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Etsuro Yamaguchi

Publications and source records attributed to Etsuro Yamaguchi.

At least 19 recordsLinked to original sources
PubMed2006

Polymorphisms in the muscarinic receptor 1 gene confer susceptibility to asthma in Japanese subjects.

RATIONALE: 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. OBJECTIVES: To determine the role of the CHRM1 gene polymorphisms in asthma. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: This study, together with an in vitro functional study, suggests that the CHRM1 gene is an important susceptibility locus for asthma on chromosome11q13.

Adolescent↗
PubMed2006

Epidemiological and clinical features of idiopathic pulmonary alveolar proteinosis in Japan.

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.

Adolescent↗
PubMed2005

[A case of nonclostridial gas gangrene of the leg complicated by severe pneumonia].

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.

Aged↗
PubMed2005

Enhanced expression of interleukin-18 receptor alpha chain by CD4+ T cells in sarcoidosis.

STUDY OBJECTIVES: 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. SUBJECTS AND METHODS: The study subjects consisted of 21 patients with sarcoidosis and 8 normal control subjects. The expression of IL-18Ralpha was examined by flow cytometry. RESULTS: 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. CONCLUSION: 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.

Bronchoalveolar Lavage Fluid↗
PubMed2005

Roles of functional polymorphisms in the interleukin-18 gene promoter in sarcoidosis.

BACKGROUND AND AIM OF THE WORK: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adolescent↗
PubMed2004

A case of idiopathic pulmonary alveolar proteinosis accompanied by T-cell receptor gene rearrangement in bronchoalveolar lavage fluid cells.

We describe a case of a patient with idiopathic pulmonary alveolar proteinosis (PAP), who had an elevated serum level of antigranulocyte-macrophage colony stimulating factor (anti-GM-CSF) antibody accompanied by T-cell receptor gene rearrangements in BAL fluid cells. Histopathological examination of the lung excluded lymphoma but revealed PAP and silicosis. There was no detectable serum anti-GM-CSF antibody in 50 outpatients with advanced silicosis who did not have PAP, suggesting that anti-GM-CSF antibody is directly linked to PAP but not to silicosis. We speculate that monoclonal expansion of a T-cell population may play a role in the production of anti-GM-CSF antibody and the development of PAP.

Aged↗
PubMed2004

[A case of paclitaxel-induced pneumonitis].

A 79-year-old woman with small-cell lung cancer was treated weekly with paclitaxel after previous treatment with carboplatin and etoposide. Within the first course of paclitaxel, chest radiography and CT revealed thickening of the bronchovascular bundle and interlobular septa, and infiltrates in both lung fields. A marked increase in the number of lymphocytes was found on bronchoalveolar lavage (BAL). Microorganisms such as Cytomegalovirus, Mycobacteria, and Pneumocystis carinii were absent from the BAL fluid. Interstitial infiltration was partially improved simply by stopping paclitaxel administration, without the need for any additional therapy. Drug-induced pneumonitis caused by paclitaxel was diagnosed on the basis of the clinical course and findings, although a drug lymphocyte stimulation test yielded negative results for paclitaxel. Interstitial infiltrates on imaging, symptoms and arterial blood gas results improved with administration of oral prednisolone. The possibility of pneumonitis induced by paclitaxel should be considered even in cases without interstitial lung disease.

Aged↗
PubMed2004

[A case of farmer's lung disease manifested by smoking cessation].

A 40-year-old man, a cattle hoof-chipper, was admitted to Hokkaido University Hospital in June 2002 for a workup of the occasional fever, cough and dyspnea that had affected him at work since March 2002. He had not smoked since January 2001. On admission, he had a marked increase in the proportion of lymphocytes (62.9%) and the CD 4/CD 8 ratio (3.0) in the bronchoalveolar lavage fluid. Serum precipitating antibody against Thermoactinomyces vulgaris was detected. The results of a transbronchial lung biopsy were unremarkable. Since his chest radiographs at the previous clinic showed small nodular opacities, we diagnosed farmer's lung on the basis of the diagnostic criteria defined by the Research Group of the Ministry of Health, Labor and Welfare. He was treated with prednisolone and advised to wear a protective mask, and his symptoms have not recurred since. This is an interesting case in which smoking cessation appears to have unmasked latent farmer's lung.

Adult↗
PubMed2004

[Studies on airway hyperresponsiveness by the Astograph(r) method in asthmatics and young adult non-asthmatic asymptomatics].

We investigated airway hyperresponsiveness (AHR) by the continuous inhalation method using an Astograph(R) in 105 asthmatics and 141 non-asthmatic asymptomatics. The range of Dmin (1 U=one minute inhalation of 1 mg/ml of methacholine) of asthmatics was 0.001 to 28.70 U, and that of adjusted Dmin of non-asthmatic asymptomatics was 0.28 to 190 U; thus, an apparent overlap was recognized in the distributions of Dmin. Ninety-five percent of asthmatics had a Dmin lower than 7 U, and 95% of non-asthmatic asymptomatics had a Dmin higher than 0.9 U. Presuming that almost all asthmatics had AHR, it was inferred that nearly half of non-asthmatic asymptomatics had AHR, too. Comparison with previous reports suggests that AHR in healthy people may be increasing generally. When Dmin is determined to be>7 U by the Astograph(R) method, it is likely that the patient does not have asthma. When a patient has a Dmin<0.9 U, it is highly probable that the patient has asthma.

Adolescent↗
PubMed2004

[Case of drug-induced pneumonia followed by sequential bronchoalveolar lavage].

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.

Adult↗
PubMed2003

Retinoic acid inhibits interleukin-4-induced eotaxin production in a human bronchial epithelial cell line.

Retinoic acid (RA) is known to accelerate wound healing and induce cell differentiation. All-trans RA (ATRA) exerts its effect by binding retinoic acid receptors, which are members of the nuclear receptor family. We investigated whether RA can alter expression of eotaxin, a potent eosinophil chemoattractant that is regulated by the transcription factors signal transducer and activator of transcription 6 (STAT6) and NF-kappaB. We examined the effects of RA on eotaxin expression in a human bronchial epithelial cell line BEAS-2B. ATRA and its stereodimer 9-cis retinoic acid (9-cis RA) inhibited IL-4-induced release of eotaxin at 10(-6) M by 78.0 and 52.0%, respectively (P < 0.05). ATRA and 9-cis RA also significantly inhibited IL-4-induced eotaxin mRNA expression at 10(-6) M by 52.3 and 53.5%, respectively (P < 0.05). In contrast, neither ATRA nor 9-cis RA had any effects on TNF-alpha-induced eotaxin production. In transfection studies using eotaxin promoter luciferase plasmids, the inhibitory effect of ATRA on IL-4-induced eotaxin production was confirmed at the transcriptional level. Interestingly, ATRA had no effects on IL-4-induced tyrosine phosphorylation, nuclear translocation, or DNA binding activity of STAT6. Activating protein-1 was not involved in ATRA-mediated transrepression of eotaxin with IL-4 stimulation. The mechanism of the inhibitory effect of ATRA on IL-4-induced eotaxin production in human bronchial epithelial cells has not been elucidated but does not appear to be due to an effect on STAT6 activation. These findings raise the possibility that RA may reduce eosinophilic airway inflammation, one of the prominent pathological features of allergic diseases such as bronchial asthma.

Active Transport, Cell Nucleus↗
PubMed2003

Granulocyte-macrophage colony-stimulating factor gene-transduced tumor cells combined with tumor-derived gp96 inhibit tumor growth in mice.

Granulocyte-macrophage colony-stimulating factor (GM-CSF)-based cancer cell vaccines have been shown to be potent inducers of antitumor immunity in several murine models, but the antitumor effects on established tumors have been minimal. Conversely, the major role of the heat shock protein gp96, localized in the endoplasmic reticulum (ER), is to act as a molecular chaperone to assist the folding of nascent polypeptide chains in the ER. gp96 derived from tumor cells elicits specific protective immunity against parental tumors, presumably through the transport of tumor-specific peptides to antigen-presenting cells and the maturation of dendritic cells (DCs). However, the therapeutic effects of tumor-derived gp96 on established tumors have not been promising. The present study analyzes the therapeutic effects of GM-CSF gene-transduced Lewis lung cancer (LLC/GM) cells combined with LLC-derived gp96 on established wild-type LLC tumors in immunocompetent C57BL/6 mice. Therapy with either irradiated LLC/GM cells or LLC-derived gp96 barely affected established LLC tumor growth. The antitumor effect was significantly enhanced when 1 microg of LLC-derived gp96 was administered together with 1 x 10(6) irradiated LLC/GM cells (p < 0.05). The antitumor effects of irradiated LLC/GM cells and LLC-derived gp96 required mainly CD8(+) T cells. Spleen cells obtained from mice vaccinated with irradiated LLC/GM cells and LLC-derived gp96 showed specific CD8 cytotoxic activities against LLC cells (specific lysis rate of approximately 28%). This antibody response was not associated with a synergic effect of the combination therapy. Moreover, draining lymph nodes from mice immunized with irradiated LLC/GM cells and LLC-derived gp96 contained more migrating mature CD11c(+) cells (higher levels of CD86 and major histocompatibility complex [MHC] class II molecules) compared with those from any other immunization protocols. These results suggest that the combination of irradiated LLC/GM cells and tumor-derived gp96 has potential as a new immunogene therapeutic strategy against lung cancer.

Animals↗
PubMed2003

Effects of IL-1beta, TNF-alpha, and macrophage migration inhibitory factor on prostacyclin synthesis in rat pulmonary artery smooth muscle cells.

OBJECTIVE: Cytokines have been implicated in the pathophysiology of pulmonary hypertension. We sought to explore the possibility that prostacyclin is a link. METHODOLOGY: We tested the effects of the cytokines interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha), and macrophage migration inhibitory factor (MIF) on arachidonic acid metabolism of pulmonary artery smooth muscle cells (PASMCs) with special regard to prostacyclin (PGI2) that protects against pulmonary hypertension. Cultured rat PASMCs were treated with IL-1beta, TNF-alpha, or MIF. Expression of prostacyclin synthase (PGIS) and cyclooxygenase-2 (COX-2) mRNAs, and PGI2 synthesis, were measured. RESULTS: We found that PGIS mRNA expression was suppressed by high concentrations of TNF-alpha and MIF, while COX-2 mRNA was induced by all three cytokines tested. IL-1beta increased PGI2 production in a dose-dependent manner. TNF-alpha and MIF also increased PGI2 production, but to a far lesser degree at high concentrations. TNF-alpha paradoxically decreased PGI2 production at a low concentration. CONCLUSIONS: These results suggest that TNF-alpha and MIF are potentially antagonistic to the action of PGI2 in rat PASMCs via down-regulation of PGIS mRNA. Simultaneous induction of COX-2 mRNA may further counteract the action of PGI2 by increasing the levels of eicosanoids other than PGI2.

6-Ketoprostaglandin F1 alpha↗
PubMed2003

[A case of Mycobacterium avium pulmonary disease detected as multiple small nodular shadows and diagnosed by CT guided transbronchial biopsy with ultrathin bronchoscopy].

A 65-year-old man was admitted to our hospital because multiple small nodular shadows measuring five to 12 mm in diameter in both lung fields were noticed on chest radiographs and CT scans during a regular checkup for pulmonary emphysema. The levels of ESR and CRP were within normal limits, but those of CEA and CYFRA were slightly elevated. Mycobacterium avium (M. avium) was detected in sputum cultures and in a sputum examination using PCR. Non-necrotizing granulomas were detected in the specimens obtained from a lesion of the right S6b by CT-guided transbronchial biopsy using an ultrathin bronchoscope after navigation with virtual bronchoscopy. On the basis of these findings, M. avium pulmonary disease was diagnosed. The patient is being followed up, but because he has no symptoms, without medication. To our knowledge, there have been no previous reports of M. avium-intracellulare complex pulmonary disease, which is characterized by multiple small nodular shadows. It is speculated that multiple centrilobular lesions developed simultaneously without extension to the bronchial walls, leading in this case to multiple small nodules in both lung fields.

Aged↗
PubMed2003

[A case of idiopathic pulmonary upper lobe fibrosis complicated by invasive pulmonary aspergillosis].

A 72-year-old man with idiopathic pulmonary upper lobe fibrosis who had been followed for a year developed a high fever and yellow sputum in July 2001. Chest radiography and chest computed tomography (CT) showed a rapidly enlarging cavity with an internal mass and infiltration in the left upper lung field. Pulmonary aspergillosis was diagnosed by examination of bronchoalveolar lavage fluid (BALF). Administration of itraconazole improved his condition. The concentrations of surfactant proteins A (SP-A) and D (SP-D) in serum and in BALF were decreased during the clinical course. It is known that SP-A and SP-D are critical factors for host defense against aspergillus. The lowering of SP-A and SP-D in the serum and BALF seemed to reflect destructive changes of lung structure and impaired innate lung immunity that could to lead invasive pulmonary aspergillosis.

Aged↗
PubMed2003

[Science in taking medicine].

It is a well-known fact that medicine plays an important role in treatment of several diseases. New development of many drugs led to not only benefits but also unexpected damage to human beings. In Japan, we are plunged into an aging society we have never experienced. We have far more opportunities to take medicine. Under these circumstances, it is very important for each one of us to learn how more reliable to take medicine to prevent unexpected side effects. In this citizen joint symposium, we focused on how to take medicine more logically and effectively from the viewpoint of patients. Participation in this symposium could hopefully help promoting our health care in Hokkaido.

Drug Therapy↗