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31.
Groth M Szafranski K Taudien S Huse K Mueller O Rosenstiel P Nygren AO Schreiber S Birkenmeier G Platzer M 《Human mutation》2008,29(10):1247-1254
One unexpected feature of the human genome is the high structural variability across individuals. Frequently, large regions of the genome show structural polymorphisms and many vary in their abundance. However, accurate methods for the characterization and typing of such copy number variations (CNV) are needed. The defensin cluster at the human region 8p23.1 is one of the best studied CNV regions due to its potential clinical relevance for innate immunity, inflammation, and cancer. The region can be divided into two subclusters, which harbor predominantly either alpha- or beta-defensin genes. Previous studies assessing individual copy numbers gave different results regarding whether the complete beta-defensin cluster varies or only particular genes therein. We applied multiplex ligation-dependent probe amplification (MLPA) to measure defensin locus copy numbers in 42 samples. The data show strict copy number concordance of all 10 loci typed within the beta-defensin cluster in each individual, while seven loci within the alpha-defensin cluster are consistently found as single copies per chromosome. The exception is DEFA3, which is located within the alpha-defensin cluster and was found to also differ in copy number interindividually. Absolute copy numbers ranged from two to nine for the beta-defensin cluster and zero to four for DEFA3. The CNV-typed individuals, including HapMap samples, are publicly available and may serve as a universal reference for absolute copy number determination. On this basis, MLPA represents a reliable technique for medium- to high-throughput typing of 8p23.1 defensin CNV in association studies for diverse clinical phenotypes. 相似文献
32.
目的通过对阴道局部固有免疫特点的研究,探讨复发性外阴阴道假丝酵母菌病(RVVC)的发病机制。方法采用酶联免疫吸附试验测定30例外阴阴道假丝酵母菌病(VVC)患者(VVC组)、24例RVVC患者(RVVC组)及26例健康妇女(对照组)的宫颈阴道灌洗液Toll样受体4(TLR4)及人防御素5(HD5)的水平。结果 VVC组、RVVC组妇女宫颈阴道灌洗液中,TLR4含量明显高于对照组,差异均有统计学意义(t分别=4.41、7.19,P均<0.05),但VVC组TLR4含量虽然高于RVVC组,但差异无统计学意义(t=1.04,P>0.05);VVC组、RVVC组HD5浓度高于对照组,但差异无统计学意义(t分别=1.03、1.57,P均>0.05)。结论阴道局部免疫环境TLR4异常可能是VVC、RVVC发作的主要原因之一,HD5可能与VVC、RVVC的发病无关系。 相似文献
33.
Yoshihiro Goto Takahiro Suzuki Yoko Suzuki Kazushi Anzawa Takashi Mochizuki Takashi Tamura Koichi Makimura Masahiro Aoshima Taisuke Ito Yoshiki Tokura 《The Journal of dermatology》2019,46(9):794-797
We report a case of kerion celsi due to Trichophyton tonsurans. An 18‐year‐old male student judo practitioner had alopecic patches, black dots and subcutaneous abscesses on the right temporal region. The damaged hair represented endothrix infection with T. tonsurans, as assessed by mycological examinations. He was treated with oral itraconazole without any therapeutic effect, followed by terbinafine with good effect. A skin biopsy showed neutrophil, lymphocyte and histiocyte infiltration into the dermis and subcutaneous tissue with abscesses around a number of dilated hair follicles. Immunostaining showed that the expression level of human β‐defensin 2 (HBD‐2) was decreased in the epidermis of the alopecic and adjacent skin. Because interleukin (IL)‐17A generally induces HBD‐2 production by epidermal keratinocytes, we also immunohistochemically investigated IL‐17A expression. Unexpectedly, many IL‐17A‐bearing cells were found around destructed hair follicles, indicating that IL‐17A expression was not attenuated, but rather increased in the skin lesion. Our case suggests that IL‐17A‐upregulated antimicrobial peptide expression is disordered in kerion celsi, and severe inflammation with IL‐17A may cause tissue damage and resultant scar. 相似文献
34.
目的:检测人β防御素(hBD)1、2mRNA在口咽部溃疡组织和正常组织中的表达,分析口咽部黏膜在天然免疫中的作用。方法:应用逆转录聚合酶链反应检测60例口咽部溃疡组和40例正常对照组中hBD-1mRNA和hBD-2mRNA的表达。结果:hBD-1 mRNA在口咽部溃疡组和正常对照组中均有表达,且两组间无显著性差异(P〉0.05)。hBD-2 mRNA在正常对照组中仅有微弱表达,而在口咽部溃疡组中表达明显增强(P〈0.05)。结论:口咽部黏膜通过表达hBD在天然免疫中发挥重要作用。 相似文献
35.
36.
目的体外研究Th22细胞因子(IL-22、TNF-α)在小鼠输卵管上皮细胞抵抗沙眼衣原体感染过程中的作用。方法体外培养Th22细胞,ELISA检测Th22上清中细胞因子含量及其对体外培养的小鼠输卵管上皮细胞(MOECs)表达Th1趋化因子、抗菌肽的影响;Transwell实验检测MOECs上清对Th1细胞的趋化能力;分别用免疫荧光法、PCR及7-乙氧基试卤灵(7-ethoxyresrufin, 7-ER)法检测Th22上清对输卵管上皮细胞抑制Chlamydia trichomatis (Ct)能力、促进胰岛再生源蛋白3g(regenerating islet-derived protein-3g,Reg3g) Reg3g表达及细胞活性的影响。结果Th22细胞以分泌IL-22、TNF-α为主。Th22上清可诱导MOECs表达Th1细胞趋化因子CXCL9/10/11及抗菌肽mBD-2表达,活化MOECs对Th1细胞具有趋化作用并抑制Ct生长。同时,Th22上清可促进MOECs Reg3g表达及增强其活性。结论Th22细胞因子能增强MOECs介导的天然免疫功能,促进其损伤修复,在Ct及其它性传播疾病中可能发挥重要作用。 相似文献
37.
38.
Hardwick RJ Machado LR Zuccherato LW Antolinos S Xue Y Shawa N Gilman RH Cabrera L Berg DE Tyler-Smith C Kelly P Tarazona-Santos E Hollox EJ 《Human mutation》2011,32(7):743-750
Beta-defensins are a family of multifunctional genes with roles in defense against pathogens, reproduction, and pigmentation. In humans, six beta-defensin genes are clustered in a repeated region which is copy-number variable (CNV) as a block, with a diploid copy number between 1 and 12. The role in host defense makes the evolutionary history of this CNV particularly interesting, because morbidity due to infectious disease is likely to have been an important selective force in human evolution, and to have varied between geographical locations. Here, we show CNV of the beta-defensin region in chimpanzees, and identify a beta-defensin block in the human lineage that contains rapidly evolving noncoding regulatory sequences. We also show that variation at one of these rapidly evolving sequences affects expression levels and cytokine responsiveness of DEFB103, a key inhibitor of influenza virus fusion at the cell surface. A worldwide analysis of beta-defensin CNV in 67 populations shows an unusually high frequency of high-DEFB103-expressing copies in East Asia, the geographical origin of historical and modern influenza epidemics, possibly as a result of selection for increased resistance to influenza in this region. 相似文献
39.
Role of matrix metalloproteinase-7 in the modulation of a Chlamydia trachomatis infection 总被引:3,自引:0,他引:3
To determine the role of matrix metalloproteinase-7 (MMP-7) in the pathogenesis of chlamydial infection, C57BL/6 wild-type (WT) and MMP-7 knockout (KO) mice were infected intravaginally with Chlamydia trachomatis mouse pneumonitis (MoPn). Over a period of 6 weeks postinfection, various organs were cultured for C. trachomatis. Other infected animals were mated to assess their fertility status. No significant differences were observed between WT and KO mice in the number of animals with positive vaginal cultures, length of time of C. trachomatis shedding, or the number of C. trachomatis inclusion-forming units (IFU) recovered from their genital tracts. Likewise, the number of animals with hydrosalpinx, and the fertility rates and the number of embryos per mouse, were similar in WT and KO mice. Cultures from the spleen, lungs, kidneys and large intestine yielded similar numbers of IFU from WT and KO mice. However, the number of C. trachomatis IFU recovered from the small intestine of KO mice was significantly higher than that recovered from the small intestine of WT mice at 2 weeks postinfection. Because MMP-7 KO mice are deficient in active intestinal alpha-defensins, the results suggest that these components play a role in regulating colonization of the gastrointestinal tract by Chlamydia. By contrast, MMP-7 is dispensable in the progression and resolution of the genital tract infection. 相似文献
40.
《Pediatric hematology and oncology》2013,30(8):573-582
Recent studies investigated the role of an unusual immune response to infective agents in the etiology of acute lymphoblastic leukemia (ALL) in children. Human β-defensin-1 (hBD-1) is an anti-microbial peptide of the innate immune system, which exerts a killing role against pathogens. In the present study, three polymorphisms have been genotyped, namely, -52G/A, -44C/G and -20G/A, of DEFB1 gene, coding for hBD-1, in 40 ALL patients and 40 healthy children, and tested for an association between genetic variants of the protein and seroprevalence of antibodies for herpes viruses. The seroprevalence of cytomegalovirus (CMV), herpes simplex viruses (HSV) and Epstein-Barr virus (EBV) IgG antibodies in leukemic children was higher than that in controls (CMV: 61.5 vs. 27.3%, p = .008; HSV: 50 vs. 24.2%, p = .04; EBV: 61.3 vs. 46.2%, p = ns, respectively). Carriers of the GCA haplotype were found to have a significantly higher rate of immunization against CMV and HSV in ALL children compared to controls (CMV: 68 vs. 29%, p = .006; HSV: 56 vs. 26%, p = .04, respectively). No such observation was made when we analyzed the immunization against Epstein-Barr virus (EBV) by GCA haplotype in case and controls (58 vs. 40%, p = ns). These findings suggest that leukemic patients carrying untranslated variants of hBD-1 display a higher susceptibility to herpes viruses infections than controls. 相似文献