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Restriction factors are a collection of antiviral proteins that form an important aspect of the innate immune system. Their constitutive expression allows immediate response to viral infection, ahead of other innate or adaptive immune responses. We review the molecular mechanism of restriction for four categories of restriction factors; TRIM5, tetherin, APOBEC3G and SAMHD1 and go on to consider how the TRIM5 and TRIMCyp proteins in particular, show promise for exploitation using gene therapy strategies. Such approaches could form an important alternative to current anti-HIV-1 drug regimens, especially if combined with strategies to eradicate HIV reservoirs. Autologous CD4+ T cells or their haematopoietic stem cell precursors engineered to express TRIMCyp restriction factors, and provided in a single therapeutic intervention could then be used to restore functional immunity with a pool of cells protected against HIV. We consider the challenges ahead and consider how early clinical phase testing may best be achieved. 相似文献
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Adil H. Al Kindi Nasser Al Kimyani Tarek Alameddine Qasim Al Abri Baskaran Balan Hilal Al Sabti 《Journal of the Saudi Heart Association》2014,26(3):152-161
Aortic arch aneurysm is a relatively rare entity in cardiac surgery. Repair of such aneurysms, either in isolation or combined with other cardiac procedures, remains a challenging task. The need to produce a relatively bloodless surgical field with circulatory arrest, while at the same time protecting the brain, is the hallmark of this challenge. However, a clear understanding of the topic allows a better and less morbid approach to such a complex surgery.Literature has shown the advantage of selective cerebral perfusion techniques in comparison with only circulatory arrest. Ability to perfuse the brain has allowed circulatory arrest temperatures at moderate hypothermia without the need for deep hypothermia. Even though cannulation site selection appears to be a minor issue, literature has shown that the subclavian/axillary route has the best outcomes and that femoral cannulation should only be reserved for no access patients. Although different techniques for arch anastomosis have been described, we routinely perform the distal first technique as we find it to be less cumbersome and easiest to reproduce.In this review our aim is to outline a systematic approach to aortic arch surgery. Starting with indications for intervention and proceeding with approaches on site of cannulation, approaches to brain protection with hypothermia and selective cerebral perfusion and finally surgical steps in performing the distal and arch vessels anastomosis. 相似文献
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Qasim Al Hinai Anthony Zeitouni Denis Sirhan David Sinclair Denis Melancon John Richardson Richard Leblanc 《Skull base》2013,74(2):68-74
Background Large vestibular schwannomas (VSs) can cause hydrocephalus by obstructing the fourth ventricle. Little is known about the communicating hydrocephalus that is seen with a smaller VS.Methods The clinicopathological findings and follow up of three patients with communicating hydrocephalus associated with a small VS are presented.Results Four patients aged 40 to 66 years (mean: 57.7) presented with ataxia, dementia, and urinary incontinence. The VS were 2.0 to 2.4 cm. The cerebrospinal fluid (CSF) protein was elevated in three patients in whom it was measured (1.7 to 6 times normal). The VS was resected in two patients. All of the patients required ventriculoperitoneal shunting (VPS). All of the patients were asymptomatic or improved at follow-up at 9 months to 13 years.Conclusion Communicating hydrocephalus associated with a VS can occur in younger patients than was previously thought. An elevated CSF protein appears to be important, but other factors may be involved. A shunting procedure is often required to relieve the symptoms of hydrocephalus even if the tumor is resected. Possible etiological causes of communicating hydrocephalus in patients with a small VS are discussed. 相似文献
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El-Dwairi Qasim A. Ghaida Jamaledin H. Abu Isa Hanan M. Al-Mousa Arwa A. Marashdeh Wael Al-Muqbel Kusai M. 《Anatomical science international / Japanese Association of Anatomists》2021,96(1):70-78
Anatomical Science International - Foramina transversaria are bilateral landmarks of human cervical vertebrae. Morphometric analysis of foramina transversaria is valuable in both clinical and... 相似文献
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Proof‐of‐concept studies have demonstrated the therapeutic potential of engineered T cells. Transfer of recombinant antigen‐specific T cell receptors (TCR) and chimaeric antigen receptors (CARs) against tumour and viral antigens are under investigation by multiple approaches, including viral‐ and nonviral‐mediated gene transfer into both autologous and allogeneic T cell populations. There have been notable successes recently using viral vector‐mediated transfer of CARs specific for B cell antigens, but also reports of anticipated and unanticipated complications in these and other studies. We review progress in this promising area of cellular therapy, and consider developments in antigen receptor therapies including the application of emerging gene‐editing technologies. 相似文献