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排序方式: 共有9523条查询结果,搜索用时 31 毫秒
81.
Enhanced viral clearance in interleukin-18 gene-deficient mice after pulmonary infection with influenza A virus 总被引:3,自引:0,他引:3
Van Der Sluijs KF Van Elden LJ Arens R Nijhuis M Schuurman R Florquin S Kwakkel J Akira S Jansen HM Lutter R Van Der Polls T 《Immunology》2005,114(1):112-120
T helper 1 driven immune responses facilitate host defence during viral infections. Because interleukin-18 (IL-18) mediates T helper 1 driven immune responses, and since mature IL-18 is up-regulated in human macrophages after influenza virus infection in vitro, it has been suggested that IL-18 plays an important role in the immune response to influenza. To determine the role of IL-18 in respiratory tract infection with influenza, IL-18 gene-deficient (IL-18(-/-)) and normal wildtype mice were intranasally inoculated with influenza A virus. Influenza resulted in an increase in constitutively expressed IL-18 in the lungs of wildtype mice. The clearance of influenza A was inhibited by IL-18, as indicated by reduced viral loads on day 8 and day 12 after infection in IL-18(-/-) mice. This enhanced viral clearance correlated with increased CD4(+) T-cell activation in the lungs as reflected by CD69 expression on the cell surface. Surprisingly, interferon-gamma (IFN-gamma) levels were similar in the lungs of IL-18(-/-) mice and wildtype mice. Intracellular IFN-gamma staining revealed similar expression levels in lung-derived natural killer cells, CD4(+) and CD8(+) T cells, indicating that IFN-gamma production is IL-18-independent during influenza virus infection. Tumour necrosis factor-alpha production by CD4(+) T cells was significantly lower in IL-18(-/-) mice than in wildtype mice. Our data indicate that endogenous IL-18 impairs viral clearance during influenza A infection. 相似文献
82.
Kennedy J Jackson G Ramsden S Taylor J Newman W Wright MJ Donnai D Elles R Briggs MD 《European journal of human genetics : EJHG》2005,13(5):547-555
The skeletal dysplasias are a clinically and genetically heterogeneous group of conditions affecting the development of the osseous skeleton and fall into the category of rare genetic diseases in which the diagnosis can be difficult for the nonexpert. Two such diseases are pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED), which result in varying degrees of short stature, joint pain and stiffness and often resulting in early onset osteoarthritis. PSACH and some forms of MED result from mutations in the cartilage oligomeric matrix protein (COMP) gene and to aid the clinical diagnosis and counselling of patients with a suspected diagnosis of PSACH or MED, we developed an efficient and accurate molecular diagnostic service for the COMP gene. In a 36-month period, 100 families were screened for a mutation in COMP and we identified disease-causing mutations in 78% of PSACH families and 36% of MED families. Furthermore, in several of these families, the identification of a disease-causing mutation provided information that was immediately used to direct reproductive decision-making. 相似文献
83.
Kennedy J Jackson GC Barker FS Nundlall S Bella J Wright MJ Mortier GR Neas K Thompson E Elles R Briggs MD 《Human mutation》2005,25(6):593-594
Pseudoachondroplasia (PSACH) and some forms of multiple epiphyseal dysplasia (MED) result from mutations in the gene encoding cartilage oligomeric matrix protein (COMP). COMP is a large pentameric glycoprotein found predominantly in the extracellular matrix of cartilage, tendon, and ligament. As a modular protein, it is composed of a coiled-coil domain, four type II (T2) repeats, eight type III (T3) repeats, and a large globular C-terminal domain (CTD). The majority (>85%) of COMP mutations causing PSACH or MED are found in the exons encoding the T3 repeats, and the disease mechanism has been characterised in detail. Much less is known about disease-causing mutations in the CTD; in 10 years only seven mutations have been identified. In this study, we describe eight novel and two recurrent mutations that we have recently identified in patients with PSACH or MED. Interestingly, these mutations result in a spectrum of disease, ranging from mild MED to severe PSACH. Mapping of all known COMP CTD mutations on a three-dimensional model of the C-terminal domain shows that the CTD mutations cluster in two distinct regions. These regions are probably important in stabilising the T3-CTD structure and mediating intra- or intermolecular interactions. 相似文献
84.
Thymidine kinase-negative bovine herpesvirus type 1 mutant is stable and highly attenuated in calves 总被引:3,自引:0,他引:3
Summary Calves were vaccinated intranasally (IN) or intravenously (IV) with a thymidine kinase-negative (tk–) BHV-1 mutant. Vaccinated calves developed neutralizing antibodies but did not show clinical signs of infectious bovine rhinotracheitis (IBR). Vaccination also prevented clinical signs of IBR disease following IN challenge exposure of the calves to parental Los Angeles (LA) and USDA Cooper strains of tk+ BHV-1. Nasal swabs were collected for 10 days after the vaccination and the challenge exposures to monitor BHV-1 multiplication. At both 91 and 121 days post vaccination (PV), calves were also stressed for 5 days with dexamethasone (DEX) to induce reactivation of BHV-1 and nasal swabs were obtained. tk– BHV-1 multiplied in the nasal mucosa of IN vaccinated calves and was also recovered after DEX treatment. Likewise, tk– BHV-1 was isolated from the buffy coat fraction of IV vaccinated calves, but not from nasal swabs. tk– BHV-1 vaccination reduced the multiplication of tk+ BHV-1 in the nasal mucosa, but did not completely prevent development of a persistent infection by the challenge virus. The phenotypes of viruses isolated from the nasal swabs and buffy coats were analyzed by enzyme assays of extracts from virus-infected cells and by plaque autoradiography. These assays showed that tk– BHV-1 can persist for at least 3 months in vaccinated calves and may also be transmitted from vaccinated to control calves without revertingin vivo to tk+. The results demonstrate that the tk– BHV mutant is attenuated and efficacious as a vaccine.With 1 Figure 相似文献
85.
Protective role of endothelial nitric oxide synthase 总被引:30,自引:0,他引:30
Nitric oxide is a versatile molecule, with its actions ranging from haemodynamic regulation to anti-proliferative effects on vascular smooth muscle cells. Nitric oxide is produced by the nitric oxide synthases, endothelial NOS (eNOS), neural NOS (nNOS), and inducible NOS (iNOS). Constitutively expressed eNOS produces low concentrations of NO, which is necessary for a good endothelial function and integrity. Endothelial derived NO is often seen as a protective agent in a variety of diseases.This review will focus on the potential protective role of eNOS. We will discuss recent data derived from studies in eNOS knockout mice and other experimental models. Furthermore, the role of eNOS in human diseases is described and possible therapeutic intervention strategies will be discussed. 相似文献
86.
Inge Van de Walle Karen Silence Kevin Budding Liesbeth Van de Ven Kim Dijkxhoorn Elisabeth de Zeeuw Cafer Yildiz Sofie Gabriels Jean-Michel Percier Johanna Wildemann Jan Meeldijk Peter J. Simons Louis Boon Linda Cox Rob Holgate Rolf Urbanus Henny G. Otten Jeanette H.W. Leusen Peter Boross 《The Journal of allergy and clinical immunology》2021,147(4):1420-1429.e7
87.
Eldeirawi K McConnell R Freels S Persky VW 《The Journal of allergy and clinical immunology》2005,116(1):42-48
BACKGROUND: There are wide global variations in the prevalence of asthma and wheezing. OBJECTIVES: We examined the associations of place of birth with doctor-diagnosed asthma, wheezing in the past 12 months, and other allergic conditions in Mexican American children. METHODS: The study used data on 4121 Mexican American children age 2 months to 16 years who participated in the Third National Health and Nutrition Examination Survey. RESULTS: The risk of asthma was associated with being born in the United States after adjusting for sex, age, history of ear infection, and having a regular place for health care (odds ratio, 2.19; 95% CI, 1.09-4.40). Among children with no previous history of ear infection, US-born children were more likely to report wheezing in the past 12 months than their peers born in Mexico after controlling for confounding variables (odds ratio, 2.05; 95% CI, 1.09-3.87). Mexican American children born in the United States were more likely to have positive skin reaction to cat, house mite, Alternaria alternata , peanut, Bermuda grass, and short ragweed but were less likely to have a positive skin test to German cockroaches after adjusting for sex, age, ear infection, having a regular place for health care, and area of residence. CONCLUSION: Our study indicated significant associations of place of birth with respiratory symptoms and allergic conditions in Mexican American children. These findings highlight the need for further studies to examine environmental factors that change by migration and explain the observed differential in the risk of asthma or wheezing. 相似文献
88.
Henriques C Sanchez MA Tryon R Landfear SM 《Molecular and biochemical parasitology》2003,130(2):101-110
African trypanosomes are unable to synthesize purines and depend upon purine nucleoside and nucleobase transporters to salvage these compounds from their hosts. To understand the crucial role of purine salvage in the survival of these parasites, a central objective is to identify and characterize all of the purine permeases that mediate uptake of these essential nutrients. We have cloned and functionally expressed in a purine nucleobase transport deficient strain of Saccharomyces cerevisiae a novel nucleobase transporter gene, TbNT8.1, from Trypanosoma brucei. The permease encoded by this gene mediates the uptake of hypoxanthine, adenine, guanine, and xanthine with Kms in the low micromolar range. The TbNT8.1 protein is a member of the equilibrative nucleoside transporter (ENT) family of permeases that occur in organisms as diverse as protozoa and mammals. TbNT8.1 is distinct from other ENT permeases that have been identified in trypanosomes in utilizing multiple purine nucleobases, rather than purine nucleosides, as substrates and is hence the first bona fide nucleobase permease identified in these parasites. Furthermore, unlike the mRNAs for other purine transporters, TbNT8.1 mRNA is significantly more abundant in insect stage procyclic forms than in mammalian stage bloodstream forms, and the TbNT8.1 permease thus may represent a major route for purine nucleobase uptake in procyclic trypanosomes. 相似文献
89.
90.