Corkscrew appearance in the right coronary artery in a patient with Buerger's disease.
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Adult↗
Biomedical subjects
J Kadota
Publications and source records attributed to J Kadota.
Swing-like movement of pigtail catheter in a patient with ruptured chordae tendinae.
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Aged↗
High plasma concentrations of osteopontin in patients with interstitial pneumonia.
Osteopontin (OPN) produced by alveolar macrophages functions as a fibrogenic cytokine in the development of bleomycin (BLM)-induced murine pulmonary fibrosis, and OPN mRNA is expressed on lung tissues from patients with idiopathic pulmonary fibrosis (IPF). The present study investigates plasma OPN levels in human interstitial pneumonia (IP) and their relationships with disease severity by analyzing the correlation between plasma OPN concentrations and pulmonary functions. The concentrations of OPN in plasma were measured in 17 patients with IP, in 9 with sarcoidosis and in 20 healthy controls using an antigen-capture enzyme-linked immunosorbent assay. The concentrations of OPN in plasma were significantly higher in IP patients than in those with sarcoidosis or in controls. Based on a Receiver Operating Characteristic curve analysis, cut-off points between 300 and 380 ng/ml discriminated between IP and control subjects with 100% sensitivity and 100% specificity. In such case, the sensitivity for sarcoidosis decreased (55.5-33.3%) in cut-offs with 100% specificity. Plasma OPN levels inversely and closely correlated with arterial oxygen tension (PaO2) in patients with IP. Immunohistochemically, OPN was localized predominantly in macrophages and airway epithelium. These findings suggest that plasma OPN levels were found to be associated with the presence of IP, and that OPN play an important role in the development of IP.
Adult↗
Pirfenidone attenuates expression of HSP47 in murine bleomycin-induced pulmonary fibrosis.
Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen. The present study was undertaken to investigate whether treatment with the antifibrotic drug pirfenidone attenuates the bleomycin (BL)-induced overexpression of HSP47 in the lungs. Male ICR mice were intravenously injected with BL or saline (SA). Pirfenidone or control drug (CD) was administered 14 days after commencement of BL or SA, and continued throughout the course of the experiment. The mice were randomly divided into three experimental groups: 1) SA-treated with CD (SA group); 2) BL-treated with CD (BL group); and 3) BL-treated with pirfenidone (pirfenidone group). Lungs of the pirfenidone group showed a marked reduction of fibrotic lesions compared with the corresponding BL group. Immunohistochemical studies showed that BL treatment significantly increased the number of macrophages, myofibroblasts, HSP47-positive type II pneumocytes and HSP47-positive interstitial spindle-shaped cells. Treatment with pirfenidone significantly reduced the number of these cells compared with the corresponding BL group. Furthermore, treatment with pirfenidone significantly suppressed the BL-induced increase of the positive ratio of HSP47 and alpha-smooth muscle actin to interstitial spindle-shaped cells. The present study results showed that pirfenidone inhibited heat shock protein 47-positive cells and myofibroblasts, the principal cells responsible for the accumulation and deposition of extracellular matrix seen in pulmonary fibrosis.
Analysis of Variance↗
Immunokinetics in severe pneumonia due to influenza virus and bacteria coinfection in mice.
Coinfections of bacteria and influenza are a major cause of excessive mortality during influenza epidemics. However, the mechanism of the synergy between influenza virus and bacteria are poorly understood. In this study, mice were inoculated with influenza virus, followed 2 days later by inoculation with Streptococcus pneumoniae. The kinetics of viral titres, bacterial numbers and the immune response (cytokine and chemokine production) were also analysed. Short-term survival correlated with pathological changes in the lungs of infected mice. Influenza virus or S. pneumoniae infection alone induced moderate pneumonia; however, severe bronchopneumonia with massive haemorrhage in coinfected mice, which caused death of these mice approximately 2 days after inoculation with S. pneumoniae, was noted. Intrapulmonary levels of inflammatory cytokines/chemokines, type-1 T-helper cell cytokines and Toll-like receptors, and the related mitogen-activated protein kinase signalling molecules (phosphorylated extracellular signal-regulated kinase -1 and - 2, p38 and c-Jun N-terminal kinase), were increased in coinfected mice. These results suggest that immune mediators, including cytokines and chemokines, through Toll-like receptors/mitogen-activated protein kinase pathways, play important roles in the pathology of coinfection caused by influenza virus and Streptococcus pneumoniae.
Animals↗
Long-term efficacy and safety of clarithromycin treatment in patients with diffuse panbronchiolitis.
Diffuse panbronchiolitis (DPB) can now be cured with long-term erythromycin treatment. Our group conducted a prospective open trial of long-term treatment with a macrolide antibiotic, clarithromycin. We studied ten patients who were treated for 4 years with oral clarithromycin (200 mg once a day). Pulmonary function test, blood gas analysis, comprehensive improvement score, and bacterial culture of sputum were examined at 3, 6, 12 months, and at 2, 3, 4 years after the initiation of the therapy. Pulmonary function improved in most of the patients within 6 months: the forced expiratory volume in one second showed a maximal increase from a mean (SE) value of 1.74 (0.12) l at baseline to 2.31 (0.22) l at 6 months (P < 0.01) and the volume (l) of forced vital capacity also showed a maximal increase within 6 months. The partial pressure of arterial oxygen at rest significantly increased at 3-6 months. The comprehensive improvement score also reached maximum within 6 months in nine of the patients. The majority of patients have developed sputum culture in which bacteria were negative within 6 months after the therapy. All of the patients maintained a stable condition with continued therapy, and no side effects of clarithromycin were observed during the study. This prospective study demonstrated that 6-month treatment with clarithromycin might be necessary to improve the clinical conditions of patients with DPB and the drug could be safely used for a long term.
Adult↗
High serum concentrations of surfactant protein A in usual interstitial pneumonia compared with non-specific interstitial pneumonia.
BACKGROUND: The pathological diagnosis of interstitial lung diseases (ILD) by surgical lung biopsy is important for clinical decision making. There is a need, however, to use serum markers for differentiating usual interstitial pneumonia (UIP) from other ILD. Surfactant protein (SP)-A, SP-D, KL-6, sialyl SSEA-1 (SLX), and sialyl Lewis(a) (CA19-9) are useful markers for the diagnosis and evaluation of activity of ILD. We have investigated the usefulness of these proteins as markers of UIP. METHODS: Serum and bronchoalveolar lavage (BAL) fluid levels of the above five markers were measured in 57 patients with various forms of ILD (19 with UIP, 12 with non-specific interstitial pneumonia (NSIP), eight with bronchiolitis obliterans organising pneumonia (BOOP), and 10 with sarcoidosis), eight patients with the control disease (diffuse panbronchiolitis (DPB)), and nine healthy volunteers. RESULTS: Serum levels of SP-A, SP-D, and KL-6 in patients with UIP and NSIP were significantly higher than in healthy volunteers. In particular, the serum levels of SP-A in patients with UIP were significantly higher than in patients with NSIP (p<0.0001, mean difference -58.3 ng/ml, 95% confidence interval -81.6 to -35.0), and BAL fluid levels of SP-D in patients with UIP were significantly lower than in patients with NSIP (p=0.01, mean difference 322.4 ng/ml, 95% confidence interval 79.3 to 565.5). CONCLUSION: Serum SP-A levels may be clinically useful as a biomarker to differentiate between UIP and NSIP.
Adult↗
Pulmonary lesions associated with Sjögren's syndrome: radiographic and CT findings.
The aim of this study was to analyse and compare the chest radiographic and CT findings in patients with primary and secondary Sjögren's syndrome. We retrospectively evaluated the frequency of abnormality and findings of both the chest radiography (n=107) and CT (n=59) in patients with Sjögren's syndrome. Abnormal cases were classified into five patterns based on predominant CT findings. Chest radiographic and CT abnormalities were seen in 24 (22%) and in 34 (58%) patients, respectively. Most frequently observed abnormal findings were linear and reticular opacities on chest radiograph, and ground-glass opacity, interlobular septal thickening and intralobular interstitial thickening on CT in both primary and secondary Sjögren's syndrome. Centrilobular abnormalities were significantly more common in patients with primary Sjögren's syndrome (p=0.018). According to our CT classification, interstitial pneumonia (IP) pattern was the most common in patients with both primary and secondary Sjögren's syndrome. Bronchiolitis pattern was more common in patients with primary Sjögren's syndrome and lymphoproliferative disorder (LPD) pattern was only observed in primary Sjögren's syndrome. In conclusion, although the most frequently observed pattern in our CT classification was IP pattern in both primary and secondary Sjögren's syndrome, centrilobular abnormalities and LPD pattern were relatively characteristic in patients with primary Sjögren's syndrome.
Adolescent↗
Raised plasma concentrations of alpha-defensins in patients with idiopathic pulmonary fibrosis.
BACKGROUND: Neutrophils are thought to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Human neutrophils contain antimicrobial and cytotoxic peptides in the azurophil granules which belong to a family of mammalian neutrophil peptides named alpha-defensins. A study was undertaken to investigate the role of alpha-defensins in the pathogenesis of IPF. METHODS: The concentrations of alpha-defensins (human neutrophil peptides (HNPs) 1, 2, and 3) in plasma and bronchoalveolar lavage (BAL) fluid of 30 patients with IPF and 15 healthy subjects were measured by radioimmunoassay. RESULTS: The concentrations of alpha-defensins in plasma, but not in BAL fluid, were significantly higher in IPF patients than in controls. BAL fluid concentrations of interleukin (IL)-8 in patients with IPF, which were significantly higher than in controls, correlated with those of alpha-defensins. An inverse relationship was seen between plasma alpha-defensin levels and the arterial oxygen tension (PaO(2)) and pulmonary function (vital capacity (%VC), forced expiratory volume in 1 second (FEV(1)), and carbon monoxide transfer factor (%TLCO)) in patients with IPF. Plasma levels of alpha-defensins also correlated with the clinical course in IPF patients with an acute exacerbation. Immunohistochemically, positive staining was observed inside and outside neutrophils in the alveolar septa, especially in dense fibrotic areas. CONCLUSION: These findings suggest that alpha-defensins play an important role in the pathogenesis of IPF, and that the plasma alpha-defensin level may be a useful marker of disease severity and activity.
Bronchoalveolar Lavage Fluid↗
Characterization of CD44 expressed on alveolar macrophages in patients with diffuse panbronchiolitis.
Interleukin (IL)-8 may play an important role in neutrophil infiltration in the airways of patients with diffuse panbronchiolitis (DPB). Furthermore, alveolar macrophages could produce IL-8 subsequent to CD44-hyaluronic acid (HA) interaction. The purpose of this study was to evaluate the contribution of CD44 expressed on alveolar macrophages to the pathogenesis of DPB. We examined the concentration of soluble CD44 (sCD44) in bronchoalveolar lavage fluid (BALF) and CD44 expression on macrophages in BALF from patients with DPB before and after low-dose, long-term macrolide therapy. We also assessed the HA-binding ability of alveolar macrophages as a functional analysis of the CD44 molecule. The sCD44 concentration in BALF was significantly lower in patients with DPB than in healthy volunteers. Percentages of alveolar macrophages expressing low CD44 (CD44 low(+)) and HA-nonbinding alveolar macrophages were higher in patients with DPB compared with healthy volunteers. Furthermore, macrolide therapy normalized CD44 expression and HA-binding ability of macrophages in BALF from DPB patients. Our findings suggest that alveolar macrophage dysfunction could result from abnormalities of CD44 expression in patients with DPB and that these events could contribute to the pathogenesis of DPB.
Adult↗
[Clinical characterization of blaIMP positive gram-negative rods isolated cases].
We detected the metallo-beta-lactamase gene blaIMP positive strains of the gram-negative rods (GNR) isolated in Oita Medical University Hospital between 1993 and 1999 and studied the clinical characteristics of patients infected or colonized with blaIMP positive GNR. 25 strains (20 Pseudomonas aeruginosa and 5 Serratia marcescens) were detected and most of them were isolated from urinary samples after 1997. In the studies of antimicrobial susceptibility, some strains had sensitivity to aztreonum or imipenem although most of the strains showed multidrug resistance. When blaIMP positive GNR were isolated from patients, these strains were thought to have caused infection in 88% of the patients. About half of the patients were over 65 years old and had malignant diseases. Most of the patients had inserted urinary tract catheters, intratracheal tube or intravernous catheters. It was suggested that the insertion of the catheters were related to infection of blaIMP positive GNRs. Two patients were not treated with any antibiotics before the isolation of blaIMP positive GNRs although more than half of the patients were administered carbapenems and cephems. Most of strains were isolated in the same department and showed the same genotype by pulsed field gel electrophoresis.
Bacterial Proteins↗
High concentrations of beta-chemokines in BAL fluid of patients with diffuse panbronchiolitis.
BACKGROUND: T cells are important cellular components of bronchial inflammation in diffuse panbronchiolitis (DPB). beta-Chemokines such as RANTES (regulated on activation, normal T-cell expressed and secreted) and macrophage inflammatory peptide (MIP)-1alpha are closely related to the migration of inflammatory cells into the lung. In this study, we investigate the contribution of beta-chemokines to the accumulation of T cells in the lungs of patients with DPB. PATIENTS AND METHODS: We determined the levels of beta-chemokines in BAL fluid (BALF) and the correlation between these levels and T-cell subsets in BALF of 23 patients with DPB and 16 healthy subjects by sandwich enzyme-linked immunosorbent assay and flow cytometry. RESULTS: Percentages of CD3+ human leukocyte antigen (HLA)-DR+, CD8+, and CD8+HLA-DR+ cells in BALF of patients were significantly higher than in the control BALF. The absolute number of CD8+HLA-DR+ cells was also higher in BALF of patients than in the control BALF (p < 0.0001). Phenotypic analysis of CD4+ cells in BALF showed a similar percentage of CD4+CD45RA+ cells and CD4+CD29+ cells in patients and normal subjects. The concentrations of RANTES and MIP-1alpha in BALF of patients with DPB were significantly higher than in BALF of normal subjects (p < 0.05). In addition, there was a significant correlation between the absolute number or percentage of CD8+HLA-DR+ cells and MIP-1alpha concentration in BALF. CONCLUSIONS: Our results suggest that the interaction between activated CD8+ T cells and MIP-1alpha may contribute to the pathogenesis of DPB.
Adolescent↗
Disopyramide-induced pneumonitis, diagnosed by lymphocyte stimulation test using bronchoalveolar lavage fluid.
A 72-year-old man was admitted to our hospital with fever and cough. He had been on disopyramide treatment for nine days to control cardiac arrhythmia. On admission, chest X-ray examination revealed reticulonodular opacities in both lungs, and impending respiratory failure was evident. A differential cell count of the bronchoalveolar lavage fluid (BALF) showed a marked increase of lymphocytes. A lymphocyte stimulation test (LST) for disopyramide using BALF was positive, although the test using peripheral blood was negative. This case suggests that LST using BALF is useful for the diagnosis of drug-induced pneumonitis.
Aged↗
[A case of primary pleural leiomyosarcoma].
A 70-year-old man was admitted to our hospital with complaints of chest pain and exertional dyspnea. Chest radiography and computed tomography (CT) revealed right pleural effusion and pleural thickening on admission. The pleural fluid was bloody. Microbiological and cytologic examinations of the fluid were negative. The chest CT revealed progress of pleural thickening after hospitalization. A thoracoscopic pleural biopsy was performed, and the histological finding of the excised specimen was leiomyosarcoma. Because no organ of origin of the leiomyosarcoma, other than the pleura, was detected, this case was diagnosed as a primary pleural leiomyosarcoma. It is thought that leiomyosarcoma originating from the pleura is rare.
Aged↗
Effects of macrophage colony-stimulating factor (M-CSF) on anti-fungal activity of mononuclear phagocytes against Trichosporon asahii.
Trichosporon asahii is an emerging opportunistic pathogen in immunocompromised patients. Little is known about the mechanisms of host defence against T. asahii. We investigated the fungicidal activity of human peripheral blood monocytes and murine peritoneal macrophages against T. asahii isolates, and the effects of M-CSF on the anti-fungal activity of mononuclear phagocytes. We also established a neutropenic mouse model of disseminated trichosporonosis with T. asahii. M-CSF enhanced the phagocytic fungicidal activity of mononuclear cells, and infected mice treated with human M-CSF at 10 x 106 U/kg showed a significant improvement in survival rate, with fewer fungal colony counts in the lung compared with control mice. Mice treated with human M-CSF showed higher concentrations of tumour necrosis factor-alpha (TNF-alpha) in the lung and plasma compared with control mice. The survival rate was significantly reduced in mice treated with anti-mouse TNF-alpha. Our results showed that M-CSF enhanced the fungicidal activity of mononuclear phagocytes partly by production of TNF-alpha, and suggest that the administration of M-CSF to patients with disseminated trichosporonosis may be a useful adjunct to conventional anti-microbial therapy and prophylaxis.
Animals↗
Up-regulation of human T lymphotropic virus type 1 (HTLV-1) tax/rex mRNA in infected lung tissues.
HTLV-1 has been implicated in certain pulmonary diseases. We previously demonstrated that expression of HTLV-1 tax/rex mRNA, encoding the transcriptional transactivator Tax, was closely associated with infiltration of activated T lymphocytes into lung tissue. To explore mechanisms of tax/rex expression in the lung, tax/rex mRNA expression and proviral DNA load were compared between peripheral blood mononuclear cells (PBMC) and bronchoalveolar lavage cells (BALC) from four patients with HTLV-1-associated myelopathy (HAM/TSP) and 13 carriers with various pulmonary symptoms. Semiquantitative detection of tax/rex mRNA strongly suggested that the lung was a preferential site for its expression. Proviral DNA loads in non-HAM/TSP carriers were variable but correlated well between PBMC and BALC in each individual, and revealed no relationship with tax/rex mRNA expression. In contrast, both cell groups from four HAM/TSP patients expressed detectable tax/rex mRNA accompanied by high proviral DNA load. The ratio of tax/rex mRNA expression to proviral DNA load was higher in BALC than in PBMC in three of four carriers and in three of four HAM/TSP patients, suggesting up-regulation of tax/rex mRNA in infected lung tissue. To analyse differences in distribution of HTLV-1 quasispecies between the two tissues, phylogenetic analysis was performed for sequence sets of the proviral tax open reading frame (ORF: 1059 bp) derived from PBMC and BALC of two infected individuals. Sequences derived from the two tissues distributed similarly to branches of phylogenetic trees, and there was no evidence of selective distribution of certain quasispecies in the lung. Our results suggest the presence of tissue-specific conditions that activate viral expression in infected cells in the lung. Constitutive exposure of this tissue to foreign antigens leading to up-regulation of basal viral promoter activity is likely to be one such mechanism.
Adolescent↗
Possible role of L-selectin in T lymphocyte alveolitis in patients with active pulmonary sarcoidosis.
A number of adhesion molecules participate in the recruitment of inflammatory cells to the site of inflammation, and selectins together with their ligands are important in the early transient adhesion phase. In this study, we evaluated the role of L-selectin in T lymphocyte alveolitis in patients with active pulmonary sarcoidosis. We measured serum and bronchoalveolar lavage fluid (BALF) concentrations of soluble (s)L-selectin using an ELISA. Serum and BALF concentrations of sL-selectin were significantly elevated in patients with sarcoidosis compared with control healthy subjects and idiopathic pulmonary fibrosis (IPF) patients (P < 0.05 and P < 0. 01, respectively). The lymphocyte surface marker was also examined in peripheral blood and BALF by flow cytometric analysis. The percentage of CD3+CD62L+ cells (L-selectin-bearing T lymphocytes) was significantly lower in peripheral blood of sarcoidosis than in that of healthy subjects (P < 0.01). In contrast, the percentage of CD3+CD62L- cells (L-selectin-negative T lymphocytes) in BALF of patients with sarcoidosis was significantly higher than in healthy subjects (P < 0.05) and IPF patients (P < 0.01). Furthermore, there was a significant correlation between serum concentrations of sL-selectin and the number of L-selectin-negative T lymphocytes in BALF (r = 0.535, P < 0.01). Our results suggest that L-selectin may be involved in T lymphocyte alveolitis in patients with active pulmonary sarcoidosis.
Adult↗
Intrapulmonary concentrations of inflammatory cytokines in a mouse model of chronic respiratory infection caused by Pseudomonas aeruginosa.
We investigated the role of inflammatory cytokines in a mouse model of chronic Pseudomonas aeruginosa infection mimicking diffuse panbronchiolitis (DPB), and determined the effects of clarithromycin therapy on the production of these cytokines. The concentrations of IL-1beta, IL-2, IL-4, IL-5, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) were measured serially in the lungs of mice with experimentally induced chronic respiratory P. aeruginosa infection until 60 days after inoculation. The concentrations of these cytokines during the course of the disease were significantly higher than baseline (before inoculation, P<0.01 for all cytokines). Clarithromycin significantly inhibited the production of IL-1beta and TNF-alpha in the lung (P<0.01). The same treatment also reduced the levels of other cytokines, albeit insignificantly. Treatment with anti-TNF-alpha antibody significantly reduced the number of pulmonary lymphocytes and concentration of IL-1beta in the lung (P<0.01), but did not change the number of viable bacteria. Our findings resemble those detected in bronchoalveolar lavage fluid of patients with DPB and indicate that inflammatory cytokines play an important role in chronic P. aeruginosa lung infection. Our results also show that macrolides modulated the production of these cytokines, ultimately reducing lymphocyte accumulation in the lung. Our data suggest that anti-TNF-alpha antibody might be a useful new strategy for the treatment of chronic respiratory P. aeruginosa infection.
Animals↗