[Show abstract][Hide abstract] ABSTRACT: We investigated the correlation between fecal bacteria composition in early infancy and the prevalence of allergic diseases in late infancy. The fecal microbiota in the first 2 months was profiled using the 16S rRNA V6 short-tag sequences in the community and statistically compared between two groups of subjects who did and did not show allergic symptoms in the first 2 years (n = 11 vs. 11). In the allergic group, genus Bacteroides at 1 month and genera Propionibacterium and Klebsiella at 2 months were more abundant, and genera Acinetobacter and Clostridium at 1 month were less abundant than in the nonallergic group. Allergic infants who showed high colonization of Bacteroides and/or Klebsiella showed less colonization of Clostridium perfringens/butyricum, suggesting antagonism between these bacterial groups in the gastrointestinal tract. It was also remarkable that the relative abundance of total Proteobacteria, excluding genus Klebsiella, was significantly lower in the allergic than in the nonallergic group at the age of 1 month. These results indicate that pyrosequence-based 16S rRNA gene profiling is valid to find the intestinal microbiotal disorder that correlates with allergy development in later life.
[Show abstract][Hide abstract] ABSTRACT: Atopy is a common disorder characterized by increased general IgE responsiveness . Atopy is also an important cause of
disorder in the skin (eczema), lungs (asthma), and nose (rhinitis); family studies suggest variable combinations of organ-specific
clinical syndromes in individuals within atopic families [1-10].
[Show abstract][Hide abstract] ABSTRACT: The most common type of pollinosis in Japan is Japanese cedar pollinosis (JCP). While forest walking is a common form of recreation for Japanese people, it has been unclear whether forest walkers with JCP still choose to visit forested areas during the pollen season or whether they avoid those areas, and as such, the aim of this study was to investigate this question.
The study participants were all healthy men and women volunteers aged 20 years or over who visited the Tokyo University Forest in Chiba during 4 different days. The survey was conducted using self-administered questionnaires.
The number of available responses was 498. Of these, 112 participants who experienced JCP were included in the analysis. Seventy-three participants (65.2%) responded that they visit forests even during the pollen season. The association between forest walking choices during the pollen season and self-rated levels of pollinosis symptoms was not statistically significant (Cramer's V = 0.13, p = 0.47). As many as 60% of the participants who reported serious symptom levels responded that they visit forested areas even during the pollen season.
These results revealed that two thirds of forest walkers who had experienced JCP visited forests even during the pollen season. This indicates the further need for public service announcements informing people with JCP that the risk of pollen exposure and subsequent JCP reaction is increased by visiting forested areas during the pollen season.
[Show abstract][Hide abstract] ABSTRACT: The influence of antibiotic exposure in the early postnatal period on the development of intestinal microbiota was monitored in 26 infants including five antibiotic-treated (AT) subjects orally administered a broad-spectrum antibiotic for the first 4 days of life and three caesarean-delivered (CD) subjects whose mothers were intravenously injected by the similar type of antibiotics in the same period. The faecal bacterial composition was analysed daily for the first 5 days and monthly for the first 2 months. Terminal restriction fragment length polymorphisms in the AT subjects showed less diversity with the attenuation of the colonization of some bacterial groups, especially in Bifidobacterium and unusual colonization of Enterococcus in the first week than the control antibiotic-free infants (AF, n=18). Quantitative real-time PCR showed overgrowth of enterococci (day 3, P=0.01; day 5, P=0.003; month 1, P=0.01) and arrested growth of Bifidobacterium (day 3, P=0.03) in the AT group. Furthermore, after 1 month, the Enterobacteriaceae population was markedly higher in the AT group than in the AF group (month 1, P=0.02; month 2, P=0.02). CD infants sustained similar, although relatively weaker, alteration in the developing microbiota. These results indicate that antibiotic exposure at the beginning of life greatly influences the development of neonatal intestinal microbiota.
[Show abstract][Hide abstract] ABSTRACT: CARD15 was first identified as a susceptibility gene for Crohn's disease. More recently, CARD15 mutations were shown to be associated with the pediatric granulomatous inflammatory diseases, Blau syndrome and early-onset sarcoidosis (EOS). The aim of the present study was to evaluate whether CARD15 variants also play a role in patients with ordinary sarcoidosis other than EOS. We enrolled 135 Japanese sarcoidosis patients with uveitis as well as 95 healthy individuals and performed mutation analysis by direct sequencing of CARD15 exon 4. Direct DNA sequencing in the sarcoidosis patients showed eight CARD15 variants, including five novel mutations (13402C>T, 13543C>T, 13775C>A, 13937G>A, and 14079C>T). Compared with healthy individuals, CARD15 mutations are not common in the Japanese patients with sarcoidosis. Based on the results, we examined the clinical manifestations in patients with sarcoidosis according to their CARD15 mutations. Sarcoidosis patients with these mutations have no specific clinical features with regard to course of the disease or disease severity. Our results indicate that in general, CARD15 mutations may not contribute to the risk of sarcoidosis.
[Show abstract][Hide abstract] ABSTRACT: In order to identify a novel candidate gene in systemic lupus erythematosus (SLE), we analysed a panel of six genes encoding molecules involved in the type I interferon (IFN) system. We first identified variants in the five genes related to type I IFN pathway by sequencing. Genotyping of a panel of eight selected single-nucleotide polymorphisms (SNPs) in six candidate genes (TLR9, MYD88, IRF3, IRF7, IFNB1, IFNA17) was performed in 137 patients with SLE and matched with 152 healthy controls using polymerase chain reaction-restriction fragment length polymorphism analysis. In functional assay, quantitative real-time polymerase chain reaction was performed to assess constitutive IRF3 mRNA expression in peripheral blood mononuclear cells from healthy subjects with different IRF3 promoter haplotypes. Among eight SNPs genotyped, an IRF3 SNP at -925 was found to be associated with SLE after correction for multiple tests (corrected P=0.016). Of total five IRF3 SNPs genotyped, the promoter IRF3 SNPs -925A/G and -776C/T showed the most significant association with SLE. With regard to -925A/G, the frequency of GG genotype was significantly decreased among SLE patients compared with the control group (1.5% vs. 9.9%; chi(2)=10.0, P=0.0015, odds ratio 0.12, 95% confidence interval 0.027-0.554). Our experimental data indicated that constitutive IRF3 mRNA expression was significantly lower in cells carrying the minor G-T/G-T haplotype pair compared with those carrying the major A-C haplotype. In conclusion, we showed that the promoter SNPs of the IRF3 gene were significantly associated with resistance against SLE.
[Show abstract][Hide abstract] ABSTRACT: Type I interferons (IFNs) play a pivotal role not only in antiviral immunity but also in the surveillance of cancer development. In order to quantify the critical function of type I IFNs in the suppression of human cancer development, IFN-alpha production in response to Sendai virus stimulation has been compared between healthy control subjects and hepatitis C virus (HCV)-infected patients, the latter being an ideal population for longterm monitoring of cancer development. Data for IFN-alpha production were obtained retrospectively over a 17-year period by examining medical records in a study population of 2315 individuals, of which 112 healthy controls and 20 HCV-infected patients were selected. Sixty percent of the HCV-infected patients had impaired or declining IFN-alpha production, in comparison to 17% in the healthy control group. Mean IFN-alpha levels were lower in patients who developed hepatocellular carcinoma than in the HCV-infected patients who remained cancer free. Our findings suggest that impairment of IFN-alpha production may be linked to an increased cancer risk and that dysfunction of the IFN system is associated with some types of cancer. Therefore, periodic assessment and quantification of IFN-alpha production can be a potential test for the early detection of cancer in humans.
Journal of Interferon & Cytokine Research 01/2008; 27(12):1013-7. · 3.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The bacterial compositions of feces were monitored in the first 2 months for 15 infants born in Japan, including eight subjects who developed allergy by the age of 2 years. Primer sets targeting six predominant bacterial groups in the infant intestine, Bacteroidaceae, Enterobacteriaceae, bifidobacteria, enterococci, lactobacilli, and the Clostridium perfringens group, were used for real-time PCR to quantitate each population in the feces. The population of Bacteroidaceae was significantly higher in the allergic group at the ages of 1 month (P=0.03) and 2 months (P=0.05) than in the non-allergic group, while no statistically significant difference was observed for the other bacterial populations.
Bioscience Biotechnology and Biochemistry 10/2007; 71(9):2338-42. · 1.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Suppressor of cytokine signaling (SOCS) 1 is an essential physiologic regulator of the IFN-gamma signaling that is crucial to lead appropriate immune responses, and impaired IFN-gamma production is considered a hallmark of atopic diseases. Recent study has shown that SOCS1 is also crucial in attenuating type 1 IFN signaling and in limiting the host response to viral infection. Clinical and experimental evidence suggest an important role for respiratory viral infections in the development of asthma. To assess genetic functional variants of SOCS1 related to susceptibility and clinical phenotypes in adult asthma in a Japanese population, we conducted association and haplotype analyses of 462 subjects with adult asthma and 639 control subjects. After screening for polymorphisms, we identified a total of 13 variants and characterized the linkage disequilibrium (LD) mapping of the gene. Three variants were selected for genotyping with regard to the LD pattern, and we found a significant association between an SOCS1 promoter polymorphism -1478CA > del and adult asthma (P = 0.0063). The three-locus haplotype of SOCS1 using these three polymorphisms also showed a positive association with a haplotype T-C-del (-5388T, -3969C, and -1478 del; P = 0.0097). Furthermore, reporter gene analysis revealed that related promoter variant -1478 del enhanced the transcriptional level of SOCS1 in human lung epithelial cells, and induced higher levels of protein expression of SOCS1 and lower phosphorylation of STAT1 stimulated with IFN-beta. These findings suggest that the SOCS1 gene might be involved in the development of adult asthma through functional genetic polymorphism.
American Journal of Respiratory Cell and Molecular Biology 05/2007; 36(4):491-6. · 4.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous reports have shown genetic predisposition for atopic dermatitis (AD). Some of the severe complications of AD manifest in the eye, such as cataract, retinal detachment, and keratoconjunctivitis. This study was conducted to examine the genetic association between the atopy-related genes and patients with ocular complications (ocular AD).
Seventy-eighty patients with ocular AD and 282 healthy control subjects were enrolled in an investigation of the association between the atopy-related genes (FCERB, IL13, and IFNGR1) and ocular AD. Genetic association studies and functional analysis of single nucleotide polymorphisms (SNPs) were performed.
The -56TT genotype in the IFNGR1 promoter region was significantly associated with an increased risk of ocular AD under recessive models (chi(2) test, raw P = 0.0004, odds ratio 2.57). The -56TT genotype was more common in atopic cataracts. A reporter gene assay showed that, after stimulation with IFN-gamma, the IFNGR1 gene promoter construct that contained the -56T allele, a common allele in ocular AD patients, manifested higher transcriptional activity in lens epithelial cells (LECs) than did the construct with the -56C allele. Real-time PCR analysis demonstrated higher IFNGR1 mRNA expression in the LECs in atopic than in senile cataracts. iNOS expression by IFNGR1-overexpressing LECs was enhanced on stimulation with IFN-gamma and LPS.
The -56T allele in the IFNGR1 promoter results in higher IFNGR1 transcriptional activity and represents a genetic risk factor for atopic cataracts.
[Show abstract][Hide abstract] ABSTRACT: Bronchial asthma is a chronic airway disorder characterized by bronchial inflammation. Oxidative stress is a key component of inflammation. Glutathione S-transferase P1 (GSTP1), the abundant isoform of glutathione S-transferases (GSTs) in lung epithelium, plays a key role in cellular protection against oxidative stress. Several studies have shown that the GSTP1 geneis involved in the pathogenesis of asthma and a gene-gene interaction may occur within the GST gene superfamily.
We screened single-nucleotide polymorphisms (SNPs) at the GSTP1 locus and performed an association study in the Japanese population using two independent case-control groups (group 1: 391 pediatric patients with asthma, 462 adult patients with asthma, and 639 controls, and group 2: 115 pediatric patients with asthma and 184 controls). The effect of GSTM1 null/present genotype on the association between GSTP1 Ile105Val and asthma was also investigated.
We identified 20 SNPs at this locus and found this region consisted of one linkage disequilibrium block represented by four SNPs (tag SNPs). The association between the Ile105Val polymorphism in the GSTP1 gene and childhood asthma was significant in both groups (p = 0.047 in group 1, and p = 0.021 in group 2). This association was only significant in patients with GSTM1-positive genotype in both groups (group 1: GSTM1 present p = 0.013 and GSTM1 null p = 0.925, and group 2: GSTM1 present p = 0.015 and GSTM1 null p = 0.362).
These findings suggest that the GSTP1 gene is a childhood asthma susceptible gene, and the GSTM1 gene is a modifier gene of GSTP1 for the risk of childhood asthma in the Japanese population.
International Archives of Allergy and Immunology 02/2007; 144(4):275-86. · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Shinrin-yoku (walking and/or staying in forests in order to promote health) is a major form of relaxation in Japan; however, its effects have yet to be completely clarified. The aims of this study were: (1) to evaluate the psychological effects of shinrin-yoku in a large number of participants; and (2) to identify the factors related to these effects.
Four hundred and ninety-eight healthy volunteers took part in the study. Surveys were conducted twice in a forest on the same day (forest day) and twice on a control day. Outcome measures were evaluated using the Multiple Mood Scale-Short Form (hostility, depression, boredom, friendliness, wellbeing and liveliness) and the State-Trait Anxiety Inventory A-State Scale. Statistical analyses were conducted using analysis of variance and multiple regression analyses.
Hostility (P<0.001) and depression (P<0.001) scores decreased significantly, and liveliness (P=0.001) scores increased significantly on the forest day compared with the control day. The main effect of environment was also observed with all outcomes except for hostility, and the forest environment was advantageous. Stress levels were shown to be related to the magnitude of the shinrin-yoku effect; the higher the stress level, the greater the effect.
This study revealed that forest environments are advantageous with respect to acute emotions, especially among those experiencing chronic stress. Accordingly, shinrin-yoku may be employed as a stress reduction method, and forest environments can be viewed as therapeutic landscapes. Therefore, customary shinrin-yoku may help to decrease the risk of psychosocial stress-related diseases, and evaluation of the long-term effects of shinrin-yoku is warranted.
Public Health 01/2007; 121(1):54-63. · 1.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a complex genetic basis that includes many susceptibility genes on multiple chromosomes. As complex human diseases like SLE involve multiple, interacting genetic and environmental determinants, identifying genes for complex traits is challenging and has had limited success so far. However, recent advances in genetic resources and technology have been providing new tools to identify the novel pathways or the sequence variants that contribute to autoimmune diseases. During the past several years, several new candidate genes have been implicated in development of SLE though association studies. In this article we describe an overview of the latest findings in the genetics of SLE, especially focusing on the genetic variations in the signalling or immunoregulatory molecules including CD28 and IRF family members.
Seminars in Immunology 09/2006; 18(4):224-9. · 6.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Burnout and stress are common, related problems in service professionals, and post-traumatic stress disorder (PTSD) is a major concern among fire service workers. The purpose of this study was to evaluate the impact of PTSD and job-related stressors on burnout. A total of 243 fire service workers completed questionnaires, including the Impact of Event Scale-Revised (IES-R), Maslach Burnout Inventory (MBI), and Japan Brief Job Stress Questionnaire. Relationships were found between PTSD and burnout, and between job stressors and burnout. Social support reduced the impact on burnout. Stressors that impacted on burnout in fire service personnel were PTSD-related acute stress and general job-related chronic stress. Countermeasures, not only against job stress, but also against PTSD-related stress, are essential to prevent burnout. Social support and the development of human relationships in the work place are crucial in mitigating burnout.
Journal of Emergency Medicine 08/2006; 31(1):7-11. · 1.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ADAM33, a member of the ADAM (a disintegrin and metalloprotease) family, is a putative asthma susceptibility gene recently identified by positional cloning. It is important to know whether the association exists in ethnically diverse populations.
To assess whether genetic functional variants of ADAM33 relate to the susceptibility or some phenotypes in adult patients with bronchial asthma in a Japanese population.
We searched for single nucleotide polymorphisms (SNPs) in ADAM33 by PCR-directed sequencing and identified 48 SNPs. Fourteen SNPs were selected with regard to the LD pattern, and genotyped by Taq-Man and PCR-RFLP methods. We conducted an association study of ADAM33 with 504 adult asthmatic patients and 651 controls, and haplotype analyses of related variants were performed.
Significant associations with asthma were found for the SNPs T1 (Met764Thr), T2 (Pro774Ser), S2 and V-3 (with the lowest P-value for T1, P = 0.0015; OR 0.63). We analysed the haplotype using these four polymorphisms, and found a positive association with haplotype CCTG (P = 0.0024).
Our results replicate associations reported recently in other ethnic populations, and suggest that the ADAM33 gene is involved in the development of asthma through genetic polymorphisms.
[Show abstract][Hide abstract] ABSTRACT: We investigated the effect of autogenic training (AT) on cardiac autonomic nervous activity in fire services workers with the use of the questionnaire of the Japanese-language version of Impact of Event Scale-Revised (IES-R-J) and indexes of heart rate variability.
We studied 22 male fire services workers who were divided into posttraumatic stress disorder (PTSD)-related stress group (n=10) and control group (n=12). They underwent AT twice or three times a week for 2 months.
Posttraumatic stress disorder-related stress group showed a significantly higher cardiac sympathetic nervous activity and a significantly lower cardiac parasympathetic nervous activity than control group at baseline. Autogenic training significantly decreased cardiac sympathetic nervous activity and significantly increased cardiac parasympathetic nervous activity in both groups. These changes were accompanied by a significant decrease in the total points of IES-R-J.
Autogenic training is effective for ameliorating the disturbance of cardiac autonomic nervous activity and psychological issues secondary to PTSD.
Journal of Psychosomatic Research 06/2006; 60(5):439-44. · 2.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although MMP-9 has been suggested to be important in inflammation and in the connective tissue remodeling associated with asthma, the genetic influences of the polymorphisms of MMP-9 are unclear. To examine whether polymorphisms in MMP-9 are associated with childhood atopic asthma, we identified a total of 17 polymorphisms and conducted an association study with asthma (n = 290) and controls (n = 638). 2127G>T and 5546G>A (R668Q) were significantly associated with the risk of childhood atopic asthma (p = 0.0032 and 0.0016, respectively). In haplotype analysis, we also found a positive association with a haplotype (p = 0.0053). MMP-9 was expressed in cultured human bronchial epithelial cells, and the mRNA expression level was upregulated by dsRNA. Furthermore, the promoter SNP -1590C>T, in strong linkage disequilibrium with 2127G>T, enhanced the transcriptional level of MMP-9. Thus, the MMP-9 gene might be involved in the development of asthma through functional genetic polymorphisms.
Biochemical and Biophysical Research Communications 05/2006; 344(1):300-7. · 2.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We studied the correlations among sunspot numbers, business cycles, and suicide mortalitites. Based on data from Japan between 1971 and 2001, a significant negative correlation between sunspot numbers and unemployment rate was found, R= -.17. The correlation between suicide mortality and unemployment rate was positive for males (R=.46) and negative for females (R =-.69). Both are statistically significant. The hypothesis that variation of sun activity may affect the economy and the unemployment rate and hence increase the male suicide mortality is raised.
Perceptual and Motor Skills 05/2006; 102(2):603-8. · 0.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Remarkable growth in use of alternative and complementally medicine (CAM) has recently been noted from consume to trends, detail surveys are limited. In this study, to clarify the actual state of use of CAM and associated problem, we performed a cross sectional study in a town using a self-administrated questionnaire.
The questionnaire including demographic variables, subjective health status and health practices was addressed by people in Oguni town in Kumamoto. Use of kampo, supplements/healthy food, chiropractic, massage, yoga/meditation, acupuncture, kiko/thai-chi, aromatherapy/herbal medicine and hot springs was assessed in the questionnaire in terms of frequency, prescription or advice from physicians, purpose, and satisfaction.
The response rate was 83.33%. Use increased with aging and female employed CAM more frequently than male subjects. Most frequently consumed were supplement/health foods in both females (47.0%) and males (35.3%). The most prescribed was Kampo in both sexes (24.8% and 11.4%) About 70% of the subjects had visited chiropractics therapies.
From 57.0% of subjects had used at least one CAM in the past six months, a high value compared with results from other countries. The rates were particularly large in female and elderly subjects. It is thus possible that the impact of CAM on health promotion policy is not inconsequential.
[Nippon kōshū eisei zasshi] Japanese journal of public health 05/2006; 53(4):293-300.
[Show abstract][Hide abstract] ABSTRACT: Receptor-interacting protein (RIP)-2 is a serine/threonine kinase containing a caspase recruitment domain (CARD) that is involved in the Toll-like receptor-signaling pathway. Although associations between endotoxin exposure or respiratory infection and asthma have been recognized, the genetic influences in these conditions are unclear. The aim of our study was to examine whether polymorphisms or haplotypes in RIP2 were associated with childhood atopic asthma in a Japanese population.
We screened the RIP2 gene for polymorphisms by direct sequencing and characterized the linkage disequilibrium (LD) mapping of the gene. Seven variants were genotyped in childhood atopic asthma (n = 300) and normal controls (n = 637) . We conducted case-control and case-only association studies between the variants and asthma-related phenotypes. Haplotype association analyses were also performed.
A total of 31 variants were identified and none of the alleles or haplotypes of RIP2 were associated with asthma susceptibility. In the case-only study, an association between an RIP2 promoter polymorphism and childhood severe asthma (P=0.0032; odds ratio (OR) 3.37, 95% confidence interval (CI) 1.45-7.87) was observed.
Although polymorphisms in RIP2 are not likely to be associated with the development of asthma, the genetic variants might contribute to asthma severity in the Japanese population.