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Bobardt MD Cheng G de Witte L Selvarajah S Chatterji U Sanders-Beer BE Geijtenbeek TB Chisari FV Gallay PA 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(14):5525-5530
In the absence of an effective vaccine, there is an urgent need for safe and effective antiviral agents to prevent transmission of HIV. Here, we report that an amphipathic alpha-helical peptide derived from the hepatitis C virus NS5A anchor domain (designated C5A in this article) that has been shown to be virocidal for the hepatitis C virus (HCV) also has potent antiviral activity against HIV. C5A exhibits a broad range of antiviral activity against HIV isolates, and it prevents infection of the three in vivo targets of HIV: CD4(+) T lymphocytes, macrophages, and dendritic cells by disrupting the integrity of the viral membrane and capsid core while preserving the integrity of host membranes. C5A can interrupt an ongoing T cell infection, and it can prevent transmigration of HIV through primary genital epithelial cells, infection of mucosal target cells and transfer from dendritic cells to T cells ex vivo, justifying future experiments to determine whether C5A can prevent HIV transmission in vivo. 相似文献
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Angelika Varga Agnes Jenes Timothy H. Marczylo Joao Sousa-Valente Jie Chen Jonothan Austin Srikumaran Selvarajah Fabiana Piscitelli Anna P. Andreou Anthony H. Taylor Fiona Kyle Mohammed Yaqoob Sue Brain John P. M. White Laszlo Csernoch Vincenzo Di Marzo Laki Buluwela Istvan Nagy 《Pflügers Archiv : European journal of physiology》2014,466(7):1421-1435
The endogenous lipid agent N-arachidonoylethanolamine (anandamide), among other effects, has been shown to be involved in nociceptive processing both in the central and peripheral nervous systems. Anandamide is thought to be synthesised by several enzymatic pathways both in a Ca2+-sensitive and Ca2+-insensitive manner, and rat primary sensory neurons produce anandamide. Here, we show for the first time, that cultured rat primary sensory neurons express at least four of the five known Ca2+-insensitive enzymes implicated in the synthesis of anandamide, and that application of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-arachidonoyl, the common substrate of the anandamide-synthesising pathways, results in anandamide production which is not changed by the removal of extracellular Ca2+. We also show that anandamide, which has been synthesised in primary sensory neurons following the application of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-arachidonoyl induces a transient receptor potential vanilloid type 1 ion channel-mediated excitatory effect that is not inhibited by concomitant activation of the cannabinoid type 1 receptor. Finally, we show that sub-populations of transient receptor potential vanilloid type 1 ion channel-expressing primary sensory neurons also express some of the putative Ca2+-insensitive anandamide-synthesising enzymes. Together, these findings indicate that anandamide synthesised by primary sensory neuron via a Ca2+-insensitive manner has an excitatory rather than an inhibitory role in primary sensory neurons and that excitation is mediated predominantly through autocrine signalling. Regulation of the activity of the Ca2+-insensitive anandamide-synthesising enzymes in these neurons may be capable of regulating the activity of these cells, with potential relevance to controlling nociceptive processing. 相似文献
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Selvarajah S Yoshimoto M Prasad M Shago M Squire JA Zielenska M Somers GR 《Cancer Genetics and Cytogenetics》2007,174(1):35-41
Pediatric undifferentiated soft tissue sarcomas (USTS) are a rare group of neoplasms that are unclassifiable despite the application of immunohistochemical, cytogenetic, and molecular techniques. To date, there is a dearth of studies looking at the cytogenetic and molecular genetic alterations in such tumors. Trisomy 8, a frequent molecular alteration in neoplasia, is seen in several soft tissue sarcomas, including Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET), synovial sarcoma, and leiomyosarcoma. Because USTS share several clinicobiological features with the aforementioned tumors, the occurrence of alterations in chromosome 8 was studied in 11 pediatric USTS using a combination of interphase fluorescence in situ hybridization (FISH), spectral karyotyping (SKY), and genomic profiling with oligonucleotide array comparative genomic hybridization (aCGH). The copy number status of MYC was also assessed on the same tumors using dual-color FISH, with the aim of delineating the degree and intratumoral distribution of MYC amplification in this tumor. A near-uniform presence of an increase in MYC copy number was observed, along with an increase in chromosome 8 copy number in all the tumors. SKY and aCGH analysis of tumors exhibiting trisomy 8 confirmed the numerical imbalances. The occurrence of trisomy 8 in a subset of pediatric USTS confirms a shared genomic alteration with several other soft tissue sarcomas. Further studies are required to determine the clinical implications of such a finding. 相似文献
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Wen Yea Hwong Swee Hung Ang Michiel L. Bots Sheamini Sivasampu Sharmini Selvarajah Wan Chung Law Lydia Abdul Latif Ilonca Vaartjes 《Global Heart》2021,16(1)
Background:Data on nationwide trends for stroke metrics are crucial to understand the extent of the disease burden to a country’s health system. Yet, this information remains scarce in low- and middle-income countries.Objectives:This study investigated trends of stroke incidence and 28-day all-cause mortality after a stroke from 2008 to 2016 in Malaysia, through linkage across national data sources.Methods:Hospital admissions with a principal diagnosis of stroke or transient ischemic attack were included. Cases with first stroke were identified through linkage of hospital admission registers where age and sex-standardized trends of stroke incidence and its subtypes were calculated. By linking hospital registers to the National Death Register, the 28-day all-cause mortality rates after a stroke were estimated. Mann-Kendall’s test was used for trend evaluation.Results:From 243,765 records, the trend of stroke incidence showed an increase of 4.9% in men and a drop of 3.8% among women. Incidences were higher in men, at 99.1 per 100,000 population in 2008 and 103.9 per 100,000 in 2016 than women (80.3 per 100,000 in 2008 and 77.2 per 100,000 in 2016). There was a substantial increase in stroke incidence among those below 65 years old, with the largest increase of 53.3% in men aged between 35–39 years and 50.4% in women of similar age group. The trend for 28-day all-cause mortality showed a decline for men at –13.1% and women, –10.6%. Women had higher mortality from stroke (22.0% in 2008 and 19.7% in 2016) than men (19.4% in 2008 to 17.2% in 2016).Conclusion:This first empirical study on stroke trends in Malaysia revealed a worrying increase in stroke incidence among the younger population. Despite a declining trend, mortality rates remained moderately high especially in women. Comprehensive strategies to strengthen the prevention and management of stroke care are warranted. 相似文献
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Sharmini Selvarajah Gurpreet Kaur Jamaiyah Haniff Kee Chee Cheong Tee Guat Hiong Yolanda van der Graaf Michiel L. Bots 《International journal of cardiology》2014