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排序方式: 共有213条查询结果,搜索用时 78 毫秒
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The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1 总被引:234,自引:0,他引:234
The feline c-fms proto-oncogene product is a 170 kd glycoprotein with associated tyrosine kinase activity. This glycoprotein was expressed on mature cat macrophages from peritoneal inflammatory exudates and spleen. Similarly, the receptor for the murine colony-stimulating factor, CSF-1, is restricted to cells of the mononuclear phagocytic lineage and is a 165 kd glycoprotein with an associated tyrosine kinase. Rabbit antisera to a recombinant v-fms-coded polypeptide precipitated the feline c-fms product and specifically cross-reacted with a 165 kd glycoprotein from mouse macrophages. This putative product of the murine c-fms gene exhibited an associated tyrosine kinase activity in immune complexes, specifically bound murine CSF-1, and, in the presence of the growth factor, was phosphorylated on tyrosine in membrane preparations. The murine c-fms proto-oncogene product and the CSF-1 receptor are therefore related, and possibly identical, molecules. 相似文献
3.
Macrophage lineage switching of murine early pre-B lymphoid cells expressing transduced fms genes. 总被引:14,自引:2,他引:12 下载免费PDF全文
fms genes encoding either wild-type or constitutively activated colony-stimulating factor 1 receptors (CSF-1R) were introduced by retroviral infection into long-term mouse lymphoid cultures. Four early pre-B-cell lines transformed by the feline v-fms oncogene underwent spontaneous and irreversible differentiation to macrophages when transferred from RPMI 1640 to Iscove modified Dulbecco medium. Expression of wild-type human CSF-1R in early pre-B cells conferred no proliferative advantage unless human CSF-1 was added to the culture medium. A clonal, factor-dependent early pre-B-cell line (D1F9), selected for continuous growth on NIH 3T3 cell feeder layers producing human CSF-1, could be maintained in RPMI 1640 medium containing interleukin-7 (IL-7) but also differentiated to macrophages when grown in Iscove modified Dulbecco medium containing human CSF-1. The macrophages retained parental immunoglobulin gene rearrangements and proviral insertions, lost B-cell antigens, expressed butyrate esterase and MAC-1, were actively phagocytic, and no longer survived in IL-7. Unlike factor-independent v-fms transformants, the irreversible commitment of D1F9 cells to differentiate in the macrophage lineage could be suppressed by IL-7, depended on human (but not mouse) CSF-1, and was inhibited by an antibody to human CSF-1R. Signals mediated by transduced CSF-1R can therefore play a deterministic role in cell differentiation. 相似文献
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R M O'Hara P B Hausman D H Sherr S R Abromson-Leeman M E Dorf 《Cellular immunology》1988,116(2):423-438
The cellular requirements for the in vitro induction of antigen-specific suppressor T cells were examined. Previous reports indicated that Ia-bearing macrophages and anti-idiotypic B cells are required as accessory cells to facilitate the generation of suppressor effector (TS3) cells which regulate the response to the 4-hydroxy-3-nitrophenyl acetyl (NP) hapten. The present study describes two distinct T cell populations which interact to generate antigen-specific TS3. Fractionation of the T cell populations with monoclonal antibody to the L3T4 determinant led to the identification of an NP-specific L3T4- TS3 progenitor population and an L3T4+ helper/inducer subset. In the presence of NP-coupled antigen, the L3T4+ subset could induce progenitor TS3 to differentiate into mature TS3 cells. The activity of the L3T4+ inducer population could be replaced with specifically activated cloned helper cells which were not NP-reactive since an I-Ab-restricted, insulin-reactive, L3T4+ clone was capable of supporting the generation of NP-specific TS3. Inducer activity appeared to be confined to the Th1 but not the Th2 subset. In addition, 18-hr supernatants from antigen-activated clones were capable of substituting for L3T4+ cells or T cell clones in TS3 induction cultures. The TS maturation/differentiation factor(s) active in these supernatants does not appear to be IL-1, IL-2, IL-3, or interferon-gamma alone since purified sources of these lymphokines failed to induce TS3 activity. 相似文献
6.
Naiara Akizu Nuri?M. Shembesh Tawfeg Ben-Omran Laila Bastaki Asma Al-Tawari Maha?S. Zaki Roshan Koul Emily Spencer Rasim?Ozgur Rosti Eric Scott Elizabeth Nickerson Stacey Gabriel Gilberto da?Gente Jiang Li Matthew?A. Deardorff Laura?K. Conlin Margaret?A. Horton Elaine?H. Zackai Elliott?H. Sherr Joseph?G. Gleeson 《American journal of human genetics》2013,92(3):392-400
The corpus callosum is the principal cerebral commissure connecting the right and left hemispheres. The development of the corpus callosum is under tight genetic control, as demonstrated by abnormalities in its development in more than 1,000 genetic syndromes. We recruited more than 25 families in which members affected with corpus callosum hypoplasia (CCH) lacked syndromic features and had consanguineous parents, suggesting recessive causes. Exome sequence analysis identified C12orf57 mutations at the initiator methionine codon in four different families. C12orf57 is ubiquitously expressed and encodes a poorly annotated 126 amino acid protein of unknown function. This protein is without significant paralogs but has been tightly conserved across evolution. Our data suggest that this conserved gene is required for development of the human corpus callosum. 相似文献
7.
Andrew Speakman Alison Rodger Andrew N. Phillips Richard Gilson Margaret Johnson Martin Fisher Ed Wilkins Jane Anderson Rebecca O’Connell Monica Lascar Kazeem Aderogba Simon Edwards Jeffrey McDonnell Nicky Perry Lorraine Sherr Simon Collins Graham Hart Anne M. Johnson Alec Miners Jonathan Elford Anna-Maria Geretti William J. Burman Fiona C. Lampe 《PloS one》2013,8(10)
Life expectancy for people diagnosed with HIV has improved dramatically however the number of new infections in the UK remains high. Understanding patterns of sexual behaviour among people living with diagnosed HIV, and the factors associated with having condom-less sex, is important for informing HIV prevention strategies and clinical care. In addition, in view of the current interest in a policy of early antiretroviral treatment (ART) for all people diagnosed with HIV in the UK, it is of particular importance to assess whether ART use is associated with increased levels of condom-less sex. In this context the ASTRA study was designed to investigate current sexual activity, and attitudes to HIV transmission risk, in a large unselected sample of HIV-infected patients under care in the UK. The study also gathered background information on demographic, socio-economic, lifestyle and disease-related characteristics, and physical and psychological symptoms, in order to identify other key factors impacting on HIV patients and the behaviours which underpin transmission. In this paper we describe the study rationale, design, methods, response rate and the demographic characteristics of the participants. People diagnosed with HIV infection attending 8 UK HIV out-patient clinics in 2011-2012 were invited to participate in the study. Those who agreed to participate completed a confidential, self-administered pen-and-paper questionnaire, and their latest CD4 count and viral load test results were recorded. During the study period, 5112 eligible patients were invited to take part in the study and 3258 completed questionnaires were obtained, representing a response rate of 64% of eligible patients. The study includes 2248 men who have sex with men (MSM), 373 heterosexual men and 637 women. Future results from ASTRA will be a key resource for understanding HIV transmission within the UK, targeting prevention efforts, and informing clinical care of individuals living with HIV. 相似文献
8.
Narayana PB Fazolini André LS Cruz Miriam BF Werneck Jo?o PB Viola Clarissa M Maya-Monteiro Patrícia T Bozza 《Cell cycle (Georgetown, Tex.)》2015,14(16):2667-2676
Accumulating evidence suggests that obesity and enhanced inflammatory reactions are predisposing conditions for developing colon cancer. Obesity is associated with high levels of circulating leptin. Leptin is an adipocytokine that is secreted by adipose tissue and modulates immune response and inflammation. Lipid droplets (LD) are organelles involved in lipid metabolism and production of inflammatory mediators, and increased numbers of LD were observed in human colon cancer. Leptin induces the formation of LD in macrophages in a PI3K/mTOR pathway-dependent manner. Moreover, the mTOR is a serine/threonine kinase that plays a key role in cellular growth and is frequently altered in tumors. We therefore investigated the role of leptin in the modulation of mTOR pathway and regulation of lipid metabolism and inflammatory phenotype in intestinal epithelial cells (IEC-6 cells). We show that leptin promotes a dose- and time-dependent enhancement of LD formation. The biogenesis of LD was accompanied by enhanced CXCL1/CINC-1, CCL2/MCP-1 and TGF-β production and increased COX-2 expression in these cells. We demonstrated that leptin-induced increased phosphorylation of STAT3 and AKT and a dose and time-dependent mTORC activation with enhanced phosphorilation of the downstream protein P70S6K protein. Pre-treatment with rapamycin significantly inhibited leptin effects in LD formation, COX-2 and TGF-β production in IEC-6 cells. Moreover, leptin was able to stimulate the proliferation of epithelial cells on a mTOR-dependent manner. We conclude that leptin regulates lipid metabolism, cytokine production and proliferation of intestinal cells through a mechanism largely dependent on activation of the mTOR pathway, thus suggesting that leptin-induced mTOR activation may contribute to the obesity-related enhanced susceptibility to colon carcinoma. 相似文献
9.
Rescue of key features of the p63‐null epithelial phenotype by inactivation of Ink4a and Arf 下载免费PDF全文
Mice lacking p63 cannot form skin, exhibit craniofacial and skeletal defects, and die soon after birth. The p63 gene regulates a complex network of target genes, and disruption of p63 has been shown to affect the maintenance of epithelial stem cells, the differentiation of keratinocytes, and the preservation of the adhesive properties of stratified epithelium. Here, we show that inactivation of p63 in mice is accompanied by aberrantly increased expression of the Ink4a and Arf tumour suppressor genes. In turn, anomalies of the p63‐null mouse affecting the skin and skeleton are partially ameliorated in mice lacking either Ink4a or Arf. Rescue of epithelialization is accompanied by restoration of keratinocyte proliferative capacity both in vivo and in vitro and by expression of markers of squamous differentiation. Thus, in the absence of p63, abnormal upregulation of Ink4a and Arf is incompatible with skin development. 相似文献