Publications (39)100.56 Total impact
-
Article: Total serum IgE levels and atopic status in patients with sarcoidosis.
[show abstract] [hide abstract]
ABSTRACT: To date, two studies have reported lower total serum immunoglobulin E (IgE) levels and lower prevalence of atopy in patients with sarcoidosis compared with healthy subjects. However, those reports did not consider age or gender differences between cases and controls. In addition, the association between total serum IgE levels and clinical manifestations of sarcoidosis has not been clarified. This study assessed total serum IgE levels and prevalence of atopy in patients with sarcoidosis after taking age and sex differences into account and evaluated associations between total serum IgE levels and clinical manifestations of sarcoidosis. Total serum IgE levels and prevalence of atopy on initial visits were compared between 189 patients with sarcoidosis and 378 age- and sex-matched controls. Associations between total serum IgE levels and involvement of each affected organ were evaluated. Changes in total serum IgE levels during the clinical course of sarcoidosis were also evaluated. Total serum IgE levels were significantly lower in patients with sarcoidosis than in controls, independent of atopic status (atopic subjects, p = 0.025; nonatopic subjects, p < 0.001). Total serum IgE levels did not differ according to the involvement of different organs. Total serum IgE levels decreased further, albeit only slightly, after disease remission (p < 0.001). Increased susceptibility to sarcoidosis may be attributable to several underlying genetic or environmental factors that result in lower total serum IgE levels.Allergy and Asthma Proceedings 01/2012; 33(1):90-4. · 2.17 Impact Factor -
Article: Direct evidence that GM-CSF inhalation improves lung clearance in pulmonary alveolar proteinosis.
[show abstract] [hide abstract]
ABSTRACT: Autoimmune pulmonary alveolar proteinosis (aPAP) is caused by granulocyte/macrophage-colony stimulating factor (GM-CSF) autoantibodies in the lung. Previously, we reported that GM-CSF inhalation therapy improved alveolar-arterial oxygen difference and serum biomarkers of disease severity in these patients. It is plausible that inhaled GM-CSF improves the dysfunction of alveolar macrophages and promotes the clearance of the surfactant. However, effect of the therapy on components in bronchoalveolar lavage fluid (BALF) remains unclear. To figure out changes in surfactant clearance during GM-CSF inhalation therapy. We performed retrospective analyses of BALF obtained under a standardized protocol from the same bronchus in each of 19 aPAP patients before and after GM-CSF inhalation therapy (ISRCTN18931678, JMA-IIA00013; total dose 10.5-21 mg, duration 12-24 weeks). For evaluation, the participants were divided into two groups, high responders with improvement in alveolar-arterial oxygen difference ≥13 mmHg (n = 10) and low responders with that < 13 mmHg (n = 9). Counts of both total cells and alveolar macrophages in BALF did not increase during the therapy. However, total protein and surfactant protein-A (SP-A) were significantly decreased in high responders, but not in low responders, suggesting that clearance of surfactant materials is correlated with the efficacy of the therapy. Among 94 biomarkers screened in bronchoalveolar lavage fluid, we found that the concentration of interleukin-17 and cancer antigen-125 were significantly increased after GM-CSF inhalation treatment. GM-CSF inhalation decreased the concentration of total protein and SP-A in BALF, and increase interleukin-17 and cancer antigen-125 in improved lung of autoimmune pulmonary alveolar proteinosis.Respiratory medicine 11/2011; 106(2):284-93. · 2.33 Impact Factor -
Article: Age-dependent deterioration of peak inspiratory flow with two kinds of dry powder corticosteroid inhalers (Diskus and Turbuhaler) and relationships with asthma control.
[show abstract] [hide abstract]
ABSTRACT: Inhaled corticosteroid (ICS) therapy has improved the quality of life (QOL) for many asthmatics and reduced mortality rates associated with asthma. However, some patients do not obtain therapeutic benefit despite satisfactory adherence. To determine whether asthmatic patients were using ICS devices appropriately, and to clarify relationships between these results and QOL. We studied 100 adult asthmatics, divided into two groups: 50 patients consecutively registered as using Diskus (fluticasone; D-group) and 50 consecutively registered as using Turbuhaler (budesonide; T-group). We measured peak inspiratory flows (PIFs) using the In-Check Dial device. Subjects also completed the Asthma Control Test for evaluation of QOL. In the D-group, no patients showed PIF below the optimal range (30-90 L/min), whereas 52% of patients had PIF≥91 L/min. In the T-group, 6% of patients showed PIF over the optimal range (60-90 L/min), and 44% had PIF≤59 L/min. When patients in the T-group were required to deliberately make a maximal inhalation, 14% still had PIF≤59 L/min. The proportion of patients with poor control was significantly greater in the T-group than in the D-group. According to univariate logistic regression analyses, low PIF tended to be associated with poor asthma control in the T-group. No significant correlation was found between PIF and age in the D-group, but PIF decreased significantly with age in the T-group. Appropriate measures for patients in whom PIF has been judged as lower than optimal include adequate education for inhalation and/or changing to a different inhalation device. These measures should be kept in mind for elderly asthma patients in particular, where appropriate selection of a corticosteroid inhalation device in the early stages of therapy would also be important.Journal of Aerosol Medicine and Pulmonary Drug Delivery 11/2011; 24(6):293-301. · 2.20 Impact Factor -
Article: [Case of von Recklinghausen disease complicated with a solitary lung lesion located mainly in the upper lung field].
[show abstract] [hide abstract]
ABSTRACT: A 72-year-old man presented with grade III dyspnea according to the Hugh-Jones scale in February, 2007, and he was referred to our department. Massive fibrosis of upper lung field dominance and bilateral pleural effusion were observed on chest X-ray films and CT. A respiratory function test revealed mixed ventilatory disturbance. Thereafter, left-sided pneumothorax developed in February 2008, followed by right-sided pneumothorax. He recovered once; however, respiratory failure progressed. He was re-hospitalized due to pneumonia and CO2 narcosis. Respiratory failure could not be prevented, and he died in September 2008. Macroscopic autopsy findings included fibrous adhesion of the pleura and fibrous consolidation of lung parenchyma which was most dominant in the bilateral apices. These were accompanied by bronchiectasis and brochiolectasis. Microscopically, the core pathology was organizing bronchiolitis and organizing pneumonia. Reported cases of diffuse lung lesions complicated with von Recklinghausen disease mostly comprise fibrosis and emphysematous changes. The unique pathological findings in this case seemed unrelated to any known disease entity.Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 11/2010; 48(11):871-5. -
Article: Genetic variants in mannose receptor gene (MRC1) confer susceptibility to increased risk of sarcoidosis.
[show abstract] [hide abstract]
ABSTRACT: Mannose receptor (MR) is a member of the C-type lectin receptor family involved in pathogen molecular-pattern recognition and thought to be critical in shaping host immune response. The aim of this study was to investigate potential associations of genetic variants in the MRC1 gene with sarcoidosis. Nine single nucleotide polymorphisms (SNPs), encompassing the MRC1 gene, were genotyped in a total of 605 Japanese consisting of 181 sarcoidosis patients and 424 healthy controls. Suggestive evidence of association between rs691005 SNP and risk of sarcoidosis was observed independent of sex and age in a recessive model (P = 0.001). These results suggest that MRC1 is an important candidate gene for sarcoidosis. This is the first study to imply that genetic variants in MRC1, a major member of the C-type lectin, contribute to the development of sarcoidosis.BMC Medical Genetics 10/2010; 11:151. · 2.33 Impact Factor -
Article: Inhaled granulocyte/macrophage-colony stimulating factor as therapy for pulmonary alveolar proteinosis.
[show abstract] [hide abstract]
ABSTRACT: Inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) is a promising therapy for pulmonary alveolar proteinosis (PAP) but has not been adequately studied. To evaluate safety and efficacy of inhaled GM-CSF in patients with unremitting or progressive PAP. We conducted a national, multicenter, self-controlled, phase II trial at nine pulmonary centers throughout Japan. Patients who had lung biopsy or cytology findings diagnostic of PAP, an elevated serum GM-CSF antibody level, and a Pa(O(2)) of less than 75 mm Hg entered a 12-week observation period. Those who improved (i.e., alveolar-arterial oxygen difference [A-aDO(2)] decreased by 10 mm Hg) during observation were excluded. The rest entered sequential periods of high-dose therapy (250 microg Days 1-8, none Days 9-14; x six cycles; 12 wk); low-dose therapy (125 microg Days 1-4, none Days 5-14; x six cycles; 12 wk), and follow-up (52 wk). Fifty patients with PAP were enrolled in the study. During observation, nine improved and two withdrew; all of these were excluded. Of 35 patients completing the high- and low-dose therapy, 24 improved, resulting in an overall response rate of 62% (24/39; intention-to-treat analysis) and reduction in A-aDO(2) of 12.3 mm Hg (95% confidence interval, 8.4-16.2; n = 35, P < 0.001). No serious adverse events occurred, and serum GM-CSF autoantibody levels were unchanged. A treatment-emergent correlation occurred between A-aDO(2) and diffusing capacity of the lung, and high-resolution CT revealed improvement of ground-glass opacity. Twenty-nine of 35 patients remained stable without further therapy for 1 year. Inhaled GM-CSF therapy is safe, effective, and provides a sustained therapeutic effect in autoimmune PAP. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN18931678), www.jmacct.med.or.jp/english (JMA-IIA00013).American Journal of Respiratory and Critical Care Medicine 02/2010; 181(12):1345-54. · 11.08 Impact Factor -
Article: Deficiency in the serum-derived hyaluronan-associated protein-hyaluronan complex enhances airway hyperresponsiveness in a murine model of asthma.
[show abstract] [hide abstract]
ABSTRACT: Serum-derived hyaluronan (HA)-associated proteins (SHAPs), the heavy chains of inter-α-trypsin inhibitor, covalently bind to HA to form the SHAP-HA complex. The SHAP-HA complex is involved in the pathophysiology of inflammatory diseases, including rheumatoid arthritis. We investigated whether this complex is also involved in airway allergy. SHAP-HA-deficient (bikunin knockout, KO) mice and wild-type (WT) mice were immunized twice by intraperitoneal injection of ovalbumin (OVA) and exposed to aerosol OVA for 30 min each day for 2 weeks. Twenty-four hours after the final OVA challenge, airway responsiveness to inhaled methacholine (MCh) was measured, and analysis of bronchoalveolar lavage fluid (BALF) and lung histological studies were done. Compared to WT mice, KO mice showed higher airway hyperresponsiveness to inhaled MCh and higher late-phase responses to OVA whereas the early-phase responses were similar. Cell differentials of BALF showed an increased number of macrophages and neutrophils in KO mice. Furthermore, decreased concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1) were found in BALF from KO mice whereas the levels of Th1 and Th2 cytokines were not different from WT mice. Immunochemical study of the lung tissues revealed stronger staining of sTNFR1 in KO than in WT mice. Our results suggest that in this murine asthma model, the SHAP-HA complex has an inhibitory role in the development of airway hyperresponsiveness and allergic airway inflammation which may be attributed, at least in part, to negative feedback mechanisms exerted by sTNFR1, the shedding of which from the cell surface might also be promoted by the SHAP-HA complex.International Archives of Allergy and Immunology 01/2010; 153(3):223-33. · 2.40 Impact Factor -
Article: Adherence with long-term asthma management in patients who experienced hospitalized asthma exacerbation.
[show abstract] [hide abstract]
ABSTRACT: In Japan, the number of asthma deaths has been gradually decreasing. However, in the management of asthma, there are still some problems originating from patient-related factors and iatrogenic factors, both of which should be further analyzed. We investigated clinical and background characteristics of 164 patients with asthma who were admitted to our hospital with acute exacerbations, by reviewing their clinical records. Fifty-two patients had received long-term management (LTM) based on the guidelines (the LTM group), while 112 had not (the non-LTM group). In patients whose asthma severity had been intermittent (step 1), the proportion of severe and near fatal exacerbations was significantly higher in the non-LTM group than in the LTM group. However, even in the LTM-group, 23% of mild persistent (step 2) and 38% of moderately and severely persistent (step 3 & 4) patients had severe or near fatal exacerbations. In these patients, the peak expiratory flow rate significantly improved after discharge, and poor adherence was also significantly higher in the non-LTM group than in the LTM group. A multivariate analysis revealed that the factors associated with poor adherence were: 1) no history of previous admission due to asthma exacerbation; 2) the patient was male; and 3) the patient was young (<60 years). In the LTM group, re-evaluation of the actual severity of asthma and prompt treatment corresponding to the severity of disease should still be encouraged. In the non-LTM group, establishing countermeasures against factors causing poor adherence would be the next step in ensuring strong adherence with LTM.Allergology International 03/2009; 58(2):217-24. -
Article: A combination therapy of whole lung lavage and GM-CSF inhalation in pulmonary alveolar proteinosis.
[show abstract] [hide abstract]
ABSTRACT: Systemic and inhalation therapy of granulocyte-macrophage colony-stimulating factor (GM-CSF) is usually effective in controlling autoimmune pulmonary alveolar proteinosis (PAP), but some cases are refractory to GM-CSF therapy and subjected to whole lung lavage (WLL). A 9-year-old girl developed severe respiratory failure due to autoimmune PAP was treated with inhalational 250 microg of GM-CSF daily, however, it was ineffective. Unilateral WLL was performed three times and subsequent GM-CSF inhalation therapy yielded marked physiological and radiological improvement and was continued for 1 year.Pediatric Pulmonology 08/2008; 43(8):828-30. · 2.53 Impact Factor -
Article: The efficacy of montelukast and airway mast cell profiles in patients with cough variant asthma.
[show abstract] [hide abstract]
ABSTRACT: Cough variant asthma (CVA) is characterized by chronic cough without apparent wheezing; its pathophysiology is considered to be similar to that of classic asthma. The clinical effects of montelukast, a cysteinyl-leukotriene receptor antagonist, on cough variant asthma were assessed, and the activation profile of airway mast cells was examined. Montelukast (10 mg/day) was given orally to 36 CVA patients (25 women and 11 men; median age, 37.5 years). Before treatment, the patients' bronchial mucosa underwent a biopsy with a fiberoptic bronchoscope. The biopsy specimens were double stained with anti-CD63 antibody and anti-human tryptase antibody. After 2 weeks of montelukast treatment, cough symptoms improved in 22 patients (the effective group) but did not improve in 14 patients (the ineffective group); in the ineffective group, the symptoms disappeared 2 weeks after they were switched to fluticasone propionate (400 microg/day) inhalation therapy. In the effective group, the time interval from the onset of symptoms to the initiation of treatment was significantly shorter than in the ineffective group. The bronchial mucosa biopsy specimens showed that the proportion of CD63-positive cells in tryptase-positive mast cells was significantly higher in the effective group than in the ineffective group; although the total numbers of mast cells were not different between the two groups. There is a subgroup of CVA patients in whom leukotrienes are closely involved in the pathogenesis of their chronic cough; activation of airway mast cells may be an essential feature in these patients.Journal of Asthma 05/2008; 45(3):243-50. · 1.52 Impact Factor -
Article: Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan.
[show abstract] [hide abstract]
ABSTRACT: Acquired pulmonary alveolar proteinosis (PAP) is a syndrome characterized by pulmonary surfactant accumulation occurring in association with granulocyte/macrophage colony-stimulating factor autoantibodies (autoimmune PAP) or as a consequence of another disease (secondary PAP). Because PAP is rare, prior reports were based on limited patient numbers or a synthesis of historical data. To describe the epidemiologic, clinical, physiologic, and laboratory features of autoimmune PAP in a large, contemporaneous cohort of patients with PAP. Over 6 years, 248 patients with PAP were enrolled in a Japanese national registry, including 223 with autoimmune PAP. Autoimmune PAP represented 89.9% of cases and had a minimum incidence and prevalence of 0.49 and 6.2 per million, respectively. The male to female ratio was 2.1:1, and the median age at diagnosis was 51 years. A history of smoking occurred in 56%, and dust exposure occurred in 23%; instances of familial onset did not occur. Dyspnea was the most common presenting symptom, occurring in 54.3%. Importantly, 31.8% of patients were asymptomatic and were identified by health screening. Intercurrent illnesses, including infections, were infrequent. A disease severity score reflecting the presence of symptoms and degree of hypoxemia correlated well with carbon monoxide diffusing capacity and serum biomarkers, less well with pulmonary function, and not with granulocyte/macrophage colony-stimulating factor autoantibody levels or duration of disease. Autoimmune PAP had an incidence and prevalence higher than previously reported and was not strongly linked to smoking, occupational exposure, or other illnesses. The disease severity score and biomarkers provide novel and potentially useful outcome measures in PAP.American Journal of Respiratory and Critical Care Medicine 05/2008; 177(7):752-62. · 11.08 Impact Factor -
Article: Genetic factors in lung disease: Atopy and bronchial asthma
[show abstract] [hide abstract]
ABSTRACT: Abstract Atopy defined as high IgE responsiveness has now been subject to genetic studies at the molecular level owing to the development of a great number of DNA markers over the human genome. Either by linkage analysis or by association study strong candidate genes of atopy have been proposed to be located on chromosomes 11q13 and 5q31 where high-affinity IgE Fc receptor β subunit and allergy-associated cytokines, respectively, have been mapped. Meanwhile, we found a novel association between one of alleles of D11S97, an anonymous DNA marker on 11g13, and high total serum IgE in a large number of Japanese general population and atopic family members. However, failure to replicate linkage or association studies by different investigators suggest polygenic nature of atopy. In addition to the genes regulating IgE synthesis, the requirement of local (pulmonary) genetic factors in the development of bronchial asthma have been speculated. Linkage analysis suggested possible existence of gene(s) regulating susceptibility and/or clinical characteristics of bronchial asthma also on chromosome 5q. One of the candidate is β2-adrenergic receptor gene polymorphism. Mutated gene transfection studies suggested functional significance of some polymorphisms and clinical evaluations have revealed their contribution to airway responsiveness and severity of asthma.Respirology 02/2008; 2(1):7 - 15. · 2.42 Impact Factor -
Article: [Hypersensitivity pneumonitis caused by the use of goose feather coverlet].
Nihon Naika Gakkai Zasshi 12/2007; 96(11):2519-21. -
Article: Polymorphisms in the muscarinic receptor 1 gene confer susceptibility to asthma in Japanese subjects.
[show abstract] [hide abstract]
ABSTRACT: The human cholinergic receptor muscarinic-1 (CHRM1) is widely distributed in the lungs. In patients with asthma, CHRM1 may be involved in airway constriction, airway epithelial cell proliferation, and airway inflammation. The CHRM1 gene is located on chromosome 11q13, which is one of the candidate loci for asthma and atopy. To determine the role of the CHRM1 gene polymorphisms in asthma. We studied nine single-nucleotide polymorphisms (-18379G > A, -9697C > T, -6965T > C, -4953A > G, +267A > C, +1353C > T, +3970C > G, +5418C > G, and +5455G > T) in a case-control study using 326 patients with asthma and 333 healthy control subjects. We also examined functional consequences of the -9697C > T and -4953A > G polymorphisms at the regulatory region using an mRNA reporter assay. Two common single-nucleotide polymorphisms (-9697C > T and -4953A > G) were associated with asthma. The odds ratio for the TT homozygotes at the -9697C > T polymorphism was 0.29 compared with the CC homozygotes (95% confidence interval, 0.12-0.73; p = 0.008), and the odds ratio for the GG homozygotes at the -4953A > G polymorphism was 1.86 compared with the AA homozygotes (95% confidence interval, 1.04-3.34; p = 0.038). Haplotype analysis showed that the -9697T/-6965T/-4953A haplotype was associated with a lower risk of asthma (p = 0.00055) and the -9697C/-6965T/-4953G haplotype was associated with an increased risk of asthma (p = 0.020). The -9697T/-4953A haplotype was also associated with lower luciferase activity in vitro compared with the -9697C/-4953G haplotype. This study, together with an in vitro functional study, suggests that the CHRM1 gene is an important susceptibility locus for asthma on chromosome11q13.American Journal of Respiratory and Critical Care Medicine 12/2006; 174(10):1119-24. · 11.08 Impact Factor -
Article: A case of sarcoidosis with multiple endobronchial mass lesions that disappeared with antibiotics.
Sarcoidosis, vasculitis, and diffuse lung diseases: official journal of WASOG / World Association of Sarcoidosis and Other Granulomatous Disorders 04/2006; 23(1):78-9. · 1.27 Impact Factor -
Article: Epidemiological and clinical features of idiopathic pulmonary alveolar proteinosis in Japan.
[show abstract] [hide abstract]
ABSTRACT: Idiopathic pulmonary alveolar proteinosis (IPAP) is a rare disease characterized by excessive amounts of lipoproteinaceous material in the alveolus. This report presents an interim analysis of nationwide epidemiological data from Japanese patients with pulmonary alveolar proteinosis, and the roles of serum markers for IPAP. (i) The nationwide demographic data from 166 Japanese patients with IPAP are shown. The female to male ratio was 1:2, and the average age was 51 +/- 14 years old (age range: 15-79 years) at registration or diagnosis. A total of 30% of patients with IPAP have a poor clinical course. In total, 30% of patients were treated with whole lung lavage therapy (WLL). Under WLL, the patients significantly improved in the short term, but 40% of the patients who underwent WLL worsened again. A new strategy such as granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy for intractable PAP is required. (ii) The correlation of serum KL-6, carcinoembryonic antigen, surfactant proteins D and A, and LDH with disease severity suggests their potential as disease markers. In contrast, serum anti-GM-CSF antibody did not correlate with disease severity, but is a specific marker for the diagnosis of IPAP. The combined measurements of the serum markers may well prove very useful for both the diagnosis and the management of IPAP patients.Respirology 02/2006; 11 Suppl:S55-60. · 2.42 Impact Factor -
Article: [A case of nonclostridial gas gangrene of the leg complicated by severe pneumonia].
[show abstract] [hide abstract]
ABSTRACT: A 73-year-old man admitted for febrile left leg pain with dyspnea, who had poorly controlled diabetes was found on admission to have severe hypoxia and chest X-ray showed infiltrates in the middle to lower left lung. X-rays of the left leg showed gas around the knee joint. These findings suggested severe pneumonia with gas gangrene, necessitating immediate debridement of the gas gangrene lesion and hyperbaric oxygenation. Antibiotics were also administered intravenously (panipenem/betamipron 0.5 g x 3/day, clindamycin 600 mg x 2/day, and erythromycin 500 mg x 3/day). We conducted fiberoptic bronchoscope daily because consolidation of the whole left lung developed with purulent sputum expectoration. Both pneumonia and gas gangrene gradually ameliorated avoiding amputation of theleg. Gas gangrene was cured without leaving sequelae such as motor dysfunction. Staphylococcus aureus was detected in both pus from the leg and sputum collected by bronchoscopy. Microorganisms showed the same pattern of sensitivity to antibiotics, suggesting a causal relationship between pneumonia and gas gangrene through the blood stream. Gas gangrene was considered the primary infection followed by pneumonia, since pain and swelling of the left leg preceded the airway symptoms. The present case illustrates in compromised hosts including diabetics, gas gangrene may develop taking an opportunity of airway infection, and that in some cases, early debridement of the lesion and optimal use of antibiotics may help cure this disease without aggressive surgery. Hyperbaric oxygenation may also be useful, although its validity must be investigated further.Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 11/2005; 79(10):818-23. -
Article: Enhanced expression of interleukin-18 receptor alpha chain by CD4+ T cells in sarcoidosis.
[show abstract] [hide abstract]
ABSTRACT: To investigate the expression of interleukin-18 receptor alpha chain (IL-18Ralpha) in BAL and peripheral blood (PB) T cells in patients with sarcoidosis compared with control subjects, to evaluate the relationship between the expression and clinical manifestations, and to clarify the mechanisms of altered expression. The study subjects consisted of 21 patients with sarcoidosis and 8 normal control subjects. The expression of IL-18Ralpha was examined by flow cytometry. The proportions of BAL CD4+ and PB CD4+ T cells expressing IL-18Ralpha were significantly increased in patients with sarcoidosis compared to control subjects. BAL CD4+ T cells expressed IL-18Ralpha in a higher proportion than did paired CD8+ T cells in patients with sarcoidosis but not in control subjects. Greater proportions of BAL CD4+ T cells and BAL CD8+ T cells than of their PB counterparts expressed IL-18Ralpha in both patients and control subjects. CD4+ T cells were more sensitive to the induction of IL-18Ralpha by cytokines in vitro, such as interleukin (IL)-2, IL-12, and tumor necrosis factor-alpha than were CD8+ T cells. Increased expression of IL-18Ralpha by BAL T cells commonly observed in patients and control subjects was associated with the expansion of CD45RO+ cells in BAL T cells. However, there were no significant correlations between the expression of IL-18Ralpha by any cell populations and BAL findings, serum angiotensin-converting enzyme activities, radiograph stages, or clinical courses. The overexpression of IL-18Ralpha predominantly by CD4+ T cells in sarcoidosis emphasizes crucial roles played by T-helper type 1 cells in the IL-18/IL-18Ralpha system in sarcoidosis.Chest 11/2005; 128(4):2497-503. · 5.25 Impact Factor -
Article: Roles of functional polymorphisms in the interleukin-18 gene promoter in sarcoidosis.
[show abstract] [hide abstract]
ABSTRACT: Interleukin (IL)-18 plays important roles in sarcoidosis by inducing interferon-gamma in synergy with IL-12. Results of case-control studies on the association between sarcoidosis and single nucleotide polymorphisms (SNPs) in the IL-18 gene promoter are conflicting. We reexamined the association and evaluated the clinical significance of the SNPs in sarcoidosis. Genotyping of three SNPs, -137 G/C, -607 C/A, and -656 G/T, in the IL-18 gene promoter was performed in 161 patients with sarcoidosis and 176 healthy controls using the amplification refractory mutation system. Promoter activities were examined by a dual luciferase assay system in a cell line, THP-1. There was no significant difference in the genotype distribution or allele frequency of all three SNPs between controls and patients with sarcoidosis. However, -607 C/A and -656 G/T were significantly associated with serum levels of IL-18 in patients with sarcoidosis, but not in controls. The promoter activity of the haplotype -137G/-607C/-656G, one of the most common haplotypes, was significantly higher than that of the other common haplotype, -137G/-607A/-656T, accounting for the association between serum IL-18 levels and the SNPs. Meanwhile, there was no strong association between the three SNPs and the clinical phenotypes, such as patient characteristics and clinical courses. Our results indicate that the differences in the promoter activity according to promoter haplotypes of the IL-18 gene result in an altered protein expression in sarcoidosis. However, it is unlikely that the three SNPs examined confer susceptibility to sarcoidosis.Sarcoidosis, vasculitis, and diffuse lung diseases: official journal of WASOG / World Association of Sarcoidosis and Other Granulomatous Disorders 07/2005; 22(2):105-13. · 1.27 Impact Factor -
Article: [Case of drug-induced pneumonia followed by sequential bronchoalveolar lavage].
[show abstract] [hide abstract]
ABSTRACT: A 30-year-old woman who had been receiving minocycline for 11 days to treat a skin burn presented with high fever and progressive dyspnea. Chest radiography demonstrated bilateral pulmonary infiltrates with ground glass opacities. She was admitted to our hospital under a tentative diagnosis of minocycline-induced pneumonia. Minocycline therapy was discontinued at hospital admission, which led to dramatic clinical and radiographic improvement. Bronchoalveolar lavage fluid (BALF) analysis three days after the onset of the pneumonia showed increased numbers of total cells (7.68 x 10(5)/ml), neutrophils (33%) and eosinophils (14%). An increased number of peripheral blood neutrophils was also noted at the time of hospital admission. Follow-up evaluations of BALF 10 days and 34 days after the onset showed rapidly declining numbers of neutrophils and eosinophils. We also measured the levels of several cytokines in BALF, suggesting that TNF-alpha and IL-8 contributed to the accumulation of neutrophils, whereas IL-5 contributed to the accumulation of eosinophils. In summary, we report here the temporal change in the inflammatory cell and cytokine profile in BALF, serum, or both, in a case of drug-induced pneumonia.Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 09/2004; 42(8):743-8.
Top co-authors
Top Journals
Institutions
-
2003–2012
-
Hokkaido University Hospital
Sapporo-shi, Hokkaido, Japan
-
-
2010
-
Niigata University
- Bioscience Medical Research Center
Niigata-shi, Niigata-ken, Japan
-
-
2009
-
Aichi Medical University
- Department of Internal Medicine
Japan
-
-
2002–2005
-
Hokkaido University
- • Graduate School of Medicine
- • Department of Medicine I
Sapporo-shi, Hokkaido, Japan
-
