首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 15 毫秒
1.
BackgroundGoblet cell hyperplasia is a classic but variable pathologic finding in COPD. Current literature shows that smoking is a risk factor for chronic bronchitis but the relationship of these clinical features to the presence and magnitude of large airway goblet cell hyperplasia has not been well described. We hypothesized that current smokers and chronic bronchitics would have more goblet cells than nonsmokers or those without chronic bronchitis (CB), independent of airflow obstruction.MethodsWe recruited 15 subjects with moderate to severe COPD, 12 healthy smokers, and 11 healthy nonsmokers. Six endobronchial mucosal biopsies per subject were obtained by bronchoscopy and stained with periodic acid Schiff-Alcian Blue. Goblet cell density (GCD) was quantified as goblet cell number per millimeter of basement membrane. Mucin volume density (MVD) was quantified as volume of mucin per unit area of basement membrane.ResultsHealthy smokers had a greater GCD and MVD than nonsmokers and COPD subjects. COPD subjects had a greater GCD than nonsmokers. When current smokers (healthy smokers and COPD current smokers, n = 19) were compared with all nonsmokers (nonsmoking controls and COPD ex-smokers, n = 19), current smokers had a greater GCD and MVD. When those with CB (n = 12) were compared to those without CB (n = 26), the CB group had greater GCD. This finding was also seen in those with CB in the COPD group alone. In multivariate analysis, current smoking and CB were significant predictors of GCD using demographics, lung function, and smoking pack years as covariates. All other covariates were not significant predictors of GCD or MVD.ConclusionsCurrent smoking is associated with a more goblet cell hyperplasia and number, and CB is associated with more goblet cells, independent of the presence of airflow obstruction. This provides clinical and pathologic correlation for smokers with and without COPD.  相似文献   

2.
Francisella tularensis is the etiological agent of tularemia, or rabbit fever. Although F. tularensis is a recognized biothreat agent with broad and expanding geographical range, its mechanism of infection and environmental persistence remain poorly understood. Previously, we identified seven F. tularensis proteins that induce a rapid encystment phenotype (REP) in the free-living amoeba, Acanthamoeba castellanii. Encystment is essential to the pathogen''s long term intracellular survival in the amoeba. Here, we characterize the cellular and molecular function of REP34, a REP protein with a mass of 34 kDa. A REP34 knock-out strain of F. tularensis has a reduced ability to both induce encystment in A. castellanii and invade human macrophages. We determined the crystal structure of REP34 to 2.05-Å resolution and demonstrate robust carboxypeptidase B-like activity for the enzyme. REP34 is a zinc-containing monomeric protein with close structural homology to the metallocarboxypeptidase family of peptidases. REP34 possesses a novel topology and substrate binding pocket that deviates from the canonical funnelin structure of carboxypeptidases, putatively resulting in a catalytic role for a conserved tyrosine and distinct S1′ recognition site. Taken together, these results identify REP34 as an active carboxypeptidase, implicate the enzyme as a potential key F. tularensis effector protein, and may help elucidate a mechanistic understanding of F. tularensis infection of phagocytic cells.  相似文献   

3.
Two kinds of cilia have been observed in the pharynx of Glossobalanus minutus Kowalewsky. From the present study, a ciliary specialization can be found in order to move a determinate substance, i.e. mucus or water. Mucus-moving cilia (type I cilia) have a single basal centriole and poorly developed ciliary rootlets. Their tips are rounded, bearing an inner, asymmetrical cap attached to some tubules. Water-moving cilia (type II cilia) are exclusively located at lateral epithelia of branchial bars, giving rise to the water current through the gills. They have two basal centrioles, proximal and distal, and a complex system of ciliary rootlets made up of a principal rootlet, a secondary or accessory rootlet and a 'fan' rootlet. The tips of type II cilia have a long process with some tubules inside. All basal structures are precisely orientated in order to assure a good coordination of ciliary beat. The possible functional significance of ciliary substructure is also discussed. From these observations a model for mucus and water currents through gill slits is postulated.  相似文献   

4.
5.
6.
Plant water transport occurs through interconnected xylem conduits that are separated by partially digested regions in the cell wall known as pit membranes. These structures have a dual function. Their porous construction facilitates water movement between conduits while limiting the spread of air that may enter the conduits and render them dysfunctional during a drought. Pit membranes have been well studied in woody plants, but very little is known about their function in more ancient lineages such as seedless vascular plants. Here, we examine the relationships between conduit air seeding, pit hydraulic resistance, and pit anatomy in 10 species of ferns (pteridophytes) and two lycophytes. Air seeding pressures ranged from 0.8 ± 0.15 MPa (mean ± sd) in the hydric fern Athyrium filix-femina to 4.9 ± 0.94 MPa in Psilotum nudum, an epiphytic species. Notably, a positive correlation was found between conduit pit area and vulnerability to air seeding, suggesting that the rare-pit hypothesis explains air seeding in early-diverging lineages much as it does in many angiosperms. Pit area resistance was variable but averaged 54.6 MPa s m−1 across all surveyed pteridophytes. End walls contributed 52% to the overall transport resistance, similar to the 56% in angiosperm vessels and 64% in conifer tracheids. Taken together, our data imply that, irrespective of phylogenetic placement, selection acted on transport efficiency in seedless vascular plants and woody plants in equal measure by compensating for shorter conduits in tracheid-bearing plants with more permeable pit membranes.Water transport in plants occurs under tension, which renders the xylem susceptible to air entry. This air seeding may lead to the rupture of water columns (cavitation) such that the air expands within conduits to create air-vapor embolisms that block further transport. (Zimmermann and Tyree, 2002). Excessive embolism such as that which occurs during a drought may jeopardize leaf hydration and lead to stomatal closure, overheating, wilting, and possibly death of the plant (Hubbard et al., 2001; Choat et al., 2012; Schymanski et al., 2013). Consequently, strong selection pressure resulted in compartmentalized and redundant plant vascular networks that are adapted to a species habitat water availability by way of life history strategy (i.e. phenology) or resistance to air seeding (Tyree et al., 1994; Mencuccini et al., 2010; Brodersen et al., 2012). The spread of drought-induced embolism is limited primarily by pit membranes, which are permeable, mesh-like regions in the primary cell wall that connect two adjacent conduits. The construction of the pit membrane is such that water easily moves across the membrane between conduits, but because of the small membrane pore size and the presence of a surface coating on the membrane (Pesacreta et al., 2005; Lee et al., 2012), the spread of air and gas bubbles is restricted up to a certain pressure threshold known as the air-seeding pressure (ASP). When xylem sap tension exceeds the air-seeding threshold, air can be aspirated from an air-filled conduit into a functional water-filled conduit through perhaps a large, preexisting pore or one that is created by tension-induced membrane stress (Rockwell et al., 2014). Air seeding leads to cavitation and embolism formation, with emboli potentially propagating throughout the xylem network (Tyree and Sperry, 1988; Brodersen et al., 2013). So, on the one hand, pit membranes are critical to controlling the spread of air throughout the vascular network, while on the other hand, they must facilitate the efficient flow of water between conduits (Choat et al., 2008; Domec et al., 2008; Pittermann et al., 2010; Schulte, 2012). Much is known about such hydraulic tradeoffs in the pit membranes of woody plants, but comparatively little data exist on seedless vascular plants such as ferns and lycophytes. Given that seedless vascular plants may bridge the evolutionary transition from bryophytes to woody plants, the lack of functional data on pit membrane structure in early-derived tracheophytes is a major gap in our understanding of the evolution of plant water transport.In woody plants, pit membranes fall into one of two categories: the torus-margo type found in most gymnosperms and the homogenous pit membrane characteristic of angiosperms (Choat et al., 2008; Choat and Pittermann, 2009). In conifers, water moves from one tracheid to another through the margo region of the membrane, with the torus sealing the pit aperture should one conduit become embolized. Air seeding occurs when water potential in the functional conduit drops low enough to dislodge the torus from its sealing position, letting air pass through the pit aperture into the water-filled tracheid (Domec et al., 2006; Delzon et al., 2010; Pittermann et al., 2010; Schulte, 2012; but see Jansen et al., 2012). Across north-temperate conifer species, larger pit apertures correlate with lower pit resistance to water flow (rpit; MPa s m−1), but it is the ratio of torus-aperture overlap that sets a species cavitation resistance (Pittermann et al., 2006, 2010; Domec et al., 2008; Hacke and Jansen, 2009). A similar though mechanistically different tradeoff exists in angiosperm pit membranes. Here, air seeding reflects a probabilistic relationship between membrane porosity and the total area of pit membranes present in the vessel walls. Specifically, the likelihood of air aspirating into a functional conduit is determined by the combination of xylem water potential and the diameter of the largest pore and/or the weakest zone in the cellulose matrix in the vessel’s array of pit membranes (Wheeler et al., 2005; Hacke et al., 2006; Christman et al., 2009; Rockwell et al., 2014). As it has come to be known, the rare-pit hypothesis suggests that the infrequent, large-diameter leaky pore giving rise to that rare pit reflects some combination of pit membrane traits such as variation in conduit membrane area (large or small), membrane properties (tight or porous), and hydrogel membrane chemistry (Hargrave et al., 1994; Choat et al., 2003; Wheeler et al., 2005; Hacke et al., 2006; Christman et al., 2009; Lee et al., 2012; Plavcová et al., 2013; Rockwell et al., 2014). The maximum pore size is critical because, per the Young-Laplace law, the larger the radius of curvature, the lower the air-water pressure difference under which the contained meniscus will fail (Jarbeau et al., 1995; Choat et al., 2003; Jansen et al., 2009). Consequently, angiosperms adapted to drier habitats may exhibit thicker, denser, smaller, and less abundant pit membranes than plants occupying regions with higher water availability (Wheeler et al., 2005; Hacke et al., 2007; Jansen et al., 2009; Lens et al., 2011; Scholz et al., 2013). However, despite these qualitative observations, there is no evidence that increased cavitation resistance arrives at the cost of higher rpit. Indeed, the bulk of the data suggest that prevailing pit membrane porosity is decoupled from the presence of the single largest pore that allows air seeding to occur (Choat et al., 2003; Wheeler et al., 2005 Hacke et al., 2006, 2007).As water moves from one conduit to another, pit membranes offer considerable hydraulic resistance throughout the xylem network. On average, rpit contributes 64% and 56% to transport resistance in conifers and angiosperms, respectively (Wheeler et al., 2005; Pittermann et al., 2006; Sperry et al., 2006). In conifers, the average rpit is estimated at 6 ± 1 MPa s m−1, almost 60 times lower than the 336 ± 81 MPa s m−1 computed for angiosperms (Wheeler et al., 2005; Hacke et al., 2006; Sperry et al., 2006). Presumably, the high porosity of conifer pits compensates for the higher transport resistance offered by a vascular system composed of narrow, short, single-celled conduits (Pittermann et al., 2005; Sperry et al., 2006).Transport in seedless vascular plants presents an interesting conundrum because, with the exception of a handful of species, their primary xylem is composed of tracheids, the walls of which are occupied by homogenous pit membranes (Gibson et al., 1985; Carlquist and Schneider, 2001, 2007; but see Morrow and Dute, 1998, for torus-margo membranes in Botrychium spp.). At first pass, this combination of traits appears hydraulically maladaptive, but several studies have shown that ferns can exhibit transport capacities that are on par with more recently evolved plants (Wheeler et al., 2005; Watkins et al., 2010; Pittermann et al., 2011, 2013; Brodersen et al., 2012). Certainly, several taxa possess large-diameter, highly overlapping conduits, some even have vessels such as Pteridium aquilinum and many species have high conduit density, all of which could contribute to increased hydraulic efficiency (Wheeler et al., 2005; Pittermann et al., 2011, 2013). But how do the pit membranes of seedless vascular plants compare? Scanning electron micrographs of fern and lycopod xylem conduits suggest that they are thin, diaphanous, and susceptible to damage during specimen preparation (Carlquist and Schneider 2001, 2007). Consistent with such observations, two estimates of rpit imply that rpit in ferns may be significantly lower than in angiosperms; Wheeler et al. (2005) calculated rpit in the fern Pteridium aquilinum at 31 MPa s m−1, while Schulte et al. (1987) estimated rpit at 1.99 MPa s m−1 in the basal fern Psilotum nudum. The closest structural analogy to seedless vascular plant tracheids can be found in the secondary xylem of the early-derived vesselless angiosperms, in which tracheids possess homogenous pit membranes with rpit values that at 16 MPa s m−1 are marginally higher than those of conifers (Hacke et al., 2007). Given that xylem in seedless vascular plants is functionally similar to that in vesselless angiosperms, we expected convergent rpit values in these two groups despite their phylogenetic distance. We tested this hypothesis, as well as the intrinsic cavitation resistance of conduits in seedless vascular plants, by scrutinizing the pit membranes of ferns and fern allies using the anatomical and experimental approaches applied previously to woody taxa. In particular, we focused on the relationship between pit membrane traits and cavitation resistance at the level of the individual conduit.  相似文献   

7.
植物抗病基因结构、功能及其进化机制研究进展   总被引:9,自引:0,他引:9  
植物与病原菌在长期的共进化和相互选择的过程中,逐渐形成了组织障碍、非寄主抗性和小种专化抗性等有效的防御机制。小种专化抗性(基因对基因抗性)主要是由植物抗病基因识别相应的病原菌无毒基因并激活植物体内抗病信号进而抵御病原菌的侵染。从目前已克隆的 70 多个抗病基因来看,它们在结构上具有高度保守性,主要包括核苷酸结合位点(NBS),亮氨酸重复结构(LRR), 蛋白激酶结构域(PK), 果蝇蛋白 Toll 和哺乳动物蛋白质白细胞介素 1 受体[interleukin(IL)-1 receptor]类似结构域(TIR), 双螺旋结构(CC)或亮氨酸拉链(LZ)和跨膜结构域(TM)等,其在抗病基因与病原菌无毒(效应)蛋白互作以及植物内部免疫信号传导中起着重要的作用。同时,抗病基因又通过基因复制、遗传重组等进化机制形成多基因家族,为植物抗病的专化性和多样性提供了重要的遗传基础。本文主要讨论了近来已克隆抗病基因的结构特征、功能以及抗病基因进化机制研究的进展。  相似文献   

8.
The nucleotide excision repair of certain bulky DNA lesions is abrogated in some specific non-canonical DNA base sequence contexts, while the removal of the same lesions by the nucleotide excision repair mechanism is efficient in duplexes in which all base pairs are complementary. Here we show that the nucleotide excision repair activity in human cell extracts is moderate-to-high in the case of two stereoisomeric DNA lesions derived from the pro-carcinogen benzo[a]pyrene (cis- and trans-B[a]P-N 2-dG adducts) in a normal DNA duplex. By contrast, the nucleotide excision repair activity is completely abrogated when the canonical cytosine base opposite the B[a]P-dG adducts is replaced by an abasic site in duplex DNA. However, base excision repair of the abasic site persists. In order to understand the structural origins of these striking phenomena, we used NMR and molecular spectroscopy techniques to evaluate the conformational features of 11mer DNA duplexes containing these B[a]P-dG lesions opposite abasic sites. Our results show that in these duplexes containing the clustered lesions, both B[a]P-dG adducts adopt base-displaced intercalated conformations, with the B[a]P aromatic rings intercalated into the DNA helix. To explain the persistence of base excision repair in the face of the opposed bulky B[a]P ring system, molecular modeling results suggest how the APE1 base excision repair endonuclease, that excises abasic lesions, can bind productively even with the trans-B[a]P-dG positioned opposite the abasic site. We hypothesize that the nucleotide excision repair resistance is fostered by local B[a]P residue—DNA base stacking interactions at the abasic sites, that are facilitated by the absence of the cytosine partner base in the complementary strand. More broadly, this study sets the stage for elucidating the interplay between base excision and nucleotide excision repair in processing different types of clustered DNA lesions that are substrates of nucleotide excision repair or base excision repair mechanisms.  相似文献   

9.
A Cd-resistant strain of yeast (Saccharomyces cerevisiae, strain30IN) accumulated Cd with the concomitant synthesis of a Cd-bindingprotein of low molecular weight when grown in Cd2+-containingmedium. Analysis of the amino acid composition, N-terminal sequenceand immunological properties of the protein revealed its structuralhomology to Cu-metallothionein (Cu-MT) in S. cerevisiae 2186,a Cu-resistant strain of yeast (Winge et al. 1985). The synthesisof MT in Cu-resistant strains of yeast is known to be underthe strict control of Cu2+ ions, while that in 301N was inducedboth by Cd2+ and Cu2+ ions. When 301N was precultured for 48h in the presence of 1 mM CuSO4, its resistance to Cu2+ andthe synthesis of MT in response to Cu2+ were enhanced whileanalogous responses to Cd2+ were conversely reduced. These resultssuggest that the synthesis of MT is controlled by Cd2+ and Cu2+in a counteractive manner in strain 301N and, therefore, theregulation of the synthesis of MT plays a role in the adaptationof this strain to conditions when either metal is present. (Received November 1, 1990; Accepted February 22, 1991)  相似文献   

10.
11.
CD133(Prominin-1)是五次跨膜糖蛋白Prominin家族的成员之一,最初作为特异性标志物用于筛选人造血干细胞和祖细胞,随后用于分离鉴定各种肿瘤干细胞的特定细胞亚群。研究表明,CD133是肿瘤治疗预后的标志物,能与血管内皮生长因子等物质相互作用,参与细胞通路的信号转导,在维持视网膜形态和功能中发挥着重要作用。根据是否与CD133的糖基化表位结合,可将CD133的相关抗体分为糖基化抗体、非糖基化抗体以及其他未指明是否与糖基化表位结合的抗体。围绕CD133近年的研究成果对Prominin家族、CD133的功能、相关抗体和相关研究方法进行综述。  相似文献   

12.
13.
目的:探讨精神分裂症患者暴力行为与全脑皮质厚度、甲状腺功能和辅助性T细胞17(Th17)相关炎症因子的相关性。方法:选择常德市康复医院2020年1月~2021年4月收治的精神分裂症患者82例为研究对象。采用修订版外显攻击行为量表(MOAS)评分将患者分成暴力组(n=37)与无暴力组(n=45)。比较两组全脑皮质厚度、甲状腺功能、Th17相关炎症因子水平,利用Pearson相关系数分析MOAS评分与全脑皮质厚度、甲状腺功能指标和Th17相关炎症因子的相关性。结果:暴力组左侧枕中回、顶上回、顶下角回、顶下缘上回、枕极以及右侧枕上回、顶上回、顶下角回、顶下缘上回皮质厚度低于无暴力组(P<0.05)。暴力组血清游离三碘甲状腺原氨酸(FT3)、总甲状腺激素(TT4)、游离甲状腺素(FT4)、总三碘甲状腺原氨酸(TT3)、促甲状腺激素(TSH)、白介素-17(IL-17)、白介素-23(IL-23)、转化生长因子-β1(TGF-β1)水平高于无暴力组(P<0.05)。Pearson相关性分析结果显示,精神分裂症患者MOAS评分与左侧枕中回、顶上回、顶下角回、顶下缘上回、枕极以及右侧枕上回、顶上回、顶下角回、顶下缘上回皮质厚度呈负相关,与血清FT3、TT4、FT4、TT3、TSH、IL-17、IL-23、TGF-β1水平呈正相关(P<0.05)。结论:有暴力行为的精神分裂症患者伴有明显的全脑皮质厚度降低与甲状腺功能指标、Th17相关炎症因子水平升高,这可能对此类患者暴力行为的防治有一定参考意义。  相似文献   

14.
The response of leaf water potential to change in transpirationrate was examined in young soybean and cotton plants. Leaf waterpotential measured 1 h after transpiration became constant followinga change in humidity and was constant over a wide range of transpirationrates in both species. However, leaf water potential was notin equilibrium with flow until 3 h after transpiration becameconstant. At equilibrium an increase in transpiration alwaysresulted in a decrease in leaf water potential. It was alsofound that different responses of equilbrium leaf water potentialto transpiration rate occurred depending on whether transpirationwas altered by changing humidity, light intensity, or leaf area.Low light and decreased leaf area caused lower leaf water potentialsfor a given transpiration rate. These increases in root resistancecorrelated with lower rates of root elongation. The data indicatethat shoot-root interactions are occurring which affect apparentroot resistance to water flow, and complicate interpretationof whole plant data on leaf water potential and transpirationin terms of the flow dependence of root hydraulic characteristics.  相似文献   

15.
16.

Background

The microbial metabolite Trimethylamine-N-oxide (TMAO) has been linked to adverse cardiovascular outcome and mortality in the general population.

Objective

To assess the contribution of TMAO to inflammation and mortality in chronic kidney disease (CKD) patients ranging from mild-moderate to end-stage disease and 1) associations with glomerular filtration rate (GFR) 2) effect of dialysis and renal transplantation (Rtx) 3) association with inflammatory biomarkers and 4) its predictive value for all-cause mortality.

Methods

Levels of metabolites were quantified by a novel liquid chromatography/tandem mass spectrometry-based method in fasting plasma samples from 80 controls and 179 CKD 3–5 patients. Comorbidities, nutritional status, biomarkers of inflammation and GFR were assessed.

Results

GFR was the dominant variable affecting TMAO (β = -0.41; p<0.001), choline (β = -0.38; p<0.001), and betaine (β = 0.45; p<0.001) levels. A longitudinal study of 74 CKD 5 patients starting renal replacement therapy demonstrated that whereas dialysis treatment did not affect TMAO, Rtx reduced levels of TMAO to that of controls (p<0.001). Following Rtx choline and betaine levels continued to increase. In CKD 3–5, TMAO levels were associated with IL-6 (Rho = 0.42; p<0.0001), fibrinogen (Rho = 0.43; p<0.0001) and hsCRP (Rho = 0.17; p = 0.022). Higher TMAO levels were associated with an increased risk for all-cause mortality that remained significant after multivariate adjustment (HR 4.32, 95% CI 1.32–14.2; p = 0.016).

Conclusion

Elevated TMAO levels are strongly associated with degree of renal function in CKD and normalize after renal transplantation. TMAO levels correlates with increased systemic inflammation and is an independent predictor of mortality in CKD 3–5 patients.  相似文献   

17.
The root cell walls of the resistant cultivars of the date palm were more resistant to the action of the cell wall-degrading enzymes (CWDE) of Fusarium oxysporum f. sp. albedinis than those of the susceptible cultivars. Date palm roots contain four cell wall-bound phenolics identified as p-hydroxybenzoic acid, p-coumaric acid, ferulic acid and sinapic acid. The contents of p-coumaric acid and ferulic acid in the resistant cultivars (IKL, SLY, BSTN) were about 2 times higher than those in the susceptible cultivars (BFG, JHL, BSK). The contents of p-hydroxybenzoic acid and sinapic acid in the resistant cultivars were 8.4 and 4.5 times, respectively, higher than those in the susceptible cultivars. The lignin contents in roots of the resistant cultivars were 1.8 times higher than those of the susceptible cultivars. The cell wall-bound phenols accumulated particularly in resistant cultivars reduced strongly the mycelial growth and the CWDE production in vitro.  相似文献   

18.
小麦近缘种簇毛麦携带许多尚未克隆的抗病(R)基因。NBS-LRR类型的R基因占已克隆植物R基因的绝大多数,因此,本研究根据NBS-LRR类型R基因的保守序列设计引物,从簇毛麦基因组DNA和cDNA中扩增获得23条相关序列。基于其中5条抗病基因同源序列(RGAs)H-56/d6、H-66/b2和CDS40设计引物,对小麦、簇毛麦、硬-簇双二倍体及其杂种以及已知携带个别簇毛麦染色体或染色体臂的小麦材料进一步进行PCR扩增,结果表明:3对引物均可对簇毛麦、硬-簇双二倍体进行特异扩增;同时,源于序列H-66/b2的引物可对1VL和6VL染色体臂进行特异扩增;源于序列CDS40的引物可在同时携带1VL和2VS或同时携带2VS和4V的小麦材料以及具有6VL的小麦材料中特异扩增,而H-56/d6的引物在携带1VL、2VS、4V和6V染色体臂或染色体的小麦背景中都不能获得目的片段的扩增。这些结果不仅为外源染色体臂在小麦背景中的追踪与鉴定提供了新的分子标记,而且这些标记还与外源染色体或染色体臂上的抗病基因或抗病基因同源物紧密连锁或共分离。  相似文献   

19.
植物角质层生物学特性及水分渗透性研究进展   总被引:1,自引:0,他引:1  
植物角质层作为植物体与外界环境的第一道保护屏障, 其最主要的功能是防止植物体过度失水。揭示植物角质层的生物学功能及其原理将为现代农业的发展以及仿生材料的开发应用提供科学指导。该文综述了植物角质层的生物学特性及其与水分渗透性关系的研究进展, 并展望了角质层水分渗透研究的应用前景。  相似文献   

20.
Accumulating evidence suggests that alterations in immune function may be important in the etiology of papillary thyroid cancer (PTC). To identify genetic markers in immune-related pathways, we evaluated 3,985 tag single nucleotide polymorphisms (SNPs) in 230 candidate gene regions (adhesion-extravasation-migration, arachidonic acid metabolism/eicosanoid signaling, complement and coagulation cascade, cytokine signaling, innate pathogen detection and antimicrobials, leukocyte signaling, TNF/NF-kB pathway or other) in a case-control study of 344 PTC cases and 452 controls. We used logistic regression models to estimate odds ratios (OR) and calculate one degree of freedom P values of linear trend (PSNP-trend) for the association between genotype (common homozygous, heterozygous, variant homozygous) and risk of PTC. To correct for multiple comparisons, we applied the false discovery rate method (FDR). Gene region- and pathway-level associations (PRegion and PPathway) were assessed by combining individual PSNP-trend values using the adaptive rank truncated product method. Two SNPs (rs6115, rs6112) in the SERPINA5 gene were significantly associated with risk of PTC (PSNP-FDR/PSNP-trend = 0.02/6×10−6 and PSNP-FDR/PSNP-trend = 0.04/2×10−5, respectively). These associations were independent of a history of autoimmune thyroiditis (OR = 6.4; 95% confidence interval: 3.0–13.4). At the gene region level, SERPINA5 was suggestively associated with risk of PTC (PRegion-FDR/PRegion = 0.07/0.0003). Overall, the complement and coagulation cascade pathway was the most significant pathway (PPathway = 0.02) associated with PTC risk largely due to the strong effect of SERPINA5. Our results require replication but suggest that the SERPINA5 gene, which codes for the protein C inhibitor involved in many biological processes including inflammation, may be a new susceptibility locus for PTC.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号