Peptide growth factors in the prostate as mediators of stromal epithelial interaction

Peptide growth factors play a role in the maintenance of normal prostatic growth and differentiation (Fig. 2). It seems likely that the androgen sensitivity of human prostate is mediated by the production of peptide growth factors from stromal cells which act as the direct intermediate of androgen action on epithelial cells. TGF-beta 1 inhibition of epithelial cells is opposed by the stimulatory action of EGF, IGF and FGFs to maintain an equilibrium of epithelial cell numbers. The indirect mitogenic action of androgens appear to act by down-regulation of TGF-beta 1 and possibly EGF receptors. There is also interaction with the effects of IGF-II, produced by prostatic stromal cells and acting on epithelial cells to increase proliferation. The growth of normal prostatic fibroblasts is under the control of bFGF and TGF-beta 1. However, although our understanding of the actions of these growth factors in the normal prostate has improved over the last decade, their role in the development and maintenance of prostate cancer is less clearly defined. TGF-beta 1, classically considered to be inhibitory for epithelial cells, may be up-regulated in prostatic tumours, stimulating growth. Alternatively, autocrine production of such growth factors by tumour cells may lead to loss of inhibitory effects from exogenous TGF-beta 1, a mechanism also witnessed with TGF-alpha and bFGF. The role of EGF in the development of prostate cancer is confusing because results from the use of different cell types and experimental conditions is contradictory. It may be that a switch in the production of the predominant EGFr ligand from EGF to TGF-alpha is an important feature in the development and maintenance of the malignant phenotype. The presence of TGF-alpha autocrine loops has been shown clearly in some tumour cell lines. This switch in the production of a particular ligand may also be a feature of IGFs in prostate cancer. IGF-II may be replaced by IGF-I during malignant progression, both of which are able to act via the type 1 receptor. This change in IGF expression appears to be accompanied by altered expression of the IGF-BP2, with less detectable within prostatic tissues but elevated serum levels [58]. Basic FGF is normally produced by prostatic fibroblasts but is also produced by some prostatic cancer cell lines [64]. However, as with all growth factors, the expression of the bFGF protein and its receptor is dependent on the cell line examined. The autocrine and paracrine control of normal and abnormal prostatic growth by growth factors is important in determining their role in the development and maintenance of prostate cancer. Better understanding of such mechanisms is essential for the development of novel therapeutic strategies in the control and treatment of prostate cancer.     

In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission

PURPOSE: To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS: Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS: Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION: This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.     

Dynamics and organization of MAP kinase signal pathways

In the budding yeast, Saccharomyces cerevisiae, four separate but structurally related mitogen-activated protein kinase (MAPK) activation pathways are known. The best understood of these regulates mating. Pheromone binding to receptor informs cells of the proximity of a mating partner and induces differentiation to a mating competent state. The MAPK activation cascade mediating this signal is made up of Ste11 (a MEK kinase [MEKK]), Ste7 (a MAPK/ERK kinase [MEK]), and the redundant MAPK-related Fus3 and Kss1 enzymes. Another MAPK activation pathway is important for cell integrity and regulates cell wall construction. This cascade consists of Bck1 (a MEKK), the redundant Mkk1 and Mkk2 enzymes (MEKs), and Mpk1 (a MAPK). We exploited these two pathways to learn about the coordination and signal transmission fidelity of MAPK activation cascades. Two lines of evidence suggest that the activities of the mating and cell integrity pathways are coordinated during mating differentiation. First, cells deficient in Mpk1 are susceptible to lysis when they make a mating projection in response to pheromone. Second, Mpk1 activation during pheromone induction coincides with projection formation. The mechanism underlying this coordination is still unknown to us. Our working model is that projection formation generates a mobile second messenger for activation of the cell integrity pathway. Analysis of a STE7 mutation gave us some unanticipated but important insights into parameters important for fidelity of signal transmission. The Ste7 variant has a serine to proline substitution at position 368. Ste7-P368 has higher basal activity than the wild-type enzyme but still requires Ste11 for its function. Additionally, the proline substitution enables the variant to transmit the signal from mammalian Raf expressed in yeast. This novel activity suggests that Ste7-P368 is inherently more permissive than Ste7 in its interactions with MEKKs. Yet, Ste7-P368 cross function in the cell integrity pathway occurs only when it is highly overproduced or when Ste5 is missing. This behavior suggests that Ste5, which has been proposed to be a tether for the kinases in the mating pathway, contributes to Ste7 specificity and fidelity of signal transmission.     

Electrocatalytic oxidation of ethanol on Pt–Mo bimetallic electrodes in acid medium

Pt–Mo alloy electrocatalysts were prepared by an arc-melting furnace process to investigate the origin of their enhanced activity toward ethanol oxidation. Two Mo contents were chosen in zones of the binary phase diagram where they are supposed to form either a pure alloy mixture or a solid solution. Pt–Mo alloy catalysts were more active than Pt-alone. Gradual Mo dissolution at the electrode surface was observed after voltammetric and chronoamperometric measurements. The dissolved Mo contributed to the catalytic effect of the electrode as underpotentially deposited (upd) adatoms. This dissolution probably also leads to an increase in the electrode surface roughness. Low molybdenum content in the electrode material enhances the activity toward ethanol oxidation when compared to Pt-alone. Ethanol oxidation was also investigated by in situ infrared reflectance spectroscopy in order to determine the presence of adsorbed intermediates like CO species. Acetaldehyde, acetic acid and CO₂ were also found by spectroscopic experiments.     

新能源分比例渗透下基于博弈的多主体效益综合评估方法

“双碳”目标下新能源大规模发展,新能源的发展给各能源主体带来了影响,如何量化评估新能源渗透给能源主体带来的影响成为研究重点。首先,基于改进的K-means算法构建基于典型场景集的新能源出力模型;然后,从源-网-荷-储出发,构建火力发电商、电网、用户、储能运营商的决策优化模型;其次,构建考虑新能源渗透的多能源主体效益评估模型;最后,进行算例分析,算例结果验证了模型的有效性。     

The purchaser-provider split in NHS care in the United Kingdom and the role of the community dental service in planning

The former purchaser-provider split underwent an important change during the last years in UK. Especially since the new government came into office in 1997 the approach to equity and equality in dental health care has been characterised by two decisions. Firstly, the level of commissioning services was shifted from the centre to so-called natural communities of about 100,000 people. Secondly, the groups responsible for planning and providing care are constituted from local medical practitioners, community nurses and social services representatives, in line with the Regional Health Authority and the national framework "Our Healthier Nation". The new community dental service is expected to be in a better position to improve the situation in areas of social exclusion.     

Community resources for clients with mobility problems

Clients are leaving the hospital "quicker and sicker," and they frequently have acute care needs that must be met by resources outside the hospital setting. Community resources are diverse, vary widely from place to place, and have no central administration. Thus, using them can be challenging for both the nurse, client, and family. Reimbursement mechanisms underlie a person's ability to use resources and receive health care. By presenting two actual case scenarios where clients have mobility problems commonly seen by orthopaedic nurses, the authors discuss the community resources available, avenues of access to them, and their reimbursement mechanisms.     

基于MPLS的IPTV QoS研究

MPLS(Multi-Protocol Label Switch)和服务质量(QoS)是与下一代网络相关的重要技术.作者首先介绍了QoS的两种模型:综合服务(IntServ)和区分服务(DiffServ)模型,然后描述了基于MPLS网络的DiffServ模型的实现.文中介绍了网络电视(IPTV)系统的组成和存在的问题,并提出了一个基于MPLS的QoS区分服务模型改进方案.     

The removal of arsenic from （ground）-water by adsorbent loaded in polymeric microspheres

Arsenic is a natural tasteless and odourless element,existing in the earth’s crust at average levels of between two and five thousands micrograms per liter (parts per million) . Arsenic is highly toxic to humans, who are exposed to it primarily from air,food and water. The occurrence of arsenic in groundwater is due to geological composition of soil. High concentrations of arsenic in water are the result of dissolution or desorption of ferric oxides and the oxidation of mineral arsenopyrites. Arsenic in drinking water has an important impact on the human health,especially in the less developed countries. Different methods exist to remove arsenic from aquatic media,and one of them is by adsorption. In this work,the adsorption of both As(III) and As(V) by means of novel microspheres has been investigated. In particular,TiO2 has been embedded into polymeric microspheres PES (PolyEtherSulphone) and PEEK-WC (PolyEtherEther-Ketone) . The main advantages of this encapsulation adsorption material are: no loss of adsorbents into the water stream,easy to be used and scaled-up.