6,085 research outputs found

    Human Placental Trophoblast As A Model For Tumor Progression

    Get PDF
    The human placenta is comprised of extravillous trophoblast (EVT) cells which invade the uterus and its vasculature establishing maternal-fetal exchange of key molecules. The mechanisms of in vitro EVT cell invasiveness are similar to those of malignant tumor cells but are regulated in situ by locally derived factors. This invasiveness is insufficient for malignancy. The goal of this laboratory is to transform normal EVT cells and induce premalignant, malignant and/or metastatic phenotypes to identify genetic changes relevant to tumor progression.;Two SV40 T antigen (Tag) transformed cell lines (long lived RSVT-2; immortal RSVT2/C) derived from the invasive first trimester EVT cell line, HTR8 were characterized. Both lines exhibited EVT cell markers cytokeratin and cytoplasmic hPL, and were more proliferative and invasive than the parental cells. Increased invasiveness can be explained by (i) reduced expression of tissue inhibitor of metalloprotease (TIMP)-1 mRNA in both lines and (ii) reduced expression of TIMP-2, and plasminogen activator inhibitor (PAI)-1 in RSVT2/C cells. RSVT-2 cells retained sensitivity to the anti-proliferative action of TGF{dollar}\beta{dollar}. RSVT2/C cells were also resistant to its anti-invasive action. Resistance to the anti-invasive action of TGF{dollar}\beta{dollar} may be explained by a lack of TGF{dollar}\beta{dollar}-mediated upregulation of TIMP-1 and PAI-1 mRNA noted with normal HTR8 cells. These results, and the finding that neither cell line was tumorigenic in nude mice, suggest that the SV40 Tag transformants acquired a premalignant phenotype, and RSVT2/C cells were possibly more advanced along the tumor progression pathway.;GJIC (dye coupling) and the expression of various connexin proteins and mRNA were also compared in HTR8 and SV40 Tag transformed cells. Only Cx43 was expressed by HTR8 cells. This expression was reduced in RSVT-2, and detectable in RSVT2/C cells. GJIC was also reduced in RSVT-2 cells, and drastically reduced in RSVT2/C cells. TGF{dollar}\beta{dollar} reduced Cx43 mRNA expression and GJIC in HTR8 cells, but not in the SV40 Tag transformants. These findings suggest that a down regulation of connexins and resultant impairment in GJIC are early events in tumor progression.;Gene(s) gained or lost during normal EVT cell transition to premalignancy achieved by SV40 Tag immortalization were also examined. Using differential display, a putatively novel gene was isolated. This gene was identified in RSVT2/C and JAR choriocarcinoma cells but not in the RSVT-2 or HTR8 cells. Sequencing revealed partial homology with Homo sapiens clone 135069 and EST 29905 cDNA. A complete sequence and the function of this gene remain undetermined

    Liquid crystal hyperbolic metamaterial for wide-angle negative-positive refraction and reflection

    Get PDF
    We show that nanosphere dispersed liquid crystal (NDLC) metamaterial can be characterized in near IR spectral region as an indefinite medium whose real parts of effective ordinary and extraordinary permittivities are opposite in signs. Based on this fact we design a novel electrooptic effect: external electric field driven switch between normal refraction, negative refraction and reflection of TM incident electromagnetic wave from the boundary vacuum/NDLC. A detailed analysis of its functionality is given based on effective medium theory combined with a study of negative refraction in anisotropic metamaterials, and Finite Elements simulations

    A Computerized Constructionist Approach To Simulation And Modeling Pedagogy

    Get PDF
    A major limitation in traditional class lectures on simulation and modeling, that uses assignments, handouts, transparencies, and textbooks, is that students often are unable to appreciate the "experience" of simulating a real problem.  This limitation can be overcome by using an active real case study approach to allow students to simulate a real-time queuing problem through interactive visual simulation software (EXTEND®).  Actual raw data had been collected prior to the case assignment and students are taught to develop the simulation model, based on the actual raw data.  The intent is that by "doing" or "constructing" the simulation model from actual data, the students will understand better and remember

    Motives for adult participation in physical activity: type of activity, age, and gender

    Get PDF
    Background In recent years, there has been a decline in physical activity among adults. Motivation has been shown to be a crucial factor in maintaining physical activity. The purpose of this study was to examine whether motives for participation could accurately discriminate gender, age, and type of physical activity. Methods A quantitative, cross-sectional descriptive research design was employed. The Physical Activity and Leisure Motivation Scale (PALMS) was used to assess motives for physical activity in 1,360 adults (703 males, 657 females) who had been exercising regularly for at least six months. The PALMS consists of 40 items that constitute eight sub-scales (mastery, enjoyment, psychological condition, physical condition, appearance, others’ expectations, affiliation, competition/ego). Respondents were divided into two age groups (young adults aged 20 to 40 years and middle-aged adults 41 to 64 years) and five types of activity (individual racing sports plus bowls, team sports, racquet sports, martial arts, and exercise). Results The group discriminant function analyses revealed significant canonical functions correctly classifying the cases into gender (82%), age group (83%), team sport players 76%, individual racing sport plus bowls players 91%, racquet sport players 90%, exercisers 84%, and martial art players 91%. The competition/ego, appearance, physical condition, and mastery sub-scales contributed most to gender differences. Five sub-scales (mastery, psychological condition, others’ expectations, affiliation, and enjoyment) contributed most to the discriminant function for age. For type of activity, different sub-scales were the strongest contributors to the discriminant function for each type of PA. Conclusion The findings in this study suggest that strong and important motives for participation in physical activity are different across type of activity, age, and gender in adults. Understanding the motives that influence physical activity participation is critical for developing interventions to promote higher levels of involvement

    DNA methylation of ESR-1 and N-33 in colorectal mucosa of patients with Ulcerative Colitis (UC)

    Get PDF
    Introduction: Epigenetic marking such as DNA methylation influence gene transcription and chromosomal stability and may also be affected by environmental exposures. Few studies exist on alteration in DNA methylation profiles (genomic and gene specific methylation) in patients with Ulcerative Colitis (UC) and none assessing its relationship with lifestyle exposures. Aims & Methods: To assess genomic methylation and promoter methylation of the ESR-1 (oestrogen receptor - 1) and N-33 (tumour suppressor candidate-3) genes in the macroscopically normal mucosa of UC patients as well as to investigate effects of anthropometric and lifestyle exposures on DNA methylation. Sixty eight subjects were recruited (24 UC and 44 age and sex matched controls). Colorectal mucosal biopsies were obtained and DNA was extracted. Genomic DNA methylation was quantified using the tritium-labelled cytosine extension assay (3[H] dCTP) whilst gene specific methylation was quantified using the COBRA method. Results: The methylation level of both ESR-1 and N-33 genes were significantly higher in UC subjects compared with controls (7.9% vs 5.9%; p = 0.015 and 66% vs 9.3%; p < 0.001 respectively). There was no detectable difference in global DNA methylation between patients with UC and age and sex matched controls. No associations between indices of DNA methylation and anthropometric measures or smoking patterns were detected. Conclusions: For the first time, we have shown increased methylation in the promoter regions of the putative tumour suppressor gene N-33 in macroscopically normal mucosa of patients with UC. In addition, we have confirmed that methylation of ESR-1 promoter is higher in UC patients compared with age and sex matched controls. These findings suggests that, inactivation through methylation of the putative tumour suppressor genes N-33 and ESR-1, may not be associated with colorectal carcinogenesis in UC

    Modeling the Autonomic and Metabolic Effects of Obstructive Sleep Apnea: A Simulation Study

    Get PDF
    Long-term exposure to intermittent hypoxia and sleep fragmentation introduced by recurring obstructive sleep apnea (OSA) has been linked to subsequent cardiovascular disease and Type 2 diabetes. The underlying mechanisms remain unclear, but impairment of the normal interactions among the systems that regulate autonomic and metabolic function is likely involved. We have extended an existing integrative model of respiratory, cardiovascular, and sleep–wake state control, to incorporate a sub-model of glucose–insulin–fatty acid regulation. This computational model is capable of simulating the complex dynamics of cardiorespiratory control, chemoreflex and state-related control of breath-to-breath ventilation, state-related and chemoreflex control of upper airway potency, respiratory and circulatory mechanics, as well as the metabolic control of glucose–insulin dynamics and its interactions with the autonomic control. The interactions between autonomic and metabolic control include the circadian regulation of epinephrine secretion, epinephrine regulation on dynamic fluctuations in glucose and free-fatty acid in plasma, metabolic coupling among tissues and organs provided by insulin and epinephrine, as well as the effect of insulin on peripheral vascular sympathetic activity. These model simulations provide insight into the relative importance of the various mechanisms that determine the acute and chronic physiological effects of sleep-disordered breathing. The model can also be used to investigate the effects of a variety of interventions, such as different glucose clamps, the intravenous glucose tolerance test, and the application of continuous positive airway pressure on OSA subjects. As such, this model provides the foundation on which future efforts to simulate disease progression and the long-term effects of pharmacological intervention can be based

    Impact of modern antiviral therapy of chronic hepatitis B and C on clinical outcomes of liver disease

    Get PDF
    Chronic infections with the hepatitis B and C viruses have significant worldwide health and economic impacts. Previous treatments for hepatitis C such as interferon and ribavirin therapy were ineffective and poorly tolerated by patients. The introduction of directly acting curative antiviral therapy for hepatitis C and the wider use of nucleos(t)ide analogues for suppression of chronic Hepatitis B infection have resulted in many positive developments. Decreasing the prevalence of hepatitis B and C have concurrently reduced transmission rates and hence, the number of new infections. Antiviral treatments have decreased the rates of liver decompensation and as a result, lowered hospitalisation and mortality rates for both chronic hepatitis B and C infection. The quality of life of chronically infected patients has also been improved significantly by modern treatment. Antiviral therapy has stopped the progression of liver disease to cirrhosis in certain patient cohorts and prevented ongoing hepatocellular damage in patients with existing cirrhosis. Longer term benefits of antiviral therapy include a reduced risk of developing hepatocellular carcinoma and decreased number of patients requiring liver transplantation. This review article assesses the literature and summarises the impact of modern antiviral therapy of chronic hepatitis B and C on clinical outcomes from liver disease
    corecore