280 resultados para Epithelial Sodium Channel
Resumo:
Utilizing a mono-specific antiserum produced in rabbits to hog kidney aromatic L-amino acid decarboxylase (AADC), the enzyme was localized in rat kidney by immunoperoxidase staining. AADC was located predominantly in the proximal convoluted tubules; there was also weak staining in the distal convoluted tubules and collecting ducts. An increase in dietary potassium or sodium intake produced no change in density or distribution of AADC staining in kidney. An assay of AADC enzyme activity showed no difference in cortex or medulla with chronic potassium loading. A change in distribution or activity of renal AADC does not explain the postulated dopaminergic modulation of renal function that occurs with potassium or sodium loading.
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Changing sodium intake from 70-200 mmol/day elevates blood pressure in normotensive volunteers by 6/4 mmHg. Older people, people with reduced renal function on a low sodium diet and people with a family history of hypertension are more likely to show this effect. The rise in blood pressure was associated with a fall in plasma volume suggesting that plasma volume changes do not initiate hypertension. In normotensive individuals the most common abnormality in membrane sodium transport induced by an extra sodium load was an increased permeability of the red cell to sodium. Some normotensive individuals also had an increase in the level of a plasma inhibitor that inhibited Na-K ATPase. These individuals also appeared to have a rise in blood pressure. Sodium intake and blood pressure are related. The relationship differs in different people and is probably controlled by the genetically inherited capacity of systems involved in membrane sodium transport.
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The effect of plasma taken from normotensive humans, while on a low and high sodium diet, on [Na + K]-ATPase and 3H-ouabain binding was measured in tubules from guinea-pig kidneys. Plasma from the high sodium, compared to the low sodium, diet period: (a) inhibited [Na + K]-ATPase activity; (b) decreased 3H-ouabain affinity for binding sites; (c) increased the number of available 3H-ouabain binding sites; (d) decreased [Na + K]-ATPase turnover (activity/3H-ouabain binding sites). The inhibition of [Na + K]-ATPase suggests an increase in a (possible) natriuretic factor. The decreased affinity of 3H-ouabain binding suggests an endogenous ouabainoid, which may be the natriuretic factor.
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LiteSteel beam (LSB) is a new cold-formed steel hollow flange channel section produced using a patented manufacturing process involving simultaneous cold-forming and dual electric resistance welding. The LSBs are commonly used as floor joists and bearers with web openings in residential, industrial and commercial buildings. Their shear strengths are considerably reduced when web openings are included for the purpose of locating building services. Shear tests of LSBs with web openings have shown that there is up to a 60% reduction in the shear capacity due to the inclusion of web openings. Hence there is a need to improve the shear capacity of LSBs with web openings. A cost effective way to eliminate the shear capacity reduction is to attach suitable stiffeners around the web openings. Hence experimental studies were undertaken to investigate the shear behaviour and strength of LSBs with stiffened web openings. In this research, various stiffening methods using plate and LSB stiffeners attached to LSBs using both welding and screw-fastening were attempted. Our test results showed that the stiffening arrangements recommended by past research for cold-formed steel channel beams are not adequate to restore the shear strengths of LSBs with web openings. Therefore new stiffener arrangements were proposed for LSBs with web openings. This paper presents the details of this experimental study and the results including the details of the optimum stiffener details for LiteSteel beams.
Resumo:
This LiteSteel beam (LSB) is a new cold-formed steel hollow flange channel section produced using a patented manufacturing process involving simultaneous cold-forming and dual electric resistance welding. The LSBs are commonly used as floor joists and bearers with web openings in buildings. Their shear strengths are considerably reduced when web openings are included for the purpose of locating building services. Shear tests of LSBs with web openings have shown that there is up to 60% reduction in the shear capacity. Hence there is a need to improve the shear capacity of LSBs with web openings. A cost effective way to eliminate the shear capacity reduction is to stiffen the web openings using suitable stiffeners. Hence numerical studies were undertaken to investigate the shear capacity of LSBs with stiffened web openings. In this research, finite element models of LSBs with stiffened web openings in shear were developed to simulate the shear behaviour and strength of LSBs. Various stiffening methods using plate and LSB stiffeners attached to LSBs using both welding and screw-fastening were attempted. The developed models were then validated by comparing their results with experimental results and used in further studies. Both finite element and experimental results showed that the stiffening arrangements recommended by past research for cold-formed steel channel beams are not adequate to restore the shear strengths of LSBs with web openings. Therefore new stiffener arrangements were proposed for LSBs with web openings. This paper presents the details of this research project using numerical studies and the results.
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Cold-formed steel members are increasingly used as primary structural elements in buildings due to the availability of thin and high strength steels and advanced cold-forming technologies. Cold-formed lipped channel beams (LCB) are commonly used as flexural members such as floor joists and bearers. Shear behaviour of LCBs with web openings is more complicated and their shear capacities are considerably reduced by the presence of web openings. However, limited research has been undertaken on the shear behaviour and strength of LCBs with web openings. Hence a numerical study was undertaken to investigate the shear behaviour and strength of LCBs with web openings. Finite element models of simply supported LCBs with aspect ratios of 1.0 and 1.5 were considered under a mid-span load. They were then validated by comparing their results with test results and used in a detailed parametric study. Experimental and numerical results showed that the current design rules in cold-formed steel structures design codes are very conservative for the shear design of LCBs with web openings. Improved design equations were therefore proposed for the shear strength of LCBs with web openings. This paper presents the details of this numerical study of LCBs with web openings, and the results.
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Unsteady numerical simulation of Rayleigh Benard convection heat transfer from a 2D channel is performed. The oscillatory behavior is attributed to recirculation of ascending and descending flows towards the core of the channel producing organized rolled motions. Variation of the parameters such as Reynolds number, channel outlet flow area and inclination of the channel are considered. Increasing Reynolds number (for a fixed Rayleigh number), delays the generation of vortices. The reduction in the outflow area leads to the later and the less vortex generation. As the time progresses, more vortices are generated, but the reinforced mean velocity does not let the eddies to enter the core of the channel. Therefore, they attach to the wall and reduce the heat transfer area. The inclination of the channel (both positive and negative) induces the generated vortices to get closer to each other and make an enlarged vortex.
Resumo:
Cold-formed steel lipped channel beams (LCB) are used extensively in residential, industrial and commercial buildings as load bearing structural elements. Their shear strengths are considerably reduced when web openings are included for the purpose of locating building services. Past research has shown that the shear capacities of LCBs were reduced by up to 70% due to the inclusion of these web openings. Hence there is a need to improve the shear capacities of LCBs with web openings. A cost effective way of eliminating the detrimental effects of large web openings is to attach suitable stiffeners around the web openings and restore the original shear strength and stiffness of the LCBs. Hence detailed experimental studies were undertaken to investigate the shear behaviour and strength of LCBs with stiffened web openings. Both plate and stud stiffeners with varying sizes and thicknesses were attached to the web elements of LCBs using different screw-fastening arrangements. Simply supported test specimens of LCBs with aspect ratios of 1.0 and 1.5 were loaded at mid-span until failure. Test results showed that the plate stiffeners established using AISI recommendations are inadequate to restore the shear strengths of LCBs with web openings. Hence new stiffener arrangements have been proposed for LCBs based on experimental results. This paper presents the details of this experimental study on the shear strength of lipped channel beams with stiffened web openings, and the results.
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Background We have previously demonstrated that human kidney proximal tubule epithelial cells (PTEC) are able to modulate autologous T and B lymphocyte responses. It is well established that dendritic cells (DC) are responsible for the initiation and direction of adaptive immune responses and that these cells occur in the renal interstitium in close apposition to PTEC under inflammatory disease settings. However, there is no information regarding the interaction of PTEC with DC in an autologous human context. Methods Human monocytes were differentiated into monocyte-derived DC (MoDC) in the absence or presence of primary autologous activated PTEC and matured with polyinosinic:polycytidylic acid [poly(I:C)], while purified, pre-formed myeloid blood DC (CD1c+ BDC) were cultured with autologous activated PTEC in the absence or presence of poly(I:C) stimulation. DC responses were monitored by surface antigen expression, cytokine secretion, antigen uptake capacity and allogeneic T-cell-stimulatory ability. Results The presence of autologous activated PTEC inhibited the differentiation of monocytes to MoDC. Furthermore, MoDC differentiated in the presence of PTEC displayed an immature surface phenotype, efficient phagocytic capacity and, upon poly(I:C) stimulation, secreted low levels of pro-inflammatory cytokine interleukin (IL)-12p70, high levels of anti-inflammatory cytokine IL-10 and induced weak Th1 responses. Similarly, pre-formed CD1c+ BDC matured in the presence of PTEC exhibited an immature tolerogenic surface phenotype, strong endocytic and phagocytic ability and stimulated significantly attenuated T-cell proliferative responses. Conclusions Our data suggest that activated PTEC regulate human autologous immunity via complex interactions with DC. The ability of PTEC to modulate autologous DC function has important implications for the dampening of pro-inflammatory immune responses within the tubulointerstitium in renal injuries. Further dissection of the mechanisms of PTEC modulation of autologous immune responses may offer targets for therapeutic intervention in renal medicine.
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Abstract—In this paper we investigate the capacity of a general class of the slotted amplify and forward (SAF) relaying protocol where multiple, though a finite number of relays may transmit in a given cooperative slot and the relay terminals being half-duplex have a finite slot memory capacity. We derive an expression for the capacity per channel use of this generalized SAF channel assuming all source to relay, relay to destination and source to destination channel gains are independent and modeled as complex Gaussian. We show through the analysis of eigenvalue distributions that the increase in limiting capacity per channel use is marginal with the increase of relay terminals.
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This is the first study to describe the association between expression of MUC1 and MUC2 mucins and prognosis in ovarian cancer. Paraffin sections of epithelial ovarian tumours (n=182: 29 benign, 21 low malignant potential, and 132 invasive tumours) were analysed immunohistochemically for expression of MUC1 and MUC2 mucin core proteins. Most benign, low malignant potential, and invasive tumours showed high MUC1 expression in the cytoplasm. Low cytoplasmic expression of MUC1 was a predictor for good prognosis, particularly within stage III tumours. A minority of benign epithelial tumours, but most low malignant potential and invasive non-mucinous tumours, showed high MUC1 expression on the cell membrane. High apical MUC1 reactivity was associated with non-mucinous tumours. Low expression of MUC1 in the apical membrane was associated with early stage and good outcome for invasive tumours. Most benign and low malignant potential tumours, but only a minority of invasive tumours, showed MUC2 expression. MUC2 was found in non-mucinous as well as in mucinous tumours. The presence of MUC2 was inversely associated with high tumour grade but was not associated with altered survival. These results support experimental evidence that MUC1 influences the metastatic ability of ovarian cancer.
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BACKGROUND: Cell shape and tissue architecture are controlled by changes to junctional proteins and the cytoskeleton. How tissues control the dynamics of adhesion and cytoskeletal tension is unclear. We have studied epithelial tissue architecture using 3D culture models and found that adult primary prostate epithelial cells grow into hollow acinus-like spheroids. Importantly, when co-cultured with stroma the epithelia show increased lateral cell adhesions. To investigate this mechanism further we aimed to: identify a cell line model to allow repeatable and robust experiments; determine whether or not epithelial adhesion molecules were affected by stromal culture; and determine which stromal signalling molecules may influence cell adhesion in 3D epithelial cell cultures. METHODOLOGY/PRINCIPAL FINDINGS: The prostate cell line, BPH-1, showed increased lateral cell adhesion in response to stroma, when grown as 3D spheroids. Electron microscopy showed that 9.4% of lateral membranes were within 20 nm of each other and that this increased to 54% in the presence of stroma, after 7 days in culture. Stromal signalling did not influence E-cadherin or desmosome RNA or protein expression, but increased E-cadherin/actin co-localisation on the basolateral membranes, and decreased paracellular permeability. Microarray analysis identified several growth factors and pathways that were differentially expressed in stroma in response to 3D epithelial culture. The upregulated growth factors TGFβ2, CXCL12 and FGF10 were selected for further analysis because of previous associations with morphology. Small molecule inhibition of TGFβ2 signalling but not of CXCL12 and FGF10 signalling led to a decrease in actin and E-cadherin co-localisation and increased paracellular permeability. CONCLUSIONS/SIGNIFICANCE: In 3D culture models, paracrine stromal signals increase epithelial cell adhesion via adhesion/cytoskeleton interactions and TGFβ2-dependent mechanisms may play a key role. These findings indicate a role for stroma in maintaining adult epithelial tissue morphology and integrity.
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BACKGROUND: Broccoli consumption has been associated with a reduced risk of prostate cancer. Isothiocyanates (ITCs) derived from glucosinolates that accumulate in broccoli are dietary compounds that may mediate these health effects. Sulforaphane (SF, 4-methylsulphinylbutyl ITC) derives from heading broccoli (calabrese) and iberin (IB, 3-methylsulphinypropyl ITC) from sprouting broccoli. While there are many studies regarding the biological activity of SF, mainly undertaken with cancerous cells, there are few studies associated with IB. METHODS: Primary epithelial and stromal cells were derived from benign prostatic hyperplasia tissue. Affymetrix U133 Plus 2.0 whole genome arrays were used to compare global gene expression between these cells, and to quantify changes in gene expression following exposure to physiologically appropriate concentrations of SF and IB. Ontology and pathway analyses were used to interpret results. Changes in expression of a subset of genes were confirmed by real-time RT-PCR. RESULTS: Global gene expression profiling identified epithelial and stromal-specific gene expression profiles. SF induced more changes in epithelial cells, whereas IB was more effective in stromal cells. Although IB and SF induced different changes in gene expression in both epithelial and stromal cells, these were associated with similar pathways, such as cell cycle and detoxification. Both ITCs increased expression of PLAGL1, a tumor suppressor gene, in stromal cells and suppressed expression of the putative tumor promoting genes IFITM1, CSPG2, and VIM in epithelial cells. CONCLUSION: These data suggest that IB and SF both alter genes associated with cancer prevention, and IB should be investigated further as a potential chemopreventative agent.