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In this study, we discovered a turbulence transition in a large helical device. The turbulence level and turbulence-driven energy transport decrease to a specific transition density and increase above it. The ruling turbulences below and above the transition density were ion-temperature gradient (ITG) and resistive-interchange (RI) turbulences, consistent with the predictions of gyrokinetic theory and two-fluid MHD model, respectively. Isotope experiments on hydrogen (H) and deuterium (D) clarified the role of transitions. In the ITG regime, turbulence levels and energy transport were comparable in the H and D plasmas. In contrast, in the RI regime, they were clearly suppressed in the D plasma. The results provide crucial knowledge for understanding isotope effects and future optimization of stellarator and heliotron devices.
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In recent years, there has been a growing trend in the use of immune checkpoint inhibitors (ICIs) for treating a larger patient population. However, it is important to note that immune-related adverse events (irAEs) frequently arise as a result. Therefore, precise patient monitoring becomes essential. We present the findings of a retrospective study conducted at the International University of Health and Welfare Narita Hospital (referred to as "our hospital") that aimed to identify risk factors linked to the occurrence of irAEs. The study focused on analyzing various factors, including therapeutic and lifestyle backgrounds, as well as laboratory values of patients who received ICI treatment and were subsequently diagnosed with irAE. The study included patients who met the eligibility criteria for ICIs (both single agent and combination therapy) as well as ICI in combination with anticancer drugs. The inclusion period for the study encompassed April 2020 to May 2022 at our hospital. The fifty patients were divided into two groups based on the severity of irAEs: the first group consisted of patients with irAE Grade 2 or lower (referred to as irAE Grade under 2), while the second group included patients with irAE Grade 3 or higher (referred to as irAE Grade over 3). Statistical analysis revealed significant differences in age (p=0.027) and CRP (C-reactive protein) levels (p=0.008) among the background factors when comparing the two groups. Additionally, statistically significant differences were observed among different ICI treatment groups in the occurrence of irAEs (p=0.035). however, it was indicated to be a relatively weak correlation. Moving forward, we shifted our focus to examine the frequency of irAEs in relation to exposure. However, we did not observe any significant correlation between exposure and irAE grade. Additionally, even when exposure was doubled through the use of ipilimumab in combination with ICIs (referred to as "Mod exposure"), no correlation was found. Exposure was further categorized into three groups: the PD-1 group, PD-L1 group, and PD-1 + CTLA-4 group. However, no significant correlation was observed between exposure in any of these groups and the grade of irAEs. Similarly, no significant correlation was observed between the dosage of ICI in the fixed-dose group and the weight-based dosage group with exposure and irAE Grade. Based on our study findings, there is a suggestive relationship between age and CRP levels and the occurrence of irAEs of Grade 3 or higher. These factors may play a role in contributing to the development of more severe irAEs.
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Inibidores de Checkpoint Imunológico , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Fatores de Risco , Idoso de 80 Anos ou mais , Neoplasias/tratamento farmacológico , Adulto , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologiaRESUMO
This population-based cohort study with a 3-year follow-up revealed that the annual incidence rates of vertebral fracture (VF) and severe VF (sVF) were 5.9%/year and 1.7%/year, respectively. The presence of mild VF at the baseline was a significant risk factor for incident sVF in participants without prevalent sVF. INTRODUCTION: This study aimed to estimate the incidence of morphometric vertebral fracture (VF) and severe VF (sVF) in men and women and clarify whether the presence of a mild VF (mVF) increases the risk of incident sVF. METHODS: Data from the population-based cohort study, entitled the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study, were analyzed. In total, 1190 participants aged ≥ 40 years (mean age, 65.0 ± 11.2) years completed whole-spine lateral radiography both at the third (2012-2013, baseline) and fourth surveys performed 3 years later (2015-2016, follow-up). VF was defined using Genant's semi-quantitative (SQ) method: VF as SQ ≥ 1, mVF as SQ = 1, and sVF as SQ ≥ 2. Cumulative incidence of VF and sVF was estimated. Multivariate logistic regression analyses were performed to evaluate risk factors for incident sVF. RESULTS: The baseline prevalence of mVF and sVF were 16.8% and 6.0%, respectively. The annual incidence rates of VF and sVF were 5.9%/year and 1.7%/year, respectively. The annual incidence rates of sVF in participants without prevalent VF, with prevalent mVF, and with prevalent sVF were 0.6%/year, 3.8%/year, and 11.7%/year (p < 0.001), respectively. Multivariate logistic regression analyses in participants without prevalent sVF showed that the adjusted odds ratios for incident sVF were 4.12 [95% confident interval 1.85-9.16] and 4.53 [1.49-13.77] if the number of prevalent mVF at the baseline was 1 and ≥ 2, respectively. CONCLUSIONS: The annual incidence rates of VF and sVF were 5.9%/year and 1.7%/year, respectively. The presence of prevalent mVF was an independent risk factor for incident sVF.
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Osteoartrite , Osteoporose , Fraturas da Coluna Vertebral , Adulto , Idoso , Densidade Óssea , Estudos de Coortes , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Osteoporose/complicações , Prevalência , Fatores de Risco , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologiaRESUMO
AIMS: Diabetic nephropathy, a pathologically diagnosed microvascular complication of diabetes, is a strong risk factor for cardiovascular events, which mainly involve arteries larger than those affected in diabetic nephropathy. However, the association between diabetic nephropathy pathological findings and cardiovascular events has not been well studied. We aimed to investigate whether the pathological findings in diabetic nephropathy are closely associated with cardiovascular event development. METHODS: This retrospective cohort study analysed 377 people with type 2 diabetes and biopsy-proven diabetic nephropathy, with a median follow-up of 5.9 years (interquartile range 2.0 to 13.5). We investigated how cardiovascular events were impacted by two vascular diabetic nephropathy lesions, namely arteriolar hyalinosis and arterial intimal thickening, and by glomerular and interstitial lesions. RESULTS: Of the 377 people with diabetic nephropathy, 331 (88%) and 295 (78%) had arteriolar hyalinosis and arterial intimal thickening, respectively. During the entire follow-up period, those with arteriolar hyalinosis had higher cardiovascular event rates in the crude Kaplan-Meier analysis than those without these lesions (P = 0.005, log-rank test). When fully adjusted for clinically relevant confounders, arteriolar hyalinosis independently predicted cardiovascular events [hazard ratio (HR) 1.99; 95% confidence interval (CI) 1.12, 3.86], but we did not find any relationship between arterial intimal thickening and cardiovascular events (HR 0.89; 95% CI 0.60, 1.37). Additionally, neither glomerular nor interstitial lesions were independently associated with cardiovascular events in the fully adjusted model. CONCLUSIONS: Arteriolar hyalinosis, but not intimal thickening of large arteries, was strongly associated with cardiovascular events in people with diabetic nephropathy.
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Arteríolas/patologia , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/patologia , Hialina , Rim/patologia , Artéria Renal/patologia , Túnica Íntima/patologia , Idoso , Amputação Cirúrgica/estatística & dados numéricos , Arritmias Cardíacas/mortalidade , Doenças Cardiovasculares/mortalidade , Causas de Morte , Estudos de Coortes , Morte Súbita/epidemiologia , Nefropatias Diabéticas/etiologia , Feminino , Insuficiência Cardíaca/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Rim/irrigação sanguínea , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/mortalidade , Revascularização Miocárdica/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/mortalidadeRESUMO
OBJECTIVE: To clarify the genetic mechanisms underlying intervertebral disc degeneration (IDD), we examined the associations between single-nucleotide polymorphisms (SNPs) and indicated as coefficient of interaction term (IDD) in a general population in Japan. METHODS: This was a cross-sectional study. In 1,605 participants, C2-3 to L5/S1 in the total spine magnetic resonance imaging (MRI) were evaluated using the Pfirrmann's scoring system. Disc scores of 4 and 5 were defined as IDD. Eight SNPs in eight genes associated with IDD were examined at each disc level, considering the non-genetic risk factors of age, sex, and body mass index (BMI). RESULTS: The highest odds ratio was found for rs9406328 in the THBS2 gene at disc level T12-L1 (OR 1.27, 95%CI 1.05 to 1.53), and this association was strengthened after adjustment for age using logistic regression (OR 1.37, 95%CI 1.12 to 1.67). Among participants aged <50 years and 50-59, the average IDD score in those with 2 risk alleles of rs9406328 was markedly higher than in those with 0 or 1 risk allele, and the difference is much wider than the elderly participants. It indicates the genetic effect of rs9406328 is stronger in the younger age groups. Finally, multiple linear regression analyses of the association between rs9406328 and IDD, adjusted for age, sex, and BMI at each disc level, showed a statistical interaction between age and the number of risk alleles at C7-T1, T3-4 and T4-T5 as well as T12-L1. CONCLUSION: CONCLUSION: The association between rs9406328 in THBS2 and IDD was replicated. The contributions of genetic and environmental factors to IDD differed by disc level.
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Degeneração do Disco Intervertebral/genética , Polimorfismo de Nucleotídeo Único , Trombospondinas/genética , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-IdadeRESUMO
We devise and introduce the principle of wavelength-scan-free spectroscopy for the pump light in pump/probe measurement (action spectroscopy) using supercontinuum light; we demonstrate its implementation by measuring transmission spectra. We use the supercontinuum light noise as a code in order to discriminate wavelength. We extract the stimulation at the desired wavelength by correlating the noise at that wavelength observed separately and the observed total stimulation carried by the probe light. The wavelength-scan-free spectroscopy is enabled with a simultaneous procedure for multiple wavelengths.
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The isotope effect on energy confinement time and thermal transport has been investigated for plasmas confined by a stellarator-heliotron magnetic field. This is the first detailed assessment of an isotope effect in a stellarator heliotron. Hydrogen and deuterium plasmas heated by neutral beam injection on the Large Helical Device have exhibited no significant dependence on the isotope mass in thermal energy confinement time, which is not consistent with the simple gyro-Bohm model. A comparison of thermal diffusivity for dimensionally similar hydrogen and deuterium plasmas in terms of the gyroradius, collisionality, and thermal pressure has clearly shown robust confinement improvement in deuterium to compensate for the unfavorable mass dependence predicted by the gyro-Bohm model.
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OBJECTIVE: The present study examined the progression, incidence, and risk factors for intervertebral disc degeneration (DD) throughout the lumbar spine using magnetic resonance imaging (MRI) in a large population-based cohort. METHODS: We followed up 617 subjects for more than 4 years as part of the Wakayama Spine Study. 1) "Progression of DD" in each of the entire, upper (L1/2 to L3/4) and lower (L4/5 and L5/S1) lumbar spine was defined as Pfirrmann grade progression at follow-up in at least one disc in the affected region. 2) "Incidence of DD" in each of these regions was defined if all discs were grade 3 or lower (white disc) at baseline, and at least one disc had progressed to grade 4 or higher (black disc) at follow-up. Logistic regression analyses were used to determine the risk factors for progression and incidence of DD. RESULTS: DD progression and incidence in the entire lumbar spine were 52.0% and 31.6% in men, and 60.4% and 44.7% in women, respectively. Women was associated with DD progression in the upper lumbar spine (odds ratio [OR] = 1.68, 95% confidence interval [CI] = 1.18-2.42). Aging was associated with the incidence of DD in each region (entire: OR = 1.14, CI = 1.06-1.14; upper: OR = 1.10, CI = 1.05-1.15; lower: OR = 1.11, CI = 1.05-1.19). Diabetes mellitus (DM) was associated with the incidence of DD in the upper lumbar spine (OR = 6.83, CI = 1.07-133.7). CONCLUSION: This 4-year longitudinal study is the first to demonstrate DD progression and incidence in the lumbar spine and their risk factors in a large population-based cohort.
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Degeneração do Disco Intervertebral/etiologia , Vértebras Lombares , Idoso , Complicações do Diabetes/complicações , Complicações do Diabetes/epidemiologia , Progressão da Doença , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Incidência , Degeneração do Disco Intervertebral/epidemiologia , Japão/epidemiologia , Estudos Longitudinais , Dor Lombar/epidemiologia , Dor Lombar/etiologia , Imageamento por Ressonância Magnética , Masculino , Obesidade/complicações , Obesidade/epidemiologia , Fatores de RiscoRESUMO
UNLABELLED: The cathepsin K inhibitor, ONO-5334, improves bone mineral density in postmenopausal women with osteoporosis. The effects of morning versus evening administration of ONO-5334 were investigated by measuring bone turnover marker levels in healthy postmenopausal women. Morning administration of ONO-5334 showed a more consistent suppressive effect on bone resorption than evening administration. INTRODUCTION: Bone turnover is thought to be subject to circadian variation, and the efficacy of osteoporosis treatments may be optimized by regulating the time of dosing. This study assessed whether evening administration of the cathepsin K inhibitor, ONO-5334, had a differential effect on the bone turnover marker, C-terminal telopeptide of type I collagen (CTX-I), compared with morning administration. METHODS: This was a single-center, single blind crossover study. Fourteen healthy postmenopausal women were assigned to receive ONO-5334 150 mg once daily for 5 days in each period; they were randomized to receive either evening doses in the first period and morning doses in the second or vice versa. Serum and urinary levels of CTX-I were measured throughout the study. RESULTS: Both regimens showed similar patterns of reduction in serum and urinary CTX-I; however, CTX-I suppression was more consistently >60% over 24 h following morning administration. Morning administration led to 6% greater suppression of 24-h serum CTX-I area under the effect curve (AUE; 69 vs 63%; P < .05) and 7% greater suppression of urinary CTX-I/creatinine AUE (93 vs 86%; P < .01) than evening administration. Higher plasma ONO-5334 concentrations were observed between 12 and 24 h postdose following morning administration, with mean trough concentrations for the morning and evening regimens at 9.4 and 4.0 ng/mL, respectively. There were no safety findings of concern. CONCLUSION: Morning dosing of ONO-5334 is more efficacious at reducing markers of bone turnover in healthy postmenopausal women than evening dosing. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01384188 , registered on June 27, 2011 EudraCT: 2008-006284-37.
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Conservadores da Densidade Óssea/administração & dosagem , Reabsorção Óssea/prevenção & controle , Catepsina K/antagonistas & inibidores , Tiazolidinas/administração & dosagem , Idoso , Biomarcadores/sangue , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Reabsorção Óssea/sangue , Reabsorção Óssea/fisiopatologia , Relógios Circadianos/fisiologia , Colágeno Tipo I/sangue , Estudos Cross-Over , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/prevenção & controle , Peptídeos/sangue , Pós-Menopausa/sangue , Pós-Menopausa/fisiologia , Método Simples-Cego , Tiazolidinas/farmacologia , Tiazolidinas/uso terapêuticoRESUMO
It is shown that charged defect generation, through argon ion-based plasma processing, in few layer graphene, could substantially enhance the electrical capacitance for electrochemical energy storage. Detailed consideration of the constituent space charge and quantum capacitances were used to delineate a new length scale, correlated to electrically active defects contributing to the capacitance, and was found to be smaller than a structural correlation length determined through Raman spectroscopy. The study offers insights into an industrially viable method (i.e., plasma processing) for modifying and enhancing the energy density of graphene-based electrochemical capacitors.
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We created Na(+)/HCO3(-) cotransporter 1 (NBCe1) p.W516* knock-in mice as a model of isolated proximal renal tubular acidosis showing early lethality associated with severe metabolic acidosis to investigate the therapeutic effects of prenatal alkalization or posttranscriptional control 124 (PTC124). NBCe1(W516*/W516*) mice were treated with non-alkalization (control, n=12), prenatal alkalization postcoitus (prenatal group, n=7) and postnatal alkalization from postnatal day 6 (postnatal group, n=12). Mutation-specific therapy, PTC124 (60 mg kg(-1)) or gentamicin (30 mg kg(-1)), was administered intraperitoneally from postnatal day 6. Blood and urine biochemistry, acid-base analysis, survival rate and renal histology were examined. NBCe1 protein, mRNA abundance and activity ex vivo were assessed after PTC124 and gentamicin treatment. Prenatal group mice had similar initial body weight to wild-type mice and achieved significant weight gain thereafter compared with controls. They had higher serum bicarbonate level (15.5 ± 1.4 vs 5.5 ± 0.1 mmol l(-1), P<0.05) on postnatal day 14 and better renal function, histology and survival rates (60.8 ± 23.5 vs 41.1 ± 15.8 days, P<0.05) than the postnatal group. Compared with the control and gentamicin therapies, PTC124 therapy significantly increased NBCe1 protein abundance despite unchanged mRNA transcription. Only PTC124 therapy significantly increased survival rate and partially rescued NBCe1 activity ex vivo. In NBCe1(W516*/W516*) mice, prenatal alkali therapy achieved higher survival rates and ameliorated organ dysfunction. PTC124 therapy for this nonsense mutation was partially effective in increasing NBCe1 expression and activity.
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Acidose Tubular Renal/terapia , Terapia Genética , Oxidiazóis/uso terapêutico , Simportadores de Sódio-Bicarbonato/genética , Acidose Tubular Renal/genética , Álcalis/sangue , Álcalis/urina , Animais , Gentamicinas/administração & dosagem , Gentamicinas/uso terapêutico , Camundongos , Oxidiazóis/administração & dosagem , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Simportadores de Sódio-Bicarbonato/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: Endoplasmic reticulum (ER) stress is the cell response that activates the unfolded protein response (UPR) pathway in a variety of conditions, such as inflammation and bone metabolism. The UPR may be associated with the pathogenesis of periodontal disease because the disease is inflammatory in nature, and alveolar bone resorption is a characteristic feature of the disease. However, the relationship between ER stress and alveolar bone resorption observed in periodontal disease remains elusive. MATERIAL AND METHODS: C57BL/6 mice were orally administered Porphyromonas gingivalis, a representative periodontopathic bacterium, in the presence or absence of a chemical chaperone, 4-phenylbutyrate (4-PBA). The gene expression of UPR-related molecules and cytokines in gingival tissues were analyzed using real-time polymerase chain reaction, and alveolar bone resorption and osteoclast numbers were evaluated histologically. The in vitro effect of 4-PBA on the differentiation of mouse bone marrow cells induced by receptor activator of nuclear factor-κB ligand in the presence of macrophage colony-stimulating factor was analyzed. RESULTS: The gene expression levels of UPR-related molecules and proinflammatory cytokines and alveolar bone resorption were significantly increased in P. gingivalis-administered mice. UPR-related gene expression and alveolar bone resorption were significantly suppressed by the administration of 4-PBA. However, no effect of 4-PBA was observed for proinflammatory cytokine expression in gingival tissues. Osteoclastic differentiation of bone marrow cells was also suppressed by 4-PBA with a concomitant reduction in the gene expression of cathepsin K and tartrate-resistant alkaline phosphatase genes. CONCLUSION: ER stress induced by oral administration of P. gingivalis is involved in alveolar bone resorption independent of inflammatory cytokines in mice.
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Perda do Osso Alveolar/microbiologia , Estresse do Retículo Endoplasmático/fisiologia , Periodontite/microbiologia , Perda do Osso Alveolar/patologia , Animais , Células da Medula Óssea/efeitos dos fármacos , Catepsina K/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/análise , Modelos Animais de Doenças , Gengiva/química , Gengiva/efeitos dos fármacos , Mediadores da Inflamação/análise , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Chaperonas Moleculares/farmacologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/patologia , Fenilbutiratos/farmacologia , Porphyromonas gingivalis/fisiologia , Ligante RANK/farmacologia , Fosfatase Ácida Resistente a Tartarato/efeitos dos fármacos , Resposta a Proteínas não Dobradas/fisiologiaRESUMO
BACKGROUND/PURPOSE: In oxidative coloring, the hair cuticle layers are not only the penetration pathway for active ingredients but also one of the most important dyeing regions. The dyeing mechanism of oxidative dyes in fine structures of the cuticle remains unclear. To investigate the dyeing behavior of oxidative dyes in fine structures of the cuticle, hair cross-sections were analyzed by nanoscale secondary ion mass spectrometry (NanoSIMS). METHODS: The preparation method of hair cross-section for NanoSIMS measurement was improved. Improved hair cross-sections were analyzed using NanoSIMS. RESULTS: The cuticle layer thickness of the hair cross-section could be widened. It was confirmed that (12) C(-) ions were more strongly detected from endocuticle than from other fine structures of cuticle. The NanoSIMS (12) C(-) image and hue saturation intensity (HSI) D(-) /(1) H(-) ratio image of the hair, dyed with deuterium-labeled oxidative dye, indicated that the endocuticle had a higher D(-) /(1) H(-) ratio than the other fine structures of the cuticle. It was substantiated that more colored chromophores were fixated in the endocuticle than in other fine structures of the cuticle. CONCLUSION: The dyeing behavior of oxidative dyes in fine structures of hair cuticle was substantiated by NanoSIMS analysis using the improved hair cross-section preparation method.
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Tinturas para Cabelo/química , Cabelo/química , Cabelo/ultraestrutura , Oxidantes/química , Fenilenodiaminas/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Absorção Fisico-Química , Humanos , Japão , Nanotecnologia/métodos , Distribuição TecidualRESUMO
Viper bites in pregnant women have rarely been reported thus far. Moreover, there is no consensus regarding the treatment of such cases. In this paper, the authors report the successful treatment of viper bite during pregnancy without using antivenom.
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Complicações na Gravidez , Mordeduras de Serpentes , Feminino , Humanos , GravidezRESUMO
BACKGROUND: It is increasingly clear that asthma is not a single disease, but a disorder with vast heterogeneity in pathogenesis, severity, and treatment response. To date, 30 genomewide association studies (GWASs) of asthma have been performed, including by our group. However, most gene variants identified so far confer relatively small increments in risk and explain only a small proportion of familial clustering. OBJECTIVE: To identify additional genetic determinants of susceptibility to asthma using a selected Japanese population with reduced tobacco smoking exposure. METHODS: We performed a GWAS by genotyping a total of 480 098 single-nucleotide polymorphisms (SNPs) for a Japanese cohort consisting of 734 healthy controls and 240 patients with asthma who had smoked for no more than 10 pack-years. The SNP with the strongest association was genotyped in two other independent Japanese cohorts consisting of a total of 531 healthy controls and 418 patients with asthma who had smoked for no more than 10 pack-years. For the hyaluronan synthase 2 (HAS2) gene, we investigated SNP-gene associations using an expression quantitative trait loci (eQTL) database and also analysed its gene expression profiles in 13 different normal tissues. RESULTS: In the discovery GWAS, a SNP located upstream of HAS2, rs7846389, showed the strongest statistical significance (P = 1.43 × 10(-7) ). In the two independent replication cohorts, rs7846389 was consistently associated with asthma (nominal P = 0.0152 and 0.0478 in the first and second replication cohorts, respectively). In the meta-analysis, association of rs7846389 with susceptibility to asthma reached the level of genomewide significance (P = 7.92 × 10(-9) ). This variant was strongly correlated with HAS2 mRNA expression. The strongest expression of the gene was detected in the lung. CONCLUSIONS: Our study identified HAS2 as a novel candidate gene for susceptibility to adult asthma.
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Povo Asiático/genética , Asma/genética , Predisposição Genética para Doença , Glucuronosiltransferase/genética , Adulto , Idoso , Asma/diagnóstico , Estudos de Casos e Controles , Cromossomos Humanos Par 8 , Enganação , Feminino , Expressão Gênica , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Hialuronan Sintases , Japão , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , RNA Mensageiro/genética , Fatores de RiscoRESUMO
OBJECTIVES: The purposes of this study were to investigate the prevalence and distribution of intervertebral disc degeneration (DD) over the entire spine using magnetic resonance imaging (MRI), and to examine the factors and symptoms potentially associated with DD. DESIGN: This study included 975 participants (324 men, mean age of 67.2 years; 651 women, mean age of 66.0 years) with an age range of 21-97 years in the Wakayama Spine Study. DD on MRI was classified into Pfirrmann's system (grades 4 and 5 indicating DD). We assessed the prevalence of DD at each level in the cervical, thoracic, and lumbar regions and the entire spine, and examined DD-associated factors and symptoms. RESULTS: The prevalence of DD over the entire spine was 71% in men and 77% in women aged <50 years, and >90% in both men and women aged >50 years. The prevalence of an intervertebral space with DD was highest at C5/6 (men: 51.5%, women: 46%), T6/7 (men: 32.4%, women: 37.7%), and L4/5 (men: 69.1%, women: 75.8%). Age and obesity were associated with the presence of DD in all regions. Low back pain was associated with the presence of DD in the lumbar region. CONCLUSION: The current study established the baseline data of DD over the entire spine in a large population of elderly individuals. These data provide the foundation for elucidating the causes and mechanisms of DD.
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Degeneração do Disco Intervertebral/epidemiologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Vértebras Cervicais/patologia , Estudos de Coortes , Feminino , Humanos , Degeneração do Disco Intervertebral/etiologia , Degeneração do Disco Intervertebral/patologia , Japão/epidemiologia , Dor Lombar/epidemiologia , Dor Lombar/etiologia , Vértebras Lombares/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Prevalência , Índice de Gravidade de Doença , Distribuição por Sexo , Vértebras Torácicas/patologia , Adulto JovemRESUMO
The objective of this study was to investigate ethnic differences in the glyoxylate reductase/hydroxypyruvate reductase (GRHPR) gene in patients with primary hyperoxaluria type 2 (PH2). GRHPR was genotyped in Japanese patients with PH2 and all GRHPR mutations described to date were reviewed in terms of geographic and ethnic association. We identified a novel mutation, a two-nucleotide deletion (c.248_249delTG) in exon 3 creating a premature 'stop' at codon 91. Also, we found that the c.864_865delTG mutation was associated with the rs35891798 single-nucleotide polymorphism. The allelic frequencies of the c.103delG, c.494G>A, c.403_404+2 delAAGT, and c.864_865delTG mutations in PH2 patients were 37.8%, 15.6%, 10.0%, and 10.0%, respectively. All patients with the c.103delG mutation were Caucasian. Patients with the c.494G>A mutation and 78% (7/9) of those with the c.403_404+2 delAAGT mutation were from the Indian subcontinent, whereas those with the c.864_865delTG mutation were Chinese or Japanese. Molecular analysis of GRHPR of four Japanese PH2 patients identified a novel mutation (c.248_249delTG in exon 3). Caucasians with PH2 should be screened for the c.103delG mutation; patients from the Indian subcontinent for c.494G>A; and patients of East Asian origin (particularly) for c.864_865delTG. The prevalence of the latter mutation in PH2 patients from East Asia was 75.0%.
Assuntos
Oxirredutases do Álcool/genética , Hiperoxalúria Primária/genética , Adulto , Povo Asiático/genética , Criança , Pré-Escolar , Etnicidade/genética , Feminino , Humanos , Hiperoxalúria Primária/etiologia , Lactente , Masculino , Mutação , Polimorfismo de Nucleotídeo Único , Deleção de Sequência , População Branca/genéticaRESUMO
SUMMARY: The prevalence of radiographic cervical ossification of the posterior longitudinal ligament (OPLL) in 1,562 Japanese from a population-based cohort was 1.9 %. The presence of OPLL showed a significant association with the femoral neck bone mineral density (BMD), presence of diffuse idiopathic skeletal hyperostosis (DISH) and plasma pentosidine levels. Only one new case of radiographic OPLL was detected, but OPLL progressed in all affected subjects. INTRODUCTION: The purpose of this study was to clarify the prevalence and progression of radiographic OPLL and the associated factors, using the population-based cohort Research on Osteoarthritis/osteoporosis Against Disability (ROAD). METHODS: In the ROAD study, 1,690 participants underwent X-ray examination of the entire spine and both knees. Radiographic OPLL, lumbar spondylosis, knee osteoarthritis and DISH were diagnosed by a single, well-experienced orthopaedic surgeon. An interviewer-administered questionnaire and tests for anthropometric measurements were administered, and the BMDs of the lumbar spine and proximal femur were determined. A new OPLL case was considered if heterotopic ossification in the posterior longitudinal ligament was absent at baseline but present during follow-up. Progression was defined as an increase in the maximum length or width of the ossification at follow-up over that at baseline. RESULTS: Radiographic OPLL was detected in 30 (17 men, 13 women) of 1,562 individuals who underwent X-ray examination of the cervical spine (prevalence = 1.9 %). Its prevalence was significantly higher in men than in women (p = 0.007), but no association with age was observed. In a logistic regression analysis, OPLL showed a significant association with the femoral neck BMD, presence of DISH and plasma pentosidine levels. Only one new case of radiographic OPLL was detected, but OPLL progressed in all affected subjects. CONCLUSION: This population-based study clarified the prevalence of radiographic OPLL in the Japanese population as well as its progression. OPLL showed significant association with plasma pentosidine levels, BMD and DISH.
Assuntos
Ossificação do Ligamento Longitudinal Posterior/epidemiologia , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Antropometria/métodos , Arginina/análogos & derivados , Arginina/sangue , Biomarcadores/sangue , Densidade Óssea/fisiologia , Comorbidade , Progressão da Doença , Feminino , Colo do Fêmur/fisiopatologia , Seguimentos , Humanos , Hiperostose Esquelética Difusa Idiopática/epidemiologia , Hiperostose Esquelética Difusa Idiopática/fisiopatologia , Japão/epidemiologia , Vértebras Lombares/fisiopatologia , Lisina/análogos & derivados , Lisina/sangue , Masculino , Pessoa de Meia-Idade , Ossificação do Ligamento Longitudinal Posterior/sangue , Ossificação do Ligamento Longitudinal Posterior/diagnóstico por imagem , Ossificação do Ligamento Longitudinal Posterior/fisiopatologia , Prevalência , Radiografia , Distribuição por SexoRESUMO
BACKGROUND AND OBJECTIVE: T and B cells are known to be involved in the disease process of periodontitis. However, the role of natural killer T cells in the pathogenesis of periodontitis has not been clarified. MATERIALS AND METHODS: To examine the role of these cells, C57BL/6J (wild-type), CD1d(-/-) and α-galactosylceramide (αGC)-stimulated wild-type mice were orally infected with Porphyromonas gingivalis strain W83. RESULTS: Apart from CD1d(-/-) mice, the level of alveolar bone resorption was elevated by the infection and was further accelerated in αGC-stimulated mice. The infection induced elevated levels of serum amyloid A and P. gingivalis-specific IgG in the sera, although the degree of elevation was much smaller in the CD1d(-/-) mice. Infection-induced RANKL elevation was only observed in αGC-stimulated mice. Although the cytokines produced by splenocytes were mainly T-helper 1 type in wild-type mice, those in αGC-stimulated mice were predominantly T-helper 2 type. In the liver, the infection demonstrated no effect on the gene expression for interferon-γ, interleukin-4 and RANKL except αGC-stimulated mice in which the infection upregulated the gene expressions. CONCLUSION: This study is the first to show that natural killer T cells upregulated systemic and local inflammatory responses induced by oral infection with P. gingivalis, thereby contributing to the progression of alveolar bone resorption.