Home About us Contact
|
Home About us Contact | ||
|
|
||
Inducing Agents (inducing + agent)
Selected AbstractsProdrugs of 9-Benzyl-8-hydroxy-2-(2-hydroxyethylthio)adenine: Potent Interferon Inducing Agents in Monkeys.CHEMINFORM, Issue 35 2004Ayumu Kurimoto Abstract For Abstract see ChemInform Abstract in Full Text. [source] The effect of hyaluronic acid on IL-1,-induced chondrocyte apoptosis in a rat model of osteoarthritisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 12 2008Pang-Hu Zhou Abstract The purpose of this article was to study the effect of hyaluronic acid (HA) on chondrocyte apoptosis in a rat osteoarthritis in vitro model (exposure to IL-1,) and explore its mechanism. A rat in vitro model of osteoarthritis (OA) was established using 10 ng/mL IL-1, as a modulating and chondrocyte apoptosis inducing agent. Different doses of HA (10, 20, and 40 µg/mL) were added 1 h prior to the addition of IL-1, to a monolayer culture of freshly isolated juvenile rat chondrocytes. The ratio of apoptotic cell death was surveyed by Annexin V-FITC and propidium iodide double-labeling FACS analysis. The mitochondrial membrane potential of chondrocytes was evaluated by rhodamine-123 fluorescence. The mitochondrial function was evaluated through detecting the ATP production by a luciferase assay. The reverse transcription polymerase chain reaction (RT-PCR) was performed to measure mRNA expression levels of inducible oxide synthase (iNOS). HA could inhibit IL-1,-induced chondrocyte apoptosis in our cell culture model system. It was showed that addition of HA to the medium was able in a dose-dependent way to reduce the impairment of the mitochondrial membrane potential and to restore mitochondrial ATP production. This study shows that HA could suppress in a dose-dependent way chondrocyte apoptosis in our IL-1,-induced osteoarthritis model. The suppression of inflammatory cytokine activity within the joint might be one important mechanism of the clinical action of intraarticular injection of HA in the treatment of OA. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] Priming of plant innate immunity by rhizobacteria and ,-aminobutyric acid: differences and similarities in regulationNEW PHYTOLOGIST, Issue 2 2009Sjoerd Van der Ent Summary ,,Pseudomonas fluorescens WCS417r bacteria and ,-aminobutyric acid can induce disease resistance in Arabidopsis, which is based on priming of defence. ,,In this study, we examined the differences and similarities of WCS417r- and ,-aminobutyric acid-induced priming. ,,Both WCS417r and ,-aminobutyric acid prime for enhanced deposition of callose-rich papillae after infection by the oomycete Hyaloperonospora arabidopsis. This priming is regulated by convergent pathways, which depend on phosphoinositide- and ABA-dependent signalling components. Conversely, induced resistance by WCS417r and ,-aminobutyric acid against the bacterial pathogen Pseudomonas syringae are controlled by distinct NPR1-dependent signalling pathways. As WCS417r and ,-aminobutyric acid prime jasmonate- and salicylate-inducible genes, respectively, we subsequently investigated the role of transcription factors. A quantitative PCR-based genome-wide screen for putative WCS417r- and ,-aminobutyric acid-responsive transcription factor genes revealed distinct sets of priming-responsive genes. Transcriptional analysis of a selection of these genes showed that they can serve as specific markers for priming. Promoter analysis of WRKY genes identified a putative cis -element that is strongly over-represented in promoters of 21 NPR1-dependent, ,-aminobutyric acid-inducible WRKY genes. ,,Our study shows that priming of defence is regulated by different pathways, depending on the inducing agent and the challenging pathogen. Furthermore, we demon-strated that priming is associated with the enhanced expression of transcription factors. [source] Plant defence reactions against fusarium wilt in chickpea induced by incompatible race 0 of Fusarium oxysporum f.sp. ciceris and nonhost isolates of F. oxysporumPLANT PATHOLOGY, Issue 6 2002J. M. Cachinero Germinated seeds of ,kabuli' chickpea cv. ICCV 4 were inoculated with a conidial suspension of the incompatible race 0 of Fusarium oxysporum f.sp. ciceris (Foc) or of nonhost F. oxysporum resistance ,inducers', and 3 days later were challenged by root dip with a conidial suspension of highly virulent Foc race 5. Prior inoculation with inducers delayed the onset of symptoms and/or significantly reduced the final amount of fusarium wilt caused by race 5. However, the extent of disease suppression varied with the nature of the inducing agent; the nonhost isolates of F. oxysporum were more effective at disease suppression than the incompatible Foc race 0. Inoculation with the inducers gave rise to synthesis of maackiain and medicarpin phytoalexins in inoculated seedlings; these did not accumulate in plant tissues but were released into the inoculum suspension. Inoculation with inducers also resulted in accumulation of chitinase, ,-1,3-glucanase and peroxidase activities in plant roots. These defence-related responses were induced more consistently and intensely by nonhost isolates of F. oxysporum than by incompatible Foc race 0. The phytoalexins and, to a lesser extent, the antifungal hydrolases, were also induced after challenge inoculation with Foc race 5. However, in this case the defence responses were induced in both preinduced and noninduced plants infected by the pathogen. It is concluded that the suppression of fusarium wilt in this study possibly involved an inhibitory effect on the pathogen of preinduced plant defences, rather than an increase in the expression of defence mechanisms of preinduced plants following a subsequent challenge inoculation. [source] Interstrand crosslink inducing agents in pretransplant conditioning therapy for hematologic malignanciesENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 6 2010Benigno C. Valdez Abstract Despite successful molecularly targeted, highly specific, therapies for hematologic malignancies, the DNA interstrand crosslinking agents, which are among the oldest and least specific cytotoxic drugs, still have an important role. This is particularly true in stem cell transplantation, where virtually every patient receives conditioning therapy with a DNA-alkylating agent-based program. However, due to concern about serious additive toxicities with combinations of different alkylating drugs, the last several years have seen nucleoside analogs, whose cytotoxic action follows vastly different molecular pathways, introduced in combination with alkylating agents. The mechanistic differences paired with different metabolic pathways for the respective drugs have clinically translated into increased safety without appreciable loss of antileukemic activity. In this report, we review pre-clinical evidence for synergistic antileukemic activity when nucleoside analog(s) and DNA-alkylating agent(s) are combined in the most appropriate manner(s), without a measurable decrease in clinical efficacy compared with the more established alkylating agent combinations. Data from our own laboratory using combinations of fludarabine, clofarabine, and busulfan as prototype representatives for these respective classes of cytotoxic agents are combined with information from other investigators to explain how the observed molecular events will result in greatly enhanced synergistic cytotoxicity. We further present possible mechanistic pathways for such desirable cytotoxic synergism. Finally, we propose how this information-backed hypothesis can be incorporated in the design of the next generation conditioning therapy programs in stem cell transplantation to optimize antileukemic efficacy while still safeguarding patient safety. Environ. Mol. Mutagen., 2010. © 2010 Wiley-Liss, Inc. [source] Functions and regulation of human artemis in double strand break repair,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2007Kirsten Dahm Abstract Cells, which lacked the activity of the nuclease Artemis, retained approximately 10% of unrepaired double strand breaks (DSBs) at later timepoints after ionizing radiation. Ionizing radiation induced hyperphosphorylation of Artemis mainly by ATM and in ATM deficient cells to a minor extent by DNA PK. After induction of DSBs with modified ends by a high dose of calicheamicin ,1, Artemis was phosphorylated by DNA PK. The type of calicheamicin ,1-induced DSBs is likely to represent a subclass of DSBs induced by ionizing radiation. DNA PK-dependent phosphorylation of Artemis after treatment with DSB inducing agents increased the cellular retention of Artemis, maintained its interaction with DNA ends and activated its endonucleolytic activity. The following model is suggested: ATM-dependent phosphorylation of Artemis after ionizing radiation could prevent DNA PK-dependent phosphorylation and activation of undesired endonucleolytic activity at DSBs, which do not require endonucleolytic processing by Artemis. The Artemis:DNA PK complex could be involved in the repair of DSBs, which carry modified ends and are refractory to repair by otherwise lesion specific enzymes because of the presence of an inhibitory lesion in the opposite strand. J. Cell. Biochem. 100: 1346,1351, 2007. © 2007 Wiley-Liss, Inc. [source] Safe general anesthesia in a hyperkalemic infantPEDIATRIC ANESTHESIA, Issue 10 2008MOHANAD SHUKRY Summary A 10-day-old boy treated in the intensive care unit and operating room due to hyperkalemia and renal failure. After admission to the intensive care unit and treatment for hyperkalemia, the patient required insertion of dialysis catheter in the operating room. Treatment for hyperkalemia continued while the patient was under general anesthesia. The operation was carried out successfully and cardiac signs and symptoms of hyperkalemia did not occur despite of potassium blood levels of 8.1 mEq·l,1. General anesthesia could be safe in hyperkalemic patients as long as the treatment for hyperkalemia is initiated before and during the surgery and hyperkalemia inducing agents are avoided. [source] Clinical relevance of the homologous recombination machinery in cancer therapyCANCER SCIENCE, Issue 2 2008Kiyoshi Miyagawa Cancer chemotherapy and radiotherapy kill cancer cells by inducing DNA damage, unless the lesions are repaired by intrinsic repair pathways. DNA double-strand breaks (DSB) are the most deleterious type of damage caused by cancer therapy. Homologous recombination (HR) is one of the major repair pathways for DSB and is thus a potential target of cancer therapy. Cells with a defect in HR have been shown to be sensitive to a variety of DNA-damaging agents, particularly interstrand crosslink (ICL)-inducing agents such as mitomycin C and cisplatin. These findings have recently been applied to clinical studies of cancer therapy. ERCC1, a structure-specific endonuclease involved in nucleotide excision repair (NER) and HR, confers resistance to cisplatin. Patients with ERCC1-negative non-small-cell lung cancer were shown to benefit from adjuvant cisplatin-based chemotherapy. Imatinib, an inhibitor of the c-Abl kinase, has been investigated as a sensitizer in DNA-damaging therapy, because c-Abl activates Rad51, which plays a key role in HR. Furthermore, proteins involved in HR have been shown to repair DNA damage induced by a variety of other chemotherapeutic agents, including camptothecin and gemcitabine. These findings highlight the importance of HR machinery in cancer therapy. (Cancer Sci 2008; 99: 187,194) [source] | |||||||||||||