Author
Kiyohisa Sekizawa
Other affiliations: Gunma University
Bio: Kiyohisa Sekizawa is an academic researcher from Tohoku University. The author has contributed to research in topics: Lung cancer & Pneumonia. The author has an hindex of 40, co-authored 208 publications receiving 6120 citations. Previous affiliations of Kiyohisa Sekizawa include Gunma University.
Topics: Lung cancer, Pneumonia, Swallowing, Histamine, Asthma
Papers published on a yearly basis
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TL;DR: It is demonstrated that Nrf2 regulates the inflammation process downstream of 15d-PGJ2 by orchestrating the recruitment of inflammatory cells and regulating the gene expression within those cells.
Abstract: Activated macrophages express high levels of Nrf2, a transcription factor that positively regulates the gene expression of antioxidant and detoxication enzymes. In this study, we examined how Nrf2 contributes to the anti-inflammatory process. As a model system of acute inflammation, we administered carrageenan to induce pleurisy and found that in Nrf2-deficient mice, tissue invasion by neutrophils persisted during inflammation and the recruitment of macrophages was delayed. Using an antibody against 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), it was observed that macrophages from pleural lavage accumulate 15d-PGJ2. We show that in mouse peritoneal macrophages 15d-PGJ2 can activate Nrf2 by forming adducts with Keap1, resulting in an Nrf2-dependent induction of heme oxygenase 1 and peroxiredoxin I (PrxI) gene expression. Administration of the cyclooxygenase 2 inhibitor NS-398 to mice with carrageenan-induced pleurisy caused persistence of neutrophil recruitment and, in macrophages, attenuated the 15d-PGJ2 accumulation and PrxI expression. Administration of 15d-PGJ2 into the pleural space of NS-398-treated wild-type mice largely counteracted both the decrease in PrxI and persistence of neutrophil recruitment. In contrast, these changes did not occur in the Nrf2-deficient mice. These results demonstrate that Nrf2 regulates the inflammation process downstream of 15d-PGJ2 by orchestrating the recruitment of inflammatory cells and regulating the gene expression within those cells.
378 citations
TL;DR: Observations suggest that peripheral airways are the predominant site of airflow obstruction, irrespective of the different pathogenesis of chronic airflow obstruction.
Abstract: To partition the central and peripheral airway resistance in awake humans, a catheter-tipped micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a 3-mm-ID bronchus in 5 normal subjects, 7 patients with chronic bronchitis, 8 patients with emphysema, and 20 patients with bronchial asthma. We simultaneously measured mouth flow, transpulmonary pressure, and intra-airway lateral pressure during quiet tidal breathing. Total pulmonary resistance (RL) was calculated from transpulmonary pressure and mouth flow and central airway resistance (Rc) from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (Rp) was obtained by the subtraction of Rc from RL. The technique permitted identification of the site of airway resistance changes. In normal subjects, RL was 3.2 +/- 0.2 (SE) cmH2O.l-1.s and the ratio of Rp to RL was 0.24 during inspiration. Patients with bronchial asthma without airflow obstruction showed values of Rc and Rp similar to those of normal subjects. Although Rc showed a tendency to increase, only Rp significantly increased in those patients with bronchial asthma with airflow obstruction and patients with chronic bronchitis and emphysema. The ratio of Rp to RL significantly increased in three groups of patients with airflow obstruction (P less than 0.01). These observations suggest that peripheral airways are the predominant site of airflow obstruction, irrespective of the different pathogenesis of chronic airflow obstruction.
334 citations
TL;DR: Scanning of the thorax demonstrated that 71% of patients aspirated, whereas aspiration was observed in only 10% of control subjects, which may indicate an important role of silent aspiration in the development of community-acquired pneumonia in the elderly.
Abstract: Pneumonia is a major cause of death in the elderly. To investigate the role of silent aspiration in community-acquired pneumonia, we examined the occurrence of silent aspiration during sleep in 14 elderly patients with acute episode of pneumonia and 10 age-matched control subjects by a new technique using indium111 chloride. Scanning of the thorax demonstrated that 71% of patients aspirated, whereas aspiration was observed in only 10% of control subjects. The percentage of positive scans was significantly higher in patients with acute episode of pneumonia than in control subjects (p < 0.02). The results may indicate an important role of silent aspiration in the development of community-acquired pneumonia in the elderly.
325 citations
206 citations
TL;DR: Basal ganglia strokes might predispose patients to develop pneumonia owing to frequent aspiration during sleep, and the possible relationship between the location of cerebral hemispheric infarctions and the incidence of pneumonia is examined.
Abstract: Background: Pneumonia is a major cause of death in patients with cerebral infarction. We assessed morbidity associated with pneumonia in 276 patients 65 years of age or older who were admitted to a long-term care facility. Furthermore, we studied the swallowing reflex during the day and at night and monitored the occurrence of silent aspiration during sleep. Objectives: To examine the possible relationship between the location of cerebral hemispheric infarctions and the incidence of pneumonia and to evaluate the role of silent aspiration in the development of pneumonia. Methods: The incidence of pneumonia was analyzed in 4 groups of patients who were assigned to a group on the basis of the following computed tomographic findings: no infarct (group A); 1 or more unilateral basal ganglia infarcts (group B); bilateral basal ganglia infarcts (group C); and 1 or more cerebral hemispheric infarcts outside the basal ganglia (group D). Criteria for diagnosis of pneumonia were (1) a new pulmonary infiltrate seen on a chest radiograph and (2) 1 or more of the following features: cough, temperature greater than 37.8°C, or subjective dyspnea. Before the study, the patients with stroke were followed up for more than 1 year after their ictus and were monitored to determine if they sustained affecting cerebral hemispheric structures. The average duration of observation for incidence of pneumonia was 22 months. To study the swallowing reflex and to monitor for the occurrence of silent aspiration during sleep, 15 of the patients who were confined to bed or chair were randomly selected from each of groups A through C. The swallowing reflex was examined at both 1 PM and 1 AM and was evaluated according to latency of response, which was timed from the injection of 1 mL of distilled water into the pharynx through a nasal catheter to the onset of swallowing. The incidence of silent aspiration during sleep was examined using indium-111 chloride as a radioactive tracer attached to the teeth, and scanning of the thorax was performed the next morning. Results: The incidence of pneumonia was 2.12 times higher in the patients of group B (27.4%;P Conclusion: Basal ganglia strokes might predispose these patients to develop pneumonia owing to frequent aspiration during sleep. Arch Intern Med. 1997;157:321-324
201 citations
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TL;DR: These guidelines supersede the prior 2007 guidelines and 2009 updates and support the overarching concept of stroke systems of care and detail aspects of stroke care from patient recognition; emergency medical services activation, transport, and triage; through the initial hours in the emergency department and stroke unit.
Abstract: Background and Purpose—The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke. The intended audienc...
7,214 citations
TL;DR: The evidence for adverse effects on health of selected air pollutants is discussed, and it is unclear whether a threshold concentration exists for particulate matter and ozone below which no effect on health is likely.
4,010 citations
TL;DR: These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks.
Abstract: Background and Purpose- The purpose of these guidelines is to provide an up-to-date comprehensive set of recommendations in a single document for clinicians caring for adult patients with acute arterial ischemic stroke. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators. These guidelines supersede the 2013 Acute Ischemic Stroke (AIS) Guidelines and are an update of the 2018 AIS Guidelines. Methods- Members of the writing group were appointed by the American Heart Association (AHA) Stroke Council's Scientific Statements Oversight Committee, representing various areas of medical expertise. Members were not allowed to participate in discussions or to vote on topics relevant to their relations with industry. An update of the 2013 AIS Guidelines was originally published in January 2018. This guideline was approved by the AHA Science Advisory and Coordinating Committee and the AHA Executive Committee. In April 2018, a revision to these guidelines, deleting some recommendations, was published online by the AHA. The writing group was asked review the original document and revise if appropriate. In June 2018, the writing group submitted a document with minor changes and with inclusion of important newly published randomized controlled trials with >100 participants and clinical outcomes at least 90 days after AIS. The document was sent to 14 peer reviewers. The writing group evaluated the peer reviewers' comments and revised when appropriate. The current final document was approved by all members of the writing group except when relationships with industry precluded members from voting and by the governing bodies of the AHA. These guidelines use the American College of Cardiology/AHA 2015 Class of Recommendations and Level of Evidence and the new AHA guidelines format. Results- These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks. The guidelines support the overarching concept of stroke systems of care in both the prehospital and hospital settings. Conclusions- These guidelines provide general recommendations based on the currently available evidence to guide clinicians caring for adult patients with acute arterial ischemic stroke. In many instances, however, only limited data exist demonstrating the urgent need for continued research on treatment of acute ischemic stroke.
3,819 citations
TL;DR: Progression of COPD is associated with the accumulation of inflammatory mucous exudates in the lumen and infiltration of the wall by innate and adaptive inflammatory immune cells that form lymphoid follicles, coupled to a repair or remodeling process that thickens the walls of these airways.
Abstract: Background Chronic obstructive pulmonary disease (COPD) is a major public health problem associated with long-term exposure to toxic gases and particles. We examined the evolution of the pathological effects of airway obstruction in patients with COPD. Methods The small airways were assessed in surgically resected lung tissue from 159 patients — 39 with stage 0 (at risk), 39 with stage 1, 22 with stage 2, 16 with stage 3, and 43 with stage 4 (very severe) COPD, according to the classification of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Results The progression of COPD was strongly associated with an increase in the volume of tissue in the wall (P<0.001) and the accumulation of inflammatory mucous exudates in the lumen (P<0.001) of the small airways. The percentage of the airways that contained polymorphonuclear neutrophils (P<0.001), macrophages (P<0.001), CD4 cells (P=0.02), CD8 cells (P=0.038), B cells (P<0.001), and lymphoid aggregates containing follicles (P=0.003) and the abs...
3,401 citations
TL;DR: This systematic review and meta-analyses confirmed the findings of a previous study published in “Rhinitis and Asthma: Causes and Prevention, 2nd Ed.” (2015) as well as new findings of “Mechanisms of Respiratory Disease and Allergology,” which confirmed the role of EMTs in the development of these diseases.
Abstract: Authors Jan L. Brozek, MD, PhD – Department of Clinical Epidemiology & Biostatistics and Medicine, McMaster University, Hamilton, Canada Jean Bousquet, MD, PhD – Service des Maladies Respiratoires, Hopital Arnaud de Villeneuve, Montpellier, France, INSERM, CESP U1018, Respiratory and Environmental Epidemiology Team, France, and WHO Collaborating Center for Rhinitis and Asthma Carlos E. Baena-Cagnani, MD – Faculty of Medicine, Catholic University of Cordoba, Cordoba, Argentina Sergio Bonini, MD – Institute of Neurobiology and Molecular Medicine – CNR, Rome, Italy and Department of Medicine, Second University of Naples, Naples, Italy G. Walter Canonica, MD – Allergy & Respiratory Diseases, DIMI, Department of Internal Medicine, University of Genoa, Genoa, Italy Thomas B. Casale, MD – Division of Allergy and Immunology, Department of Medicine, Creighton University, Omaha, Nebraska, USA Roy Gerth van Wijk, MD, PhD – Section of Allergology, Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands Ken Ohta, MD, PhD – Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan Torsten Zuberbier, MD – Department of Dermatology and Allergy, Charite Universitatsmedizin Berlin, Berlin, Germany Holger J. Schunemann, MD, PhD, MSc – Department of Clinical Epidemiology & Biostatistics and Medicine, McMaster University, Hamilton, Canada
3,368 citations