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91.
Dysfunction of axonemal dynein heavy chain Mdnah5 inhibits ependymal flow and reveals a novel mechanism for hydrocephalus formation 总被引:8,自引:0,他引:8
Ibañez-Tallon I Pagenstecher A Fliegauf M Olbrich H Kispert A Ketelsen UP North A Heintz N Omran H 《Human molecular genetics》2004,13(18):2133-2141
Motility of unicellular organisms occurred early in evolution with the emergence of cilia and flagella. In vertebrates, motile cilia are required for numerous functions such as clearance of the airways and determination of left-right body asymmetry. Ependymal cells lining the brain ventricles also carry motile cilia, but their biological function has remained obscure. Here, we show that ependymal cilia generate a laminar flow of cerebrospinal fluid through the cerebral aqueduct, which we term as 'ependymal flow'. The axonemal dynein heavy chain gene Mdnah5 is specifically expressed in ependymal cells, and is essential for ultrastructural and functional integrity of ependymal cilia. In Mdnah5-mutant mice, lack of ependymal flow causes closure of the aqueduct and subsequent formation of triventricular hydrocephalus during early postnatal brain development. The higher incidence of aqueduct stenosis and hydrocephalus formation in patients with ciliary defects proves the relevance of this novel mechanism in humans. 相似文献
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Sarah Curran Lindsey Kent Alison Gould Louise Huckett Sandra Richards Eric Taylor Philip Asherson 《American journal of medical genetics. Part A》2002,114(3):269-271
Several lines of evidence implicate synaptosomal‐associated protein of 25 kDa (SNAP‐25) in the etiology of attention deficit hyperactivity disorder (ADHD). Most notably, the coloboma mouse mutant, considered to be a good animal model of hyperactivity, has a deletion spanning this gene. Introducing a SNAP‐25 transgene into these animals alleviates hyperlocomotion. We have identified a novel microsatellite repeat in SNAP‐25 located between the 5′UTR and the first coding exon, and tested for association with ADHD. Case‐control analyses suggest there may be a role of this polymorphism in ADHD, with one allele over‐represented in controls and another over‐represented in probands. Within‐family tests of linkage and association confirmed these findings. Further work is needed to ascertain the role of SNAP‐25 in ADHD and assess the functional significance of this polymorphism. © 2002 Wiley‐Liss, Inc. 相似文献
94.
Diversity of enteric viruses detected in patients with gastroenteritis in a tertiary referral paediatric hospital 总被引:7,自引:0,他引:7
The genetic diversity of enteric viruses co-circulating in a cohort of patients with viral gastroenteritis in a large tertiary paediatric hospital in London, UK, was determined. Multiple strains of noroviruses (NV), sapoviruses (SV) and astroviruses (HAsV) were detected in these patients, indicating the likelihood of multiple introductions from different sources, possible sub-clinical infections and simultaneous infection with different viruses in immunocompromised and other patients. Routine screening of immunocompromised patients and infection control procedures are important to prevent nosocomial infection. 相似文献
95.
Hand involvement in Schmid metaphyseal chondrodysplasia 总被引:1,自引:0,他引:1
Elliott AM Field FM Rimoin DL Lachman RS 《American journal of medical genetics. Part A》2005,(2):191-193
Schmid metaphyseal chondrodysplasia (Schmid MCD, MIM 156500) is caused by mutations in the COL10A1 gene and is clinically characterized by short stature, bowed legs, and a waddling gait. Radiographic findings include anterior cupping, sclerosis and splaying of the ribs, diffuse metaphyseal flaring, and irregularity that is most pronounced at the knees, coxa vara, and femoral bowing. We reviewed the radiographs of Schmid MCD patients at the International Skeletal Dysplasia Registry in Los Angeles for evidence of hand involvement. We found hand involvement in 47% (7/15) of cases included in our analysis. These changes were subtle and consisted of shortening of the tubular bones and metaphyseal cupping of the proximal phalanges and metacarpals. Mild hand involvement is a common feature of Schmid MCD. 相似文献
96.
The expression pattern of platelet-derived growth factor (PDGF) and its receptor suggest a role in lens cell proliferation. PDGF is strongly expressed in the iris and ciliary body, situated opposite the proliferative cells of the lens epithelium which express the PDGF-alpha receptor. In this study, using lens epithelial explant cultures, we report that PDGF can induce a dose and time dependent increase in lens cell DNA synthesis. Culturing lens explants with both PDGF and FGF (a mitogen and differentiation factor for lens cells) resulted in responses greater than those induced by either growth factor alone. PDGF did not induce any changes typical of fibre differentiation; however, in combination with FGF it potentiated the fibre differentiating activity of FGF. Results obtained in this study support previous indications that PDGF has an important role in regulating lens cell proliferation. In addition, PDGF may have a role in potentiating FGF-induced lens fibre differentiation in vivo. 相似文献
97.
Alison Severn Damo Xu Jacqueline Doyle Ludmila M. C. Leal Catherine A. O'Donnell Sara J. Brett David W. Moss Foo Y. Liew 《European journal of immunology》1993,23(7):1711-1714
Murine macrophages produce nitric oxide (NO) from L-arginine on stimulation with lipopolysaccharide (LPS), alone or with interferon-γ (IFN-γ). The effect of incubation of macrophages with low concentrations of LPS on NO synthesis on subsequent stimulation was investigated, using a murine macrophage cell line, J774, and peritoneal macrophages from CBA mice. Cells which had been incubated with LPS produced significantly lower amounts of NO, and expressed lower levels of NO synthase activity, following stimulation with IFN-γ and LPS, or with a high concentration of LPS. This effect was not reversed by tumor necrosis factor-α. The ability of CBA macrophages to kill the intracellular parasite Leishmania major was markedly reduced by pre-incubation with LPS. Reduced NO production by macrophages previously exposed to LPS is a manifestation of endotoxin tolerance, and may represent an important means of regulation of NO synthesis and thus a survival mechanism for intracellular parasites. 相似文献
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100.
Surfactant proteins A (SP-A) and D (SP-D) play an important role in the innate immune defenses of the respiratory tract. SP-A binds to the lipid A region of lipopolysaccharide (LPS), and SP-D binds to the core oligosaccharide region. Both proteins induce aggregation, act as opsonins for neutrophils and macrophages, and have direct antimicrobial activity. Bordetella pertussis LPS has a branched core structure and a nonrepeating terminal trisaccharide. Bordetella bronchiseptica LPS has the same structure, but lipid A is palmitoylated and there is a repeating O-antigen polysaccharide. The ability of SP-A and SP-D to agglutinate and permeabilize wild-type and LPS mutants of B. pertussis and B. bronchiseptica was examined. Previously, wild-type B. pertussis was shown to resist the effects of SP-A; however, LPS mutants lacking the terminal trisaccharide were susceptible to SP-A. In this study, SP-A was found to aggregate and permeabilize a B. bronchiseptica mutant lacking the terminal trisaccharide, while wild-type B. bronchiseptica and mutants lacking only the palmitoyl transferase or O antigen were resistant to SP-A. Wild-type B. pertussis and B. bronchiseptica were both resistant to SP-D; however, LPS mutants of either strain lacking the terminal trisaccharide were aggregated and permeabilized by SP-D. We conclude that the terminal trisaccharide protects Bordetella species from the bactericidal functions of SP-A and SP-D. The O antigen and palmitoylated lipid A of B. bronchiseptica play no role in this resistance. 相似文献