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41.
Evaluation of beta defensin 2 production by chicken heterophils using direct MALDI mass spectrometry
Lakshmi Kannan Rohana Liyanage Jackson O. Lay Jr. Narayan C. Rath 《Molecular immunology》2009,46(15):3151-3156
Beta defensins (BD) are cysteine rich, cationic antimicrobial peptides (AMP) produced mainly by epithelial and myeloid cells such as neutrophils. In birds, the neutrophil equivalent heterophils produce avian beta defensins (AvBD) of which AvBD2 is the major isoform. Heterophils recognize pathogens or their derived products through a series of pattern recognition receptors called toll-like receptors (TLR) leading to their antimicrobial activities. This work is the first report of TLR modulation of AvBD2 expression in chickens. To measure the effect of TLR activation on AvBD2 production, the heterophils were cultured with different TLR agonists for 6 h. Modulation of AvBD2 levels by TLR activation was measured using direct MALDI mass spectrometry without stable isotopic labeling or chromatographic separation. Chemical modification of the conditioned media was performed using reduction/alkylation with dithiothreitol/iodoacetamide to distinguish TLR treated AvBD2 (reduced/alkylated) from controls (non-reduced). Changes in corrected ion intensity ratios were assumed to reflect AvBD2 modulation in heterophils upon activation with different TLR agonists. In general, TLR agonists increased AvBD2 production with LPS showing the greatest induction and CpG-ODN showing little or no effect. These data show that the direct MALDI-MS coupled with reduction/alkylation may provide a rapid relative quantitative approach to the measurement of agonist-induced differential expression of AvBD2. 相似文献
42.
The impact of interindividual variation in NAT2 activity on benzidine urinary metabolites and urothelial DNA adducts in exposed workers. 总被引:5,自引:0,他引:5 下载免费PDF全文
N Rothman V K Bhatnagar R B Hayes T V Zenser S K Kashyap M A Butler D A Bell V Lakshmi M Jaeger R Kashyap et al. 《Proceedings of the National Academy of Sciences of the United States of America》1996,93(10):5084-5089
Several epidemiologic studies indicate that NAT2-related slow N-acetylation increases bladder cancer risk among workers exposed to aromatic amines, presumably because N-acetylation is important for the detoxification of these compounds. Previously, we showed that NAT2 polymorphisms did not influence bladder cancer risk among Chinese workers exposed exclusively to benzidine (BZ), suggesting that NAT2 N-acetylation is not a critical detoxifying pathway for this aromatic amine. To evaluate the biologic plausibility of this finding, we carried out a cross-sectional study of 33 workers exposed to BZ and 15 unexposed controls in Ahmedabad, India, to evaluate the presence of BZ-related DNA adducts in exfoliated urothelial cells, the excretion pattern of BZ metabolites, and the impact of NAT2 activity on these outcomes. Four DNA adducts were significantly elevated in exposed workers compared to controls; of these, the predominant adduct cochromatographed with a synthetic N-(3'- phosphodeoxyguanosin-8-yl)-N'-acetylbenzidine standard and was the only adduct that was significantly associated with total BZ urinary metabolites (r = 0.68, P < 0.0001). To our knowledge this is the first report to show that BZ forms DNA adducts in exfoliated urothelial cells of exposed humans and that the predominant adduct formed is N-acetylated, supporting the concept that monofunctional acetylation is an activation, rather than a detoxification, step for BZ. However, because almost all BZ-related metabolites measured in the urine of exposed workers were acetylated among slow, as well as rapid, acetylators (mean +/- SD 95 +/- 1.9% vs. 97 +/- 1.6%, respectively) and NAT2 activity did not affect the levels of any DNA adduct measured, it is unlikely that interindividual variation in NAT2 function is relevant for BZ-associated bladder carcinogenesis. 相似文献
43.
How Do Hospitalized Patients Feel About Resident Work Hours,Fatigue, and Discontinuity of Care? 下载免费PDF全文
Fletcher KE Wiest FC Halasyamani L Lin J Nelson V Kaufman SR Saint S Schapira M 《Journal of general internal medicine》2008,23(5):623-628
BACKGROUND: Patient-centered care requires that physicians understand patients' perspectives. Since the resident work hour rules were instituted, little information is available about how patients perceive these issues. Our objectives were to explore patients' knowledge, concerns, and attitudes about resident work hours, fatigue, and continuity of inpatient care and to evaluate the association between patients' trust and satisfaction with these concerns and attitudes. METHODS: We conducted a cross-sectional survey of 134 internal medicine inpatients at 3 institutions including a tertiary care academic health center, a Veterans Affairs medical center, and a private community teaching hospital. RESULTS: Mean age was 59 (range, 24-90), with 60% men and 70% white. Most patients agreed (50%) or felt neutral (38%) toward resident work hours being limited. Patients estimated that residents worked 60 h per week but thought that they should work no more than 51 h per week (p < .01 for the difference). Twenty-seven percent of patients had some concern about fatigue in the residents, and 28% reported concern about how often hand-offs of care occurred. Factor analysis yielded 3 factors: "worried about discontinuity/fatigue," "attitude toward resident/nurse work hours," and "perceived resident/nurse fatigue." In multivariable analyses, the "worried about fatigue/discontinuity" factor significantly predicted trust and satisfaction, and the "perceived resident/nurse fatigue" factor also predicted satisfaction. CONCLUSIONS: Some inpatients are concerned about both fatigue in resident physicians and discontinuity of care. This may play a role in trust and satisfaction for patients. Taking steps to design systems to minimize fatigue and discontinuity would be ideal. 相似文献
44.
45.
Effect of defibrillation threshold testing on effectiveness of the subcutaneous implantable cardioverter defibrillator 下载免费PDF全文
46.
Brian M Cox Macdonald J Christie Lakshmi Devi Lawrence Toll John R Traynor 《British journal of pharmacology》2015,172(2):317-323
Recent developments in the study of the structure and function of opioid receptors raise significant challenges for the definition of individual receptor types and the development of a nomenclature that precisely describes isoforms that may subserve different functions in vivo. Presentations at the 2013 meeting of the International Narcotics Research Conference in Cairns, Australia, considered some of the new discoveries that are now unravelling the complexities of opioid receptor signalling. Variable processing of opioid receptor messenger RNAs may lead to the presence of several isoforms of the μ receptor. Each opioid receptor type can function either as a monomer or as part of a homo- or heterodimer or higher multimer. Additionally, recent evidence points to the existence of agonist bias in the signal transduction pathways activated through μ receptors, and to the presence of regulatory allosteric sites on the receptors. This brief review summarizes the recent discoveries that raise challenges for receptor definition and the characterization of signal transduction pathways activated by specific receptor forms.
LINKED ARTICLES
This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 相似文献47.
Several studies suggest that heteromerization between μ (MOP) and δ (DOP) opioid receptors modulates the signalling properties of the individual receptors. For example, whereas activation of MOP receptors by an agonist induces G protein-mediated signalling, the same agonist induces β-arrestin-mediated signalling in the context of the MOP-DOP receptor heteromer. Moreover, heteromer-mediated signalling is allosterically modulated by a combination of MOP and DOP receptor ligands. This has implications in analgesia given that morphine-induced antinociception can be potentiated by DOP receptor ligands. Recently reagents selectively targeting the MOP-DOP receptor heteromer such as bivalent ligands, antibodies or membrane permeable peptides have been generated; these reagents are enabling studies to elucidate the contribution of endogenously expressed heteromers to analgesia as well as to the development of side-effects associated with chronic opioid use. Recent advances in drug screening technology have led to the identification of a MOP-DOP receptor heteromer-biased agonist that activates both G protein-mediated and β-arrestin-mediated signalling. Moreover, this heteromer-biased agonist exhibits potent antinociceptive activity but with reduced side-effects, suggesting that ligands targeting the MOP-DOP receptor heteromer form a basis for the development of novel therapeutics for the treatment of pain. In this review, we summarize findings regarding the biological and functional characteristics of the MOP-DOP receptor heteromer and the in vitro and in vivo properties of heteromer-selective ligands.
LINKED ARTICLES
This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 相似文献48.
Nimmakayala Sridhar Duggirala Suguna Lakshmi Puchchakayala Goverdhan 《Indian journal of pharmacology》2015,47(2):177-180
Objective:The main objective of this study is to evaluate the analgesic and anti-pyretic activities of ethanolic extracts of Justicia neesii Ramam. by different experimental models.Results:In the hot plate model 400 mg/kg p.o. dose of J. neesii has shown its maximal effect at 3 h. The results are significant (P < 0.05) and comparable to the values of standard drug pentazocine (30 mg/kg i.p.). In acetic acid induced writhing model 400 mg/kg p.o. of plant extracts have shown highly significant activity (P < 0.001) and better than standard drug indomethacin (10 mg/kg p.o.). The 400 mg/kg p.o. dose of plant extract has given significant results against both yeast induced pyrexia and TAB vaccine induced pyrexia (P< 0.01 and 0.05 respectively). These values are comparable to that of paracetamol 100 mg/kg p.o. standard dose.Conclusion:This study shows that the ethanol extract of J. neesii has significant analgesic and antipyretic activity.KEY WORDS: Brewer''s yeast, hot plate, pyrexia, TAB vaccine, writhing 相似文献
49.
Budhwani Henna Gakumo C. Ann Yigit Ibrahim Rice Whitney S. Fletcher Faith E. Whitfield Samantha Ross Shericia Konkle-Parker Deborah J. Cohen Mardge H. Wingood Gina M. Metsch Lisa R. Adimora Adaora A. Taylor Tonya N. Wilson Tracey E. Weiser Sheri D. Sosanya Oluwakemi Goparaju Lakshmi Gange Stephen Kempf Mirjam-Colette Turan Bulent Turan Janet M. 《AIDS and behavior》2022,26(5):1422-1430
AIDS and Behavior - In this mixed-methods study, we examine the relationship between provider communication and patient health literacy on HIV continuum of care outcomes among women living with HIV... 相似文献
50.
Xiang B Chatti K Qiu H Lakshmi B Krasnitz A Hicks J Yu M Miller WT Muthuswamy SK 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(34):12463-12468
Amplification of the receptor tyrosine kinase ErbB2 is frequently observed in breast cancer. Amplification of erbB2 is also associated with multiple genomic gains and losses; however, the importance of these associated changes is largely unknown. We demonstrate that Brk, a cytoplasmic tyrosine kinase, is coamplified and coexpressed with ErbB2 in human breast cancers. ErbB2 interacts with Brk and increases its intrinsic kinase activity. Expression of Brk enhances the ErbB2-induced activation of Ras/MAPK signaling and cyclin E/cdk2 activity to induce cell proliferation of mammary 3-dimensional acini in culture. In a murine model of breast cancer, expression of Brk was found to shorten the latency of ErbB2-induced tumors by promoting cell proliferation, with no effect on protection from apoptosis. Furthermore, overexpression of Brk conferred resistance to the ability of Lapatinib, an ErbB2 kinase inhibitor, to inhibit ErbB2-induced proliferation. Thus, we identified Brk as a drug target for ErbB2-positive cancers. 相似文献