1 SmithKline Beecham Pharmaceuticals, Department of Biotechnology, Yew Tree Bottom Road, Epsom, Surrey KT18 5XQ, UK
2 New Frontiers Science Park North, Third Avenue, Harlow, Essex CM19 5AW, UK
3 ...Department of Molecular Virology & Host Defence
4 Department of Gene Expression Sciences, Upper Merion, 709 Swedeland Road, King of Prussia, PA 194 06, USA
Human papillomavirus type 6b (HPV-6b) is one of the most common causes of human genital warts, an important sexually transmitted disease. Discovery of antiviral therapies for this condition has been hampered by the inability to propagate the virus using standard tissue culture techniques and through difficulties in expressing sufficient recombinant viral proteins in vitro . Replication of papillomavirus DNA requires to viral proteins, E1 and E2. In an effort to establish assays to discover compounds active against this virus, we have co-expressed HPV-6b E1 and E2 proteins in insect cells. We demonstrate that the two proteins form a heteromeric complex which can be purified by sequence-specific DNA affinity chromatography. We also demonstrate that the complex has both E1-associated ATPase and ATP-dependent DNA helicase activity and report further characterization of these functions.
Received 1 March 1996;
accepted 12 March 1996.
Over the past two decades, our understanding of interleukin-16 (IL-16) has increased substantially. Initial studies characterizing IL-16 as a chemotactic cytokine (but not a chemokine) just scratched ...the surface of the unique properties of this cytokine. Since then, scientists have determined that IL-16 has a wide range of effects on cells, including upregulation of CD25, induction of cells to progress to the G(1) phase, inhibition of antigen- specific proliferation yet with retained antigen nonspecific proliferative properties, and discovery of a novel neuronal form with unique properties. Recently, a plethora of studies have implicated IL-16 in exacerbation of infectious, immune-mediated, and autoimmune inflammatory disorders, including atopic dermatitis, irritable bowel syndrome, systemic lupus erythematosus, neurodegenerative disorders, and viral infections. Herein, we review the body of evidence supporting a role for IL-16 in infectious and immune-mediated inflammatory disorders and explore the known and possible mechanism of actions in the numerous diseases.
Ectopic parotid: case report Barbuscia, M A; Caizzone, A; Vecchio, D A ...
Il Giornale di chirurgia,
10/2011, Letnik:
32, Številka:
10
Journal Article
Recenzirano
A recent case led the authors to re-examine the clinical characteristics of the cervical ectopia of the major salivary glands. These glands develop in the embryo between the sixth and seventh week, ...starting with the formation of endodermal invaginations of the branchial section of the floor of the primitive mouth. These cell cords, initially solid, proliferate in the underlying mesenchyme, starting from the opening of the future excretory duct, and subsequently branch and canalize. During embryogenesis, the endodermal invaginations become closely interconnected with the adjacent lymphatic tissue. It is thus possible for lymphoid tissue to migrate into the parotid or the other major salivary glands, or conversely, for salivary tissue to become included in the cervical lymph nodes. Very rarely, ectopic salivary gland tissue can also be found in other unusual locations, including the neck region, as a result of a developmental abnormality of the branchial apparatus. The base of the neck is the most common location, while ectopia of the mid third of the neck is quite rare. The authors discuss the clinical details and diagnostic procedure leading to preoperative diagnosis. This congenital anomaly can, albeit rarely, degenerate into cancer, and surgical excision is thus imperative.
We developed a convenient colorimetric assay for monitoring RNA synthesis from DNA-dependent RNA polymerases (DdRp) and viral RNA-dependent RNA polymerases (RdRp). ATP and GTP with a p-nitrophenyl ...moiety attached to the γ-phosphate were synthesized (PNP–NTPs). These PNP–NTPs can be used for RNA synthesis by several RNA polymerases, including the RdRps from brome mosaic virus and bovine viral diarrhea virus and the DdRps from bacteriophage T7 and SP6. When the polymerase reactions were performed in the presence of alkaline phosphatase, which digests the p-nitrophenylpyrophosphate side-product of phosphoryl transfer to the chromogenic p-nitrophenylate, an increase in absorbence at 405 nm was observed. These nucleotide analogues were used in continuous colorimetric monitoring of polymerase activity. Furthermore, the PNP–NTPs were found to be stable and utilized by RNA polymerases in the presence of human plasma. This simple colorimetric polymerase assay can be performed in a standard laboratory spectrophotometer and will be useful in screens for inhibitors of viral RNA synthesis.
The discrete-time relaxation methods based on Volterra-Runge-Kutta methods for solving large system of second-kind Volterra integral equations are proposed. Convergence of the discrete-time iteration ...process with particular attention to parallel methods is investigated.
Recently, there has been a rebirth of interest in supply chain demand amplification, a trend accelerated by the availability of a wide range of simulation packages. However, although this approach ...provides some guidance on design improvements possible in a given situation, it rarely offers insight for the future. In the present paper the use of simple filter theory is proposed to help bridge this gap. The example chosen to illustrate the approach is a three-echelon system in which there are factory, distributor, and retailer activities. The results vividly confirm an optimal design previously obtained via a multi-attribute utility technique (MAUT) expert system. However, the knowledge gained via filter theory should improve yet further the effectiveness of the expert system. This is because the sequential steps to be followed when varying the echelon dynamics as part of the search procedure can be greatly improved. The paper concludes by showing how simulation results might be used to confirm the supply chain dynamic design which will minimize stockholdings in the presence of demand fluctuations. However, it should be noted that in common with the successful application of systems dynamics techniques in production-distribution systems generally, the solutions are most applicable to the medium-term operations horizon. The latter term may need re-definition for use in 'lean' supply chains. Our intuitive reaction is that a scientific definition may well turn out to be a multiple of the largest remaining process lead-time in the slimmed down supply chain rather than being the customary arbitrary choice of, for instance, a 12-month period.
In this paper necessary and sufficient conditions for the exponential stability of discrete linear Volterra systems are proved. Sufficient conditions, expressed directly in terms of the coefficients, ...are derived
Ischemic heart disease and secondary heart failure places an immense burden on society. Stimulation of adenosine G protein‐coupled receptors (ARs) represents a powerful protective mechanism to ...decrease cardiac ischemia‐reperfusion injury (IRI). Despite this, therapeutic targeting of ARs has been largely unsuccessful due to on‐target adverse effects, including pronounced bradycardia, atrioventricular block and hypotension (1). Biased agonism has the potential to overcome these limitations by enabling the separation of therapeutic from adverse effects (2).
Aim
To profile prototypical and biased AR agonism in isolated cardiac cells. Subsequent studies investigated the in vivo profile of AR biased agonism in acute and longer‐term rat models of cardiac ischemia‐reperfusion injury.
Results
In isolated rat cardiomyocytes, prototypical and biased AR agonists stimulated reperfusion injury salvage kinase (RISK) signalling pathways, including Akt and ERK1/2, and promoted cardioprotection. Exposure to in vitro simulated ischemia‐reperfusion conditions differentially influenced the RISK signalling stimulated by prototypical and biased AR agonists. Within an in vivo model of acute myocardial ischemia‐reperfusion injury, both biased and prototypical agonists stimulated an A1AR‐mediated reduction in infarct size and an improvement in cardiac function post‐IRI. However, in contrast to prototypical agonists, our biased agonist had no significant adverse hemodynamic effects. Furthermore, in a longer‐term in vivo model of myocardial IRI, an AR biased agonist improved cardiac function and decreased cardiac hypertrophy and fibrosis.
Discussion
Insights into AR signalling in cardiomyocytes under normoxic and simulated ischemia‐reperfusion conditions suggests that context‐specific biased agonism stimulates a preferential signalling profile. Furthermore, AR biased agonism can promote cardioprotection and decrease pathological cardiac remodelling in the absence of bradycardia, a profile suggestive of ligand bias. Collectively, our findings demonstrate that AR biased agonism can stimulate potent cardioprotection in the absence of adverse hemodynamic effects and therefore represents an attractive therapeutic approach for the treatment of ischemic heart disease.
Support or Funding Information
This work was supported by Project Grant APP1084487 of the National Health and Medical Research Council of Australia (NHMRC). J‐A.B., CHC and E.A.V are recipients of the Australian Government Research Training Program Scholarship. A.C. is a Senior Principal Research Fellow of the NHMRC. L.T.M. is an Australian Heart Foundation Future Leaders Fellow.
This is from the Experimental Biology 2018 Meeting. There is no full text article associated with this published in The FASEB Journal.
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