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1.
Vaccines (Basel) ; 10(8)2022 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-36016254

RESUMEN

The induction of T cell-mediated immunity is crucial in vaccine development. The most effective vaccine is likely to employ both cellular and humoral immune responses. The efficacy of a vaccine depends on T cells activated by antigen-presenting cells. T cells also play a critical role in the duration and cross-reactivity of vaccines. Moreover, pre-existing T-cell immunity is associated with a decreased severity of infectious diseases. Many technical and delivery platforms have been designed to induce T cell-mediated vaccine immunity. The immunogenicity of vaccines is enhanced by controlling the kinetics and targeted delivery. Viral vectors are attractive tools that enable the intracellular expression of foreign antigens and induce robust immunity. However, it is necessary to select an appropriate viral vector considering the existing anti-vector immunity that impairs vaccine efficacy. mRNA vaccines have the advantage of rapid and low-cost manufacturing and have been approved for clinical use as COVID-19 vaccines for the first time. mRNA modification and nanomaterial encapsulation can help address mRNA instability and translation efficacy. This review summarizes the T cell responses of vaccines against various infectious diseases based on vaccine technologies and delivery platforms and discusses the future directions of these cutting-edge platforms.

2.
Rheumatology (Oxford) ; 61(3): 1133-1140, 2022 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-34146088

RESUMEN

OBJECTIVES: No large-scale registration study has comprehensively evaluated the activities of daily living (ADL) in patients with Behçet's disease. METHODS: The Japanese government provided us with a dataset of confirmed or suspected Behçet's disease cases derived from ongoing national registration. ADL were categorized and analysed into four categories in patients who satisfied the International Criteria for Behçet's Disease. RESULTS: Data from 2960 patients (men 38.9%, women 61.1%; median age 39 years) were assessed. While 1767 patients (59.7%) had normal ADL, the others had impaired ADL comprising limited but not assisted [n = 1058 (35.7%)], partially assisted [n = 116 (3.9%)] and fully assisted [n = 19 (0.6%)]. Logistic regression analysis showed that chronic ocular lesions [odds ratio (OR) 1.85 (95% CI 1.46, 2.35), P < 0.001], paralysis [OR 2.51 (95% CI 1.58, 3.97), P < 0.001], psychosis [OR 3.16 (95% CI 2.02, 4.95), P < 0.001] and arthritis [OR 1.69 (95% CI 1.44, 1.99), P < 0.001] led to the risk of impaired ADL. Chronic ocular lesions [OR 3.61 (95% CI 2.27, 5.72), P < 0.001], paralysis [OR 3.43 (95% CI 1.87, 6.30), P < 0.001] and psychosis [OR 3.60 (95% CI 2.00, 6.50), P < 0.001] were related to the requirement of physical assistance (partially or fully assisted), although arthritis [OR 1.39 (95% CI 0.93, 2.06), P = 0.108] was not a significant factor in this model. CONCLUSION: Ocular lesions, neurological manifestations and arthritis affected ADL. Patients with ocular lesions or neurological manifestations more frequently required physical assistance.


Asunto(s)
Actividades Cotidianas , Síndrome de Behçet/fisiopatología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios
3.
Ophthalmic Res ; 65(2): 162-170, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34788757

RESUMEN

INTRODUCTION: The aim of the study was to investigate the outcomes of vitrectomy with fovea-sparing internal limiting membrane (ILM) peeling (FSIP) for epiretinal membrane (ERM) foveoschisis based on new optical coherence tomography definitions. METHODS: Twenty-three eyes of 22 patients (69.7 ± 9.9 years old) who underwent vitrectomy with FSIP without gas tamponade for ERM foveoschisis were analyzed. All patients underwent follow-up examinations for at least 12 months. In the FSIP technique, the ILM is peeled off in a donut shape, preserving the foveal ILM. The logarithm of the minimal angle of resolution best-corrected visual acuity (BCVA), central macular thickness (CMT), and surgical complications were examined. RESULTS: The BCVA at 12 months improved significantly from baseline (p < 0.001). Baseline ellipsoid zone defects were found in 2 eyes (9%), and all defective eyes had recovered at 12 months. CMT decreased significantly from baseline (p < 0.001). Acute macular edema, full-thickness macular hole, and recurrence of ERM were not observed during follow-up. DISCUSSION/CONCLUSION: FSIP achieved good visual outcome and retinal morphological change. Moreover, FSIP might avoid acute macular edema in ERM foveoschisis surgery.


Asunto(s)
Membrana Epirretinal , Edema Macular , Miopía Degenerativa , Retinosquisis , Anciano , Membrana Basal/cirugía , Membrana Epirretinal/complicaciones , Membrana Epirretinal/diagnóstico , Membrana Epirretinal/cirugía , Humanos , Edema Macular/cirugía , Persona de Mediana Edad , Miopía Degenerativa/cirugía , Retinosquisis/complicaciones , Retinosquisis/diagnóstico , Retinosquisis/cirugía , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Vitrectomía/métodos
5.
Development ; 148(8)2021 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-33766931

RESUMEN

During spermatogenesis, intricate gene expression is coordinately regulated by epigenetic modifiers, which are required for differentiation of spermatogonial stem cells (SSCs) contained among undifferentiated spermatogonia. We have previously found that KMT2B conveys H3K4me3 at bivalent and monovalent promoters in undifferentiated spermatogonia. Because these genes are expressed late in spermatogenesis or during embryogenesis, we expect that many of them are potentially programmed by KMT2B for future expression. Here, we show that one of the genes targeted by KMT2B, Tsga8, plays an essential role in spermatid morphogenesis. Loss of Tsga8 in mice leads to male infertility associated with abnormal chromosomal distribution in round spermatids, malformation of elongating spermatid heads and spermiation failure. Tsga8 depletion leads to dysregulation of thousands of genes, including the X-chromosome genes that are reactivated in spermatids, and insufficient nuclear condensation accompanied by reductions of TNP1 and PRM1, key factors for histone-to-protamine transition. Intracytoplasmic sperm injection (ICSI) of spermatids rescued the infertility phenotype, suggesting competency of the spermatid genome for fertilization. Thus, Tsga8 is a KMT2B target that is vitally necessary for spermiogenesis and fertility.


Asunto(s)
Fertilidad , Nucleoproteínas/metabolismo , Espermátides/metabolismo , Espermatogénesis , Células Madre/metabolismo , Animales , Femenino , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Infertilidad Masculina/genética , Infertilidad Masculina/metabolismo , Masculino , Ratones , Ratones Noqueados , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Nucleoproteínas/genética , Espermatogonias/metabolismo
6.
Mod Rheumatol ; 31(1): 214-218, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31851572

RESUMEN

BACKGROUND: How HLA-A26 modulates Behçet's disease (BD) ocular lesions such as iridocyclitis and retinochorioiditis has not been scrutinized. METHODS: Ministry of Health, Labour and Welfare of Japan provided us a database of BD patients who were registered from 2003 to 2014. We selected patients who satisfied International Criteria for BD and whose data for HLA-A26 was available. RESULTS: Eligible 557 patients consisting of 238 men (42.7%) and 319 women (57.3%), whose median age was 38 years old (interquartile range 29-47) were analyzed. Prevalence of general ocular lesions, iridocyclitis, retinochorioiditis, and chronic lesions were 43.1%, 30.7%, 34.1%, and 17.4%, respectively. The prevalence of ocular lesions was higher among HLA-A26 carriers compared to that among HLA-A26 non-carriers with odds ratio (OR) of 2.5 (95% confidence interval (95% CI) 1.8-3.5, p < .001) for general ocular lesions, OR of 2.5 (95% CI 1.7-3.6, p < .001) for iridocyclitis, OR of 2.8 (95% CI 1.9-4.0, p < .001) for retinochorioiditis, and OR of 2.7 (95% CI 1.7-4.3, p < .001) for 'chronic ocular lesion following iridocyclitis or retinochorioiditis'. The HLA-A26 had a similar impact on ocular lesions between HLA-B51 positive and negative cases (Breslow-Day test, p > .05). However, the HLA-A26 had a larger impact on iridocyclitis for men compared to women (Breslow-Day test, p = .040). The male HLA-A26 carriers had higher risk of iridocyclitis with OR of 3.4 (95% CI 2.0-5.9, p < .001), while the OR for women was 1.5 (95% CI 0.9-2.6, p = .146). CONCLUSION: HLA-A26 carriers had higher risk for iridocyclitis and retinochorioiditis. However, the impact was more prominent for men.


Asunto(s)
Síndrome de Behçet/genética , Antígenos HLA-A/genética , Antígeno HLA-B51/genética , Adulto , Síndrome de Behçet/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo
7.
Front Physiol ; 11: 586843, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33250779

RESUMEN

Alpha-arbutin (4-hydroxyphenyl alpha-glucopyranoside) is a known inhibitor of tyrosinase in keratinocytes; however, its effect on other genes and pathways in other skin cells has not been thoroughly investigated. In this study, we investigate the mechanism of alpha-arbutin activity in human dermal fibroblast cultures for 48 h. Results showed that the oxidative stress pathway was activated as alpha-arbutin reduced reactive oxygen species. In addition, we found a high possibility of wound healing and the upregulation of the insulin-like growth factor 1 receptor (IFG1R) pathway. We also investigated the role of the NRF2 gene in mediating the alpha-arbutin response. In silico comparative genomics analysis conducted using our original tool, SHOE, suggested transcription factors with a role in tumor suppression and toxicity response as candidates for regulating the alpha-arbutin-mediated pathway.

8.
Commun Biol ; 3(1): 465, 2020 08 21.
Artículo en Inglés | MEDLINE | ID: mdl-32826979

RESUMEN

Sarcoidosis is a genetically complex systemic inflammatory disease that affects multiple organs. We present a GWAS of a Japanese cohort (700 sarcoidosis cases and 886 controls) with replication in independent samples from Japan (931 cases and 1,042 controls) and the Czech Republic (265 cases and 264 controls). We identified three loci outside the HLA complex, CCL24, STYXL1-SRRM3, and C1orf141-IL23R, which showed genome-wide significant associations (P < 5.0 × 10-8) with sarcoidosis; CCL24 and STYXL1-SRRM3 were novel. The disease-risk alleles in CCL24 and IL23R were associated with reduced CCL24 and IL23R expression, respectively. The disease-risk allele in STYXL1-SRRM3 was associated with elevated POR expression. These results suggest that genetic control of CCL24, POR, and IL23R expression contribute to the pathogenesis of sarcoidosis. We speculate that the CCL24 risk allele might be involved in a polarized Th1 response in sarcoidosis, and that POR and IL23R risk alleles may lead to diminished host defense against sarcoidosis pathogens.


Asunto(s)
Quimiocina CCL24/genética , Sistema Enzimático del Citocromo P-450/genética , Predisposición Genética a la Enfermedad , Receptores de Interleucina/genética , Sarcoidosis/etiología , Alelos , Quimiocina CCL24/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Femenino , Estudios de Asociación Genética , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Japón , Masculino , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Receptores de Interleucina/metabolismo , Sarcoidosis/diagnóstico , Sarcoidosis/metabolismo
9.
BMC Ophthalmol ; 20(1): 252, 2020 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-32580711

RESUMEN

BACKGROUND: Immune checkpoint inhibitors can cause various adverse effects. Recently it has been shown that Vogt-Koyanagi-Harada (VKH) disease-like uveitis can occur in patients treated with nivolumab. CASE PRESENTATION: A 69-year-old man developed bilateral panuveitis after nivolumab treatment for recurrent hypopharyngeal cancer. Slit lamp examination revealed bilateral granulomatous keratic precipitates, anterior chamber cells and partial synechiae. Fundus examination revealed bilateral optic disc edema and diffuse serous retinal detachment. His human leukocyte antigen (HLA) typing showed HLA-DRB1*04:05 allele. A lumbar puncture did not demonstrate pleocytosis. Bilateral sub-tenon injections of triamcinolone acetonide were initiated. As his panuveitis did not regress completely, steroid pulse therapy was administered. That therapy led to the resolution of his serous retinal detachment and to rapid improvement in his vision. Following this, we treated him with 50 mg/day of prednisolone for 1 week and then reduced it by 5 mg every week. No bilateral uveitis relapse had occurred by his 3-month follow-up; however, he subsequently died because of his cancer. CONCLUSION: To our knowledge, this is the first report of a patient with NVKH who underwent a lumbar puncture. Unlike VKH, our case did not show meningismus or pleocytosis. NVKH may, therefore, have a different etiology from VKH. In cases of NVKH with posterior uveitis, steroid pulse therapy may be considered as a treatment option, as it is in VKH.


Asunto(s)
Panuveítis , Desprendimiento de Retina , Uveítis , Síndrome Uveomeningoencefálico , Anciano , Humanos , Masculino , Nivolumab/efectos adversos , Panuveítis/inducido químicamente , Panuveítis/diagnóstico , Panuveítis/tratamiento farmacológico , Desprendimiento de Retina/inducido químicamente , Síndrome Uveomeningoencefálico/inducido químicamente , Síndrome Uveomeningoencefálico/diagnóstico , Síndrome Uveomeningoencefálico/tratamiento farmacológico
10.
Mod Rheumatol ; 30(4): 708-714, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31386589

RESUMEN

Objectives: To scrutinize the influence of HLA-B51 to each clinical manifestation of patients with Behçet's disease (BD) using a database of the Ministry of Health, Labour and Welfare of Japan.Methods: The database of newly registered patients with BD was obtained from the Japanese Ministry of Health, Labour and Welfare. Patients who met International Criteria for Behçet's Disease (ICBD) and had data for HLA-B51 were selected and analyzed.Results: Among the 3044 analyzable cases, 1334 (43.8%) were men and 1710 (56.2%) were women; the median age was 38 years (IQR 29-48). HLA-B51 was positive for 1334 (44.5%). Prevalence of selected manifestations was 98.5% for oral ulceration, 85.5% for skin lesion, 42.1% for ocular lesion, 69.1% for genital ulceration, and 29.0% for gastrointestinal symptom. HLA-B51-positive patients had higher risk for ocular lesion (OR 1.59, 95%CI: 1.37-1.84; p < .001) and lower risk for genital ulceration (OR 0.72, 95%CI: 0.62-0.84; p < .001) and gastrointestinal symptom (OR 0.65, 95%CI: 0.55-0.77; p < .001). No significant difference was observed for other organ involvement; oral ulceration, skin lesion, positive pathergy test, arthritis, epididymitis, vascular lesion, or neurological manifestation. Subgroup analyses revealed that HLA-B51 was not related to genital ulceration in the cases with an ICBD score of 6 or higher and that HLA-B51 tended to more largely affect the risk of three manifestations for men compared to that for women.Conclusion: HLA-B51 positive is a risk factor for ocular lesion and vice versa for genital ulceration and gastrointestinal symptoms in patients with Japanese BD.


Asunto(s)
Artritis/epidemiología , Síndrome de Behçet/complicaciones , Enfermedades Gastrointestinales/epidemiología , Antígeno HLA-B51/sangre , Úlcera/epidemiología , Adulto , Síndrome de Behçet/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia
11.
Sci Rep ; 9(1): 4426, 2019 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-30872678

RESUMEN

The strongest genetic risk factor of Behçet's disease (BD) is HLA-B*51. Our group previously reported that HLA-A*26 is independently associated with the risk of the onset of BD apart from HLA-B*51. Here, we re-evaluated the association between HLA-A*26 and BD in the Japanese population. We also performed a comprehensive literature search and meta-analyzed the extracted published data concerning the relationship between HLA-A*26 and BD to estimate the odds ratio (OR) of HLA-A*26 to BD. In this study, we genotyped 611 Japanese BD patients and 2,955 unrelated ethnically matched healthy controls. Genotyping results showed that the phenotype frequency of HLA-A*26 was higher in BD patients than in controls (OR = 2.12, 95% CI: 1.75-2.56). Furthermore, within the HLA-B*51-negative populations, the phenotype frequency of HLA-A*26 was significantly higher in BD patients than in controls (OR = 3.10, 95% CI: 2.43-3.95). Results obtained from meta-analysis combined with our data showed that the modified OR of HLA-A*26 became 1.80 (95% CI:1.58-2.06), whereas within the HLA-B*51-negative population, the modified OR became 4.02 (95% CI: 2.29-7.05). A subgroup analysis arranged by the geographical regions showed HLA-A*26 is in fact associated with the onset of BD in Northeast Asia (OR = 2.11, 95% CI: 1.75-2.56), but not in the Middle East or in Europe.


Asunto(s)
Síndrome de Behçet/epidemiología , Síndrome de Behçet/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Antígenos HLA-A/genética , Estudios de Casos y Controles , Genotipo , Humanos , Incidencia , Japón/epidemiología , Fenotipo , Factores de Riesgo
12.
Mod Rheumatol ; 29(2): 357-362, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29583036

RESUMEN

OBJECTIVES: This study aimed to identify patients with high-probability of ocular involvement of Behçet's disease (BD). METHODS: The Japanese Ministry of Health, Labour and Welfare provided dataset of ongoing nationwide BD registration project. A patient who had confirmed BD and who was suspected to have BD was registered. We mainly analyzed newly registered patients who had the data for all demographic and diagnostic parameters regardless of fulfilment of any diagnostic criteria. RESULTS: Among 3213 patients with confirmed or possible BD, 1382 (43.0%) were men and 1831 (57.0%) were women with a median age of 38 years (interquartile range (IQR) 30-49 years). The median duration between onset and registration was 0 year (IQR 0-3). A binomial multivariable logistic regression analysis revealed that being female (odds ratio (OR) 0.63, 95% confidence interval (CI) 0.53-0.75, p < .001), duration since onset (OR 1.33 per 10 years, 95% CI 1.18-1.51, p < .001), genital ulceration (OR 0.28, 95% CI 0.23-0.34, p < .001), and gastrointestinal symptoms (OR 0.36, 95% CI 0.30-0.44, p < .001) were related to the ocular lesion. Analyses based on data of 2800 patients who satisfied International criteria of BD, age-, sex-, duration-based subgroup analyses, analyses targeting iridocyclitis and retino-uveitis, and analysis including patients with missing data confirmed that the four factors were associated with the probability of eye involvement. CONCLUSION: The ocular involvement did not accompany with genital ulcer or gastrointestinal symptoms at the early stage of BD.


Asunto(s)
Síndrome de Behçet , Enfermedades Gastrointestinales , Genitales , Úlcera , Uveítis , Adulto , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/epidemiología , Síndrome de Behçet/fisiopatología , Correlación de Datos , Femenino , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/etiología , Humanos , Japón/epidemiología , Masculino , Oportunidad Relativa , Sistema de Registros/estadística & datos numéricos , Factores Sexuales , Úlcera/diagnóstico , Úlcera/etiología , Uveítis/diagnóstico , Uveítis/epidemiología , Uveítis/etiología
13.
Mod Rheumatol ; 29(4): 640-646, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29954241

RESUMEN

Background: Clinical data of patients with entro-, vasculo-, and neuro-variant possible Behçet's disease (BD) based on Japanese criteria has not yet comprehensively reported. Methods: This ongoing nation-wide registration has been carried out by the Japanese Ministry of Health, Labour and Welfare. The Ministry asked physicians who diagnosed a patient with confirmed or possible BD to register the patient data by filling out a registration form. The Ministry provided us with the dataset after unlinkable anonymization. We analyzed 2003-2014 database generated from the early stage new cases. Results: Among the 7950 analyzable cases, 694 (8.7%) had variant-type possible BD without satisfying complete/incomplete criteria. Of the 694 patients, 479, 46, and 169 had entero-, vasculo-, and neuro-variant possible BD, respectively. Out of these 694 patients, 35 (5.0%) and 154 (22.2%) satisfied the International Study Group criteria and the International Criteria of BD, respectively. Entero-variant possible patients rarely (1.8%) had ocular lesions. Patients with vasculo-variant possible BD were featured by low genital ulceration risk (6.8%) and frequent positive HLA-B51 (60.0%). Neuro-variant possible BD was featured by high median age at registration (48 year). Vasculo- (69.6%) and neuro-variant (68.6%) BD patients showed clear male dominance. Epididymitis was very rare among variant-type possible BD men. Conclusion: We analyzed 694 early-stage variant-type possible BD cases. We believe the data from our study will contribute to further international discussion regarding BD diagnostic criteria and clarification of the clinical presentations of the Japanese variant-type possible BD patients.


Asunto(s)
Síndrome de Behçet/patología , Adulto , Síndrome de Behçet/epidemiología , Bases de Datos Factuales , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad
14.
Clin Ophthalmol ; 11: 2151-2156, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29263643

RESUMEN

PURPOSE: The crystallin beta A4 (CRYBA4) gene variant, rs2009066, was previously reported to be associated with high myopia in a southern Chinese population. In the present study, we investigated whether CRYBA4 variants were associated with high myopia in a Japanese population. METHODS: We recruited 1,063 Japanese patients with high myopia (spherical equivalent [SE] ≤-9.00 D in both eyes) and 1,009 healthy Japanese subjects (SE >-1.00 D). We genotyped rs2009066 and three tagging single-nucleotide polymorphisms (SNPs), rs16982456, rs2071861, and rs4276, in the CRYBA4 region. RESULTS: We did not find any significant association between these four SNPs and high myopia in an allele analysis. However, rs2009066 and rs2071861, which were in strong linkage disequilibrium (LD; r2=0.86), showed a marginal association with high myopia in the recessive genotype model of risk alleles (rs2009066 G allele: P=0.032, odds ratio [OR] =1.31; rs2071861 A allele: P=0.037, OR =1.31). Nevertheless, this association became insignificant after correcting for multiple testing (Pc >0.05). CONCLUSION: This study showed no significant association between CRYBA4 variants and high myopia in a Japanese population. Our findings did not correspond with a previous study. Further genetic studies with other populations are needed to elucidate a potential contribution of the CRYBA4 region in the development of high myopia.

15.
Rheumatology (Oxford) ; 56(11): 1918-1927, 2017 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-28968732

RESUMEN

Objective: This report aimed to scrutinize the prevalence of Behçet's disease (BD)-related clinical manifestations based on age- and sex-specific subgroups using a Japanese nationwide registration database. Methods: The database of newly registered BD was obtained from the Japanese Ministry of Health, Labour and Welfare. Patients who met the International Criteria for Behçet's Disease were selected and analysed. Results: Among 6627 International Criteria for Behçet's Disease cases, 2651 (40.0%) were men and 3976 (60.0%) were women with a median age of 39 years (interquartile range: 31-50 years). Ocular lesion was more common in male [odds ratio (male: female) 2.64 (95% CI: 2.35, 2.95, P < 0.001)] and genital ulceration was more common in female (odds ratio = 0.29, 95% CI: 0.25, 0.32, P < 0.001). Ocular lesion (P < 0.001), arthritis (P < 0.001) and vascular lesions (P < 0.001) were more frequently observed in elderly registered patients. Contrarily, genital ulceration (P < 0.001), epididymitis of males (P = 0.023) and oral ulceration (P = 0.003) were more common in younger patients. Simultaneous assessment of sex and age revealed that male predominance of ocular involvement was found in the young adult generation, but not in patients over 70 year of age. A female predominance of genital ulcer was prominently observed in patients 20-59 year of age; however, the sex difference was not found in patients over 60 years of age. Sensitivity analysis using International Study Group criteria replicated the results. Conclusion: We showed that clinical phenotype in early phase of BD was different depending on onset age and sex.


Asunto(s)
Síndrome de Behçet/fisiopatología , Sistema de Registros , Adolescente , Adulto , Factores de Edad , Anciano , Artritis/etiología , Artritis/fisiopatología , Síndrome de Behçet/complicaciones , Síndrome de Behçet/genética , Niño , Bases de Datos Factuales , Epididimitis/etiología , Epididimitis/fisiopatología , Oftalmopatías/etiología , Oftalmopatías/fisiopatología , Femenino , Enfermedades Gastrointestinales/etiología , Enfermedades Gastrointestinales/fisiopatología , Enfermedades de los Genitales Femeninos/etiología , Enfermedades de los Genitales Femeninos/fisiopatología , Enfermedades de los Genitales Masculinos/etiología , Enfermedades de los Genitales Masculinos/fisiopatología , Antígeno HLA-B51/genética , Humanos , Japón , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/fisiopatología , Oportunidad Relativa , Úlceras Bucales/etiología , Úlceras Bucales/fisiopatología , Fenotipo , Factores Sexuales , Úlcera Cutánea/etiología , Úlcera Cutánea/fisiopatología , Enfermedades Vasculares/etiología , Enfermedades Vasculares/fisiopatología , Adulto Joven
16.
Sci Rep ; 7(1): 10196, 2017 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-28860590

RESUMEN

Neuro-Behçet's disease (NBD) is subcategorized into parenchymal-NBD (P-NBD) and non-parenchymal-NBD types. Recently, P-NBD has been further subdivided into acute P-NBD (A-P-NBD) and chronic progressive P-NBD (CP-P-NBD). Although an increasing number of studies have reported the various clinical features of A-P-NBD and CP-P-NBD over the last two decades, there was a considerable inconsistency. Two investigators systematically searched four electrical databases to detect studies that provided sufficient data to assess the specific characteristics of A-P-NBD and CP-P-NBD. All meta-analysis was carried out by employing the random-model generic inverse variance method. We included 11 reports consisted of 184 A-P-NBD patients and 114 CP-P-NBD patients. While fever (42% for A-P-NBD, 5% for CP-P-NBD, p < 0.001, I2 = 93%) was more frequently observed in A-P-NBD cases; sphincter disturbances (9%, 34%, P = 0.005, I2 = 87%), ataxia (16%, 57%, P < 0.001, I2 = 92%), dementia (7%, 61%, P < 0.001, I2 = 97%), confusion (5%, 18%, P = 0.04, I2 = 76%), brain stem atrophy on MRI (4%, 75%, P < 0.001, I2 = 98%), and abnormal MRI findings in cerebellum (7%, 54%, P = 0.02, I2 = 81%) were more common in CP-P-NBD. Cerebrospinal fluid cell count (94/mm3, 11/mm3, P = 0.009, I2 = 85%) was higher in A-P-NBD cases. We demonstrated that A-P-NBD and CP-P-NBD had clearly different clinical features and believe that these data will help future studies investigating P-NBD.


Asunto(s)
Síndrome de Behçet/patología , Encéfalo/patología , Tejido Parenquimatoso/patología , Enfermedad Aguda , Encéfalo/diagnóstico por imagen , Líquido Cefalorraquídeo/citología , Enfermedad Crónica , Diagnóstico Diferencial , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Tejido Parenquimatoso/diagnóstico por imagen
17.
Nat Genet ; 49(3): 438-443, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28166214

RESUMEN

We analyzed 1,900 Turkish Behçet's disease cases and 1,779 controls genotyped with the Immunochip. The most significantly associated SNP was rs1050502, a tag SNP for HLA-B*51. In the Turkish discovery set, we identified three new risk loci, IL1A-IL1B, IRF8, and CEBPB-PTPN1, with genome-wide significance (P < 5 × 10-8) by direct genotyping and ADO-EGR2 by imputation. We replicated the ADO-EGR2, IRF8, and CEBPB-PTPN1 loci by genotyping 969 Iranian cases and 826 controls. Imputed data in 608 Japanese cases and 737 controls further replicated ADO-EGR2 and IRF8, and meta-analysis additionally identified RIPK2 and LACC1. The disease-associated allele of rs4402765, the lead marker at IL1A-IL1B, was associated with both decreased IL-1α and increased IL-1ß production. ABO non-secretor genotypes for two ancestry-specific FUT2 SNPs showed strong disease association (P = 5.89 × 10-15). Our findings extend the list of susceptibility genes shared with Crohn's disease and leprosy and implicate mucosal factors and the innate immune response to microbial exposure in Behçet's disease susceptibility.


Asunto(s)
Síndrome de Behçet/genética , Sitios Genéticos/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Alelos , Estudios de Casos y Controles , Femenino , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Humanos , Irán , Masculino , Turquía
18.
Clin Interv Aging ; 11: 1159-68, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27621603

RESUMEN

Components of fish roe possess antioxidant and antiaging activities, making them potentially very beneficial natural resources. Here, we investigated chum salmon eggs (CSEs) as a source of active ingredients, including vitamins, unsaturated fatty acids, and proteins. We incubated human dermal fibroblast cultures for 48 hours with high and low concentrations of CSE extracts and analyzed changes in gene expression. Cells treated with CSE extract showed concentration-dependent upregulation of collagen type I genes and of multiple antioxidative genes, including OXR1, TXNRD1, and PRDX family genes. We further conducted in silico phylogenetic footprinting analysis of promoter regions. These results suggested that transcription factors such as acute myeloid leukemia-1a and cyclic adenosine monophosphate response element-binding protein may be involved in the observed upregulation of antioxidative genes. Our results support the idea that CSEs are strong candidate sources of antioxidant materials and cosmeceutically effective ingredients.


Asunto(s)
Antioxidantes/metabolismo , Colágeno Tipo I/metabolismo , Huevos , Fibroblastos/efectos de los fármacos , Oncorhynchus keta , Extractos de Tejidos/farmacología , Animales , Células Cultivadas , Femenino , Expresión Génica , Humanos , Regulación hacia Arriba
19.
Graefes Arch Clin Exp Ophthalmol ; 252(6): 977-82, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24668387

RESUMEN

PURPOSE: To describe a new technique to perform trabeculotomy ab interno on eyes with open-angle glaucoma (OAG). METHODS: This was a retrospective study. We inserted a 25-gauge forceps that is usually used for internal limiting membrane peeling into the anterior chamber, and grasped and pulled the inner wall of Schlemm's canal away from the canal. The inner wall of Schlemm's canal was stripped for about 100° to 120° in 26 eyes of 23 patients. The intraocular pressure (IOP) and number of glaucoma medications were recorded before, and 1 day, 1 week, 2 weeks, and 1, 3, 6, 10, 12, 15, 17, 19, 24, 27, 30, and 33 months after the surgery. The intra- and postoperative complications were recorded. RESULTS: The mean ± standard deviation of the preoperative IOP was 20.0 ± 6.8 mmHg with a range from 10 to 38 mmHg (n = 26). The IOP was significantly reduced (P < 0.05; paired t-tests) at 1 week, 2 weeks, and 1, 3, 6, 10, 12, 15, 17, 24, 19, 27, 30, and 33 months after the surgery. The mean preoperative number of glaucoma medications was significantly reduced (P < 0.001; paired t-tests) at 1 week, 2 weeks, and 1, 3, 6, 10, 12, 15, 17, 19, 24, 27, 30, and 33 months after the surgery. No vision-threatening complications were found in any of the cases, but there were blood clots in the anterior chamber postoperatively in 92.3 % of the cases. CONCLUSIONS: Trabeculotomy ab interno for OAG is effective but with some minor complications. A larger number of patients with longer follow-up periods are needed to determine the long-term effectiveness of this procedure.


Asunto(s)
Glaucoma de Ángulo Abierto/cirugía , Trabeculectomía/instrumentación , Trabeculectomía/métodos , Anciano , Antihipertensivos/administración & dosificación , Femenino , Estudios de Seguimiento , Glaucoma de Ángulo Abierto/fisiopatología , Humanos , Presión Intraocular/fisiología , Complicaciones Intraoperatorias , Masculino , Facoemulsificación , Complicaciones Posoperatorias , Estudios Retrospectivos , Tonometría Ocular , Agudeza Visual/fisiología
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