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Loss of CD2-associated protein (CD2AP), a component of the filtration complex in the kidney, causes death in mice at 6 weeks of age. Mice with CD2AP haploinsufficiency developed glomerular changes at 9 months of age and had increased susceptibility to glomerular injury by nephrotoxic antibodies or immune complexes. Electron microscopic analysis of podocytes revealed defects in the formation of multivesicular bodies, suggesting an impairment of the intracellular degradation pathway. Two human patients with focal segmental glomerulosclerosis had a mutation predicted to ablate expression of one CD2AP allele, implicating CD2AP as a determinant of human susceptibility to glomerular disease.  相似文献   

3.
The study of human hematopoietic cells and the human immune system is hampered by the lack of a suitable experimental model. Experimental data are presented showing that human fetal liver hematopoietic cells, human fetal thymus, and human fetal lymph node support the differentiation of mature human T cells and B cells after engraftment into mice with genetically determined severe combined immunodeficiency. The resultant SCID-hu mice are found to have a transient wave of human CD4+ and CD8+ T cells and human IgG (immunoglobulin G) in the peripheral circulation. The functional status of the human immune system within this mouse model is not yet known.  相似文献   

4.
Neisseria meningitidis is a major cause of bacterial septicemia and meningitis. Sequence variation of surface-exposed proteins and cross-reactivity of the serogroup B capsular polysaccharide with human tissues have hampered efforts to develop a successful vaccine. To overcome these obstacles, the entire genome sequence of a virulent serogroup B strain (MC58) was used to identify vaccine candidates. A total of 350 candidate antigens were expressed in Escherichia coli, purified, and used to immunize mice. The sera allowed the identification of proteins that are surface exposed, that are conserved in sequence across a range of strains, and that induce a bactericidal antibody response, a property known to correlate with vaccine efficacy in humans.  相似文献   

5.
Nonobese diabetic (NOD) mice develop an autoimmune form of diabetes, becoming hyperglycemic after 3 months of age. This process was accelerated by injecting young NOD mice with CD4+ islet-specific T cell clones derived from NOD mice. Overt diabetes developed in 10 of 19 experimental animals by 7 weeks of age, with the remaining mice showing marked signs of the disease in progress. Control mice did not become diabetic and had no significant pancreatic infiltration. This work demonstrates that a CD4 T cell clone is sufficient to initiate the disease process in the diabetes-prone NOD mouse.  相似文献   

6.
本文报道了海南养殖虎纹蛙白内障病病原及其免疫学防治方法。对该典型患病个体进行病原分离并鉴定表明,被分离出的病原为脑膜炎败血黄杆菌。在所实验的20种抗菌药物中,该菌只对万古霉素敏感,对头孢哌酮中度敏感,而对其他18种药物均不敏感。通过筛选该病原强毒株制备甲醛灭活疫苗,对健康虎纹蛙进行免疫接种后,可明显提高其对该病的抵抗能力,表明在生产上用免疫学方法防治该病是可行的。  相似文献   

7.
虎纹蛙白内障病病原的分离鉴定及其免疫防治   总被引:2,自引:0,他引:2  
本文报道了海南养殖虎纹蛙白内障病病原及其免疫学防治方法。对该典型患病个体进行病原分离并鉴定表明,被分离出的病原为脑膜炎败血黄杆菌。在所实验的20种抗菌药物中,该菌只对万古霉素敏感,对头孢哌酮中度敏感,而对其他18种药物均不敏感。通过筛选该病原强毒株制备甲醛灭活疫苗,对健康虎纹蛙进行免疫接种后,可明显提高其对该病的抵抗能力,表明在生产上用免疫学方法防治该病是可行的。  相似文献   

8.
A model for human lymphocyte ontogeny has been developed in a normal mouse. Human bone marrow, depleted of mature T and B lymphocytes, and bone marrow from mice with severe combined immunodeficiency were transplanted into lethally irradiated BALB/c mice. Human B and T cells were first detected 2 to 4 months after transplantation and persisted for at least 6 months. Most human thymocytes (30 to 50 percent of total thymocytes) were CD3+CD4+CD8+. Human immunoglobulin was detected in some chimeras, and a human antibody response to dinitrophenol could be generated after primary and secondary immunization.  相似文献   

9.
转人MCP和CD59双基因小鼠的制备   总被引:4,自引:0,他引:4  
采用显微混合注射的方法制备转人MCP(膜辅因子蛋白)和CD59(膜反应性溶解抑制物)双基因小鼠,共注射478枚受精卵,移植于21只受体,其中14只受孕,8只受孕小鼠中途流产,从6只受孕小鼠获得18只仔鼠,经检测,其中9只仔鼠单基因阳性(50%),6只仔鼠双基因阳性(33.3%)。结果表明:通过显微混合注射的方法可以获得转人MCP和CD59双基因小鼠。  相似文献   

10.
Intestinal bacteria aid host health and limit bacterial pathogen colonization. However, the influence of bacteria on enteric viruses is largely unknown. We depleted the intestinal microbiota of mice with antibiotics before inoculation with poliovirus, an enteric virus. Antibiotic-treated mice were less susceptible to poliovirus disease and supported minimal viral replication in the intestine. Exposure to bacteria or their N-acetylglucosamine-containing surface polysaccharides, including lipopolysaccharide and peptidoglycan, enhanced poliovirus infectivity. We found that poliovirus binds lipopolysaccharide, and exposure of poliovirus to bacteria enhanced host cell association and infection. The pathogenesis of reovirus, an unrelated enteric virus, also was more severe in the presence of intestinal microbes. These results suggest that antibiotic-mediated microbiota depletion diminishes enteric virus infection and that enteric viruses exploit intestinal microbes for replication and transmission.  相似文献   

11.
In view of the current interest in in vivo murine models for acquired immunodeficiency syndrome (AIDS), the interaction between human immunodeficiency virus type 1 (HIV-1) and endogenous murine leukemia virus (MuLV)-related retroviruses was investigated with a human leukemic T cell line (PF-382x) that acquired xenotropic MuLV (X-MuLV) after in vivo passage in immunosuppressed mice. Despite similar levels of membrane CD4 expression and HIV-1 125I-labeled gp 120 binding, a dramatic acceleration in the time course of HIV-1 infection was observed in PF-382x compared to its X-MuLV-negative counterpart (PF-382). Moreover, PF-382 cells coinfected by X-MuLV and HIV-1 generated a progeny of phenotypically mixed viral particles, enabling HIV-1 to productively infect a panel of CD4- human cells, including B lymphoid cells and purified normal peripheral blood CD4-/CD8+ T lymphocytes. Mixed viral phenotypes were also produced by human CD4+ T cells coinfected with an amphotropic MuLV-related retrovirus (A-MuLV) and HIV-1. These data show that endogenous MuLV acquired by human cells transplanted into mice can significantly interact with HIV-1, thereby inducing important alterations of HIV-1 biological properties.  相似文献   

12.
OX2 (CD200) is a broadly expressed membrane glycoprotein, shown here to be important for regulation of the macrophage lineage. In mice lacking CD200, macrophage lineage cells, including brain microglia, exhibited an activated phenotype and were more numerous. Upon facial nerve transection, damaged CD200-deficient neurons elicited an accelerated microglial response. Lack of CD200 resulted in a more rapid onset of experimental autoimmune encephalomyelitis (EAE). Outside the brain, disruption of CD200-CD200 receptor interaction precipitated susceptibility to collagen-induced arthritis (CIA) in mice normally resistant to this disease. Thus, in diverse tissues OX2 delivers an inhibitory signal for the macrophage lineage.  相似文献   

13.
Alzheimer's disease (AD) has a substantial inflammatory component, and activated microglia may play a central role in neuronal degeneration. CD40 expression was increased on cultured microglia treated with freshly solublized amyloid-beta (Abeta, 500 nanomolar) and on microglia from a transgenic murine model of AD (Tg APPsw). Increased tumor necrosis factor alpha production and induction of neuronal injury occurred when Abeta-stimulated microglia were treated with CD40 ligand (CD40L). Microglia from Tg APPsw mice deficient for CD40L demonstrated reduction in activation, suggesting that the CD40-CD40L interaction is necessary for Abeta-induced microglial activation. Finally, abnormal tau phosphorylation was reduced in Tg APPsw animals deficient for CD40L, suggesting that the CD40-CD40L interaction is an early event in AD pathogenesis.  相似文献   

14.
MyD88 is a key downstream adapter for most Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). MyD88 deficiency in mice leads to susceptibility to a broad range of pathogens in experimental settings of infection. We describe a distinct situation in a natural setting of human infection. Nine children with autosomal recessive MyD88 deficiency suffered from life-threatening, often recurrent pyogenic bacterial infections, including invasive pneumococcal disease. However, these patients were otherwise healthy, with normal resistance to other microbes. Their clinical status improved with age, but not due to any cellular leakiness in MyD88 deficiency. The MyD88-dependent TLRs and IL-1Rs are therefore essential for protective immunity to a small number of pyogenic bacteria, but redundant for host defense to most natural infections.  相似文献   

15.
Alzheimer's disease is characterized by widespread deposition of amyloid in the central nervous system. The 4-kilodalton amyloid beta protein is derived from a larger amyloid precursor protein and forms amyloid deposits in the brain by an unknown pathological mechanism. Except for aged nonhuman primates, there is no animal model for Alzheimer's disease. Transgenic mice expressing amyloid beta protein in the brain could provide such a model. To investigate this possibility, the 4-kilodalton human amyloid beta protein was expressed under the control of the promoter of the human amyloid precursor protein in two lines of transgenic mice. Amyloid beta protein accumulated in the dendrites of some but not all hippocampal neurons in 1-year-old transgenic mice. Aggregates of the amyloid beta protein formed amyloid-like fibrils that are similar in appearance to those in the brains of patients with Alzheimer's disease.  相似文献   

16.
扩展青霉拮抗细菌发酵液在苹果保鲜中的应用   总被引:1,自引:0,他引:1  
从水果果皮上筛选出2株对扩展青霉有拮抗作用的枯草芽孢杆菌T3与T8,其发酵液在平板上对扩展青霉有较强的抑制作用。将这2株拮抗菌的发酵液应用于苹果的保鲜上,结果表明,拮抗菌T3与T8发酵液能在活体上抑制扩展青霉病斑的扩大,在接种后第6天抑制率分别为51%与46%。还研究了拮抗菌发酵液、扑海因、壳聚糖分别单独使用对贮藏苹果可溶性固形物、抗坏血酸含量、可滴定酸度和失重率的影响,分析比较它们在保鲜中的效果。结果表明,2株拮抗菌的发酵液可使贮藏苹果的可滴定酸度有一定程度的提高,分别高出对照50%与100%,而对其他指标影响不大。而壳聚糖与扑海因都能使贮藏期苹果的抗坏血酸含量保持较高水平,分别高出对照700%与180%,此外壳聚糖与扑海因对降低水果的失重率也有一定的作用,失重率分别比对照低20%和32%,但它们对苹果的可溶性固形物的影响与对照相比并不明显。  相似文献   

17.
Human immunodeficiency virus infection of human-PBL-SCID mice   总被引:32,自引:0,他引:32  
Severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID mice) have inducible human immune function and may be useful as a small animal model for acquired immunodeficiency syndrome (AIDS) research. Hu-PBL-SCID mice infected with human immunodeficiency virus-1 (HIV-1) contained virus that was recoverable by culture from the peritoneal cavity, spleen, peripheral blood, and lymph nodes for up to 16 weeks after infection; viral sequences were also detected by in situ hybridization and by amplification with the polymerase chain reaction (PCR). Mice could be infected with multiple strains of HIV-1, including LAV-1/Bru, IIIB, MN, SF2, and SF13. HIV-1 infection affected the concentration of human immunoglobulin and the number of CD4+ T cells in the mice. These results support the use of the hu-PBL-SCID mouse for studies of the pathogenesis and treatment of AIDS.  相似文献   

18.
孙档敏  冀营光  郭淑娟  李楠 《安徽农业科学》2010,38(30):16913-16915
[目的]研究小单孢菌属X46马唐致病菌的筛选方法及致病作用。[方法]采用改良的高氏I号培养基从马唐、稗草根际土壤中分离出1株马唐致病菌X46,对其最优化产毒素条件进行测定并对其安全性进行评估。[结果]经鉴定,马唐致病菌X46为小单孢菌属;其最优化培养条件为:在高氏I号培养液中,300ml三角瓶装液量30ml,初始pH值6.0~6.5,采用10%接种量,180r/min28℃发酵120h即可使毒素产生量最大。该菌对玉米、番茄和黄豆具有明显的促生长作用,对小麦有轻微的抑制作用,对黄瓜生长抑制作用明显。[结论]X46是一株具有开发为中国北方用生物除草剂的潜力菌株。  相似文献   

19.
为研究人CD46(hCD46)基因启动子的启动特性,研制具有hCD46组织特异性表达特征的转基因小鼠,设计扩增hCD46基因启动子的PCR引物,用HeLa细胞基因组DNA为模板扩增hCD46基因启动子DNA片段,测序结果表明:其序列与GenBank中hCD46完整基因5′端某片段的同源性高达99.9%。用此DNA片段替换表达载体pcD-NA3EGFP中的CMV启动子,且在该片段与EGFP基因之间插入兔β-球蛋白基因的第2内含子RGI。重构的表达载体在2种鼠源细胞CHO和SP2/0中均可启动EGFP表达,表达量与人体内同源组织中hCD46的相似,说明该研究克隆了结构和功能正确的hCD46基因启动子。  相似文献   

20.
采用反向遗传操作技术构建新城疫病毒基因组NP/P位点表达胞嘧啶脱氨酶(Cytosine deaminase,CD)基因弱毒力重组新城疫病毒rClone30-CD和中毒力重组新城疫病毒rAnhinga-CD。MTT检测结果表明,在协同5-氟胞嘧啶(5-Fluorocytosine,5-FC)条件下,两株重组新城疫病毒可在体外有效杀伤人肝癌细胞HepG2。通过Balb/c鼠尾静脉注射小鼠肝癌细胞H22构建小鼠肝癌细胞转移模型,经重组病毒协同5-FC联合治疗,荷瘤小鼠转移肿瘤体积显著缩小、肿瘤组织出现明显凋亡与坏死。体内试验结果表明,中毒力重组新城疫病毒rAnhinga-CD抑瘤效果优于弱毒力重组新城疫病毒r Clone30-CD。  相似文献   

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