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991.
992.
993.
Congenital insensitivity to pain with anhidrosis is a syndrome characterized by loss of pain and sensation. The condition frequently evolves into deep wounds and prolonged healing times. Anhidrosis is another prominent component of the disorder. Often associated with recurrent episodes of unexplained fever, it can result in patient mortality. Recent investigations point to Trk A, the high affinity receptor for nerve growth factor (NGF), as a candidate for the site of the mutation that causes the disorder. Functional NGF receptors, such as Trk A and the Trk family of tyrosine kinases, are essential for NGF signaling of human lymphocytes. In this study, we demonstrated that the presence of a trk A mutation in patient B cells results in a novel lymphocyte signaling defect. In these B cells, NGF failed to induce Trk A phosphorylation, cytoskeleton assembly, or MAP kinase activation. These abnormalities may explain some of the clinical features of the disease. 相似文献
994.
Expression of human pim family genes is selectively up-regulated by cytokines promoting T helper type 1, but not T helper type 2, cell differentiation 总被引:3,自引:0,他引:3
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Cytokines are the most important inducers of T helper (Th) cell differentiation. Interleukin-12 (IL-12) and interferon-alpha (IFN-alpha) are responsible for human Th1-cell differentiation, while IL-4 is the critical cytokine promoting Th2-cell development. These two subsets of cells co-ordinate immunological responses to pathogens as well as autoimmune or allergic reactions. The pim family of proto-oncogenes encodes serine/threonine-specific kinases involved in cytokine-mediated signalling pathways in haematopoietic cells. Here we demonstrate that expression of pim-1 and pim-2 mRNAs is selectively up- or down-regulated in human cord-blood-derived CD4+ cells freshly induced to polarize towards Th1 or Th2 cells, respectively, whereas their expression is inhibited in both cell types by the immunosuppressive transforming growth factor beta (TGF-beta). Moreover, the Th1-specific cytokines IL-12 and IFN-alpha, but not the Th2-specific cytokine IL-4, transiently up-regulate pim-1 and pim-2 mRNA expression in human peripheral blood T cells and natural killer cells. In addition, the Pim-1 protein levels are strongly up-regulated by Th1-specific cytokines in all of these cell types. Taken together, our results suggest that pim genes and their protein products are involved in the early differentiation process of T helper cells. 相似文献
995.
In prior research we have shown how linear structural equation models and computer programs (e.g., LISREL) may be simply and directly used to provide alternatives for the traditional biometric twin design. We use structural equations and path models to define biometric group differences, we write traditional common-factor models in the same way, and then we take a detailed look at some alternative multivariate and biometric models. We contrast the biometricfactors covariance structure approach used by Loehlin and Vandenberg (1968), Martin and Eaves (1977), and others with the psychometric-factors approach used by McArdle et al. (1980) and others. We use the multivariate primary mental abilities data on monozygotic (MZ) and dizygotic (DZ) twins from Loehlin and Vandenberg (1968) to detail fundamental differences in model specification and results. We extend both multivariate biometric approaches using exploratory and confirmatory multiple-factor models. These comparisons show that each alternative multivariate methodology has useful features for empirical applications.This research has been supported by grants from the National Institute on Aging (AG02695, AG04704, and AG07137) to McArdle, and a Research Career Development Award (HD00694) to Goldsmith. 相似文献
996.
We examined the action of high (2×10–8M) and low (6×10–9M) concentrations of atrial natriuretic factor (ANF) on water and urea transport in the rat inner medullary collecting duct (IMCD) using the in vitro microperfusion technique. We measured the hydraulic conductivity (Lp ×10–6 cm/atm per second) and both lumen-to-bath (P
u(lb)) and bath-to-lumen (P
u(bl)) 14C-urea permeabilities (P
u× 10–5 cm/s) in the absence and in the presence of vasopressin (VP). High concentrations of ANF were able to inhibit the maximum activity of (50 U/ml) VP-stimulated L
p but physiological concentration of ANF inhibit only submaximum activity (10 U/ml) of VP-stimulated L
p. The hydrosmotic effect of dibutyryl-cyclic 3,5 adenosine monophosphate (cAMP) (10–4M) was unchanged by high concentrations of ANF (2×10–8M). Also we found that high (10–4M) and low (10–6M) concentrations of exogenous cyclic 3,5-guanosine monophosphate (GMP) while unable to change the Lp in the absence of VP, decreased the maximum activity of VP-stimulated Lp significantly. We also found that ANF inhibits partially and in a reversible manner the VP-stimulated P
u(lb) but not the VP-stimulated P
u(bl). These results demonstrated that plasma concentrations of ANF observed during volume expansion (10–10M) are able to inhibit submaximum activity of VP-stimulated (10 U/ml) L
p in the rat IMCD, this effect seems to occur before cAMP formation and it appears to be mediated by cGMP. ANF (6× 10–9M) also reduced the VP-stimulated urea outflux. Therefore, the increase in water excretion produced by ANF could be explained, at least in part, by the inhibition by ANF of vasopressin effects on water and urea transport in the IMCD.This study was presented in part at the VI Latin American Congress of Nephrology, Brazil, October 1985 and at the Xth International Congress of Nephrology, London, July 1987. 相似文献
997.
目的探讨胰岛素及其受体、胰岛素样生长因子I及其受体在多囊卵巢综合征患者子宫内膜的表达特点。方法利用免疫组化实验技术分析INS、INS-R、IGF-I和IGF-IR在多囊卵巢综合征和非多囊卵巢综合征不孕症患者子宫内膜中的表达情况,对结果进行图像分析,并利用SPSS10.0软件进行统计学分析,比较各组间的差异。结果1.多囊卵巢综合征患者子宫内膜IGF-I和INS-R表达水平明显高于对照组,差异有显著性(P<0.01)。其中多囊卵巢综合征中子宫内膜增生症患者的IGF-I和INS-R表达水平高于多囊卵巢综合征组增殖期患者,差异有显著性(P<0.05)。2.IGF-IR和INS在多囊卵巢综合征患者与对照组子宫内膜的表达水平无明显差异(P>0.05)。结论多囊卵巢综合征患者子宫内膜异常增生可能与局部IGF-I和INS-R表达异常有关。 相似文献
998.
精神专科医院门诊抑郁症患者服药依从性影响因素分析 总被引:5,自引:0,他引:5
目的:探讨影响抑郁症患者服药依从性的影响因素.方法:选取2007年5月至10月于北京大学第六医院及北京回龙观医院门诊就诊的123例抑郁症患者,采用自编抑郁症患者就诊状况及服药依从性调查问卷进行调查,内容包括患者一般情况、患病及就诊情况调查、抑郁症发病次数、巩固治疗期坚持服药时间知晓情况及实际服药情况等.分别采用卡方检验及多元Logistic回归分析,探讨上述各因素与服药依从性的相关性.结果:完全依从组(完全按照医嘱时间和剂量服药的患者)和部分依从组(部分按照医嘱时间和剂量服药的患者)在医疗费用支付形式、病程、家属态度、抑郁症阳性家族史、对疾病性质的认识、就诊模式、第一主诉、患病次数、坚持服药时间知晓情况、家庭平均月收入等方面的差异有统计学意义(P<0.05),将患者服药依从情况作为因变量,将以上项目作为自变量进行Logistic回归,结果显示月收入、对疾病性质的认识、家属态度、就诊模式、医药费支付形式、病程进入回归方程,各变量比值比分别为:10.932、9.604、7.246、6.019、2.611、0.209.结论:抑郁症患者服药依从性与多方面因素相关,对疾病性质的认识、家属态度、就诊模式、医药费支付形式、病程、家庭平均月收入等是影响抑郁症患者服药依从性的重要因素. 相似文献
999.
Horan M Millar DS Hedderich J Lewis G Newsway V Mo N Fryklund L Procter AM Krawczak M Cooper DN 《Human mutation》2003,21(4):408-423
The proximal promoter region of the human pituitary expressed growth hormone (GH1) gene is highly polymorphic, containing at least 15 single nucleotide polymorphisms (SNPs). This variation is manifest in 40 different haplotypes, the high diversity being explicable in terms of gene conversion, recurrent mutation, and selection. Functional analysis showed that 12 haplotypes were associated with a significantly reduced level of reporter gene expression whereas 10 haplotypes were associated with a significantly increased level. The former tend to be more prevalent in the general population than the latter (p<0.01), possibly as a consequence of selection. Although individual SNPs contributed to promoter strength in a highly interactive and non-additive fashion, haplotype partitioning was successful in identifying six SNPs as major determinants of GH1 gene expression. The prediction and functional testing of hitherto unobserved super-maximal and sub-minimal promoter haplotypes was then used to test the efficacy of the haplotype partitioning approach. Electrophoretic mobility shift assays demonstrated that five SNP sites exhibit allele-specific protein binding. An association was noted between adult height and the mean in vitro expression value corresponding to an individual's GH1 promoter haplotype combination (p=0.028) although only 3.3% of the variance of adult height was found to be explicable by reference to this parameter. Three additional SNPs, identified within sites I and II of the upstream locus control region (LCR), were ascribed to three distinct LCR haplotypes. A series of LCR-GH1 proximal promoter constructs were used to demonstrate that 1) the LCR enhanced proximal promoter activity by up to 2.8-fold depending upon proximal promoter haplotype, and that 2) the activity of a given proximal promoter haplotype was also differentially enhanced by different LCR haplotypes. The genetic basis of inter-individual differences in GH1 gene expression thus appears to be extremely complex. 相似文献
1000.
《Immunobiology》2022,227(6):152298
PLPPs (Phospholipid phosphatases) are widely expressed in different human tissues, regulate cell signal transduction, and are overexpressed in cancers such as gliomas, pancreatic adenocarcinoma, lung adenocarcinoma, and so on. As a member of the PLPP family, PLPP2 (phospholipid phosphatase 2) plays a vital role in the occurrence and development of breast cancer, but its mechanism is still unclear. Our research found that PLPP2 was overexpressed in breast cancer, and the higher expression level of PLPP2 showed a worse prognosis for breast cancer patients. Further analysis showed that overexpression of PLPP2 affected the expression of CDC34 (cell-division cycle 34), LSM7 (Like-Smith 7), and SGTA (small glutamine-rich tetratricopeptide repeat-containing protein alpha) through EMT (epigenetic-mesenchymal transition) related pathways to promote the occurrence and development of breast cancer. In vitro, silencing PLPP2 significantly reduced the proliferation, invasion, and migration abilities of human breast cancer cells MDA-MB-231. ER+ is a common subtype of breast cancer. Furthermore, we found that the overexpression of PLPP2 was significantly related to the poor prognosis of ER+ breast cancer. These results indicate that PLPP2 has value as a potential therapeutic target for breast cancer, especially for ER+ breast cancer. 相似文献