Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As manifest by tubular collapse and the virtual absence of flow into the glomerulotubular junction (GTJ), filtration in most nephrons (SNGFR) of rats poisoned with 9 mg/kg body wt HgCl2 16 to 28 hours earlier was virtually absent. Arterial colloid osmotic pressure (COPA) and Bowman's space pressure (PBS) were modestly depressed (P less than 0.05 or below), and mean blood pressure was reduced from 115 +/- 2 mm Hg (SEM) to 97 +/- 1 mm Hg (P less than 0.001). Glomerular capillary hydraulic pressure (Pg), 25.6 +/- 1.3 mm Hg was some 24 mm Hg lower than control (P less than 0.001) and yielded a net afferent effective filtration pressure (Pnet) of 4.1 +/- 1.2 mm Hg. Excluding three rats with values greater than 10 mm Hg, Pnet averaged 2.0 +/- 0.9 mm Hg (N = 17 rats) versus 20.0 +/- 1.8 mm Hg in controls (N = 10, P less than 0.001), the former being statistically almost indistinguishable from 0 mm Hg and barely able to support any filtration. This decrease in Pg was caused by a major increase in preglomerular resistance (RA) and a reciprocal fall in efferent arteriolar resistance (RE), the RA/RE ratio of 7.2 +/- 0.8 being fourfold higher than control (P less than 0.001). Renocortical blood flow was not different from control (P greater than 0.2). A wide spread of Pg values in individual glomeruli and the absence of tubular flow despite the appearance of i.v. injected lissamine green in a quadrant of surface glomeruli suggested the possibility of a greatly increased, glomerular capillary resistance. It is concluded that reciprocal changes in RA and RE are the immediate cause of filtration failure in this form of ARF and that, in the virtual absence of filtration, tubular leakage can play no important role. Since PBS was depressed in both the developmental and established phases of ARF, tubular obstruction appears to play no direct role in the pathogenesis of this particular model of murine acute renal failure.
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PMID:Glomerular hemodynamics in mercury-induced acute renal failure. 365 37

The tumor suppressor p14(ARF) and protooncogene epidermal growth factor receptor (EGFR) play an important role in the development of laryngeal squamous cell carcinoma (LSCC). We explored the inhibition of proliferation and induction of differentiation in human larynx cancer cells (Hep-2) in vitro when p14(ARF) couples with antisense complementary DNA of EGFR to transfect into Hep-2 cells via the AdEasy-1 vector system. In vitro studies, using standard isobologram analyses, identified whether Ad-antisense EGFR is synergistic with Ad-14(ARF). To evaluate the cytotoxicity of these agents the gold standard clonogenic survival assay was used. Western blotting analyses, 3'(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and flow cytometer (FCM) analysis was used to detect protein expression, proliferation, and cell cycle distribution of Hep-2 cells, respectively. Meanwhile, empty vector and PBS were set as a control. The activity of proliferation of Hep-2 cells was inhibited markedly by infection of Ad-p14(ARF) combined with Ad-antisense EGFR compared with Ad-p14(ARF) or Ad-antisense EGFR alone (P = 0.001, P = 0.002, respectively), with Ad-sense EGFR (P = 0.0005), with vector control (Ad-Ctrl) (P = 0.0001), and with PBS (P = 0.0001). FCM revealed that the proportion in the G(0)/G(1) phases increased by up to 86.9% when Ad-p14(ARF) was associated with Ad-antisense EGFR to transfect Hep-2 cells. A weakened expression of EGFR protein and P14 (ARF) protein overexpression was observed. Our study in vitro indicated that association of Ad-p14(ARF) with Ad-antisense EGFR remarkably inhibited activity of proliferation and inducted differentiation of Hep-2 cells. Therefore, not only EGFR, but also p14(ARF), plays a major role in the genesis and in modulating cell growth and differentiation of LSCC, and their synergistic effect was obvious. An effective potential target of gene therapy to prevent LSCC proliferation was provided.
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PMID:Combined p14ARF and antisense EGFR potentiate the efficacy of adenovirus-mediated gene therapy in laryngeal squamous cell carcinoma (LSCC). 1732 65

The aim of this study is to target the interference therapy of signal transduction which is a novel therapeutic strategy in laryngeal squamous cell carcinoma (LSCC). We successfully constructed recombinant adenoviruses Ad-p14ARF, and Ad-antisense EGFR using AdEasy-1 vector System. Clonogenic cell assay, western blotting assay, 3'(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometer (FCM) assay, and immunocytochemical technique were designed to examine the inhibition of proliferation, protein expression of p14ARF and EGFR and induction of differentiation, respectively. Furthermore the synergistic effect of Ad-p14ARF and Ad-antisense EGFR on Hep-2 cell was examined. We successfully used AdEasy-1 vector system to construct recombinant adenoviruses Ad-p14ARF and Ad-antisense EGFR. The activity of proliferation of Hep-2 cells was inhibited markedly by infecting Ad-p14ARF or Ad-antisense EGFR by comparing Ad-sense EGFR (P=0.005) with vector control (Ad-Ctrl) (P=0.005) and with PBS (P=0.003). This effect, combining Ad-antisense-EGFR with Ad-p14ARF became more noticeable than alone (P=0.01, P=0.02, respectively). P14 ARF protein overexpression, EGFR protein down expression, and inhibition of proliferation were observed in Hep-2 cells infected by either Ad-p14ARF or Ad-antisense EGFR. FCM revealed that the proportion of apoptosis cells transfected by Ad-p14ARF and Ad-antisense EGFR increased more obviously than the control. The proportion of (Hep-2 cells in) G0/G1 phases was increased by up to 78.5, 77.7, and 86.9% in Ad-antisense EGFR, Ad-p14ARF, and Ad-antisense EGFR+Ad-p14ARF, respectively. Our findings demonstrated that not only EGFR but p14ARF also plays a major role on the genesis and in modulating the cell growth and differentiation of human laryngocarcinoma. They efficaciously blocked the signal transduction of human laryngocarcinoma cell, and may therefore, be an effective potential target of gene therapy to prevent human laryngocarcinoma cell proliferation.
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PMID:Signal transduction-related gene transfer leads to inhibition of proliferation and induction of differentiation in laryngeal squamous cell carcinoma in vitro. 1762 21