ORCID Profile
0000-0002-2816-4707
Current Organisation
The University of Edinburgh
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Publisher: The Endocrine Society
Date: 06-2016
DOI: 10.1210/EN.2016-1156
Abstract: The testicular vasculature forms a complex network, providing oxygenation, micronutrients, and waste clearance from the testis. The vasculature is also instrumental to testis function because it is both the route by which gonadotropins are delivered to the testis and by which T is transported away to target organs. Whether Sertoli cells play a role in regulating the testicular vasculature in postnatal life has never been unequivocally demonstrated. In this study we used models of acute Sertoli cell ablation and acute germ cell ablation to address whether Sertoli cells actively influence vascular structure and function in the adult testis. Our findings suggest that Sertoli cells play a key role in supporting the structure of the testicular vasculature. Ablating Sertoli cells (and germ cells) or germ cells alone results in a similar reduction in testis size, yet only the specific loss of Sertoli cells leads to a reduction in total intratesticular vascular volume, the number of vascular branches, and the numbers of small microvessels loss of germ cells alone has no effect on the testicular vasculature. These perturbations to the testicular vasculature leads to a reduction in fluid exchange between the vasculature and testicular interstitium, which reduces gonadotropin-stimulated circulating T concentrations, indicative of reduced Leydig cell stimulation and/or reduced secretion of T into the vasculature. These findings describe a new paradigm by which the transport of hormones and other factors into and out of the testis may be influenced by Sertoli cells and highlights these cells as potential targets for enhancing this endocrine relationship.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 29-08-2017
DOI: 10.1161/CIRCULATIONAHA.117.028433
Abstract: Ultrasmall superparamagnetic particles of iron oxide (USPIO) detect cellular inflammation on magnetic resonance imaging (MRI). In patients with abdominal aortic aneurysm, we assessed whether USPIO-enhanced MRI can predict aneurysm growth rates and clinical outcomes. In a prospective multicenter open-label cohort study, 342 patients with abdominal aortic aneurysm (diameter ≥40 mm) were classified by the presence of USPIO enhancement and were monitored with serial ultrasound and clinical follow-up for ≥2 years. The primary end point was the composite of aneurysm rupture or repair. Participants (85% male, 73.1±7.2 years) had a baseline aneurysm diameter of 49.6±7.7 mm, and USPIO enhancement was identified in 146 (42.7%) participants, absent in 191 (55.8%), and indeterminant in 5 (1.5%). During follow-up (1005±280 days), 17 (5.0%) abdominal aortic aneurysm ruptures, 126 (36.8%) abdominal aortic aneurysm repairs, and 48 (14.0%) deaths occurred. Compared with those without uptake, patients with USPIO enhancement have increased rates of aneurysm expansion (3.1±2.5 versus 2.5±2.4 mm/year, P =0.0424), although this was not independent of current smoking habit ( P =0.1993). Patients with USPIO enhancement had higher rates of aneurysm rupture or repair (47.3% versus 35.6% 95% confidence intervals, 1.1–22.2 P =0.0308). This finding was similar for each component of rupture (6.8% versus 3.7%, P =0.1857) or repair (41.8% versus 32.5%, P =0.0782). USPIO enhancement was associated with reduced event-free survival for aneurysm rupture or repair ( P =0.0275), all-cause mortality ( P =0.0635), and aneurysm-related mortality ( P =0.0590). Baseline abdominal aortic aneurysm diameter ( P .0001) and current smoking habit ( P =0.0446) also predicted the primary outcome, and the addition of USPIO enhancement to the multivariate model did not improve event prediction (c-statistic, 0.7935–0.7936). USPIO-enhanced MRI is a novel approach to the identification of aortic wall cellular inflammation in patients with abdominal aortic aneurysms and predicts the rate of aneurysm growth and clinical outcome. However, it does not provide independent prediction of aneurysm expansion or clinical outcomes in a model incorporating known clinical risk factors. URL: www.isrctn.com . Unique identifier: ISRCTN76413758.
Publisher: American Society of Mechanical Engineers
Date: 20-06-2012
Abstract: Abdominal aortic aneurysms (AAAs) remain a significant cause of death in the Western world with over 15,000 deaths per year in the US linked to AAA rupture. There is a general belief among the clinical and engineering community that improved methods of risk prediction are needed. The growth and expansion of AAAs over time is thought to be associated with the mechanobiological interactions within the diseased AAA wall. The stresses and strains induced in the wall by the internal blood pressure trigger increased protease activity and turnover of the extracellular matrix (ECM), thus enabling degradation and expansion of the wall. Inflammatory cells also control collagen synthesis and inflammation can reduce the tensile strength of the wall, thus contributing to the likelihood of rupture. Recently, important work by Richards et al. [1] showed that AAAs with specific sites of focal inflammation have threefold higher growth rates than AAAs with non-specific inflammation.
Publisher: The Endocrine Society
Date: 08-2014
DOI: 10.1210/JC.2014-1395
Publisher: Springer Science and Business Media LLC
Date: 14-08-2017
Publisher: Springer Science and Business Media LLC
Date: 25-09-2015
Publisher: Public Library of Science (PLoS)
Date: 31-12-2013
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Calum Gray.