of forced expiratory volume 1 s/FVC (FEV(1)/FVC ratio)) in relation to the ratio of prediabetes or DM in a cross-sectional study and development of new prediabetes in a longitudinal study. NGT, prediabetes including impaired glucose tolerance (IGT) and increased fasting glucose (IFG) and DM were diagnosed according to 75 g oral glucose tolerance tests.
%FVC at baseline, but not FEV(1)/FVC ratio at baseline, was significantly associated with the incidences of DM and prediabetes. Among prediabetes, IGT but not IFG was associated with %FVC. During follow-up, 102 subjects developed prediabetes among those with NGT. A low %FVC, but not FEV(1)/FVC ratio, was predictive of an increased risk for development of IGT, but not of IFG.
Low lung volume is associated with an increased risk for the development of prediabetes, especially IGT, in Japanese men. Although there is published evidence for an association between chronic obstructive pulmonary disease and DM, prediabetes is not associated with the early stage of COPD.
BMJ open. 01/2013; 3(2).
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Yoshiko Kida,
Shinichiro Ohshimo,
Kohei Ota,
Tomoko Tamura,
Tadatsugu Otani,
Kazunobu Une,
Takuma Sadamori,
Yasumasa Iwasaki,
Francesco Bonella,
Noboru Hattori,
Nobuyuki Hirohashi,
Josune Guzman,
Ulrich Costabel, Nobuoki Kohno,
Koichi Tanigawa
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ABSTRACT: BACKGROUND: Diffuse alveolar hemorrhage syndrome is a life threatening condition with diverse etiologies. Sensitive prognostic markers for diffuse alveolar hemorrhage have not been well investigated. Serum KL-6 is a biomarker for various interstitial lung disease associated with disease activity and prognosis. The purpose of the present study was to evaluate the clinical utility of serum KL-6 level as a prognostic marker for diffuse alveolar hemorrhage. METHODS: We retrospectively collected 41 consecutive patients clinically diagnosed as having diffuse alveolar hemorrhage who were admitted to the Intensive Care Unit of Hiroshima University Hospital between 2004 and 2011. Correlation between prognosis and age, sex, laboratory findings including serum KL-6, radiological findings, ventilatory modes or therapeutic regimens were evaluated. RESULTS: Baseline and peak serum KL-6 levels were significantly higher in non-survivors compared with survivors. An increase in KL-6 levels during the initial week was associated with a subsequent deterioration of the oxygenation index. Higher baseline KL-6 levels and higher peak KL-6 levels were strongly correlated with death. With a cut-off level of 700 U/mL for peak KL-6, the sensitivity, specificity and accuracy for non-survival were 75%, 85% and 78%, respectively. In the multivariate analysis, only the peak KL-6 level >=700 U/ml was an independent poor prognostic factor for diffuse alveolar hemorrhage. CONCLUSIONS: Peak serum KL-6 level >=700 U/ml may become a clinically useful marker of poor prognosis for diffuse alveolar hemorrhage.
Orphanet Journal of Rare Diseases 12/2012; 7(1):99. · 5.83 Impact Factor
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Yasushi Horimasu,
Noboru Hattori,
Nobuhisa Ishikawa,
Shigeo Kawase,
Sonosuke Tanaka,
Koji Yoshioka,
Akihito Yokoyama, Nobuoki Kohno,
Francesco Bonella,
Josune Guzman,
Shinichiro Ohshimo,
Ulrich Costabel
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ABSTRACT: KL-6 is a high-molecular-weight glycoprotein classified as human Mucin-1 (MUC1). KL-6 has been reported to be a sensitive biomarker for interstitial lung diseases (ILDs) in the Japanese population. It is also known that polymorphisms in the MUC1 gene affect serum levels of KL-6. This study was conducted to evaluate serum levels of KL-6 and MUC1 polymorphisms in both German and Japanese populations.
Serum levels of KL-6 were measured in 267 patients with ILDs (152 German and 115 Japanese) and 186 healthy subjects (HS) (76 German and 110 Japanese). In addition, rs4072037 single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction. The optimal cutoff values for discriminating patients with ILDs from HS was determined by receiver operating characteristic analysis based on ethnicity and rs4072037 genotypes.
The serum KL-6 levels in patients with ILDs were significantly higher compared with HS in both the German and the Japanese cohorts (both p<0.001). The discriminating cutoff value of serum KL-6 in the German cohort was significantly higher than the value in the Japanese cohort. The difference in the serum levels of KL-6 was significantly associated with the rs4072037 genotype distribution.
Even in the German cohort, the serum KL6 levels were significantly higher in patients with ILDs than HS. Because of differences in the genotype distribution of rs4072037, the KL-6 cutoff value for the German cohort that discriminated patients with ILDs from HS was significantly higher than the value in the Japanese cohort.
Respiratory medicine 09/2012; 106(12):1756-64. · 2.33 Impact Factor
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ABSTRACT: To investigate the influence of cigarette smoking on exercise capacity, respiratory responses and dynamic changes in lung volume during exercise in patients with type 2 diabetes. Forty-one men with type, 2 diabetes without cardiopulmonary disease were recruited and divided into 28 non-current smokers and 13 current smokers. All subjects received lung function tests and cardiopulmonary exercise testing using tracings of the flow-volume loop. Exercise capacity was compared using the percentage of predicted oxygen uptake at maximal workload (%VO2max). Respiratory variables and inspiratory capacity (IC) were compared between the two groups at rest and at 20%, 40%, 60%, 80% and 100% of maximum workload. Although there was no significant difference in lung function tests between the two groups, venous carboxyhemoglobin (CO-Hb) levels were significantly higher in current smokers. %VO2max was inversely correlated with CO-Hb levels. Changing patterns in respiratory rate, respiratory equivalent and IC were significantly different between the two groups. Current smokers had rapid breathing, a greater respiratory equivalent and a limited increase in IC during exercise. Cigarette smoking diminishes the increase in dynamic IC in patients with type 2 diabetes. As this effect of smoking on dynamic changes in lung volume will exacerbate dynamic hyperinflation in cases complicated by chronic obstructive pulmonary disease, physicians should consider smoking habits and lung function when evaluating exercise capacity in patients with type 2 diabetes.
Hiroshima journal of medical sciences 06/2012; 61(2):29-36.
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ABSTRACT: Small dense low-density lipoprotein (sdLDL) has been suggested to be more atherogenic than large buoyant LDL. High-density lipoprotein (HDL) consists of two major subfractions (HDL2, HDL3), and just as controversy remains regarding which of the two is the more powerful negative risk factor for atherosclerosis, associations between sdLDL and these HDL subfractions are unclear.
We measured sdLDL cholesterol (sdLDL-C), HDL2 cholesterol (HDL2-C) and HDL3 cholesterol (HDL3-C) by a newly developed method in 481 Japanese-Americans who were not using lipid-lowering medication, and examined the associations of these cholesterol concentrations with variables related to atherosclerosis.
In multivariate analysis, sdLDL-C was positively correlated with the body mass index (BMI), fasting glucose and insulin, 2-h glucose, HOMA-IR, high sensitivity C-reactive protein (hsCRP), and carotid artery intima-media thickness (IMT) after adjustment for age and sex. In particular, sdLDL-C was positively correlated with IMT, even after adjustment for sex, age, smoking status, hypertension, diabetes mellitus and hsCRP. HDL2-C was more closely inversely correlated than total HDL-C with BMI, fasting glucose and insulin, 2-h glucose, HOMA-IR, and hsCRP, whereas HDL3-C was not correlated with these factors. Additionally, HDL2-C was more closely correlated than total HDL-C or HDL3-C with sdLDL-C, LDL-C, triglycerides (TG), and apolipoprotein B (apoB).
SdLDL-C was closely associated with insulin resistance and glucose tolerance, lending credence to its potential as a useful risk marker in assessing carotid artery IMT and the present degree of atherosclerosis in Japanese-Americans. The findings also suggest that subjects with higher HDL2-C levels were better protected from atherosclerosis.
Journal of atherosclerosis and thrombosis 05/2012; 19(5):444-52. · 2.69 Impact Factor
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Rika Ago,
Ayumu Nakashima,
Takayuki Naito,
Shigehiro Doi,
Mariko Ochiai,
Naoki Hamaguchi,
Yukio Yokoyama,
Junko Tanaka,
Noriaki Yorioka,
Takao Masaki, Nobuoki Kohno
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ABSTRACT: BACKGROUND: When diagnosing hypertension (HT) it is essential to determine not only the level of raised blood pressure (BP), but also how the condition relates to organ damage. The best time to measure BP for diagnosing HT in patients on hemodialysis (HD) remains unclear. METHODS: A total of 100 HD patients (mean age 63.8 years, 60 males) were studied. Left ventricular hypertrophy (LVH) was detected by echocardiography and BP monitored for 1 week at 20 different times in the morning and night, before and after dialysis. We also checked for masked HT, i.e., patients with weekly morning HT, but not pre-dialysis HT. RESULTS: Average BP for the week was 141.9 ±19.0/79.6 ± 10.6 mmHg, with 68 patients classified as hypertensive. Average morning BP was 144.6 ± 19.8/81.7 ± 11.3 mmHg, and 71 patients had weekly morning HT. In addition, 62 patients had LVH and 51 patients had relative morning HT. Multiple logistic analyses showed that LVH was associated with weekly morning HT, morning HT on HD and non-HD days, average HT, and relative morning HT. However, evening, pre-dialysis, and post-dialysis HT showed no association with LVH. Masked HT was found in 20 % of patients. If HT had been diagnosed using only pre-dialysis BP, 20 of the 71 patients with weekly morning HT would not have been detected. CONCLUSION: Morning BP is useful for detecting LVH in HD patients. Monitoring of morning BP may be superior to measurements taken at other times for diagnosing HT.
Clinical and Experimental Nephrology 05/2012; · 1.37 Impact Factor
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Nihon Naika Gakkai Zasshi 05/2012; 101(5):1401-3.
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ABSTRACT: Interstitial lung diseases (ILDs) are a diverse group of pulmonary disorders characterized by various patterns of inflammation and fibrosis in the interstitium of the lung. Because injury and/or regeneration of type II pneumocytes are prominent histological features of ILDs, substances derived from type II pneumocytes have been the focus of research investigating potential biomarkers for ILD. One important biomarker for ILD is the high-molecular-weight glycoprotein, Krebs von den Lungen-6 (KL-6). KL-6 is now classified as a human MUC1 mucin protein, and regenerating type II pneumocytes are the primary cellular source of KL-6/MUC1 in the affected lungs of patients with ILD. KL-6/MUC1 is detectable in the serum of patients with ILD, and extensive investigations performed primarily in Japan have revealed that serum KL-6/MUC1 is elevated in 70-100% of patients with various ILDs, including idiopathic interstitial pneumonias, collagen vascular disease-associated interstitial pneumonia, hypersensitivity pneumonia, radiation pneumonitis, drug-induced ILDs, acute respiratory distress syndrome, pulmonary sarcoidosis, and pulmonary alveolar proteinosis. The results from these various studies have supported the utility of KL-6/MUC1 as a serum biomarker for detecting these various ILDs. Moreover, KL-6/MUC1 serum levels have been demonstrated to be useful for evaluating disease activity and predicting the clinical outcomes of various ILD types. Based on these observations, we believe that KL-6/MUC1 is currently one of the best and most reliable serum biomarkers available for ILD management.
Respiratory investigation. 03/2012; 50(1):3-13.
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Sonosuke Tanaka,
Noboru Hattori,
Nobuhisa Ishikawa,
Yasushi Horimasu,
Naoko Deguchi,
Atsushi Takano,
Yoshitaka Tomoda,
Koji Yoshioka,
Kazunori Fujitaka,
Koji Arihiro,
Morihito Okada,
Akihito Yokoyama, Nobuoki Kohno
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ABSTRACT: It has been reported that the type I interferon receptor subunit, interferon (alpha, beta and omega) receptor 2 (IFNAR2), is overexpressed in several malignancies, primarily adenocarcinomas (ADCs); however, the biological significance of IFNAR2 in human lung cancer has not yet been studied.
Immunohistochemical analysis of 113 surgically resected lung specimens was performed, and the results were evaluated in association with clinical variables, including survival. Serum concentrations of IFNAR2 were also determined by an enzyme-linked immunosorbent assay in 157 lung cancer patients and 164 healthy volunteers.
IFNAR2 overexpression was observed in all histological types of lung cancer examined. Furthermore, strong IFNAR2 expression was associated with shorter progression-free survival (PFS) and overall survival (OS) (p < 0.0001 and p = 0.0110, respectively) in non-small cell lung cancer patients. Multivariate analyses confirmed its independent prognostic value for PFS and OS (p < 0.0001 and p = 0.0222, respectively). IFNAR2 serum levels were also significantly higher in lung cancer patients than in healthy volunteers (p < 0.0001).
IFNAR2 overexpression was observed in various histological types of lung cancer, and appears to be associated with lung cancers that behave aggressively. The results of this study strongly support the potential of IFNAR2 to be a prognostic biomarker for lung cancer.
Pathobiology 01/2012; 79(1):24-33. · 1.18 Impact Factor
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ABSTRACT: This study aims to identify molecules that might be useful as diagnostic/prognostic biomarkers and as targets for the development of new molecular therapies for lung cancer.
We screened for genes that were highly transactivated in a large proportion of 120 lung cancers by means of a cDNA microarray representing 27,648 genes and found chondrolectin (CHODL) as a candidate. Tumor tissue microarray was applied to examine the expression of CHODL protein and its clinicopathologic significance in archival non-small cell lung cancer (NSCLC) tissues from 295 patients. A role of CHODL in cancer cell growth and/or survival was examined by siRNA experiments. Cellular invasive effect of CHODL on mammalian cells was examined by Matrigel assays.
Immunohistochemical staining revealed that strong positivity of CHODL protein was associated with shorter survival of patients with NSCLC (P = 0.0006), and multivariate analysis confirmed it to be an independent prognostic factor. Treatment of lung cancer cells with siRNAs against CHODL suppressed growth of the cancer cells. Furthermore, induction of exogenous expression of CHODL conferred growth and invasive activity of mammalian cells.
CHODL is likely to be a prognostic biomarker in the clinic and targeting CHODL might be a strategy for the development of anticancer drugs.
Clinical Cancer Research 12/2011; 17(24):7712-22. · 7.74 Impact Factor
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ABSTRACT: Lung cancer occasionally accompanies pulmonary hypertrophic osteoarthropathy (PHO) as a paraneoplastic syndrome. Here, we present an atypical case of pleomorhic carcinoma with PHO. A 59-year-old man with cough and arthralgia in both ankles was referred to our hospital and we made a diagnosis of PHO based on the typical findings in bone scintigram. Chest CT showed a 7 cm tumor in the right lung which was cytologically diagnosed as non-small cell cancer (cT2N2M0, stage IIIA). After resection of the tumor, his arthralgia and abnormal uptakes on bone scintigram disappeared. The final pathological diagnosis of the tumor was pleomorphic carcinoma. During adjuvant chemotherapy (cisplatin plus vinorelbine), relapsed lesions in the right pleural space were found. However, no symptoms of PHO were reported by the patient. Following the change of the regimen to carboplatin plus paclitaxel, the relapsed tumor went into complete remission, and this patient has now survived for three years without recurrence.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 10/2011; 49(10):765-9.
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ABSTRACT: The association between airway inflammation and asthma control level is not clear at present.
This study aimed to explore the association by using induced sputum and asthma control status as determined by the Asthma Control Test (ACT). We also evaluated the association between the scores for each ACT question item and eosinophilic or neutrophilic airway inflammation.
The ACT and sputum induction were performed at the same time. Associations between total scores or scores for each question item and sputum eosinophil or neutrophil counts were examined. The study was approved by an Institutional Review Board.
Of the 101 patients with chronic asthma enrolled, data from 98 (controlled n = 66, uncontrolled n = 32) were analyzed [60.0 years (43.0-68.0) M:F = 34:64]. Current control status determined by the ACT was not significantly associated with eosinophilic or neutrophilic inflammation. Among the ACT items, only nocturnal symptoms were associated with sputum eosinophils: patients with a positive answer to the question had significantly higher eosinophil counts than patients with a negative answer [5.4 (2.2-17.6) versus 2.1 (0.7-7.3), respectively, p = 0.08]. Furthermore, significant correlation was found between eosinophil counts and the scores for nocturnal symptoms (rs = -0.218 p = 0.031). On the other hand, patients with rescue use of a short-acting b2-agonist (SABA) had significantly higher sputum neutrophil counts than non-SABA users [73.4 (52.8-83.4) versus 61.0 (36.3-74.8), respectively, p = 0.031]. The other ACT items were not significantly associated with sputum neutrophils. The neutrophil count correlated significantly with the frequency of rescue SABA use (rs = -0.218 p = 0.031).
Asthma control level evaluated by the ACT was not associated with airway eosinophilic or neutrophilic inflammation. However, the frequency of nocturnal symptoms was associated with sputum eosinophilia, and the frequency of rescue SABA use was associated with sputum neutrophilia.
Journal of Asthma 09/2011; 48(9):907-13. · 1.52 Impact Factor
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Shintaro Miyamoto,
Noboru Hattori,
Tadashi Senoo,
Yojiro Onari,
Hiroshi Iwamoto,
Masashi Kanehara,
Nobuhisa Ishikawa,
Kazunori Fujitaka,
Yoshinori Haruta,
Hiroshi Murai,
Akihito Yokoyama, Nobuoki Kohno
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ABSTRACT: Recent studies suggest that plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of the fibrinolytic system, may promote the development of asthma. To further investigate the significance of PAI-1 in the pathogenesis of asthma and determine the possibility that PAI-1 could be a therapeutic target for asthma, this study was conducted. First, PAI-1 levels in induced sputum (IS) from asthmatic subjects and healthy controls were measured. In asthmatic subjects, IS PAI-1 levels were elevated, compared with that of healthy controls, and were significantly higher in patients with long-duration asthma compared with short-duration asthma. PAI-1 levels were also found to correlate with IS transforming growth factor-β levels. Then, acute and chronic asthma models induced by ovalbumin were established in PAI-1-deficient mice and wild-type mice that received intra-airway administrations of small interfering RNA against PAI-1 (PAI-1-siRNA). We could demonstrate that eosinophilic airway inflammation and airway hyperresponsiveness were reduced in an acute asthma model, and airway remodeling was suppressed in a chronic asthma model in both PAI-1-deficient mice and wild-type mice that received intra-airway administration of PAI-1-siRNA. These results indicate that PAI-1 is strongly involved in the pathogenesis of asthma, and intra-airway administration of PAI-1-siRNA may be able to become a new therapeutic approach for asthma.
AJP Lung Cellular and Molecular Physiology 09/2011; 301(6):L908-16. · 3.66 Impact Factor
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Ryohei Nishino,
Atsushi Takano,
Hideto Oshita,
Nobuhisa Ishikawa,
Hirohiko Akiyama,
Hiroyuki Ito,
Haruhiko Nakayama,
Yohei Miyagi,
Eiju Tsuchiya, Nobuoki Kohno,
Yusuke Nakamura,
Yataro Daigo
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ABSTRACT: This study aims to identify novel biomarkers and therapeutic targets for lung cancer.
We carried out gene expression profile analysis of 120 lung cancers to screen for genes encoding transmembrane/secretory molecules that are commonly transactivated in lung cancers. Epstein-Barr virus-induced gene 3 (EBI3), which encodes a secretory glycoprotein, was selected as a good candidate. Immunohistochemical staining using tissue microarray consisting of 414 non-small cell lung cancers was applied to examine the expression level and prognostic value of EBI3. Serum EBI3 levels in 400 individuals for training assays (274 lung cancers and 126 healthy volunteers) and those in 173 individuals for validation analysis (132 lung cancers and 41 healthy volunteers) were measured by ELISA. The role of EBI3 in cancer cell growth was examined by siRNA and cell growth assays, using cells stably expressing exogenous EBI3.
Immunohistochemical staining of EBI3 using tissue microarrays revealed that a high level of EBI3 expression was associated with a poor prognosis of lung cancer (P = 0.0014) and multivariate analysis confirmed it to be an independent prognostic factor (P = 0.0439). Serum levels of EBI3 in the training set were found to be significantly higher in lung cancer patients than in healthy volunteers; this result was also observed in the validation set. Furthermore, reduction in EBI3 expression by siRNA suppressed cancer cell proliferation whereas induction of exogenous EBI3 conferred growth-promoting activity.
EBI3 is a potential serum and tissue biomarker as well as therapeutic target for lung cancer.
Clinical Cancer Research 08/2011; 17(19):6272-86. · 7.74 Impact Factor
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ABSTRACT: Dysphagia induces silent aspiration, which is a known risk factor for aspiration pneumonia in the elderly. Dysphagia is associated with impaired substance P secretion. Because nicergoline was recently reported to enhance substance P secretion, it may improve dysphagia by upregulating substance P; however, roles for nicergoline in this process have not been demonstrated. We therefore compared the effects of nicergoline on serum substance P and dysphagia with the effects of imidapril, an angiotensin-converting enzyme (ACE) inhibitor whose efficacy in improving dysphagia and preventing pneumonia has been previously demonstrated.We randomly assigned 60 elderly patients with both dysphagia and a previous history of pneumonia to receive either imidapril (5 mg/d; n = 30) or nicergoline (15 mg/d; n = 30) for 6 months. Primary outcomes were the effects of these drugs on the substance P level and dysphagia 4 weeks after the start of treatment. Secondary outcome was the effect of these drugs on pneumonia recurrence during the 6 months of treatment.Significant elevations of serum substance P were obtained by both medications after 4 weeks of treatment. Patients whose dysphagia was improved showed significantly increased serum levels of substance P. There was no statistically significant difference in the overall proportion of patients who showed improvements in dysphagia and pneumonia recurrence with imidapril or nicergoline treatment. Nicergoline, but not imidapril, seemed to be more effective at improving dysphagia and elevating serum substance P in patients with dementia.In conclusion, nicergoline has a comparable effect to ACE inhibitors for improving dysphagia. Nicergoline might be a novel regimen for the treatment of dysphagia in the elderly who are not treatable with ACE inhibitors.
Medicine 06/2011; 90(4):279-83. · 4.35 Impact Factor
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ABSTRACT: Chronic hepatitis C virus (HCV) infection causes intra- and extra-hepatic complications. The elimination of HCV has been reported to be beneficial for asthmatic patients with HCV infection. Therefore, we hypothesized that chronic HCV infection might be associated with the severity of asthma.
Asthmatic patients were prospectively enrolled from 13 outpatient settings. Hepatitis B surface (HBs) antigen and HCV-RNA were measured at the time of enrollment and evaluated along with the clinical characteristics of the patients including the age, sex, duration of asthma, atopic status, smoking history, and treatment step according to the Global Initiative for Asthma guideline.
Of 1327 asthmatic patients, 1258 patients (94.8%) were treated with inhaled corticosteroids, 18 patients were positive for HBs antigen (1.4%), and 32 patients (2.4%) were positive for HCV-RNA. When compared with HCV-RNA-negative patients, HCV-RNA-positive patients required significantly more drugs for the treatment of asthma. No such relationship was observed in patients with positive HBs antigen. A multivariate logistic regression analysis showed that the male sex, a long duration of asthma, status as a current smoker, and HCV-RNA positivity were independently associated with more severe asthma.
These results suggest that chronic HCV infection is an independent factor that predisposes asthmatic patients to more severe asthma. The evaluation of chronic HCV infection may be helpful for the management of severe asthmatic patients without obvious factors associated with severe asthma.
Allergology International 03/2011; 60(3):299-304.
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ABSTRACT: Bisphosphonates are widely used for the treatment of metastatic skeletal tumors and hypercalcemia resulting from malignant tumors. Zoledronic acid (ZOL), a third-generation bisphosphonate agent, was recently demonstrated to show synergistic antitumor activity of ZOL when combined with chemotherapy in lung cancer patients. However, whether ZOL exerts direct antitumor activity on lung cancer remains unclear. Here, we report an atypical case encountered while treating a 57-year-old woman with pulmonary adenocarcinoma and multiple metastases of the liver, left adrenal gland, and bone. The nonskeletal lesions, consisting of the primary lesion and hepatic metastasis, regressed after treatment with ZOL alone. We believe this case demonstrates a possible antitumor effect of ZOL against lung cancer.
Hiroshima journal of medical sciences 03/2011; 60(1):7-9.
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ABSTRACT: KL-6 is a mucin-like glycoprotein expressed on the surface of alveolar type II cells. Elevated concentrations of KL-6 in serum and epithelial lining fluid (ELF) in patients with acute respiratory distress syndrome (ARDS) have been previously reported; however, kinetics and prognostic significance of KL-6 have not been extensively studied. This study was conducted to clarify these points in ARDS patients.
Thirty-two patients with ARDS who received mechanical ventilation under intubation were studied for 28 days. ELF and blood were obtained from each patient at multiple time points after the diagnosis of ARDS. ELF was collected using a bronchoscopic microsampling procedure, and ELF and serum KL-6 concentrations were measured.
KL-6 levels in ELF on days 0 to 3 after ARDS diagnosis were significantly higher in nonsurvivors than in survivors, and thereafter, there was no difference in concentrations between the two groups. Serum KL-6 levels did not show statistically significant differences between nonsurvivors and survivors at any time point. When the highest KL-6 levels in ELF and serum sample from each patient were examined, KL-6 levels in both ELF and serum were significantly higher in nonsurvivors than in survivors. The optimal cut-off values were set at 3453 U/mL for ELF and 530 U/mL for serum by receiver operating characteristic (ROC) curve analyses. Patients with KL-6 concentrations in ELF higher than 3453 U/mL or serum concentrations higher than 530 U/mL had significantly lower survival rates up to 90 days after ARDS diagnosis.
ELF and serum KL-6 concentrations were found to be good indicators of clinical outcome in ARDS patients. Particularly, KL-6 levels in ELF measured during the early period after the diagnosis were useful for predicting prognosis in ARDS patients.
Respiratory research 03/2011; 12:32. · 3.36 Impact Factor
