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E Yamaguchi

Publications and source records attributed to E Yamaguchi.

At least 19 recordsLinked to original sources
PubMed2006

Role of macrophage migration inhibitory factor in ovalbumin-induced airway inflammation in rats.

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that reportedly counteracts the anti-inflammatory effect of endogenous glucocorticoids. There have only been a few reports that demonstrate a potential link between MIF and bronchial asthma. In an attempt to further clarify the precise role of MIF in asthma, the present authors examined the effect of anti-MIF antibody (Ab) on airway inflammation and airway hyperresponsiveness in an ovalbumin-immunised rat asthma model. Actively immunised Brown Norway rats received ovalbumin inhalation with or without treatment of anti-MIF Ab. The levels of MIF in bronchoalveolar lavage fluid were significantly elevated after the ovalbumin challenge. An immunohistochemical study revealed positive immunostaining for MIF in bronchial epithelium, even in nonsensitised rats, and the MIF staining in bronchial epithelium was enhanced after the ovalbumin challenge. Anti-MIF Ab significantly decreased the number of total cells, neutrophils and eosinophils in the bronchoalveolar lavage fluid of the ovalbumin-challenged rats, and also attenuated the ovalbumin-induced airway hyperresponsiveness to ovalbumin and methacholine. However, anti-MIF Ab did not affect the level of serum ovalbumin-specific IgE, suggesting that anti-MIF Ab did not suppress immunisation itself. The results indicate that macrophage migration inhibitory factor plays a crucial role in airway inflammation and airway hyperresponsiveness in asthma.

Animals↗
PubMed2004

Trace of native cattle in Japanese Holstein assessed by mitochondrial DNA sequence polymorphism.

On the basis of sequence variation in the displacement loop region of mtDNA, 588 Japanese and North American Holstein cows were classified into 5 mitochondrial haplotypes, which were found in Japanese Black cattle. One of the haplotypes (named type 1), which was present at the highest frequency in Japanese Black cattle, was not observed in either European or African cattle. This haplotype is characterized by 2 single-nucleotide polymorphisms. One is called the type B polymorphism, and it refers to a base change from T to C at nucleotide 16042 of the mitochondrial genome (T160042C). The other is called the type I polymorphism, and it refers to the base change as G16093A. The proportion of the Japanese Holstein population with both polymorphisms was 18.3%, whereas none of the North American cows had this genotype. Because the mitochondrial types were inherited maternally, it is clear that a considerable number of Japanese Holstein cows are descended from native Japanese cattle. Polymorphisms B and I accounted for no variance in the estimated breeding value for milk production among cows from the Hyogo herd (582 cows) or the Chiba region herd (758 cows). This result suggests that most autosomal genes of native animals have been successively replaced by those of pure Holstein after grading up of over 15 generations, even though resulting animals have native animal-oriented mitochondrial types and may still have some number of the native autosomal genes.

Animals↗
PubMed2003

Association between interleukin-18 gene polymorphism 105A/C and asthma.

BACKGROUND: IL-18 has been shown to exert anti-allergic or allergy-promoting activities, but the existence of genetic polymorphisms in the coding regions of IL-18 gene has not been demonstrated. OBJECTIVE: The aim of this study was to investigate whether polymorphism is present in the coding regions of the IL-18 gene and, if so, to further analyse the association between polymorphism and asthma in a case-control study. METHODS: We screened the coding regions of the IL-18 gene for polymorphisms by using PCRsingle-stranded conformation polymorphism and direct sequencing of PCR products, followed by analysis of the association between polymorphism and asthma. RESULTS: We identified one polymorphism (105A/C) in the coding regions. The frequency of the 105A allele was significantly higher in asthmatic patients than in controls (P<0.01; odds ratio (OR)=1.83 (1.37-2.26)). Significant linkage disequilibrium was observed between the 105A/C and -137G/C polymorphisms in the 5' flanking region of the IL-18 gene (D=0.58, P<0.0001). However, in asthmatic patients the 105A allele was not associated with either total serum IgE or IL-18 levels. CONCLUSION: The 105A/C polymorphism of the IL-18 gene may be associated with the pathogenesis of asthma.

Adolescent↗
PubMed2002

Angiotensin-converting enzyme gene polymorphism in relation to HLA-DR in sarcoidosis.

OBJECTIVES: To investigate if an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene associates with HLA-DR alleles previously found to be of prognostic interest in Scandinavian sarcoidosis patients. This may contribute to characteristics associated with these HLA-DR alleles, such as a good (DR17) or poor (DR14 or 15) prognosis. DESIGN, SETTINGS AND SUBJECTS: Polymerase chain reaction (PCR) was used for analysing an I/D polymorphism in the gene coding for ACE in 138 subjects; 65 controls and 73 sarcoidosis patients, and for HLA-DR genotyping 67 patients. Serum ACE level (S-ACE) was measured in all controls and 72 patients. Sixty-one patients were classified as chronic or nonchronic after 2 years follow-up. All patients were recruited and followed at our outpatient clinic. RESULTS: No significant differences in ACE alleles or genotypes were seen between controls and patients or between patients positive and negative for DR17 or DR14/15. The ACE genotype did not differ between nonchronic and chronic patients. The ACE genotype tended to influence the S-ACE in patients, whilst in controls S-ACE significantly differed between the ACE genotypes. CONCLUSION: This study does not support an association between ACE genotype and sarcoidosis or disease outcome. However, because significantly (P < 0.001) more DR17 positive (17 of 19) than DR14/15 positive (seven of 26) patients were classified as nonchronic, these results instead strengthen the prognostic importance of HLA-DR alleles in Scandinavian sarcoidosis patients.

Adult↗
PubMed2002

Increased levels of interleukin-8 in BAL fluid from smokers susceptible to pulmonary emphysema.

BACKGROUND: It has previously been shown that smokers with computed tomographic (CT) evidence of subclinical emphysema have signs of neutrophil activation, despite having no appreciable increase in the number of neutrophils in their bronchoalveolar lavage (BAL) fluid. METHODS: The levels of the following chemoattractants in BAL fluid from 61 community based older volunteers classified into four groups according to current smoking status and the presence or absence of emphysema were determined: interleukin 8 (IL-8), epithelial neutrophil activating protein 78 (ENA-78) and leukotriene B(4) (LTB(4)) which are primarily chemotactic for neutrophils; monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) which are predominantly chemotactic for mononuclear leucocytes. RESULTS: Of the five chemoattractants studied, only the level of IL-8 in BAL fluid clearly distinguished between subjects with and without emphysema among current smokers (median values 34.7 and 12.2 pg/ml, respectively, p<0.01). In addition, the levels of IL-8 and neutrophil elastase-alpha(1) protease inhibitor complex in BAL fluid were significantly correlated (r=0.65, p<0.01). There was no difference in either the release of IL-8 from cultured alveolar macrophages at 24 hours or the expression of IL-8 messenger RNA of alveolar macrophages in the two groups of current smokers with and without emphysema. CONCLUSION: An accelerated response of IL-8 to chronic smoking is a factor that characterises those smokers who are susceptible to pulmonary emphysema, although the cellular source of IL-8 remains to be determined.

Bronchoalveolar Lavage Fluid↗
PubMed2001

Prognostic factors in hepatic metastases of colorectal carcinoma: immunohistochemical analysis of tumor biological factors.

The present study was designed to provide a systemic analysis of prognosis in 62 patients who underwent hepatic resection for colorectal liver metastasis. The analyzed factors included microvessel counts stained by CD34 and expression of two adhesion molecules, E-cadherin and CD44 variant exon 6-(v6) in these tumors. No significant factors related to recurrence were identified and only negative expression of CD44v6 tended to correlate with recurrence (P = 0.075). A short disease-free period to recurrence was noted in patients with high CEA levels (>10 ng/ml) and H2/3 classification. A short surgical margin, H2/3 classification, high microvessel counts (>60/field, x200), and negative expression of CD44v6 and E-cadherin tended to be associated with poor prognosis. A high microvessel count was the most significant prognostic factor by multivariate Cox proportional hazards regression model. Hepatic resection without tumor exposure and a careful follow-up in cases identified with poor prognostic factors are necessary.

Adult↗
PubMed2001

Measurement of serum hyaluronic acid level during the perioperative period of liver resection for evaluation of functional liver reserve.

BACKGROUND AND AIM: The serum hyaluronic acid (HA) concentrations reflect the degree of hepatic fibrosis and sinusoidal endothelial cell damage. The HA concentrations were examined to evaluate liver damage during the perioperative period of hepatectomy. METHODS: The HA level of serum samples from 79 patients who underwent a hepatectomy was measured, and the results were compared to conventional liver function tests, the degree of fibrosis, liver regeneration and complications. RESULTS: Hyaluronic acid concentrations correlated with the severe fibrosis or histological activity index, and also correlated with liver function tests including transaminase level, platelet counts, prothrombin time activity, indocyanine green retention rate at 15 min (ICG R15), liver activity at 15 min by technetium-99m galactosyl human serum albumin scintigraphy (LHL 15), and portal pressure. The HA level postoperatively correlated with liver function, especially with total bilirubin. Hyaluronic acid levels at day 28 postoperatively correlated with ICG R15 and LHL 15. The hyaluronic acid level before surgery and at day 28 postoperatively correlated with the regeneration of remnant liver in major hepatectomy. The HA levels were significantly higher in patients with hepatic failure or prolonged ascites. CONCLUSION: Our results indicate that the measurement of the HA level is useful for monitoring liver damage or predicting complications associated with liver surgery.

Adult↗
PubMed2001

The ACE gene polymorphism and cough threshold for capsaicin after cilazapril usage.

Persistent dry cough is an occasional but clinically important adverse reaction to angiotensin I-converting enzyme (ACE) inhibitors (ACEI). Its reported incidence is variable, and why cough occurs in only certain individuals has been unclear. An insertion/deletion (I/D) polymorphism of the ACE gene is associated with serum ACE activity. We have previously shown that susceptibility to cough induced by ACEI is associated with this polymorphism such that patients with genotype II are more susceptible to cough than patients with other genotypes. In order to confirm and extend our previous observation, we conducted a randomized, placebo-controlled, double-blind, cross-over study in 10 healthy volunteers with genotype II and 10 with genotype DD. The cough threshold was determined by the concentration of inhaled capsaicin causing two or more coughs. After the usage of an ACEI, cilazapril, for 4 weeks, changes in the cough threshold in subjects with genotype II [before: 6.6+/-3.7 nM (mean+/-SD); after: 5.0+/-4.6 nM] significantly differed from those in subjects with genotype DD (before: 9.0+/-9.4 nM; after: 9.3+/-9.1 nM). Skin responses to intradermal bradykinin, which is a substrate of ACE and tussigenic, were significantly increased in subjects with genotype II (before: 1.6+/-0.6 vs. after: 2.6+/-0.5 cm2, P<0.05) but not in subjects with genotype DD (before: 1.4+/-0.5 vs. after: 1.6+/-0.6 cm2, n.s.) after usage of cilazapril. By contrast, skin responses to intradermal substance P did not change in subjects with either genotype. These findings provide further evidence of a link between ACEI-induced cough and I/D polymorphism of the ACE gene and suggest that ACEIs induce cough by modulating the tissue level of bradykinin.

Adult↗
PubMed2001

Increased total serum IgE levels in patients with asthma and promoter polymorphisms at CTLA4 and FCER1B.

BACKGROUND: Increasing evidence indicates that total serum IgE levels are largely determined by genetic factors, and we recently established that the -109C/T promoter polymorphism at FCER1B is a genetic factor that affects total serum IgE levels. The gene encoding cytotoxic T lymphocyte antigen 4 (CTLA4) is another candidate factor in high IgE responsiveness, because B7-CD28/CTLA4 interaction can promote the differentiation and development of the T(H)2 lymphocyte subset. OBJECTIVE: We intended to determine whether CTLA4 is associated with increased levels of total serum IgE or with the development of asthma or atopy. METHODS: We performed a case-control study involving 339 patients with asthma and 305 healthy control subjects, of whom 226 of the patients with asthma and 219 of the healthy control subjects had previously been genotyped for the -109C/T promoter polymorphism at FCER1B. In the current study, we genotyped 2 polymorphisms in the CTLA4 gene, one involving the promoter (-318C/T) and the other involving exon 1 (+49A/G), in addition to the FCER1B promoter polymorphism. RESULTS: Patients with asthma who were homozygous for the -318C allele at the CTLA4 promoter region had higher levels of total serum IgE than patients with asthma carrying the -318T allele (P =.00470). The analysis of -318C/T (at CTLA4) and -109C/T (at FCER1B) promoter polymorphisms showed a significant correlation between the combined genotypes and increased levels of total IgE in patients with asthma (P =.000014). In contrast, no correlation between total serum IgE levels and -318C/T or +49A/G genotypes was detected in 305 healthy control subjects. There was no evidence indicating an association between a putative allele for asthma or atopy and alleles at any of the CTLA4 polymorphic loci. CONCLUSION: Our findings suggest that promoter polymorphisms of both CTLA4 and FCER1B are genetic factors that influence total serum IgE levels in patients with asthma. This supports the theory that variance in total serum IgE levels in patients with asthma is determined by mutations in multiple genes, each of which has a relatively small effect on the phenotype.

Abatacept↗
PubMed2001

(CCTTT)n repeat polymorphism in the NOS2 gene promoter is associated with atopy.

BACKGROUND: Several studies have shown that nitric oxide (NO) plays a role in the regulation of the T(H)1/T(H)2 balance, indicating the potential for NO to contribute to the development of atopy and several other allergic diseases, including bronchial asthma. NO synthase 2 (NOS2) is critically involved in the synthesis of NO during several inflammatory states, and the gene encoding NOS2 is located at chromosome 17q11.2-q12, where 2 genome scans have identified a candidate locus for atopy and asthma. OBJECTIVE: The 14-repeat allele of the (CCTTT)(n) repeat polymorphism in the NOS2 promoter region is a powerful enhancer of promoter activity in reporter constructs in vitro. We tested whether this potentially functional allele in the NOS2 gene influences the development of atopy and asthma. METHODS: We studied a total of 497 unrelated Japanese subjects (141 nonatopic healthy controls, 102 atopic healthy controls, 56 nonatopic asthmatic subjects, and 198 atopic asthmatic subjects). The odds ratio (OR) was calculated for atopy and asthma in carriers of the 14-repeat allele through use of logistic regression models. Atopy was defined as a positive specific IgE level to at least 1 of 10 common inhaled allergens. RESULTS: The 14-repeat allele was inversely associated with atopy (OR = 0.42, P < .01). The association remained significant when the model was controlled for asthmatic status (OR = 0.36, P < .01). This allele, however, was associated neither with the development of asthma nor with total serum IgE levels. CONCLUSION: Our findings suggest that the (CCTTT)(n) repeat polymorphism in the promoter of the NOS2 gene that affects promoter activity is a risk factor for the development of atopy, and this genetic effect seems independent of asthma.

Adult↗
PubMed2001

The gene polymorphism of tumor necrosis factor-beta, but not that of tumor necrosis factor-alpha, is associated with the prognosis of sarcoidosis.

OBJECTIVES: Few genetic markers for the prognosis of sarcoidosis have been found. Tumor necrosis factor (TNF)-alpha has been implicated in the pathogenesis of sarcoidosis. Induced TNF-alpha or TNF-beta levels have been shown to be associated with the polymorphisms of the TNF genes. We investigated the roles of such polymorphisms in the development and prolongation of sarcoidosis. SUBJECTS AND MEASUREMENTS: One hundred ten Japanese patients with sarcoidosis and 161 control subjects were genotyped for three biallelic polymorphisms in the promoter region of TNF-alpha gene by direct sequencing of polymerase chain reaction (PCR) products. A polymorphism of the TNF-beta gene (TNFB*1/TNFB*2) was detected by NCO: I restriction fragment length polymorphism analysis of PCR products spanning intron 1 and exon 2 of the TNF-beta gene. RESULTS: None of the polymorphisms conferred susceptibility to sarcoidosis. However, our study identified the allele TNFB*1, detected by the presence of a NCO: I restriction site, as a marker of prolonged clinical course, with the resolution of sarcoidosis being defined as the disappearance of all clinical symptoms, physical signs of active lesions, abnormal chest radiograph findings, and abnormal results of pulmonary function and biochemical tests. When the probability of remission in patients homozygous for TNFB*2 was defined as 1.00, it was 0.48 (95% confidence interval, 0.26 to 0.88; p < 0.05) in patients with TNFB*1 (genotypes TNFB*1/1 and TNFB*1/2). CONCLUSIONS: The TNFB*1 allele is a marker for prolonged clinical course in patients with sarcoidosis. Our study is the first to link a cytokine gene polymorphism to the prognosis of sarcoidosis.

Adult↗
PubMed2001

Coexpression of inducible nitric oxide synthase and COX-2 in hepatocellular carcinoma and surrounding liver: possible involvement of COX-2 in the angiogenesis of hepatitis C virus-positive cases.

Expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) has been reported to be responsible for enhanced tumor growth and angiogenesis in various tumors. However, the relationships between tumor vascularity and COX-2 and iNOS expression have not been evaluated in hepatocellular carcinoma (HCC). In this study, we examined the expression of iNOS and COX-2 and microvessel density (MVD) by immunohistochemical staining in 100 tissue sections collected from HCC patients. iNOS expression was significantly higher in hepatitis C virus (HCV)-positive HCCs (P = 0.011). COX-2 expression was significantly correlated with iNOS expression (P = 0.046) and tumor MVD (P = 0.011) in HCV-positive HCCS: iNOS expression was neither correlated with MVD nor had any influence on patient survival; however, combined negative expression of iNOS and COX-2 had a significant impact on patient survival (P = 0.041 and 0.018, log-rank test for overall and recurrence-free survival rate, respectively). The present findings suggest that combined expression of iNOS and COX-2 may play an important role in prognosis of HCV-positive HCC patients and that this could be partially attributable to modulation of angiogenesis by COX-2.

Adult↗
PubMed2000

Modulatory roles of RANTES in IL-4 production by human blood CD4(+)T cells.

An increase in serum IgE levels has been reported in several thrombotic cardiovascular diseases. Since such diseases are associated with the activation of platelets, we hypothesized that platelets are implicated in a mechanism leading to heightened IgE synthesis. To this end, we performed an in vitro investigation of the effects on IL-4 production caused by several bioactive substances potentially released from platelets. Human blood CD4(+)T cells from blood donors were stimulated with anti-CD3 antibody and costimulatory signals delivered via CD58 and CD80 in the presence or absence of IL-4. One of the following test substances was also included in the culture: platelet factor-4, beta-thromboglobulin, platelet-derived growth factor, serotonin, platelet activating factor, or RANTES. The cells were restimulated in the absence of IL-4 and test substances. Among the six substances, RANTES alone exhibited significant effects on IL-4 production. RANTES enhanced IL-4 production in the presence of IL-4, whereas it suppressed IL-4 production in the absence of IL-4. The enhancing effect of RANTES was positively correlated with plasma IgE levels in the donors. We concluded that RANTES may induce IgE synthesis by increasing IL-4 production in individuals predisposed to high IgE responses. Our observations indicate a link between platelets and immune phenomena associated with increased IgE responses.

Adult↗
PubMed2000

Gene polymorphism for microsomal epoxide hydrolase and susceptibility to emphysema in a Japanese population.

Recently, it was reported that gene polymorphism for microsomal epoxide hydrolase (mEPHX), an enzyme involved in the first-pass metabolism of epoxide intermediates, was associated with susceptibility to emphysema. This association was examined in a Japanese population, performing polymerase chain reaction (PCR)-based direct sequencing and restriction fragment length polymorphism assays for variant forms of mEPHX. The subjects consisted of 79 smokers with moderate to severe emphysema diagnosed by lung computed tomography scans, 58 smokers without emphysema, with a comparable smoking history, and 114 consecutive subjects who undertook annual health checkups. The allele frequency of exon 3 Tyr113 to His113, which was reported to confer slow mEPHX activity, was substantially higher in the population control group compared with that of the Caucasian control subjects in a previous study. However, neither the genotype distribution of exon 3, nor that of exon 4 His139 to Arg139, was significantly different between the two groups of smokers. These data indicate that the gene polymorphism for mEPHX is not associated with susceptibility to emphysema in the Japanese population. The discrepancy between the two studies may be explained either by racial difference or by the selection bias of subjects in the previous study, which examined those who had only mild to moderate emphysema with lung cancer or those who were clinically diagnosed as having chronic obstructive pulmonary disease.

Disease Susceptibility↗
PubMed2000

Macrophage migration inhibitory factor (MIF) in bronchial asthma.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine favouring the secretion of TNFalpha and IL-8 and counteracts anti-inflammatory effects of corticosteroids. Airways inflammation is a central feature of bronchial asthma and is characterized by the accumulation of eosinophils. OBJECTIVE: The aim of this study was to investigate whether MIF is related to asthma symptoms and eosinophil accumulation in the airways. METHODS: Serum MIF levels were measured by an enzyme-linked immunosorbent assay in 44 healthy subjects and 44 asthmatics. Levels of MIF in induced sputum were measured in 10 healthy subjects and 15 asthmatics. Levels of eosinophil cationic protein (ECP) in induced sputum were measured by a radioimmunosorbent assay. Fluorescence double immunostaining was conducted to examine cellular source and localization of MIF. RESULTS: Serum MIF levels were significantly increased in asthmatic patients compared with age and sex-matched control subjects. Symptomatic patients had a higher MIF level than asymptomatic patients. Induced sputum obtained from asthmatics contained higher levels of MIF than those from control subjects. MIF levels in induced sputum were correlated with ECP levels in induced sputum. MIF was colocalized with eosinophil peroxidase staining in the cytoplasm of sputum cells. CONCLUSION: Increased MIF levels are associated with asthma symptoms and one of the cellular sources of MIF in the airways are eosinophils.

Adult↗
PubMed2000

Association between a C+33T polymorphism in the IL-4 promoter region and total serum IgE levels.

Susceptibility to asthma and other atopic diseases is known to be associated with elevated total IgE levels. Several investigators have linked the interleukin-4 (IL-4) gene and nearby markers located on chromosome 5q to elevated total IgE levels. A single nucleotide polymorphism in the IL-4 gene promoter region (C+33T) has recently been identified. As part of an effort to identify genetic variants contributing to the susceptibility to elevated total serum IgE levels, an association analysis of a newly identified promoter polymorphism (C+33T) with total serum IgE levels was conducted. The study was conducted using 240 Japanese subjects (120 asthmatics and 120 healthy controls). The IL-4 C+33T polymorphism was genotyped by PCR-restriction fragment length polymorphism analysis. The frequency of the T allele was 0.675 in asthmatic subjects and 0.671 in healthy controls. An ANOVA model adjusted for age, sex and disease status suggested a genetic association of C+33T polymorphism with elevated total serum IgE levels (P < 0.05). The data suggest that IL-4 promoter C+33T polymorphism may be one of the genetic polymorphisms that explain genetic linkage or association between elevated total serum IgE levels and markers on chromosome 5q.

Aged↗