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91.
Ashley Parrott Philip R. Khoury Amy R. Shikany Angela Lorts Chet R. Villa Erin M. Miller 《American journal of medical genetics. Part C, Seminars in medical genetics》2020,184(1):116-123
Pediatric cardiomyopathies can be caused by variants in genes encoding the sarcomere and cytoskeleton in cardiomyocytes. Variants are typically inherited in an autosomal dominant manner with variable expressivity. De novo variants have been reported, however their overall frequency is largely unknown. We sought to determine the rate of de novo, pathogenic and likely pathogenic (P/LP) variants in children with a diagnosis of hypertrophic, dilated, or restrictive cardiomyopathy (HCM, DCM, or RCM), and to compare disease outcomes between individuals with and without a de novo variant. A retrospective record review identified 126 individuals with HCM (55%), DCM (37%), or RCM (8%) ≤18 years of age who had genetic testing. Overall, 50 (40%) had positive genetic testing and 18% of P/LP variants occurred de novo. The rate of de novo variation in those with RCM (80%) was higher than in those with HCM (9%) or DCM (20%). There was evidence of germline mosaicism in one family with RCM. Individuals with de novo variants were more likely than those without to have a history of arrhythmia (p = .049), sudden cardiac arrest (p = .024), hospitalization (p = .041), and cardiac transplantation (p = .030). The likelihood of de novo variation and impact on family risk and screening should be integrated into genetic counseling. 相似文献
92.
Background
Various microbial, inflammatory and immune signals regulate the activation of dendritic cells (DC), determining their ability to interact with naïve T cells and to produce cytokines that direct T cell development. In particular, CD40L and IL-1 cooperatively activate DC to secrete high levels of IL-12. The immuno-stimulatory capacity of such DC is otherwise not well-defined prompting further characterization of the effects of IL-1 and family members on DC activation in comparison with other pro-inflammatory stimuli.Results
Human DC co-activated in vitro by CD40L and IL-1β expressed numerous cytokine genes including IL-12β, IL-23 p19, IL-1β, IL-1α, IL-1Ra, IL-10, IL-6, IL-18 and IFN-γ. These DC produced high levels of IL-12 protein and appeared capable of producing IFN-γ. Potent CD4+ and CD8+ T cell-stimulatory properties were acquired by DC under conditions that also induced IL-12. Notably, these DC induced rapid differentiation of fluMP-specific CD8+ T cells. Molecules related to IL-1β, like IL-1α, co-induced IL-12 secretion whereas IL-18 did not. Conversely, the inhibitor IL-1Ra, produced endogenously by DC curtailed IL-12 production in response to CD40L.Conclusions
IL-1 and IL-1Ra play a biologically-relevant role in the positive and negative regulation of DC activation. In conjunction with CD40L, IL-1 sends a powerful activation signal to DC that could be distinguished from other modes of activation. This signal enables the production of pro-inflammatory cytokines by DC, and enhances the differentiation of naïve T cells into effectors of type-1 cellular immune responses. 相似文献93.
94.
BrkA confers resistance to killing by complement in Bordetella pertussis. Complement resistance in Bordetella bronchiseptica was examined. Four B. bronchiseptica strains possessed the brkA gene; however, only three expressed the protein. Only the strain lacking BrkA was susceptible to complement. Introduction of the B. pertussis brkA gene restored BrkA expression to this strain but did not confer resistance. brkA was mutated in the strains that naturally expressed BrkA, and loss of BrkA did not confer sensitivity to complement. As a species, B. bronchiseptica is more resistant to complement than B. pertussis, and BrkA does not mediate resistance. 相似文献
95.
Krisanaprakornkit S Kimball JR Weinberg A Darveau RP Bainbridge BW Dale BA 《Infection and immunity》2000,68(5):2907-2915
96.
Susceptible strains of mice that are naturally or experimentally infected with murine intestinal helicobacter species develop hepatic inflammatory lesions that have previously been described as chronic active hepatitis. The inflammatory infiltrates in some models of chronic autoimmunity or inflammation resemble tertiary lymphoid organs hypothesized to arise by a process termed lymphoid organ neogenesis. To determine whether hepatic inflammation caused by infection with helicobacter could give rise to tertiary lymphoid organs, we used fluorescence-activated cell sorting, immunohistochemistry, and in situ hybridization techniques to identify specific components characteristic of lymphoid organs in liver tissue sections and liver cell suspensions from helicobacter-infected mice. Small venules (high endothelial venules [HEVs]) in inflammatory lesions in Helicobacter species-infected livers were positive for peripheral node addressin. Mucosal addressin cell adhesion molecule also stained HEVs and cells with a staining pattern consistent with scattered stromal cells. The chemokines SLC (CCL 21) and BLC (CXCL13) were present, as were B220-positive B cells and T cells. The latter included a na?ve (CD45lo-CD62Lhi) population. These findings suggest that helicobacter-induced chronic active hepatitis arises through the process of lymphoid organ neogenesis. 相似文献
97.
The role of histone acetylation in SMN gene expression 总被引:7,自引:0,他引:7
Kernochan LE Russo ML Woodling NS Huynh TN Avila AM Fischbeck KH Sumner CJ 《Human molecular genetics》2005,14(9):1171-1182
98.
Prabhakar V Grinstaff MW Alarcon J Knors C Solan AK Niklason LE 《Journal of biomedical materials research. Part A》2003,67(1):303-311
Techniques have been developed to culture bovine or porcine vascular cells on polyglycolic acid (PGA) scaffolds to form engineered vessels. Previously, it was shown that smooth muscle cells (SMCs) that were in close proximity to PGA remnants after 8 weeks of culture had lower expression of SMC markers of differentiation and were more mitotic compared with SMCs that were distant from polymer residuals. Modifications of PGA were explored as a means to minimize residual polymer fragments after culture. To hasten degradation, polymer was treated with heat, NaOH, or gamma-irradiation. Differential scanning calorimetry, mass and tensile strength degradation, and inherent viscosity were used to assess polymer characteristics. When polymer was maintained in aqueous conditions, tensile strength of treated PGA degraded to zero within 3 weeks for each treatment. Engineered vessel constructs cultured on NaOH and gamma-treated polymer displayed smooth muscle alpha-actin throughout the vessel wall. Scaffold treatment impacted graft morphology, cellular differentiation, and mechanical integrity. 相似文献
99.
Bangsberg DR Bronstone A Chesney MA Hecht FM 《Journal of acquired immune deficiency syndromes (1999)》2002,31(Z3):S107-S111
Adherence to HIV antiretroviral therapy is closely associated with viral load suppression, progression to AIDS, and death in HIV-infected people. There is, however, no standardized approach to adherence assessment in routine clinical practice, and several studies suggest that providers rarely estimate adherence better than chance. Computer-assisted self-interview technology is an efficient means to identify HIV antiretroviral regimen errors and monitor adherence in order to maximize the benefits of therapy. 相似文献
100.
Wheat streak mosaic virus is a Tritimovirus, a member of the Potyviridae family, which includes the very large Potyvirus genus. We have examined wheat streak mosaic virus by electron microscopy and fiber diffraction from partially oriented sols, and analyzed the results to estimate the symmetry and structural parameters of the viral helix. The virions have an apparent radius of 63 +/- 5 A. The viral helix has a pitch of 33.4 A +/- 0.6 A. There appear to be 6.9 subunits per turn of the helix, although we cannot completely eliminate values of 5.9 or 7.9 for this parameter. 相似文献