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Biomedical subjects

Keishi Kubo

Publications and source records attributed to Keishi Kubo.

At least 19 recordsLinked to original sources
PubMed2007

Effects of bronchodilators on dynamic hyperinflation following hyperventilation in patients with COPD.

BACKGROUND AND OBJECTIVE: The present study was performed to examine the occurrence of dynamic hyperinflation following hyperventilation in COPD patients and former smokers without COPD, and the efficacy of short-acting anticholinergic agents (SAAC) and beta2-agonists (SABA) for lung hyperinflation following metronome-paced hyperventilation in COPD. METHODS: Fifty-nine patients with COPD, 20 ex-smokers without COPD and 20 healthy subjects who had never smoked were examined for dynamic hyperinflation by metronome-paced hyperventilation with respiratory rate increasing from 20 to 30 and 40 tidal breaths/min. Dynamic hyperinflation was evaluated as the decrease in inspiratory capacity (IC) following hyperventilation, and the effects of SAAC and SABA on dynamic hyperinflation were assessed. RESULTS: COPD patients showed a significant increase in end-expiratory lung volume and a decrease in IC following hyperventilation, and ex-smokers without COPD also showed mild but significant dynamic hyperinflation. Multiple stepwise linear regression analysis revealed that the carbon monoxide transfer coefficient (DLco/VA) and RV/TLC were significant and independent determinants of dynamic hyperinflation in COPD. Treatment with SAAC and SABA significantly increased IC at each respiratory rate, independently of the increases in FEV1. Furthermore, SABA significantly inhibited the decrease in IC due to hyperventilation. CONCLUSIONS: These findings suggest that lung hyperinflation following hyperventilation may be a useful method for detecting dynamic hyperinflation observed not only in patients with COPD but also in ex-smokers without COPD, and both SAAC and SABA are effective in reducing dynamic hyperinflation in COPD.

Administration, Inhalation↗
PubMed2006

IgG4-associated multifocal systemic fibrosis complicating sclerosing sialadenitis, hypophysitis, and retroperitoneal fibrosis, but lacking pancreatic involvement.

A 71-year-old man was admitted with malaise, mild fever, anorexia, body weight loss, lower back pain, thirst, and polydipsia. He showed bilateral swelling of the submandibular glands. Examinations showed panhypopituitarism and a high serum IgG4 concentration. Fluorodeoxyglucose positron emission tomography (FDG-PET) revealed uptake in the pituitary gland, bilateral submandibular gland, bilateral hilar and mediastinal lymph nodes, and a mass consistent with retroperitoneal fibrosis, but not in the pancreas. Biopsy specimens from the submandibular gland and retroperitoneal mass indicated sialadenitis and retroperitoneal fibrosis respectively, and showed severe fibrosis and inflammation with marked lymphoplasmacytic infiltration and IgG4-positive plasma cell infiltration. Hormone replacement therapy with hydrocortisone resulted in marked clinical improvement. Systemic involvement found in this patient possibly corresponded to the new concept of IgG4-associated multifocal systemic fibrosis.

Aged↗
PubMed2006

Regulation of body weight by leptin, with special reference to hypoxia-induced regulation.

Since first cloned and reported by Zhang et al in 1994 (Nature 372:425), the obese gene and its product-leptin has been studied profoundly. Our knowledge in body weight regulation and the role played by leptin has increased substantially. Leptin serves as an adiposity signal to inform the brain of the adipose tissue mass in a negative feedback loop regulating food intake and energy expenditure. Many articles have reported weight loss at high altitude, but the explanation has been limited to loss of appetite. New ideas were highlighted after studies by Grosfeld et al and Ambrosini et al on the obese gene under hypoxia condition. Cells with hypoxia treatment upregulated obese gene transcription and suggested that enhancement of leptin secretion in vivo under hypoxia environment may be one of the potential therapeutic methods for obesity treatment.

Body Weight↗
PubMed2006

Relationship between sleep-disordered breathing and lifestyle-related illnesses in subjects who have undergone health-screening.

OBJECTIVE: Simplified sleep polysomnography was performed in 207 adult men to examine the relationship between the frequency of sleep-disordered breathing (SDB) and lifestyle-related illness. METHODS: Each subject was checked for SDB using a simplified sleep polysomnograph (Auto-Set Portable; Teijin Limited, Tokyo, Japan). Apnea and hypopnea were detected with a nasal cannula type airflow sensor. Hypoxemia was checked with a percutaneous oxygen saturation (SpO2) monitor. We analyzed the relationships between SDB and body mass index (BMI) and hypertension, hyperlipidemia, liver dysfunction, fatty liver, and abnormal glucose metabolism. RESULTS: Fifty-nine subjects (29%) showed SDB with apnea hypopnea index (AHI) over 15 times/h. The frequency of obesity (BMI > or = 25), hypertension, hypercholesterolemia, fasting blood glucose level, and HbA1c were significantly higher in patients with SDB than in normal individuals (AHI < 5 times/h). The frequencies of hypertension, hyperlipidemia, and abnormal glucose metabolism were compared between the obesity-free normal AHI group and the SDB group, and only that of hypertension was significantly different between the two groups. CONCLUSIONS: The present study revealed a high frequency of SDB among Japanese individuals. The results also suggest that as SDB becomes severe, it becomes more closely linked to the onset of lifestyle-related illnesses, such as hypertension, hypercholesterolemia and abnormal glucose metabolism.

Adult↗
PubMed2006

Angiosarcoma with sacral origin metastasizing to the lung.

A 73-year-old man with fever, lumbago and hemosputum showed ground-glass opacity around multiple lung nodules on chest computed tomography. Examination of the man revealed anemia. Specimens obtained by video-assisted thoracic surgery revealed angiosarcoma, but the primary site of angiosarcoma could not be detected before autopsy. Angiosarcoma is a rare malignant neoplasm with rapid proliferation and they can arise at any region of the body. It can originate in the skin, soft tissue, liver or heart. Their multicentric and local recurrence easily leads us to misdiagnosis, and we have struggled to reach diagnosis and its origin. Angiosarcoma should be included in the different diagnosis of diffuse pulmonary hemorrhage with multiple lung nodules.

Aged↗
PubMed2006

Characteristics of asthma resistant to moderate dose inhaled corticosteroid treatment on bronchial hyperresponsiveness.

OBJECT: This study was performed to determine the clinical characteristics of asthmatics with bronchial hyperresponsiveness (BHR) that could not be normalized by 6 months of treatment with a moderate dose of an inhaled corticosteroid (ICS). METHODS: Thirty-four symptomatic patients with mild to moderate asthma, who had never received any ICS, were treated with 200 mug of inhaled fluticasone propionate twice a day for 6 months. Spirometry, BHR to methacholine, exhaled nitric oxide (NO) and eosinophils in induced sputum were examined before and 2 and 6 months after beginning treatment. RESULTS: FEV1 was increased and bronchial responsiveness, exhaled NO and sputum eosinophilia were significantly decreased 2 and 6 months after starting ICS treatment. Bronchial responsiveness was further decreased at 6 months together with a further increase in FEV1. In 13 patients, BHR was not normalized despite the 6 months of treatment. This group showed a higher prevalence of males, those with a smoking history and airflow limitation, a higher eosinophil count in the sputum following 6 months of treatment and a longer history of asthma. Multiple, stepwise, linear regression analysis showed that sputum eosinophilia and lower FEV1/FVC following 6 months of treatment and a longer history of asthma were significant independent determinants for BHR after 6 months of ICS treatment. CONCLUSIONS: These findings suggest that the resistance to a moderate dose of ICS for BHR in asthmatics may be significantly associated with remained airflow limitation, eosinophilic airway inflammation resistive to moderate dose of ICS, and delayed introduction of ICS therapy.

Administration, Inhalation↗
PubMed2006

Hypersensitivity pneumonitis induced by spores of Penicillium citrinum in a worker cultivating Enoki mushroom.

A 47-year-old Japanese woman was admitted to our hospital with a 2-week history of dry cough and shortness of breath. She had been engaged in Enoki mushroom production for 22 years. Chest X-ray and chest computed tomography (CT) scan showed bilateral fine-nodular shadows and ground glass opacity. Bronchoalveolar lavage fluid demonstrated an increase of total cell counts with predominant lymphocytosis. Pathological specimens obtained by video-assisted thoracoscopic surgery revealed alveolitis and noncaseating granuloma with giant cells. Lymphocyte stimulation test showed positive responses with Enoki mushroom, culture medium, and Penicillium citrinum. On double immunodiffusion test, a precipitation line was observed between patient's serum and Penicillium citrinum antigen. She was found to have hypersensitivity pneumonitis caused by Penicillium citrinum. This is the first report of mushroom worker's lung caused by Penicillium citrinum.

Agaricales↗
PubMed2006

Characteristics of COPD phenotypes classified according to the findings of HRCT.

The present study was performed to clarify the clinical characteristics of chronic obstructive pulmonary disease (COPD) patients classified into phenotypes according to the dominancy of emphysema and the presence of bronchial wall thickening evaluated by chest high-resolution computed tomography (HRCT). Eighty-five patients with stable COPD (FEV1 < or = 80%) were examined by chest HRCT. Emphysematous changes and bronchial wall thickening were evaluated visually, and COPD patients were classified into three phenotypes: absence of emphysema, with little emphysema with or without bronchial wall thickening (A phenotype), emphysema without bronchial wall thickening (E phenotype), and emphysema with bronchial wall thickening phenotype (M phenotype). Clinical characteristics were compared among the three phenotypes. The A phenotype group showed a higher prevalence of subjects who had never smoked and patients with wheezing, higher values of body mass index (BMI) and DLco, milder lung hyperinflation, and greater reversibility of airflow limitation responsive to inhaled beta2-agonist as compared with the other phenotypes. The degree of emphysema was significantly associated with Brinkman index, lower BMI, decrease in DLco, lower FEV1/FVC. The presence of bronchial wall thickening in A- and M- phenotype was significantly associated with reversibility responsive to treatment with inhaled corticosteroid and sputum eosinophilia. These findings suggest that the morphological phenotypes of COPD show several clinical characteristics and different responsiveness to treatment with bronchodilators and inhaled corticosteroids.

Administration, Oral↗
PubMed2006

Polymyxin B immobilized column is effective for hydrochloric acid-induced lung injury in rats.

The purpose of this study was to examine whether hemoperfusion using polymyxin B (PMX) immobilized column improves hydrochloric acid (HCl)-induced lung injury. Rats weighing 350 g underwent hemoperfusion for 30 min at a flow rate of 120 ml/h after the intratracheal instillation of hydrochloric acid or water. Rats were divided into those that underwent hemoperfusion, with or without polymyxin B column, 30 min after HCl instillation ("HCl+PMX" and "HCl"), and hemoperfusion with or without polymyxin B column 30 min after water instillation ("Aqua+PMX" and "Aqua"). Systolic blood pressure, arterial blood gas analysis and white blood cell count and neutrophils were measured before, 1 and 3h after hemoperfusion. Plasma and bronchoalveolar lavage fluid concentrations of growth-related oncogene/cytokine-induced neutrophils chemoattractant-1 (GRO/CINC-1) were measured at 1 and 3h after hemoperfusion. Arterial oxygen concentrations were higher in the "HCl+PMX" group than in the "HCl" group. The total numbers of cells and neutrophils in the bronchoalveolar lavage fluid were significantly higher in the "HCl" group than in the others. The GRO/CINC-1 concentrations in the plasma and bronchoalveolar lavage fluid and the albumin ratio in the "HCl+PMX" group were significantly lower than in the "HCl" group. Direct hemoperfusion using polymyxin B immobilized column treatment affects the recruitment of circulating neutrophils to the lungs due to the decrease in mediators for non-endotoxic lung injury.

Animals↗
PubMed2006

Clinical differences in the Global Initiative for Chronic Obstructive Lung Disease Stage 0.

This study was to examine the clinical differences between Stage 0 and normal subjects, using low-dose chest computed tomography (CT) and pulmonary function tests. Enrolled subjects performed as a health check for lung cancer screening including low-dose CT and pulmonary function tests. Subjects were divided into Stage 0, chronic obstructive pulmonary disease according to pulmonary function tests, and normal subjects. The severity of emphysema (visual score) was calculated on three low-dose CT slices. Low-dose CT and pulmonary function tests were performed in 1359 men and 888 women. The numbers and percentages of men and women smokers were 1076 (79.2%), and 107 (12.0%), respectively. A total of 722 individuals had one or more respiratory symptoms, such as cough (69.8%), sputum (75.8%), or shortness of breathing (0.83%). Of the 722 subjects, 71 (9.8%) individuals satisfied the criteria of chronic respiratory symptoms. Among the normal subjects, smoking caused differences in airflow limitation as a result of pulmonary function tests. The proportion of smokers and the visual score were significantly higher in Stage 0 than those in the normal subjects. The percentages of the maximal mid-expiratory flow (%MMF) and of the peak expiratory flow rate were significantly lower in Stage 0 than in the normal subjects. %MMF and the proportion of visual score were significantly lower in the smoking Stage 0 than in the nonsmoking Stage 0 subjects. Smoking would indicate early signs of emphysematous change between Stage 0 and normal subjects in comparison of pulmonary function tests and visual score of low-dose CT.

Female↗
PubMed2006

Therapeutic effects for hypersensitivity pneumonitis induced by Japanese mushroom (Bunashimeji).

BACKGROUND: Bunashimeji-related hypersensitivity pneumonitis is found among workers who cultivate the mushroom in indoor facilities. An evaluation of protective measures was initiated using the outcomes of clinical, immunological, and radiological findings. METHODS: Twenty-two patients presented with symptoms of HP; all were employed cultivating Bunashimeji mushrooms in indoor facilities. After hospitalization, 6 of 22 patients quit their job to avoid exposure to spores (Avoidance group). Sixteen patients continued to work used a mask for 3 months, and were then divided into two subgroups: Mask alone (seven patients) and mask plus oral prednisolone (Mask + PSL) (nine patients). The erythrocyte sedimentation rate (ESR), serum Krebs von der Lungen-6 (KL-6), surfactant protein-D (SP-D), lymphocyte stimulation test (LST), ground-glass scores in chest high-resolution computed tomography (HRCT), and bronchoalveolar lavage (BAL) were assessed before and after treatment. RESULTS: Complete avoidance resulted in a significant decrease in LST. There was a significant decrease after PSL treatment in serum KL-6, SP-D, and total cell counts in the BAL fluid in the Mask + PSL group. In the Mask alone group, serum KL-6, SP-D, ground-glass scores in chest HRCT and total cell counts in BAL fluid showed high levels compared with the other two groups. CONCLUSIONS: Complete cessation was the best treatment for hypersensitivity pneumonitis. The use of a mask was ineffective for patients with a high serum KL-6 and SP-D concentration and severe ground-glass opacity on chest HRCT. Initial treatment with PSL is recommended for these patients with high levels of total cell counts in BAL fluid.

Agaricales↗
PubMed2006

Comparison of the clinical efficacy of salmeterol and sustained-release tulobuterol (patch) on inadequately controlled asthma patients on inhaled corticosteroids.

Patients with inadequately controlled asthma on inhaled corticosteroid (400 to 1,600 microg/day chlorofluorocarbon beclomethasone equivalent) were treated with concomitant salmeterol (n = 18) or sustained-release tulobuterol (patch) (n = 18), or the inhaled corticosteroid dose was doubled (add-on) (n = 13) to compare clinical efficacy. (1) At 8 weeks, morning and evening peak expiratory flow rates were significantly improved in the salmeterol group only (p < 0.01). (2) Symptom and sleeplessness scores improved in the order, salmeterol (symptom score; p < 0.0001), inhaled corticosteroid add-on, and tulobuterol groups. (3) Only the salmeterol group showed significant improvement in the total Asthma Quality of Life Questionnaire score (p < 0.05). (4) No adverse reactions considered related to the study drugs were observed.

Administration, Cutaneous↗
PubMed2006

Genetic contribution of the endothelial nitric oxide synthase gene to high altitude adaptation in sherpas.

The Sherpas' adaptation to high altitude has been hypothesized as being due to a genetic basis since the beginning of the last century, but this has yet to be demonstrated. We randomly enrolled 105 Sherpas in Namche Bazaar (3440 m) and 111 non-Sherpa Nepalis in Kathmandu (1330 m) in Nepal. The genotypes of Glu298Asp and eNOS4b/a polymorphisms of the endothelial nitric oxide synthase (eNOS) gene were identified. The metabolites of nitric oxide (NO( x ): nitrite and nitrate) in serum were measured. The frequencies of the Glu and eNOS4b alleles were significantly higher in Sherpas (Glu: 87.5%; eNOS4b: 96.7%) than in non-Sherpas (Glu: 77.9%, p = 0.036; eNOS4b: 90.5%, p = 0.009). In addition, the combination of the wild types of Glu298Glu and eNOS4b/b was significantly greater in Sherpas (66.7%) than non-Sherpas (47.7%, p = 0.008). However, the serum NO( x ) was significantly lower in Sherpas (53.2 +/- 4.6 micromol/L) than in non-Sherpas (107.3 +/- 9.0 micromol/L, p < 0.0001). The wild alleles of the Glu298Asp and eNOS4b/a polymorphisms of the eNOS gene may be a benefit for the Sherpas' adaptation to high altitude. The nitric oxide metabolites (NO( x )) in serum vary individually, thus it is not a reliable indicator for endogenous nitric oxide production.

Acclimatization↗
PubMed2006

Symptoms of acute mountain sickness in Sherpas exposed to extremely high altitude.

Droma, Yunden, Masayuki Hanaoka, Buddha Basnyat, Amit Arjyal, Pritam Neupane, Anil Pandit, Dependra Sharma, and Keishi Kubo. Symptoms of acute mountain sickness in Sherpas exposed to extremely high altitude. High Alt. Med. Biol. 7:312-314, 2006.--The aim of this field interview was to investigate the current state of affairs concerning acute mountain sickness (AMS) in high-altitude residents, specifically the Sherpas at 3440 m above sea level, when they are exposed rapidly to altitudes significantly higher than their residing altitudes. Out of 105 Sherpas (44 men and 61 women, 31.2 +/- 0.8 yr), 104 had mountain-climbing experiences to 5701.4 +/- 119.1-m altitude in average 3.5 times each year. On the other hand, only 68 out of 111 non-Sherpas (29.9 +/- 0.8 yr) had experience of 1.4 +/- 1.5 climbs to an average 2688.6 +/- 150.4-m altitude in their mountaineering histories (p < 0.0001). Among the 104 Sherpas, 45 (43.3%) complained of at least one AMS symptom (headache, gastrointestinal symptoms, weakness, dizziness, and difficulty sleeping) in their experiences of mountaineering at an average 5518.9 +/- 195.9-m altitude. And 16 out of the 68 non-Sherpas (23.5%) reported the AMS symptoms at a mean altitude of 2750.0 +/- 288.8 m. Moreover, we also noticed that the Sherpa women showed a significantly higher Sa(O(2) ) (93.9 +/- 0.2%) than did Sherpa men (92.4 +/- 0.3%, p = 0.0001) at an altitude of 3440 m. The brief field interview evidenced that Sherpas might suffer from AMS when exposed to altitudes significantly higher than their residing altitude.

Acclimatization↗
PubMed2006

Hypoxia-sensitive molecules may modulate the development of atherosclerosis in sleep apnoea syndrome.

OBJECTIVES: Obstructive sleep apnoea hypopnoea syndrome (OSAHS) is associated with increased morbidity and mortality due to cardiovascular disease. In order to examine the association between OSAHS and cardiovascular disease, this study measured hypoxia-inducible and atherosclerosis-associated molecules in the peripheral blood. METHODS: In this study peripheral blood was obtained early in the morning from 60 consecutive male patients with OSAHS (AHI > or =10 events/h) and 30 male control subjects without OSAHS (AHI <5 events/h). Serum levels of heat shock protein-70 (Hsp-70), tissue factor (TF), monocyte chemotactic protein-1 (MCP-1), highly sensitive C-reactive protein (hs-CRP), hepatocyte growth factor and plasma vascular endothelial growth factor were measured and their relationship with severity and hypoxaemia in OSAHS examined. RESULTS: Serum hs-CRP, TF, MCP-1 and Hsp-70 levels were significantly higher in OSAHS compared with control subjects. Categorization of the patients into mild (10 < or = AHI < 30 events/h), moderate (30 < or = AHI < 60 events/h) and severe (AHI > or = 60 events/h) OSAHS subgroups showed that serum levels of hs-CRP, TF and Hsp-70 increased with severity. The hs-CRP, TF, MCP-1 and Hsp-70 levels in the non-obese OSAHS group were also significantly higher than those in the control group whereas there was no difference in BMI between the two groups. Repetitive hypoxaemia significantly correlated with hs-CRP, TF and Hsp-70 levels and appeared to be a significant determinant for these molecules. CONCLUSIONS: These findings suggest that CRP, TF and Hsp-70 may be upregulated by repetitive hypoxaemia in OSAHS and may be involved in the development of the atherogenic process in OSAHS.

Analysis of Variance↗
PubMed2006

Endobronchial argon plasma coagulation for the management of post-intubation tracheal stenosis.

Post-intubation tracheal stenosis is usually caused by pressure necrosis at the cuff. Despite the fact that this phenomenon is well known and both large volume and low pressure cuffs have been developed, this lesion nevertheless continues to occur. Although the best results for tracheal reconstruction are obtained by an experienced surgeon, not all patients are able to undergo this operation for either medical or personal reasons. Argon plasma coagulation (APC) using flexible bronchoscopy has been successfully employed in the treatment of post-intubation tracheal stenosis in two of the surgery-refused and inoperable patients. The patients immediately experienced a relief of symptoms after APC. APC was thus performed 3-4 times every 1-2 weeks for each patient. In addition, there were no complications related to this procedure. The number of published clinical reports describing APC in benign airway stenosis are increasing. APC has also been reported to have several advantages over other interventional endobronchial techniques in the management of tracheo-bronchial stenosis. We report two patients, and to our knowledge this is the first description of APC being used in the treatment of endobronchial dilatation for post-intubation tracheal stenosis.

Aged↗
PubMed2006

Clinical analysis of chronic obstructive pulmonary disease phenotypes classified using high-resolution computed tomography.

OBJECTIVE AND BACKGROUND: The present study was performed to clarify the clinical characteristics of patients with COPD classified into phenotypes according to the dominancy of emphysema and the presence of bronchial wall thickening (BWT) evaluated by chest high-resolution CT. METHODS: A total of 172 patients with stable COPD (FEV1<80%) were examined by chest high-resolution CT. Emphysematous changes and BWT were evaluated visually, and COPD patients were classified into three phenotypes: absence of emphysema, with little emphysema with or without BWT (A phenotype), emphysema without BWT (E phenotype) and emphysema with BWT phenotype (M phenotype). The clinical characteristics were compared among the three phenotypes. RESULTS: The A phenotype showed a higher prevalence of those who had never smoked and patients with wheezing both on exertion and at rest, higher values of BMI and diffusing capacity for carbon mononide (DLCO), milder lung hyperinflation, and greater reversibility of airflow limitation responsive to beta2-agonist as compared with the E phenotype. The M phenotype showed a higher prevalence of patients complaining of a large amount of sputum, productive cough and wheezing, higher rate of exacerbation or hospitalization and greater reversibility of airflow limitation responsive to beta2-agonist as compared with the E phenotype. CONCLUSIONS: These findings suggest that the morphological phenotypes of COPD show several clinical characteristics and different responsiveness to bronchodilators.

Adrenal Cortex Hormones↗