Most common SLC25A13 mutation in 400 Chinese infants with intrahepatic cholestasis

AIM:To establish the real time fluorescence polymerase chain reaction(RT-PCR) with dual labeled probes for fast detection of SLC25A13 gene mutation 851del4.METHODS:Four hundred infants(< 1 year of age) with unexplained intrahepatic cholestasis from 18 provinces or municipalities in China were enrolled in this study for detecting their SLC25A13 gene mutation 851del4.Suitable primers and fluorescence-labeled probes for detecting SLC25A13 gene mutation 841del4 were designed.Normal and mutant sequences were det...     

构建雄黄诱导维甲酸耐药急性早幼粒细胞白血病NB4-R1细胞凋亡的蛋白质双向电泳图谱

目的 构建雄黄（四硫化四砷, tetra-arsenic tetra-sulfide, As4S4）诱导急性早幼粒细胞白?。ˋPL)维甲酸耐药细胞株NB4-R1细胞凋亡前后的差异蛋白质组表达谱。     

Substance P induces expression of the corticotropin-releasing factor receptor 1 by activation of the neurokinin-1 receptor

The neuropeptide substance P (SP) has been found to be possibly involved in the etiology of affective and anxiety disorders. However, the molecular mechanisms underlying this involvement are still poorly understood. In this study, we used macroarrays to investigate the differential gene expression profile induced by SP, particularly of genes which have been shown to be involved in the pathophysiology of affective disorders. As a model system, we used the human astrocytoma cell line U373 MG as well as primary rat astroglial cells, which both are known to express functional neurokinin-1 receptors (NK-1-R) and to secret various cytokines upon stimulation with SP. Among several regulated genes, we found that SP (100 and 1000 nM) induced the expression of the corticotropin-releasing factor receptor 1 (CRF1 receptor). Further analyses revealed that this induction was mediated (a) via NK-1-R, as the selective NK-1-R-antagonist L-733,060 (1 microM) strongly inhibited SP-induced CRF1 receptor expression, and (b) intracellularly, by protein kinase C, p42/44 and p38 mitogen-activated protein kinases (MAPK), as shown by using specific inhibitors of signal transduction pathways. In conclusion, this study demonstrates that SP induces CRF1 receptor expression in cells of the CNS, which may be of potential interest for a better understanding of the interplay between SP and the stress hormone axis and, thus, diseases like affective or anxiety disorders. Further studies are needed to substantiate this link in vivo.     

Possible involvement of 5alpha-reduced neurosteroids in adrenergic and serotonergic stimulation of GFAP gene expression in rat C6 glioma cells

Influence of adrenergic and serotonergic stimulation on glial fibrillary acidic protein (GFAP) gene expression in rat C6 glioma cells was first examined as an in vitro model experiment for investigating the neuronal regulation of glial cell differentiation. Stimulation of these cells with isoproterenol and serotonin elevated GFAP mRNA levels followed by an increase in its protein contents, thus suggesting that both adrenergic and serotonergic stimulation might induce the differentiation of the glioma cells. In addition, progesterone and its 5alpha-reduced metabolite dihydroprogesterone also elevated GFAP mRNA levels in rat C6 glioma cells, consistent with their stimulatory actions on GFAP gene expression observed in rat astrocytes. Further studies showed that the elevation of GFAP mRNA levels induced by isoproterenol and serotonin as well as progesterone was abolished by pretreatment of the glioma cells with finasteride, an inhibitor of 5alpha-reduced steroid production. Moreover, the stimulatory actions of isoproterenol and serotonin on GFAP gene expression were inhibited by pretreatment with a GABA(A) receptor antagonist bicuculline and a progesterone receptor antagonist RU486. These findings suggest that both adrenergic and serotonergic stimulation may indirectly activate GFAP gene expression probably through the production of 5alpha-reduced steroid metabolites in rat C6 glioma cells, proposing the possibility that 5alpha-reduced neurosteroids may play a potential role in the neuronal regulation of glial cell differentiation.     

Aging of the brain, neurotrophin signaling, and Alzheimer's disease: is IGF1-R the common culprit?

The last decade has revealed that the lifespan of an organism can be modulated by the signaling pathway that acts downstream of the insulin/insulin-like growth factor 1 receptors (IR/IGF1-R), indicating that there is a “program” that drives the process of aging. New results have now linked the same pathway to the neurogenic capacities of the aging brain, to neurotrophin signaling, and to the molecular pathogenesis of Alzheimer's disease. Therefore, a common signaling cascade now seems to link aging to age-associated pathologies of the brain, suggesting that pharmacologic approaches aimed at the modulation of this pathway can serve to delay the onset of age-associated disorders and improve the quality of life. Work from a wide range of fields performed with different approaches has already identified some of the signaling molecules that act downstream of IGF1-R, and has revealed that a delicate checkpoint exists to balance excessive growth/“immortality” and reduced growth/“senescence” of a cell. Future research will determine how far the connection goes and how much of it we can influence.     

Personality characteristics,psychological symptoms and anxiety levels of drivers in charge of urban transportation in Istanbul

The purpose of the study was to examine whether poor working conditions influenced drivers' psychological health, and to identify drivers' personality characteristics. The subjects were 208 bus drivers working in the European sector in Istanbul. Their personality characteristics, psychological symptoms and anxiety levels were investigated using the Eysenck Personality Questionnaire (EPQ), the Symptom Check List (SCL90-R) and Spielberger's State and Trait Anxiety Inventory (STAI). The average age of drivers was 38.65 +/- 4.69 years, and the mean working period was 7.44 +/- 4.00 years. According to the EPQ, 55 drivers had average standard extroversion scores, 25 had average neuroticism scores and none of the drivers had high scores for psychoticism and lying. The STAI 'state' score of the group was 41.94 +/- 8.93 and the 'trait' score was 47.00 +/- 7.02. The mean SCL90-R of the group was 1.09 +/- 0.57. All subtest scores of SCL90-R were higher for those who suffered from back pain, were dissatisfied with their jobs or undertook long-distance driving. Subtests on somatization, anxiety, anger/hostility, paranoid ideation and general symptom index for SCL90-R and STAI trait scores were higher when comparing employees who had worked for >10 years with those working 相似文献   

AVP V1a-R expression in the rat hypothalamus around parturition: relevance to antipyresis at term

An endogenous antipyresis has been observed around parturition in several species, including rats. It has been proposed that the neuropeptide vasopressin is responsible for this antipyresis via an action on the V(1a) receptor subtype, but this concept is controversial. We therefore addressed the question of the regulation of V(1a) receptor expression within the rat hypothalamus around parturition, to assess its possible involvement in the antipyresis phenomenon observed at term. We analyzed V(1a) receptor mRNA and protein levels in the hypothalamus/preoptic area of female rats at Days 15 and 22 (parturition) of gestation, and at Day 5 of lactation. We used quantitative RT-PCR to assess the mRNA levels and designed a semiquantitative Western blot assay to analyze changes in protein levels between the three stages studied. No significant changes either in V(1a) receptor mRNA or protein levels were observed between the three stages, suggesting that variations in the hypothalamic V(1a) receptor expression levels alone cannot account for the endogenous antipyresis observed at term.