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Biomedical subjects

K Sekizawa

Publications and source records attributed to K Sekizawa.

At least 19 recordsLinked to original sources
PubMed2000

Early molecular and cellular events of oxidant-induced pulmonary fibrosis in rats.

To evaluate the early molecular events of oxidant-induced pulmonary fibrosis, rats were continuously exposed to 0.4 ppm ozone and 7 ppm nitrogen dioxide. The early responses to the combined gases could be divided into three phases. Acute pulmonary inflammation indicated by an increase in pulmonary edema as well as an influx of neutrophils into the airspaces first occurred on days 1 to 3 of the exposure. The pulmonary inflammation was reversed by day 8, and no biochemical or morphologic aspects of tissue responses were detected from days 15 to 45, suggesting that rats adapted to the stimuli during that period. Pulmonary fibrosis could be detected by an increase in the biomarker of lung collagen content at day 60 and by histopathologic evaluation by day 90. Enhanced expression of macrophage inflammatory protein-2 was observed only at day 1, whereas the pulmonary expression of transforming growth factor-beta was upregulated on days 60 and 90 of the exposure. Macrophage expressions of interleukin-1beta and interleukin-6 were enhanced during acute pulmonary inflammation; however, macrophage expression of tumor necrosis factor-alpha was elevated at both day 1 and days 60-90. Activation of nuclear factor-kappa B and increased expression of thioredoxin in the lungs was also observed at day 1 and days 60-90. The expression of antioxidant enzymes, such as manganeous superoxide dismutase and glutathione peroxidase, was not altered during exposure. These results indicate that macrophage activation and the expression of macrophage-derived cytokines may play an important role in the early pulmonary responses against the combined gases.

Administration, Inhalation↗
PubMed2000

Ebselen decreases ozone-induced pulmonary inflammation in rats.

We studied the effects of ebselen on rat lung inflammatory responses against ozone exposure. Rats were treated with ebselen every 12 h from 1 h before a single 4-h exposure to 2 ppm ozone. Treatment with ebselen (10 mg/kg) significantly decreased pulmonary inflammation as indicated by the albumin concentration and the number of neutrophils in the bronchoalveolar lavage fluid 18 h after the ozone exposure. Although treatment with ebselen did not alter the macrophage expression of inducible nitric oxide synthase after the ozone exposure, it did markedly inhibit the nitration reaction of tyrosine residues, suggesting that ebselen scavenges peroxynitrite during ozone-induced pulmonary inflammation. Treatment with ebselen also enhanced the pulmonary expression of both copper, zinc, and manganous superoxide dismutases at the same time point. These enzymes may also contribute to a decrease in the formation of peroxynitrite by lowering the concentration of superoxide. Thus, ebselen represents a useful compound for protecting against certain acute lung injuries by modulating the oxidant-related inflammatory process.

Acute Disease↗
PubMed2000

Pulmonary tuberculosis and serum IgE.

Several recent studies indicate that mycobacterium or viral infection may reduce IgE levels or suppress atopy or both. The present study was undertaken to investigate whether Mycobacterium tuberculosis infection and its successful treatment down-regulate serum total IgE levels, a marker of a Th2 response, due to enhancement of a Th1 response in adult patients with tuberculosis (TB). We prospectively studied the changes in serum total IgE and DTH response to tuberculin, a marker of a Th1 response in 10 healthy controls, 20 patients with pulmonary TB, and 19 asthma patients without TB. Measurement of serum total IgE and tuberculin skin tests were performed before initiation of treatment and after successful completion of 6 months treatment in TB patients, and at the corresponding intervals in controls and asthmatics. The initial serum total IgE concentrations were significantly higher in TB patients than in healthy controls (282 +/- 26 U/ml (mean +/- s.e.m.) in TB patients versus 126 +/- 56 U/ml in controls; P = 0.03). However, serum total IgE concentrations significantly decreased (282 +/- 26 U/ml before versus 151 +/- 12 U/ml after treatment; P = 0.03) and tuberculin indurations significantly increased (23.6 +/- 1.8 mm before versus 29.6 +/- 2.1 mm after treatment; P = 0.04) in TB patients. In contrast, initial serum IgE concentrations and tuberculin indurations did not differ significantly from post-observation data in both healthy controls and asthmatics (P>0.30). The present study confirmed that immune responses to M. tuberculosis down-regulate a Th2 immune response, and might contribute to the decreased prevalence of allergic disorders.

Asthma↗
PubMed2000

Relation between incidence of pneumonia and protective reflexes in post-stroke patients with oral or tube feeding.

OBJECTIVES: Although attenuated protective reflexes have been implicated in the development of aspiration pneumonia, the relation between the incidence of pneumonia and the state of these reflexes has not been investigated. Furthermore, the role of feeding tube placement in preventing pneumonia in patients with attenuated protective reflexes is unknown. We studied the relationship between the incidence of pneumonia and the state of cough and swallowing reflexes in post-stroke patients with oral or tube feeding. DESIGN: The incidence of pneumonia was prospectively analysed for 1 year in three groups of post-stroke patients on the basis of the following clinical conditions: oral feeding without dysphagia (n = 43); oral feeding with dysphagia (n = 48); and nasogastric tube feeding with dysphagia (n = 52). We also studied the incidence of pneumonia in bedridden patients with nasogastric tube feeding (n = 14). Before the start of the study, the swallowing and cough reflexes of each patient were measured. The swallowing reflex 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 cough threshold of citric acid aerosols was defined as the concentration at which the patient coughed five times. RESULTS.;: The incidence of pneumonia was observed in patients having both a latency of response longer than 5 s and a cough threshold for citric acid higher than a concentration of 1.35 (log mg mL-1). The incidence of pneumonia was significantly higher in patients with oral feeding than in those with tube feeding (54.3 vs. 13.2%, P < 0.001). In bedridden patients with tube feeding, the latency of response was longer than 20 s and no patient coughed at the highest concentration of citric acid. The incidence of pneumonia was 64.3% in such patients. CONCLUSIONS: The state of protective reflexes had a significant relation to the incidence of pneumonia. Feeding tube placement may have a beneficial role in preventing aspiration pneumonia in mildly or moderately disabled post-stroke patients with attenuated protective reflexes. Bedridden patients who were tube-fed had the highest incidence of pneumonia.

Aged↗
PubMed2000

Silent cerebral infarction: a potential risk for pneumonia in the elderly.

OBJECTIVE: To determine whether patients who have silent cerebral infarction are more likely to develop pneumonia than are controls without silent cerebral infarction. DESIGN: We examined 269 community-residing participants of the senior day-care centre without history of previous stroke, and then followed them over a two-year period to assess pneumonia. On the basis of computerized tomography scans, they were divided into two groups: no infarction (n = 102) and cerebral hemispheric infarction (n = 167). Cerebral infarcts were further divided into deep and superficial infarcts. RESULTS: The incidence of pneumonia was significantly higher in subjects with silent cerebral infarction (19.8%) than in controls (4. 9%) (odds ratio, 4.67 [95% CI, 1.87-11.67]; P < 0.01). Deep infarcts were more closely associated with the incidence of pneumonia (29.1%) than superficial infarcts (7.6%) (odds ratio, 5.00 [CI, 1.91-13.08]; P < 0.01). CONCLUSIONS: Elderly subjects with silent cerebral infarction were more likely to develop pneumonia than were controls without silent cerebral infarction. Amongst hemispheric silent cerebral infarcts, those located in the deep brain structures may be an important predictor of the development of pneumonia.

Aged↗
PubMed2000

Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema.

Cigarette smoke, containing reactive oxygen species, is the most important risk factor for chronic pulmonary emphysema (CPE). Heme oxygenase-1 (HO-1) plays a protective role as an antioxidant in the lung. A (GT)n dinucleotide repeat in the 5'-flanking region of human HO-1 gene shows length polymorphism and could modulate the level of gene transcription. To investigate the correlation between the length of the (GT)n repeat and susceptibility to the development of CPE, we screened the frequencies of alleles with varying numbers of (GT)n repeats in the HO-1 gene in 101 smokers with CPE and in 100 smokers without CPE. Polymorphisms of the (GT)n repeat were grouped into three classes: class S alleles (<25 repeats), class M alleles (25-29 repeats), and class L alleles (>/=30 repeats). The proportion of allele frequencies in class L, as well as the proportion of genotypic frequencies in the group with class L alleles (L/L, L/M, and L/S), was significantly higher in the smokers with CPE than in smokers without CPE. Moreover, we analyzed the promoter activities of the HO-1 gene carrying different (GT)n repeats (n=16, 20, 29, and 38), by transient-transfection assay in cultured cell lines. H2O2 exposure up-regulated the transcriptional activity of the HO-1 promoter/luciferase fusion genes with (GT)16 or (GT)20 but did not do so with (GT)29 or (GT)38. These findings suggest that the large size of a (GT)n repeat in the HO-1 gene promoter may reduce HO-1 inducibility by reactive oxygen species in cigarette smoke, thereby resulting in the development of CPE.

Aged↗
PubMed2000

Late recurrence of small-cell lung cancer: a case report.

A 67-year-old man was admitted with small-cell lung cancer (SCLC). The patient was given four courses of platinum-containing chemotherapy followed by chest irradiation, and good partial response (PR) was obtained. The patient did well for 4 years, until he sought treatment for a painful subcutaneous tumor. Chest computed tomography scan revealed the mass extending from the tumor in lung parenchyma with osteolytic lesion of the third rib bone. Pathologic examination of the subcutaneous lesion revealed SCLC. The patient was given two courses of the same combination chemotherapy administered as initial therapy. Regression of the mass was observed, and the response was evaluated as a good PR. How to approach late recurrence of SCLC is discussed.

Aged↗
PubMed2000

Effects of dexamethasone on rhinovirus infection in cultured human tracheal epithelial cells.

To examine the effects of glucocorticoid on rhinovirus (RV) infection, primary cultures of human tracheal epithelial cells were infected with either RV2 or RV14. Viral infection was confirmed by demonstrating that viral RNA in infected cells and viral titers of supernatants and lysates from infected cells increased with time. RV14 infection upregulated the expression of mRNA and protein of intercellular adhesion molecule-1 (ICAM-1), the major RV receptor, on epithelial cells, and it increased the production of interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor-alpha in supernatants. Dexamethasone reduced the viral titers of supernatants and cell lysates, viral RNA of infected cells, and susceptibility of RV14 infection in association with inhibition of cytokine production and ICAM-1 induction. In contrast to RV14 infection, dexamethasone did not alter RV2 infection, a minor group of RVs. These results suggest that dexamethasone may inhibit RV14 infection by reducing the surface expression of ICAM-1 in cultured human tracheal epithelial cells. Glucocorticoid may modulate airway inflammation via reducing the production of proinflammatory cytokines and ICAM-1 induced by rhinovirus infection.

Aged↗
PubMed2000

Dislocation of E-cadherin in the airway epithelium during an antigen-induced asthmatic response.

The airway epithelium plays a critical role in asthma. E-cadherin, located on the basolateral side of the epithelial cells, forms adherent junctions. To investigate the role of E-cadherin on the regulation of permeability of molecules and fluid in asthmatic responses, we observed the dynamics of E-cadherin after an immunochallenge against guinea pigs. Immunohistochemical studies revealed that E-cadherin was expressed on the lateral sides of epithelial cells before the immunochallenge and after immediate airway responses (IAR). However, E-cadherin immunoreactivities decreased from the basolateral region in late airway responses (LAR) 6 h after the challenge. Simultaneously, soluble E-cadherin immunoreactivities were detected in lavage fluid only in LAR, suggesting that E-cadherin is partly cleaved and released into the lumen in LAR. Airway permeability, which was examined by penetration of horseradish peroxidase from the airway side into the epithelium, increased in both IAR and LAR. These results suggest that E-cadherin detachment from the lateral side of the epithelial cells increased airway permeability in LAR but not IAR. We conclude that an antigen challenge causes an opening of adherent junctions as well as increases airway permeability in LAR. This mechanism would participate in airflow limitation during attacks and the increase of airway permeability and hyperresponsiveness in asthmatics.

Animals↗
PubMed2000

Expression of hnRNP A2/B1 proteins in human cancer cell lines.

The overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is recently reported informative as a marker of lung cancer for early detection. To examine whether the expression of the proteins is specific for lung cancer, immunological analyses were performed both in lung and non-lung cancer cell lines. In immunostaining and Western blotting, the expression of A2/B1 was observed not only in the lung cancer cells but also in non-lung cancer cells. The expression of hnRNP A2/B1 is not specific for lung cancer and quantitative determination of A2/B1 is required to elucidate their significance in carcinogenesis.

Heterogeneous-Nuclear Ribonucleoprotein Group A-B↗
PubMed2000

[Anaerobic bacillus pyothorax with the production of gas and severe mediastinal shift].

A 62-year-old man was admitted with the complaints of chronic sputum, dyspnea, and general weakness. Chest X-ray and computed tomographic films disclosed severe mediastinal shift and left lung collapse due to the accumulation of fluid and gas in the left pleural space. A puncture of the thoracic cavity yielded a milk-coffee-like purulent pleural effusion with stool odor, suggesting pyothorax with pneumothorax or broncho-pleural fistula. Chest tube drainage was performed. The elimination of gas was transient; subsequently, no air leaks were observed during deep breathing, suggesting the absence of pneumothorax and broncho-pleural fistula. An anaerobic culture of pleural effusion was prepared and a Bacteroides species was isolated. These clinical findings indicated that the intrathoracic gas could have been produced by anaerobic bacilli. Systemic antibiotic chemotherapy with chest tube drainage achieved recovery. The production of gas in focal lesions is one noted symptom of anaerobic bacillus infection. However, to our knowledge, cases of anaerobic bacillus pyothorax generating large volumes of intrathoracic gas are rare.

Anti-Bacterial Agents↗
PubMed1999

Combined effects of both bacteria and gastric juice on pneumonia in mice.

The effects of a combined inoculation of gastric juice and Streptococcus pneumoniae on the lungs of mice was investigated. Survival rates of mice inoculated with bacteria alone, gastric juice alone, and both bacteria and gastric juice were compared over 18 days. Xanthine oxidase (XO) activities in the lung tissues of mice inoculated with bacteria and gastric juice were measured and injected with a free radical scavenger, pyran-superoxide dismutase (pyran-SOD). A high mortality rate was observed in mice inoculated with both gastric juice and Streptococcus pneumoniae (81%). Mice inoculated with either Streptococcus pneumoniae or gastric juice showed a separate mortality rate of up to 10% during 18 days after inoculation. XO activity in the lung tissue of the mice inoculated with both gastric juice and bacteria was higher than in mice inoculated with either of them separately. The high mortality rate in the group inoculated with both two agents was reduced to 25% by the administration of pyran-SOD. XO activity raised by Streptococcus pneumoniae and gastric juice was significantly reduced by pyran-SOD. Thus, we suggest an important role in the combined effects of gastric juice and bacteria on pneumonia.

Animals↗