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101.
Fgl2 prothrombinase expression in mouse trophoblast and decidua triggers abortion but may be countered by OX-2 总被引:4,自引:0,他引:4
Spontaneous abortion of normal karyotype embryos in mice and in humans is associated with an increase in uterine T helper (Th) 1 type proinflammatory cytokines, tumour necrosis factor (TNF)-alpha, interferon-gamma and interleukin (IL)-1, and a deficiency of Th2/3 type cytokines, IL-4, IL-10, and transforming growth factor (TGF)-beta2. In mice, Th1 cytokines up-regulate a novel prothrombinase, fgl2, which via thrombin, leads to activation of polymorphonuclear leukocytes that terminate the pregnancy. Here we show that Th1 cytokines up-regulate fgl2 mRNA in fetal trophoblast and secondary decidua of CBA/JxDBA/2 and CBA/JxBALB/c matings, and promote fibrin deposition. This pattern is accompanied by a high rate of abortion. However, the spontaneous abortion rates in abortion-prone CBAxDBA/2 matings and in low abortion rate CBAxBALB/c matings were significantly lower than that expected from the frequency of implantations with high levels of fibrin and fgl2 mRNA(hi). As the glycoprotein OX-2 occurs in the pregnant rat uterus and can deviate cytokine responses to Th2/3, we investigated OX-2 in pregnant CBA/J mice. We found OX-2 mRNA was present at the same sites as fgl2 mRNA, but was reduced in response to Th1 cytokines. Furthermore, anti-OX-2 raised the abortion rate to predicted levels, while recombinant OX-2 dramatically reduced the abortion rate. Fgl2 prothrombinase may provide a mechanism explaining pregnancy loss, and conversely, successful pregnancy may be due in part to OX-2-dependent activation of maternal tolerance mechanisms at the feto-maternal interface. 相似文献
102.
Han W Takano T He J Ding J Gao S Noda C Yanagi S Yamamura H 《Antioxidants & redox signaling》2001,3(6):1065-1073
BLNK (B cell linker protein) represents a central linker protein that bridges the B cell receptor-associated kinases with a multitude of signaling pathways. In this study, we have investigated the role of BLNK in oxidative stress signaling in B cells. H2O2 treatment of B cells induced a rapid tyrosine phosphorylation of BLNK in a H2O2 dose-dependent manner, which was inhibited in Syk-deficient DT40 cells. Calcium mobilization in BLNK-deficient as well as Syk-deficient and phospholipase C (PLC)-gamma2-deficient cells after H2O2 treatment was completely abolished. These were derived from decreased inositol 1,4,5-trisphosphate generation through PLC-gamma2 in BLNK-deficient cells. Moreover, viability of BLNK-deficient as well as PLC-gamma2-deficient cells after exposure to low doses of H2O2 was dramatically enhanced compared with that of the wild-type cells. Furthermore, c-Jun N-terminal kinase activation following high doses of H2O2 stimulation, but not low doses of H2O2 stimulation, was abrogated in BLNK-deficient as well as Syk-deficient cells. These findings have led to the suggestion that BLNK is required for coupling Syk to PLC-gamma2, thereby accelerating cell apoptosis in B cells exposed to low doses of H2O2. 相似文献
103.
Can Ding Rolf Beetz Gabriele Rittner Oliver Bartsch 《American journal of medical genetics. Part A》2020,182(5):1032-1040
There are two forms of diabetes insipidus, central (neurohypophyseal), and nephrogenic, caused by pathogenic variants in the AVP gene and the AVPR2 or AQP2 genes, respectively. We report on a four‐generation family, seven individuals had central diabetes insipidus (CDI) and the female index patient seen from age 16 to 26 years had (mild) nephrogenic diabetes insipidus. In her father with CDI, a known pathogenic heterozygous AVP variant c.232_234del p.(Glu78del) was identified, confirming the diagnosis of CDI in him and the other affected family members. In the proband, molecular analysis disclosed a novel heterozygous AVPR2 gene variant, c.962A > T p.(Asn321Ile) and an extremely skewed X‐inactivation, confirming X‐linked nephrogenic diabetes insipidus (XL‐NDI). Whole exome sequencing showed no further causative mutation. This is the first report on the co‐existence of CDI and NDI in one family. Our review of symptomatic female AVPR2 heterozygotes includes 23 families with at least one affected female (including this study). There were 21 different causative mutations. Mutation types in females did not differ from those in males. Both severe XL‐NDI and mild forms were reported in females. All six females with severe XL‐NDI had complete loss‐of‐function (null) mutations. The remaining 17 female probands had milder XL‐NDI caused by 14 missense variants and three null variants of the AVPR2 gene. X‐inactivation was studied in nine of these females; all showed extreme or slight skewing. The review underlines that XL‐NDI in female AVPR2 heterozygotes is always accompanied by skewed X‐inactivation, emphasizing a need for X‐inactivation studies in these females. 相似文献
104.
生物陶瓷微颗粒引发的细胞和组织损害 总被引:2,自引:0,他引:2
为论证生物陶瓷烧结不完全形成的微颗粒(〈5μm)引发细胞和组织损害的假设,对该类颗粒在体内和体外的细胞和组织损害进行了研究:(1)对4种双相生物陶瓷(BCP)进行细胞毒性试验。试验发现所有的浸出液出现细胞毒性,但是浸出液经离心后,毒性消失;(2)对羟基磷灰石(HA)、p磷酸三钙(pTCP)和40%pTCP/60%HA混合物微颗粒进行细胞抑制实验。结果显示随着微颗粒的浓度增加,成纤维细胞活力下降;而当微颗粒浓度达到一万个/细胞时,细胞活力和增殖能力完全消失;(3)HA,pTCP和BCP陶瓷颗粒(500-1500um)被植入到兔子股骨远端,种植12周后β-TCP的降解率为40%,BCP为5%,但是HA接近不降解。新骨形成在β-TCP(21%)和HA(18%)比BCP(12%)更为明显。同时BCP颗粒的周围有很多的微颗粒形成,可见吞噬细胞吞噬微颗粒,形成吞噬体。以上结果提示,微颗粒可能是局部炎症和细胞损害的首要原因,而且有可能影响骨形成。因此,我们必须注意生物陶瓷烧结的重要性,它们的烧结不良就可形成微颗粒,引发细胞和组织的损害。特别是BCP陶瓷含有两种需要不同烧结温度的粉体,它的烧结难度较高,很易形成微颗粒。 相似文献
105.
丁新胜 《中国健康心理学杂志》2005,13(5):359-361
目的 从微观层面探讨归因、自我效能感、教育观念、人格因素对教师心理健康的影响。方法 使用《教师心理健康问卷》和CPSQ人格问卷》进行问卷调查。结果 能力和努力归因对教师心理健康有正向的预测作用;任务难度和运气归因对教师心理健康有负向的预测作用。工作效能和创造效能对教师心理健康都有正向的预测作用。成功教育、挫折教育和主动探索的教育观念对教师的心理健康都是正向的预测作用。神经质分数低的教师出现心理问题的几率不大;趋向于外向、开放、随和以及尽职尽责的教师,心理健康水平较高。结论 归因、自我效能感、教育观念、人格因素对教师心理健康都有程度不同的影响。 相似文献
106.
目的探讨脊肌萎缩症(SMA)的基因诊断方法.方法基于运动神经元生存基因(SMN)的两个同源拷贝碱基上的差异,应用PCR-酶切分析法对10例临床和病理诊断为Ⅰ、Ⅱ、Ⅲ型SMA的患者及其直系亲属16人、25例正常对照进行SMN基因检测.结果 10例SMA患者中9例患者缺失SMN第7、8号外显子,1例患者仅缺失第7号外显子;正常对照组及患者亲属均未发现外显子缺失.结论 PCR-酶切检测SMN基因第7号、8号外显子缺失是诊断儿童型脊肌萎缩症可靠的基因诊断方法. 相似文献
107.
Bin Yu Youming Ding Xiaofeng Liao Changhua Wang Bin Wang Xiaoyan Chen 《Pathology, research and practice》2019,215(5):939-945
Background
TONSL has been suggested to function as an oncogene in lung, esophageal and cervical cancer. This study was aimed to identify the expression of TONSL and its role in hepatocellular carcinoma (HCC).Methods
By data mining in the Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases, the expression profile of TONSL, its clinical significance, the potential mechanisms of its dysregulation and its underlying biological function in HCC were investigated.Results
TONSL was significantly upregulated in HCC tissues relative to normal liver tissues (P?<?0.05). High TONSL expression was significantly correlated with advanced TNM stage, poorly differentiated tumors, vascular invasion, elevated serum alpha-fetoprotein expression and a worse prognosis (all P?<?0.05). Multivariate analysis further confirmed that TONSL overexpression was an independent risk factor for poor overall survival (OS) and recurrence-free survival (RFS) in HCC (all P?<?0.05). Additionally, 16% of HCC cases (n?=?370) had TONSL DNA amplification. The total methylation level of TONSL was moderately and negatively correlated with its mRNA expression (P?<?0.05). TONSL was predictively targeted by miR-133b, which was downregulated in HCC and negatively related to TONSL mRNA expression (all P?<?0.05). Kaplan-Meier analyses demonstrated that low miR-133b expression was significantly associated with poor OS and RFS (all P?<?0.05). Moreover, gene set enrichment analysis revealed that cases with TONSL overexpression were enriched in cell cycle regulation pathways (all P?<?0.05).Conclusions
TONSL holds promise for serving as a prognostic biomarker for HCC. DNA amplification, hypomethylation and miR-133b downregulation could be the mechanisms associated with TONSL upregulation in HCC. TONSL might function as an oncogene via cell cycle regulation pathways in HCC. 相似文献108.
结直肠癌与人类乳头状瘤病毒(Human papilloma virus,HPV)感染有一定的关系,但由于检测方法、标本选择及样本数量不同,各研究结果之间差异很大。为进一步明确结直肠癌变与HPV16感染的关系,采用多聚酶链反应(Polymerase chain reaction,PCR)对82例原发性结直肠腺癌患者手术切除的新鲜癌及癌旁正常粘膜组织进行了前瞻性对照研究,检测了组织中HPV16E7DNA的表达并进行测序鉴定。结果显示,结直肠腺癌组织HPV16E7的表达阳性率(42/82)明显高于癌旁正常粘膜组织(4/82);直肠癌组织中HPV16E7的表达(64.10%)明显高于升结肠癌(18.18%),即癌灶部位距肛门越近,感染率越高;HPV16阳性率与Dukes分期相关,Dukes分期越晚感染率越高;与癌组织分化程度无相关性。结果提示结直肠癌的发生、发展可能与HPV16感染有关。 相似文献
109.
目的:探讨高糖对体外培养Schwann细胞生长及细胞外信号调节激酶(ERK)磷酸化的影响.方法:按照培养液中葡萄糖浓度的小同,分为对照组与高糖组.用MTT法检测Schwann细胞生长情况;用ELISA法检测对照组与高糖组ERK1/2磷酸化的程度,以及加入神经源性一氧化氮合成酶(nNOS)抑制剂后ERK1/2磷酸化的程度.结果:高糖浓度下,细胞虽有增殖但幅度及时程明显低于对照组,高糖抑制Schwann细胞生长;随着精浓度的升高.ERK1/2磷酸化的程度逐渐增加,并与加入nNOS抑制剂有相似的表现.结论:高糖抑制Schwann细胞生长,并且降低nNOS的量,减弱一氧化氮(NO)对ERK1/2的抑制作用,导致ERK1/2磷酸化水平升高. 相似文献
110.
J A Ding H Hashimoto T Sugimoto M Tsuneyoshi M Enjoji 《Acta pathologica japonica》1990,40(10):744-754
Six cases of Bednar tumor were analyzed clinicopathologically along with a review of 39 published cases. The findings were then compared with data on 44 cases of ordinary dermatofibrosarcoma protuberans (DFSP) obtained from our files. The clinical manifestations of the patients and the anatomic locations of the tumors were similar between the two categories, but the rate of recurrence was lower in cases of Bednar tumor. The histologic pattern of Bednar tumor was indistinguishable from ordinary DFSP except for scattered melanosome-containing cells. Ultrastructural and immunohistochemical examinations showed no evidence of neuroectodermal differentiation of dominant spindle-shaped cells in Bednar tumor, supporting a fibroblastic line of differentiation. The origin and pathogenesis of the melanosome-containing cells were considered. These cells failed to react with HMB-45, a melanoma-specific antibody, and the large majority of melanosomes present were mature or at Stage IV, plus a few immature ones at Stage II. These pigmented cells do not appear to be neoplastic, and cannot be used as proof to indicate that Bednar tumor is a neuroectodermal neoplasm. 相似文献