Novartis

About: Novartis is a company organization based out in Basel, Switzerland. It is known for research contribution in the topics: Alkyl & Population. The organization has 41930 authors who have published 50566 publications receiving 1978996 citations. The organization is also known as: Novartis International AG.

Detection and Typing of Human Papillomavirus in Archival Cervical Cancer Specimens by DNA Amplification With Consensus Primers

Abstract: We developed a polymerase chain reaction DNA amplification system using two distinct consensus oligonucleotide primer sets for the improved detection and typing of a broad spectrum of human genital papillomavirus (HPV) sequences, including those of novel viruses. The system incorporates one primer set designed to amplify a highly conserved L1 domain and a second primer set designed to amplify a domain within the E6 gene. We used this system to analyze 48 fixed, paraffin-embedded tissue sections (41 specimens from 33 cervical carcinomas, four normal cervical tissues, and several control tissues) for the presence of HPV DNA. HPV sequences were detected in all carcinoma samples and none of the control samples. Hybridization analyses showed that the results obtained with the two amplification schemes concurred completely. This approach allowed rapid confirmation of typing results and may improve the likelihood of detecting a wide variety of HPV sequences, including those of novel HPVs.

IL-33–Dependent Type 2 Inflammation during Rhinovirus-induced Asthma Exacerbations In Vivo

Abstract: Rationale: Rhinoviruses are the major cause of asthma exacerbations; however, its underlying mechanisms are poorly understood. We hypothesized that the epithelial cell–derived cytokine IL-33 plays ...

Fourth International Workgroup on Genotoxicity testing: results of the in vivo Comet assay workgroup.

Abstract: As part of the Fourth International Workshop on Genotoxicity Testing (IWGT), held 9-10 September 2005 in San Francisco, California, an expert working group on the Comet assay was convened to review and discuss some of the procedures and methods recommended in previous documents. Particular attention was directed at the in vivo rodent, alkaline (pH >13) version of the assay. The aim was to review those protocol areas which were unclear or which required more detail in order to produce a standardized protocol with maximum acceptability by international regulatory agencies. The areas covered were: number of dose levels required, cell isolation techniques, measures of cytotoxicity, scoring of comets (i.e., manually or by image analysis), and the need for historical negative/positive control data. It was decided that a single limit dose was not sufficient although the required number of dose levels was not stipulated. The method of isolating cells was thought not to have a qualitative effect on the assay but more data were needed before a conclusion could be drawn. Concurrent measures of cytotoxicity were required with histopathological examination of tissues for necrosis or apoptosis as the "Gold Standard". As for analysing the comets, the consensus was that image analysis was preferred but not required. Finally, the minimal number of studies required to generate a historical positive or negative control database was not defined; rather the emphasis was placed on demonstrating the stability of the negative/positive control data. It was also agreed that a minimum reporting standard would be developed which would be consistent with OECD in vivo genotoxicity test method guidelines.

Induced Disease Resistance in Plants by Chemicals

Abstract: Plants can be induced locally and systemically to become more resistant to diseases through various biotic or abiotic stresses. The biological inducers include necrotizing pathogens, non- pathogens or root colonizing bacteria. Through at network of signal pathways they induce resistance spectra and marker proteins that are characteristic for the different plant species and activation systems. The best characterized signal pathway for systemically induced resistance is SAR (systemic acquired resistance) that is activated by localized infections with necrotizing pathogens. It is characterized by protection against a broad range of pathogens, by a set of induced proteins and by its dependence on salicylic acid (SA) Various chemicals have been discovered that seem to act at various points in these defense activating networks and mimic all or parts of the biological activation of resistance. Of these, only few have reached commercialization. The best- studied resistance activator is acibenzolar-5-methyl (BION). At low rates it activates resistance in many crops against a broad spectrum of diseases, including fungi, bacteria and viruses. In monocots, activated resistance by BION typically is very long lasting, while the lasting effect is less pronounced in dicots. BION is translocated systemically in plants and can take the place of SA in the natural SAR signal pathway, inducing the same spectrum of resistance and the same set of molecular markers. Probenazole (ORYZEMATE) is used mainly on rice against rice blast and bacterial leaf blight. Its mode of action is not well understood partly because biological systems of systemically induced resistance are not well defined in rice. Treated plants clearly respond faster and in a resistant manner to infections by the two pathogens. Other compounds like beta-aminobutyric acid as wdl as extracts from plants and microorganisms have also been described as resistance inducers. For most of these, neither the mode of action nor reliable pre-challenge markers are known and still other pathways for resistance activation are suspected. Resistance inducing chemicals that are able to induce broad disease resistance offer an additional option for the farmer to complement genetic disease resistance and the use of fungicides. If integrated properly in plant health management programs, they can prolong the useful life of both the resistance genes and the fungicides presently used.

ESKAPEing the labyrinth of antibacterial discovery

Abstract: Antimicrobial drug resistance is a growing threat to global public health. Multidrug resistance among the 'ESKAPE' organisms - encompassing Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. - is of particular concern because they are responsible for many serious infections in hospitals. Although some promising agents are in the pipeline, there is an urgent need for new antibiotic scaffolds. However, antibacterial researchers have struggled to identify new small molecules with meaningful cellular activity, especially those effective against multidrug-resistant Gram-negative pathogens. This difficulty ultimately stems from an incomplete understanding of efflux systems and compound permeation through bacterial membranes. This Opinion article describes findings from target-based and phenotypic screening efforts carried out at AstraZeneca over the past decade, discusses some of the subsequent chemistry challenges and concludes with a description of new approaches comprising a combination of computational modelling and advanced biological tools which may pave the way towards the discovery of new antibacterial agents.