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Han, D.,Walsh, Matthew C.,Cejas, Pedro J.,Dang, Nicholas N.,Kim, Youngmi F.,Kim, J.,Charrier-Hisamuddin, L.,Chau, L.,Zhang, Q.,Bittinger, K.,Bushman, Frederic D.,Turka, Laurence A.,Shen, H.,Reizis, B. Cell Press 2013 Immunity Vol.38 No.6
The intracellular signaling molecule TRAF6 is critical for Toll-like receptor (TLR)-mediated activation of dendritic cells (DCs). We now report that DC-specific deletion of TRAF6 (TRAF6ΔDC) resulted, unexpectedly, in loss of mucosal tolerance, characterized by spontaneous development of T helper 2 (Th2) cells in the lamina propria and eosinophilic enteritis and fibrosis in the small intestine. Loss of tolerance required the presence of gut commensal microbiota but was independent of DC-expressed MyD88. Further, TRAF6ΔDC mice exhibited decreased regulatory T (Treg) cell numbers in the small intestine and diminished induction of iTreg cells in response to model antigen. Evidence suggested that this defect was associated with diminished DC expression of interleukin-2 (IL-2). Finally, we demonstrate that aberrant Th2 cell-associated responses in TRAF6ΔDC mice could be mitigated via restoration of Treg cell activity. Collectively, our findings reveal a role for TRAF6 in directing DC maintenance of intestinal immune tolerance through balanced induction of Treg versus Th2 cell immunity.
Walsh, Matthew C.,Pearce, Erika L.,Cejas, Pedro J.,Lee, JangEun,Wang, Li-San,Choi, Yongwon American Association of Immunologists 2014 Journal of Immunology Vol. No.
<P>Naive T cell populations are maintained in the periphery at relatively constant levels via mechanisms that control expansion and contraction and are associated with competition for homeostatic cytokines. It has been shown that in a lymphopenic environment naive T cells undergo expansion due, at least in part, to additional availability of IL-7. We have previously found that T cell–intrinsic deletion of TNFR-associated factor (TRAF) 6 (TRAF6ΔT) in mice results in diminished peripheral CD8 T cell numbers. In this study, we report that whereas naive TRAF6ΔT CD8 T cells exhibit normal survival when transferred into a normal T cell pool, proliferation of naive TRAF6ΔT CD8 T cells under lymphopenic conditions is defective. We identified IL-18 as a TRAF6–activating factor capable of enhancing lymphopenia-induced proliferation (LIP) in vivo, and that IL-18 synergizes with high-dose IL-7 in a TRAF6-dependent manner to induce slow, LIP/homeostatic-like proliferation of naive CD8 T cells in vitro. IL-7 and IL-18 act synergistically to upregulate expression of IL-18R genes, thereby enhancing IL-18 activity. In this context, IL-18R signaling increases PI3K activation and was found to sensitize naive CD8 T cells to a model noncognate self-peptide ligand in a way that conventional costimulation via CD28 could not. We propose that synergistic sensitization by IL-7 and IL-18 to self-peptide ligand may represent a novel costimulatory pathway for LIP.</P>
Pseudotumoral Presentation of Cerebral Amyloid-Beta Angiopathy: Case Report and Review of Literature
Claudia Uribe Roca,Fabio Maximiliano Gonzalez,Marta Ines Bala,Miguel Saucedo,Lucrecia Bandeo,Luciana Leon Cejas,Sol Pacha,Pablo Bonardo,Carlos Rugilo,Pablo Dezanzo,Rafael Torino,Gustavo Sevlever,Manue 대한신경정신의학회 2021 PSYCHIATRY INVESTIGATION Vol.18 No.6
Objective Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare and potentially treatable encephalopathy that usually affects people older than 50 years old and has an acute or subacute clinical presentation characterized by rapidly evolving cognitive decline, focal deficits and seizures. In a small subset of patients the disease can adopt a pseudotumoral form in the neuroimages that represents a very difficult diagnostic challenge. Methods Here in we report a patient with a tumour-like presentation of histopathologically confirmed CAA-RI. Results We also conducted a search and reviewed the clinical and radiological features of 41 cases of pseudotumoral CAA-RI previously reported in the literature in order to identify those characteristics that should raise diagnostic suspicions of the disease, there by avoiding unnecessary surgical treatments.Conclusion The therapy of CAA-RI with steroids is usually effective and clinical and radiological remission can be achieved in the first month in approximately 70% of cases.
Nelida A. Gonzalez Hernandez,Rebeca O. Millan Guerrero,Gabriel Ceja Espiritu,Luz M. Baltazar Rodriguez,Rafael Rodriguez Salazar,Bertha A. Olmedo Buenrostro,Irma G. Enriquez Maldonado,Valery Melnikov,J 한국유전학회 2008 Genes & Genomics Vol.30 No.6
The action of matrix metalloproteinases (MMPs) can weaken the arterial wall, contributing to the destabilizing and rupture of atheromatous plaque. Within the MMPs, type 2 stands out due to its action on basement membrane constituents. Previous studies have revealed elevated levels of MMP-2 in the acute phase of ischemic stroke (IS). An MMP-2 single nucleotide polymorphism, -1306T>C (rs243865), displayed strikingly high promoter activity with the C allele. Our study analyzed whether or not the MMP-2-1306T>C polymorphism contributed to the development of IS in a Mexican population. Ninety-eight patients with IS and 213 control subjects were analyzed. Genomic DNA isolation, polymerase chain reaction (PCR), and polymorphism detection by restriction enzyme digestion were performed to detect MMP-2-1306T>C polymorphism. An increased probability of IS associated with the MMP-2 CC genotype (OR, 1.70; 95% CI, 1.02-2.85) was found. IS risk associated with the CC genotype was more pronounced in hypertensive subjects (OR, 2.81; 95% CI, 1.4-5.5). The CC genotype was not associated with the development of primary hypertension. The data suggest that MMP-2-1306T>C polymorphism greatly contributes to IS development in the population studied, principally in hypertensive subjects. This case-control study lends support to the association of MMP-2 with stroke at the genetic level, an association consistent with MMP-2 participation in IS physiopathology.
Jaquelina J. Guzmán-Rodríguez,Ma. Fabiola León-Galván,José E. Barboza-Corona,Mauricio Valencia-Posadas,Pedro D. Loeza-Lara,Mónica Sánchez-Ceja,Alejandra Ochoa-Zarzosa,Joel E. López-Meza,Abner J. Gutié 대한수의학회 2020 Journal of Veterinary Science Vol.21 No.5
Background: Staphylococcus aureus is one of the main microorganisms that causes bovine mastitis, and its well-known virulence characteristics and interactions with the environment are used to aid the design of more efficient therapies. Objectives: To determine whether the virulence traits, such as antibiotic resistance and biofilm-forming and internalization abilities, of S. aureus isolated from bovine mastitis are related to dairy production system types. Methods: The study was performed in the Mexican states of Guanajuato and Michoacan. Semi-intensive dairy farms (SIDFs) and family dairy farms (FDFs) (454 and 363 cows, respectively) were included. The 194 milk samples from mastitis affected quarters were collected and 92 strains of S. aureus were isolated and identified by biochemical and molecular tests. Antibiotic resistance, biofilm and internalization assays were performed on 30 randomly selected isolated strains to determine virulence traits, and these strains were equally allocated to the 2 dairy production systems. Results: All 30 selected strains displayed a high degree of resistance (50%–91.7%) to the antibiotics tested, but no significant difference was found between SIDF and FDF isolates. S. aureus strains from SIDFs had an average biofilm forming capacity of up to 36% (18.9%–53.1%), while S. aureus strains from FDFs registered an average of up to 53% (31.5%–77.8%) (p > 0.05). Internalization assays revealed a higher frequency of internalization capacity for strains isolated from FDFs (33.3%) than for those isolated from SIDFs (6.7%) (p > 0.05). fnbpA gen was detected in 46.6% of FDF strains and 33.3% of SIDF strains, and this difference was significant (p < 0.05). Conclusions: Our findings show that the virulence traits of S. aureus isolates analyzed in this study, depend significantly on several factors, such as phenotype, genotype, and environmental conditions, which are significantly related to dairy production system type and daily management practices.