Apoptosis of alveolar macrophages by cigarette smoke
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Journal Article↗
Biomedical subjects
A Nagai
Publications and source records attributed to A Nagai.
Effect of a thromboxane A(2) antagonist on sputum production and its physicochemical properties in patients with mild to moderate asthma.
STUDY OBJECTIVE: To determine the effects of a specific thromboxane A(2) (TxA(2)) receptor antagonist, seratrodast, on asthma control and airway secretions. DESIGN: Multicenter, double-blind, randomized, placebo-controlled study. PATIENTS: Forty-five patients with mild to moderate asthma who had been continuously expectorating sputum of > 20 g/d. Patients with a current pulmonary infection or taking oral corticosteroids, antibiotics, or mucolytic agents were excluded from the trial. INTERVENTIONS: Following a 2-week run-in period, while pulmonary function, sputum production, and mucociliary function were assessed, patients were assigned to receive seratrodast, 40 mg/d, or placebo for 6 weeks. MEASUREMENTS AND RESULTS: During the treatment period, the changes in FEV(1) and peak expiratory flow (PEF) were not different between the two patient groups, but there were significant reductions in diurnal variation of PEF (p = 0.034), frequency of daytime asthma symptoms (p = 0.030), and daytime supplemental use of beta(2)-agonist (p = 0.032) in the seratrodast group. For sputum analysis, seratrodast treatment decreased the amount of sputum (p = 0.005), dynamic viscosity (p = 0. 007), and albumin concentration (p = 0.028), whereas it had no effect on elastic modulus or fucose concentration. Nasal clearance time of a saccharin particle was shortened in the seratrodast group at week 4 (p = 0.031) and week 6 (p = 0.025), compared with the placebo group. CONCLUSION: Blockade of TxA(2) receptor has minimal effects on pulmonary function, but may cause an improvement in mucociliary clearance by decreasing the viscosity of airway secretions.
Adult↗
Induction of experimental periodontitis in mice with Porphyromonas gingivalis-adhered ligatures.
BACKGROUND: Little information is available on the colonization of periodontopathic bacteria and alveolar bone loss in a mouse system, because of the difficulty in establishing bacteria in the oral cavity. The aim of this study was to establish experimental periodontitis in mice by applying a Porphyromonas gingivalis-adhered ligature onto the molars. METHODS: Specific pathogen-free C3H/HeN mice were divided into 3 groups: 80 infected, 80 sham-infected, and 48 non-treated control mice. Sterile silk ligatures were preincubated with and without P. gingivalis 381 in vitro and then physically tied on the right maxillary first molar of infected and sham-infected mice, respectively. Ten mice from the infected and sham-infected groups and 6 from the control group were sacrificed at 2-week intervals for up to 15 weeks after infection. RESULTS: Plaque samples were collected at the time of sacrifice and alveolar bone loss was examined. The results indicated that P. gingivalis was recovered from the plaque samples in 95% of the infected mice after 1 week and then gradually dropped to 58% after 15 weeks of infection, whereas P. gingivalis was not isolated in either sham-infected or control mice throughout the experimental period. The infected mice showed significant P. gingivalis-induced bone loss at the sites where the ligature was tied weeks 13 to 15. A linear regression analysis revealed a significant positive correlation between the number of P. gingivalis recovered and alveolar bone loss at 15 weeks after infection (P <0.01). CONCLUSIONS: The use of a P. gingivalis-adhered ligature supported a long-lasting infection of P. gingivalis in mice, resulting in P. gingivalis-induced alveolar bone breakdown.
Alveolar Bone Loss↗
[A case of congenital cystic adenomatoid malformation of the lung in a 4-year-old child].
A case of congenital cystic adenomatoid malformation (CCAM) of the lung is reported. A 3-year-old boy was admitted for elevation of infiltrative shadow in the right lower lung field on a chest X-ray. The clinical diagnosis was emphysematous bullae with inflammation. After 6 months, he had recurrent infected bullae, and was admitted. He received chemotherapy with antibiotics prior to the operation. Right lower lobectomy was performed on February 2, 1998. The resected lung was composed of multiple cysts with thin wall measuring 10-60 mm in diameter. The histological examination of specimen revealed CCAM (Stocker type I), which is rare in this age. The patient has been well for 16 months postoperatively.
Child, Preschool↗
[Sleep medicine in USA and European countries--now and then].
In looking to the future in a field such as sleep medicine, there seems to be two general areas: (1) the scientific accomplishments that are likely to transpire in the years ahead and (2) how sleep medicine will be practiced in our evolving medical system. As the care of apnea patients becomes more standardized and effective, sleep medicine must be expanded scientifically and clinically, thereby becoming a complete and mature field. Advancing basic science and technology is likely to improve the well-being of patients with sleep disorders.
Academic Medical Centers↗
[Role of nitric oxide in airway mucociliary dysfunction in diffuse panbronchiolitis].
Nitric oxide (NO) stimulates the ciliary motility of the airway epithelium, thereby assisting in the regulation of mucociliary transport in the respiratory tract. In the present study, to elucidate a possible involvement of NO in mucociliary disturbance in diffuse panbronchiolitis (DPB), we measured nasal clearance time (NCT) using the saccharin test, NO concentration in the exhaled air with a chemiluminescence analyzer, and electrolyte concentration in the sputum. Compared with healthy nonsmokers and smokers, patients with DPB showed a lower NO concentration in the exhaled air (p < 0.05), prolonged NCT (p < 0.01), and a higher Cl concentration in the sputum (p < 0.05). Among these variables, exhaled NO concentration was negatively correlated with NCT (p < 0.01) and sputum Cl concentration (p < 0.05). These results suggest that the inhibition of NO generation associated with an elevated Cl concentration in the airway surface liquid may contribute to airway mucociliary dysfunction in DPB.
Breath Tests↗
Macrolide antibiotics protect against immune complex-induced lung injury in rats: role of nitric oxide from alveolar macrophages.
Macrolide antibiotics have unique immunomodulatory actions apart from antimicrobial properties. We studied the effects of macrolides on IgG immune complex (IgG-ICx)-induced lung injury in rats in vivo and in vitro. Intrapulmonary deposition of IgG-ICx produced a time-dependent increase in the concentration of NO in exhaled air. There were corresponding increases in the number of neutrophils accumulated into alveolar spaces, and lung wet-to-dry weight ratio. All of these changes were inhibited by pretreatment with erythromycin or josamycin, but not by amoxicillin or cephaclor. Incubation of cultured pulmonary alveolar macrophages caused up-regulation of NO production and expression of inducible NO synthase mRNA, an effect that was dose dependently inhibited by erythromycin, roxithromycin, or josamycin. The macrolides also reduced IgG-ICx-induced release of IL-1beta and TNF-alpha, but did not alter the release of NO induced by exogenously added IL-1beta and TNF-alpha. These results suggest that macrolide antibiotics specifically inhibit immune complex-induced lung injury presumably by inhibiting cytokine release and the resultant down-regulation of inducible NO synthase gene expression and NO production by rat pulmonary alveolar macrophages.
Animals↗
Red blood cells inhibit apoptosis of human neutrophils.
Oxidative stress has been implicated in the triggering of apoptosis in neutrophils. Because red blood cells (RBCs) are well known to scavenge oxidants including H2O2, we tested the hypothesis that RBCs inhibit apoptosis of neutrophils by reducing intracellular oxidative stress. Apoptosis of neutrophils was evaluated by light microscopy and DNA gel electrophoresis. We found that coculture with RBCs protected against neutrophil apoptosis. Neither physical contact between RBCs and neutrophils nor the cellular integrity of RBCs was required to protect against neutrophil apoptosis. Neutrophil apoptosis was promoted by exogenous H2O2 but suppressed by catalase, indicating a role for H2O2 as a mediator of apoptosis. The protective effect of RBCs against apoptosis was due to catalase and glutathione metabolism because blocking of these antioxidant systems in RBCs attenuated the protective effect of RBCs. These results suggest that neutrophils are protected against apoptosis in the circulation.
Apoptosis↗
Role of p38-mitogen-activated protein kinase in spontaneous apoptosis of human neutrophils.
Neutrophils constitutively undergo apoptosis at both normal and inflamed sites: an important process that limits the toxic potential of the neutrophil. However, the signal pathway for neutrophil apoptosis is currently unknown. In this study, we evaluated the role of p38-mitogen-activated protein kinase (MAPK) in the spontaneous apoptosis of neutrophils in vitro. We found that p38-MAPK was constitutively tyrosine phosphorylated and activated during spontaneous apoptosis of neutrophils. Inhibition of p38-MAPK by SB203580 and an antisense oligonucleotide delayed apoptosis by approximately 24 h. The antioxidants catalase and N-acetylcysteine delayed neutrophil apoptosis, but failed to inhibit phosphorylation and activation of p38-MAPK. Granulocyte-macrophage CSF and anti-Fas Ab, which altered the rate of apoptosis, did not affect phosphorylation and activation of p38-MAPK. These results suggest that the constitutive phosphorylation and activation of p38-MAPK are involved in the program of spontaneous apoptosis in neutrophils.
Antioxidants↗
[Pathology of diseases responsible for the development of respiratory insufficiency].
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Humans↗
Fas and Fas ligand interaction induces apoptosis in inflammatory myopathies: CD4+ T cells cause muscle cell injury directly in polymyositis.
OBJECTIVE: To investigate the involvement of the Fas/Fas ligand (Fas/FasL) system in the inflammatory myopathies. METHODS: Frozen muscle sections obtained from 7 patients with polymyositis (PM), 4 patients with dermatomyositis (DM), and 3 controls were studied by immunochemistry. Apoptosis was detected by DNA electrophoresis and in situ labeling using the TUNEL method. RESULTS: Fas was detected on muscle fibers and infiltrating mononuclear cells (MNC) in 6 PM patients and 2 DM patients. FasL was expressed mainly on CD4+ T cells and some CD8+ T cells, and on macrophages surrounding Fas-positive muscles in 4 PM patients and 1 DM patient. In 3 of the 5 patients with FasL-positive MNC, the TUNEL method showed that both invaded myonuclei and MNC underwent apoptosis. Chromosomal DNA from the muscle tissue of these patients showed ladder formation. CONCLUSION: Fas/FasL is involved in muscle cell apoptosis in at least 2 of the inflammatory myopathies, PM and DM. Although CD8+-mediated cytotoxicity is thought to be the main mechanism of muscle injury in PM, our data suggest that CD4+ T cells also directly cause muscle cell damage.
Apoptosis↗
Atypical adrenoceptor-mediated relaxation of canine pulmonary artery through a cyclic adenosine monophosphate-dependent pathway.
To determine whether functional atypical beta-adrenoceptors (beta(3)-adrenoceptors) are present in pulmonary vascular smooth muscle, we studied isolated canine pulmonary arterial rings under isometric conditions in vitro. Addition of beta-adrenoceptor agonists produced a concentration-dependent relaxation of noradrenaline-precontracted tissues, a rank order potency being isoproterenol (1) > salbutamol (0.95) > selective beta(3)-adrenoceptor agonists, CL 316243 (0.85), and BRL 37344 (0. 83). A marked desensitization to salbutamol occurred by pretreatment with salbutamol but not with CL 316243. When beta(1)-adrenoceptors had been blocked, the relaxant responses to salbutamol were competitively antagonized by the beta(2)-adrenoceptor antagonist ICI 118551 with a pA(2) value of 7.67 +/- 0.21 (mean +/- S.E.), but the response to CL 316243 was weekly antagonized by ICI 118551 only at a high concentration of 10(-5) M, where an apparent pA(2) value was 5. 24. In contrast, cyanopindolol, a nonselective beta-adrenoceptor antagonist, antagonized CL 316243-induced relaxation in a competitive manner with a pA(2) of 6.10 +/- 0.11. This pA(2) value was lower than that when salbutamol was used as an agonist (6.69 +/- 0.14, p < 0.01). Intracellular 3',5'-cyclic adenosine monophosphate (cAMP) levels were increased by CL 316243 in a concentration-dependent fashion, an effect that was not altered by ICI 118551. These results suggest that beta(3)-adrenoceptors may exist in canine pulmonary artery smooth muscle and that stimulation of this atypical receptor causes vasodilation through a cAMP-dependent pathway.
Animals↗
H2O2 induces apoptosis in bovine tracheal epithelial cells in vitro.
Oxidants play an important role in the pathogenesis of various airway diseases. Oxidants have been shown to induce two distinct types of cell death, i.e., apoptosis and necrosis. However, whether oxidants induce apoptosis in airway epithelial cells remains unclear. To address this question, we evaluated the effect of H2O2 exposure on bovine tracheal epithelial cells cultured under different conditions. When tracheal epithelial cells were isolated and exposed to H2O2 in suspension cultures, they underwent apoptosis as demonstrated by characteristic ultrastructural changes and DNA fragmentation. Interestingly, apoptosis occurred in single cells but not in aggregated cells. In addition, apoptosis was seen in many ciliated and in fewer mucous cells. When tracheal epithelial cells were allowed to attach to the substrate and grow, they became resistant to apoptosis induced by H2O2. These results suggest that H2O2 can induce apoptosis in airway epithelial cells.
Animals↗
A diary form quality of life questionnaire for Japanese patients with lung cancer and summarization techniques for longitudinal assessment.
The aim of this study was to confirm the validity and reliability of a new diary-type quality of life (QOL) self-rating questionnaire tailored for use by Japanese inpatients with lung cancer receiving chemotherapy. Two kinds of summary statistics were tested in QOL analysis. The questionnaire has a four-scale structure; physical, psychological, daily activity and global scales. Fifty-three patients were enrolled to test the reliability and validity. Summary statistics were assessed using indices of the area under the curve (AUC) and the maximum fluctuations of QOL scores (Dif max) in patients receiving cisplatin or carboplatin. The questionnaire had satisfactory reliability and validity. The physical, psychological and global scales scores changed to the worst levels after treatment, continuing for 1 week in the cisplatin group, whereas those of the carboplatin group began to worsen from day 3, but returned to prechemotherapy levels by day 9. The cisplatin group showed significant decrease of QOL compared with the carboplatin group in the AUC of psychological and two global scales, in the Dif max of psychological and linear analogue global scales. These results suggested that this questionnaire reflects differences in the influence of chemotherapy, and that AUC and Dif max may be useful indices for the analysis of QOL as measures to assess multidimensional QOL.
Adult↗
An unusual case of fatal gas embolism.
We describe an unusual case of fatal gas embolism, in which a man died by connecting an extension tube supplying oxygen to an indwelling catheter that was inserted into the left cephalic vein.
Aged↗
Effect of azelastine on platelet-activating factor-induced microvascular leakage in rat airways.
To determine the effect of the antiallergic drug azelastine on airway mucosal inflammation, we studied airway microvascular permeability in response to platelet-activating factor (PAF) in pathogen-free rats. Vascular permeability and neutrophil accumulation were assessed by the percent area occupied by Monastral blue-labeled blood vessels and by myeloperoxidase-containing granulocytes, respectively, in whole mounts of the trachea and main bronchus. Intravenous PAF caused dose-dependent increases in the area density of Monastral blue-labeled vessels and neutrophil influx, and the former effect was inhibited by depletion of circulating neutrophils by cyclophosphamide or treatment with the neutrophil elastase inhibitor ONO-5046. Pretreatment with azelastine inhibited PAF-induced vascular leakage without affecting neutrophil accumulation. This inhibitory effect of azelastine was not seen in neutropenic rats and ONO-5046-treated rats. PAF increased neutrophil elastase contents in bronchoalveolar lavage fluid, an effect that was inhibited by azelastine. Therefore, azelastine attenuates PAF-induced airway mucosal microvascular leakage, probably involving inhibition of the release of neutrophil elastase from activated neutrophils.
Animals↗
Effect of FK506 on ATP-induced intracellular calcium oscillations in cow tracheal epithelium.
To elucidate the effect of FK506 on Ca2+ oscillations in airway epithelium, we investigated cultured cow tracheal epithelial cells with a Ca2+ image-analysis system. ATP (1 microM) induced long-lasting Ca2+ oscillations, having nearly constant peak values (300-400 nM) and intervals (20-40 s) in subconfluent cells but not in confluent cells. These responses were gradually attenuated and abolished by the addition of FK506. Rapamycin, which binds the FK506-binding protein (FKBP), likewise inhibited Ca2+ oscillations, whereas cyclosporin A, a calcineurin inhibitor, did not. Treatment of cells with FK506 decreased Ca2+ content in thapsigargin-sensitive stores, suggesting that the partial depletion of the stores causes the inhibition of Ca2+ oscillations. Immunocytochemistry revealed the existence of cytoplasmic FKBP-like immunoreactivities. The expression of a 12-kDa FKBP was greater in subconfluent cells than in confluent cells as determined by Western blotting, suggesting that the 12-kDa FKBP may be one of the factors that regulates Ca2+ oscillations. Therefore, FK506 possesses an inhibitory action on the Ca2+ response via intracellular FKBP but not via calcineurin, which may result in modification of airway epithelial functions.
Adenosine Triphosphate↗