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81.
G Slavin E J Wills J E Richmond I Chanarin T Andrews G Stewart 《Journal of clinical pathology》1975,28(9):701-710
The morphological changes in a patient with a generalized storage disease characterized by the intracellular deposition of neutral lipid are described. There is widespread accumulation of lipid in the cytoplasm of many cells and in occasional nuclei. Diagnosis may be facilitated by the recognition of clear vacuoles in the cytoplasm of granulocytes in blood films. In jejunal biopsies vacuolation of the epithelial cells may simulate the appearances of a-betalipoproteinaemia. The lipid inclusions consist largely of normal triglycerides and are free in the cytoplasm, unassociated with any organelle. The biochemical basis of the lesions is uncertain. Although there are lipoprotein abnormalities the primary defect appears to be intrinsic to the cell and may involve either a defective cytoplasmic lipase or an impaired uptake and utilization of fatty acids by mitochondria. 相似文献
82.
Nahid Tayebi David Q. Andrews Joseph K. Park Eduard Orvisky John McReynolds Donna M. Krasnewich 《American journal of medical genetics. Part A》2002,108(3):241-246
Congenital disorders of glycosylation (CDG) are a group of metabolic disorders with multisystemic involvement characterized by abnormalities in the synthesis of N‐linked oligosaccharides. The most common form, CDG‐Ia, resulting from mutations in the gene encoding the enzyme phosphomannomutase (PMM2), manifests with severe abnormalities in psychomotor development, dysmorphic features and visceral involvement. While this disorder is panethnic, we present the first cases of CDG‐Ia identified in an African American family with two affected sisters. The proband had failure to thrive in infancy, hypotonia, ataxia, cerebellar hypoplasia and developmental delay. On examination, she also exhibited strabismus, inverted nipples and an atypical perineal fat distribution, all features characteristic of CDG‐Ia. Direct sequencing demonstrated that the patient had a unique genotype, T237M/c.565‐571 delAGAGAT insGTGGATTTCC. The novel deletion–insertion mutation, which was confirmed by subcloning and sequencing of each allele, introduces a stop codon 11 amino acids downstream from the site of the deletion. The presence of this deletion–insertion mutation at cDNA position 565 suggests that this site in the PMM2 gene may be a hotspot for chromosomal breakage. Published 2002 Wiley‐Liss, Inc. 相似文献
83.
Immunogenicity of meningococcal ACYW135 polysaccharide vaccine in Saudi children 5 to 9 years of age
Khalil M Al-Mazrou Y Balmer P Bramwell J Andrews N Borrow R 《Clinical and diagnostic laboratory immunology》2005,12(10):1251-1253
Meningococcal tetravalent polysaccharide vaccines were observed to be immunogenic in Saudi children 5 to 9 years of age, with >90% having serum bactericidal antibody titers of > or = 8 for serogroups A, Y, and W135; for serogroup C, 77% were putatively protected after vaccination. 相似文献
84.
Non-secretion of mutant proteins of the glaucoma gene myocilin in cultured trabecular meshwork cells and in aqueous humor 总被引:11,自引:0,他引:11
Jacobson N Andrews M Shepard AR Nishimura D Searby C Fingert JH Hageman G Mullins R Davidson BL Kwon YH Alward WL Stone EM Clark AF Sheffield VC 《Human molecular genetics》2001,10(2):117-125
Until recently, very little was known about the molecular mechanisms responsible for the development of glaucoma, a leading cause of blindness worldwide. Mutations in the glaucoma gene myocilin (MYOC, GLC1A) are associated with elevated intraocular pressure and the development of autosomal dominant juvenile glaucoma and a subset of adult-onset glaucoma. MYOC is expressed in the trabecular meshwork (TM), a tissue responsible for drainage of aqueous humor from the eye, and the tissue involved in elevated intraocular pressure associated with glaucoma. To better understand the role of MYOC in glaucoma pathogenesis, we examined the expression of normal and mutant myocilin in cultured ocular (TM) and non-ocular cells as well as in the aqueous humor of patients with and without MYOC glaucoma. Normal myocilin was secreted from cultured cells, but very little to no myocilin was secreted from cells expressing five different mutant forms of MYOC. In addition, no mutant myocilin was detected in the aqueous humor of patients harboring a nonsense MYOC mutation (Q368X). Co-transfection of cultured cells with normal and mutant myocilin led to suppression of normal myocilin secretion. These studies suggest that MYOC glaucoma is due either to insufficient levels of secreted myocilin or to compromised TM cell function caused by congestion of the TM secretory pathway. 相似文献
85.
Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection 总被引:8,自引:0,他引:8
Walther M Tongren JE Andrews L Korbel D King E Fletcher H Andersen RF Bejon P Thompson F Dunachie SJ Edele F de Souza JB Sinden RE Gilbert SC Riley EM Hill AV 《Immunity》2005,23(3):287-296
Understanding the regulation of immune responses is central for control of autoimmune and infectious disease. In murine models of autoimmunity and chronic inflammatory disease, potent regulatory T lymphocytes have recently been characterized. Despite an explosion of interest in these cells, their relevance to human disease has been uncertain. In a longitudinal study of malaria sporozoite infection via the natural route, we provide evidence that regulatory T cells have modifying effects on blood-stage infection in vivo in humans. Cells with the characteristics of regulatory T cells are rapidly induced following blood-stage infection and are associated with a burst of TGF-beta production, decreased proinflammatory cytokine production, and decreased antigen-specific immune responses. Both the production of TGF-beta and the presence of CD4+CD25+FOXP3+ regulatory T cells are associated with higher rates of parasite growth in vivo. P. falciparum-mediated induction of regulatory T cells may represent a parasite-specific virulence factor. 相似文献
86.
Southern J Deane S Ashton L Borrow R Goldblatt D Andrews N Balmer P Morris R Kroll JS Miller E 《Clinical and diagnostic laboratory immunology》2004,11(6):1100-1104
Extensive use of meningococcal AC polysaccharide (MACP) vaccines has raised concerns about induction of immunologic hyporesponsiveness to C polysaccharide. We investigated the immunogenicity and safety of a meningococcal C-tetanus conjugate (MCC-TT) vaccine in naive adults and prior MACP vaccinees. Laboratory staff (n = 113) were recruited; 73 were naive to meningococcal vaccination, and 40 had previously received > or =1 dose of MACP vaccine. Blood was taken prior to MCC-TT vaccination and 1 week, 1 month, and 6 months later. At each time point, proportions of subjects with serum bactericidal antibody (SBA) titers of > or =8 or > or =128 were similar (P > 0.46); >94% of subjects achieved titers of > or =128 at 1 month. However, the geometric mean titer (GMT) of SBA at 1 month was higher in the naive (1,757; 95% confidence interval [95% CI], 1,102 to 2,803) than in the previously vaccinated (662; 95% CI, 363 to 1,207) group (P = 0.02), and similarly at 6 months (P < 0.001). Conversely, geometric mean concentrations (GMCs) of serogroup C-specific immunoglobulin G (IgG) were significantly higher in the previously vaccinated group pre-MCC-TT and at 1 week; the groups were similar at 1 month, and there was some evidence that the GMC for the previously vaccinated group was higher at 6 months. Qualitative differences in antibodies between groups were demonstrated by using the SBA/IgG ratio, though avidity measures were similar for the two groups throughout the study. MCC-TT was well tolerated, with similar safety profiles in the two groups. Pain in the arm and headache were the most frequently reported events following vaccination. The study shows that MCC-TT is safe and immunogenic in naive and previously MACP-vaccinated adults, though the magnitude and persistence of postvaccination SBA responses in the latter group were lower. 相似文献
87.
88.
89.
Characterization of a surface antigen of Eimeria tenella sporozoites and synthesis from a cloned cDNA in Escherichia coli 总被引:13,自引:0,他引:13
V M Brothers I Kuhn L S Paul J D Gabe W H Andrews S R Sias M T McCaman E A Dragon J G Files 《Molecular and biochemical parasitology》1988,28(3):235-247
An antigenic surface protein of Eimeria tenella sporozoites has been identified that is the target of two neutralizing monoclonal antibodies Ptn 7.2A4/4 and Ptn 9.9D12. The antigen as isolated from the parasite is composed of a 17 kDa polypeptide and a 8 kDa polypeptide linked by a disulfide bridge. De novo synthesis of the antigen does not begin until approximately 16-20 h after the initiation of oocyst sporulation. A cDNA library was constructed using mRNA from sporulated oocysts and a clone encoding the antigen was isolated. The Ta4 gene encodes a single polypeptide of 25 kDa which contains the 17 and 8 kDa polypeptides. The protein has been synthesized in Escherichia coli either directly or as part of a beta-galactosidase fusion protein. The products synthesized in E. coli are single polypeptides and are not cleaved to two polypeptides as is seen in the parasite. The products accumulate in bacteria in an insoluble form which can be solubilized and renatured to an immunoreactive form. 相似文献
90.
There continues to be no consensus definition of executive functions. One way to understand different executive function components is to study abilities at their emergence, that is, early in development, and use advanced statistical methods to understand the interrelations among executive processes. However, to fully determine the constructs of interest, these methods often require complete data on a large battery of tasks, which are difficult to obtain with young children. Path analysis is an alternative statistical technique that requires only a single measure of each construct, yet still allows researchers to investigate complex relations among measures, to compare nested models, and to compare model fit across groups. Therefore, 117 preschool children (ages 2 years 8 months to 6 years 0 months) completed several executive function tasks. Path analysis was used to determine the relations between complex problem solving and working memory, inhibition, and set shifting processes. The best-fitting model included paths from working memory and inhibition to problem solving, and a correlation between working memory and inhibition. Interestingly, in younger children, inhibition was the strongest predictor of problem solving, whereas working memory contributed more strongly in older children. Suggestions for useful statistical methods to investigate the relations among executive functions in children are discussed. 相似文献