Characterisation and identification of brown adipose tissue on positron-emission tomography and magnetic resonance imaging Since the first published description of brown adipose tissue (BAT) in 1551 its reputation has changed from that of a mere curiosity of little physiological significance in adult humans, to meriting reclassification as a metabolic organ in its own right. Obesity is a major global public health problem. Modulation of non-shivering thermogenesis through BAT manipulation presents an attractive therapeutic target for inducing weight loss. Testing the efficacy of such pharmacological agents requires the development of a reliable imaging biomarker to enable BAT quantification. In this thesis we have evaluated the effectiveness of positron-emission tomography (PET) and magnetic resonance (MR) imaging in quantifying BAT. Retrospective analysis of 3,295 consecutive PET scans performed at University Hospitals Coventry & Warwickshire NHS Trust (Coventry, UK) in 2007-2012 showed 18F-FDG uptake consistent with BAT in 5.3% of scans. Gender (female), age (younger), BMI (lower), serum glucose (lower), time of day (earlier), and temperature (lower) were all significant predictors of BAT prevalence. Regression analysis showed patients’ age and preceding day’s minimum temperature to correlate most strongly with BAT volume, while the impact of other factors is less clear. We also showed the pattern of BAT uptake within individuals to be consistent across serial PET scans. Quantitative colocalisation techniques showed this degree of colocalisation to be significant in 14/15 patients, implying fixed BAT deposits in adult humans. Concerns over the high ionising radiation dose of PET scans has stimulated research into MR as an alternative means of detecting BAT, with the potential to identify BAT irrespective of its activation state. Using IDEAL FSE sequences acquired on a 3 Tesla clinical MR scanner, we found BAT to have a significantly lower fat fraction than white adipose tissue in rats post mortem and adult humans in vivo. Our efforts to identify BAT prospectively using fat fraction yielded inconsistent results.

Changes in endothelial permeability are known to contribute to many pathologies, including inflammation seen in skin irritation. The regulation of permeability has been linked to inter-endothelial junctions, specifically the tight and adherens junctions (TJ and AJ). The functional state of the junction is thought to be associated with numerous factors including cytoskeletal changes and the interactions between junctional components. How these factors interact and respond to inflammatory stimuli is still not fully understood. This project examined two human endothelial cell-lines for use in in-vitro permeability studies, ECV304 and HMEC-1. Changes in permeability along with arrangement of the F-actin cytoskeleton and the adherens junction molecule VE-cadherin were studied in response to a variety of compounds. Macromolecular permeability was assessed by measuring the leakage of fluorescently labelled dextrans of varying molecular weights. The F-actin and VE-cadherin were visualised using immunocytochemical techniques. TEM was undertaken to examine the ultrastructure of the junctions The ECV304 cells, whilst showing an increased permeability to a variety to vaso-active mediators, did not express some of the pertinent junctional molecules of the endothelium and thus are not recommended for use. The basal permeability of the HMEC-l cell-line was shown to act in predictable fashion, giving comparable permeability coefficients to other endothelial cells. The increase in permeability following exposure to A23187, CAPB, EGTA and PMA was shown to correlate to an altered expression of VE-cadherin and F-actin. These observations were furthered using histamine, where a quantifiable change in the levels of continuous and stitch VE-cadherin staining was demonstrated. The permeability response to histamine occurred much later than the VE-cadherin and F-actin changes. This could be due to methodology and/or the cells lack of TJs. The apparent lack of mature AJs was approached by exposing the cultures to cAMP-raising media. This significantly reduced the basal permeability and increased the expression of AJ components, apart from β-catenin, at the cell-cell contacts. Indeed α-catenin was redistributed from the triton-soluble fraction of the cells to the triton-insoluble fraction, which is proposed to contain the junctional components. These results demonstrate additional information on the role that the adherens junction molecules play in endothelial permeability and characterise the HMEC-1 cell-line for further use in this field.

No description available.

The purpose of this study is to trace the development of Qur'anio illumination and calligraphy under the Mamlukes from the earliest known Qur'an of 1304 down to and including the reign of Sultan Al- Aabräf ' Shaoban , 1363-1376.. when the finest manuscripts of the period were made. As this phenomenon needs to be set in context vis-a-vis not only what was happening in Egypt prior to 1363 , but also developments in Iraq and Iran whose manuscripts are believed ';. to have had a major influence ' those areas are also examined in detail. The initial introduction surveys the development of the Qur'an as a work of art down to the beginning of the Mamluke period'", to place Mainluke 9 Iranian and Iraqi manuscripts in proper historical perspective. Existing literature is surveyed and a statemnt of problems facing the student presented. Chapter One deals with Cairo up to 1330. Most of the manuscripts examined are the work of a team of craftsmen of whom we first become aware as the producers of the Qur'an of Baybars al-Jäshankir in the British Library , which in many ways may be regarded as the key manuscript of the period. The careers of the calligrapher Ibn al- Wahid and the illuminators are studied on the basis of: i) their known works; ii) works attributable to them : iii) historical sources. The Second and Third CUpters examine what, was happening in Iraq and Iran from 1304 to 1316 and study in detail the four great Qur'anic masterpieces of ths*century s three made for Oljaytu in Baghdad 9 Mosul and Hamadan ' and one probiably commissioned by his predecessor, Ghäzän. The careers of the calligraphers and illuminators involved in these Qur'ans is surveyed here y and in all subsequent chapters on the basis of i, ii and iii in the previous chapter. At the end of Chapter Two relations between Cairo and Iraq during the early years of the century are studied and evidence produced to show that painters familiar with developments in Baghdad were in Egypt several decades before the appearance of the Hamadan Qurtan 9 to which suoh importance is usually attatched. Chapter e. `greats Iran and deals with the problem of the Hamadan Qur'an , relating it to contemporary manuscripts made for 61jaytu , explaining how it came to Cairo and examining what effect it had there. In the same chapter another closely connected fragment is studied : the only surviving juxt from a Qur'an made for Rashid al-Din ' probably at the Rabc-i Rash3dT. Chapter Four traces developments in Egypt and Syria from 1320 to 1356 and concentrates s* two different categories of manuscript. First those copied and we believe illuminated by Ahmad al-Mutatabbib in Cairo around 1330. The location is given in several colophons. These aanusoripts demonstrate the decline of the Sandal tradition in Cairo (he being the master illuminator of the Baybare Qur'an). This CM be contrasted with the situation in Damecus Where, ke believe,, an, in porrtant Qur'an was copied and illuminated at the and of the fo th decade. 'In previous chapters we 'have 'dried to assemble, "info i` on Syrian calligraphers and artists prior to 1340 , though this is difficult due to the absence of manuscripts of unquestionable Syrian proven oe. In the same chapter two problem Qur' ane by calligraphers s of "the school of Yq ,t are dealt `tirithý One Was apparl tly copied in Cairo in 1344 ' while the other was certainly there in 1356. We believe that it can be shown that the first is genuine and adds a new fact to the sparse biography of the calligrapher I Mubärak-Shäh al-Suyüfi. In Chapter Five Iran and Iraq during roughly the same period are studied. Four major series of manuscripts are examined to show what was happening in those areas. Perhaps the most imp. - octant is that made by Yaby al-Sif in Shiraz in 1344-5 which Domains tul ' and virtually complete, documentation. We also deal with atiö er Vpro"blemv group : manuscripts with Turkic inter-linear translations. These we attempt to show all date from the fourteenth century 9 though whether of Anatolian Azerbeyjani I or perhaps Central Asian origin,, is unclear. Chapters Six and Seven examine the Qurans of Sultan Sha°bän 0 his mother Khwand Barakah and several of his amirs. These can de divided into three groups, I consists of minor works. II comprises several closely related manuscripts rightly regarded as a 'classic' Mamluke type. The calligraphy and especially the illumination of this group is studied in detail to show that its origins ( the illumination at least ) lie-, in earlier Mate work. Group III is entirely different. It consists of those manuscripts illuminated by Ibrähim al-Amid!. This outstanding painter is the illuminator of Cairo National Library Ws 10 s a fact we know from his own colophon. However, so unique and distinct is his style that it is possible to at-tribute a number of Qur'ans to his hand, An attempt to define exwtly the nature of his style is made and traced through several manuscripts. We believe that it can be e xn that the painter was trained in din Iraq and Western Iran , where he worked for it time before coming to Cairo in the thirteen-sixties. The illumination produced by him marks the culmination of the Iranian/Iraqi tradition in Cairo : one which makes its appearance in the earliest Mamluke Qur'an of Baybars al-Jäshanktr. All the inscriptions found in these manuscripts have been fully translated. The originals ' Figs 1-31 are located in an appendix at the end along with such important biographical information as we have been able to uncover in printed and manuscript sources. The thesis is accompanied by a portfolio of photographs to illustrate all points made.

Johannes Oecolampadius (1482-1531) is a figure who spent a better part of the three hundred years following his death buried in relative obscurity, as both his life and thought had been relegated to dusty bookshelves in magnificent libraries throughout Europe and America. Particularly in the English-speaking world, there was little of substance written about him until approximately thirty years ago. It is true that he is named, or elements of his work are referred to, in the many extant summary histories concerning the early modern period. However, whatever mention has been made of Oecolampadius in these histories has often been in relationship to his 'Swiss theology', which many authors argue is simply a recapitulation of the better-known Zwingli. The purpose of this study will be to attempt to further 'dust off' certain aspects of Oecolampadius' theological and patristic reflection for the contemporary reader. Specifically, because he spent the better part of his adult life involved in patristic translation and the eucharistic rows of the mid-1520s to early 1530s, we will attempt to survey both. In this regard, we will concentrate on how Oecolampadius perceived and theologized the eucharist throughout his life - in other words, what were the theological anchors of his doctrine, and what or who influenced them, and did these points of focus change or evolve during his career? Second, on the patristic front, we will consider which patristic authors Oecolampadius was familiar with, how and why he sought their help (or rejected it) to make the case for the particular form of eucharistic theology that was his own, and what this can ultimately begin to tell us about his reception of the fathers.

The morphology and function of the lumbar region is poorly understood. Better understanding of lumbar regional anatomy may enable improved understanding of lumbar stability and may also improve the clinical management of low back pain. Extensive researches have been carried out on the thoracolumbar anatomy and biomechanics. However, these studies lacked detailed anatomical knowledge about the morphology and function of the lumbar region. This study aims to provide a precise and detailed description of the anatomy of the lumbar spine and its supporting structures. A detailed and thorough literature review of background data was undertaken. Gross degenerative features in the lumbar vertebrae were documented. Three dimensional models of the superior and inferior lumbar articular facets were created by Microscribe. This allowed calculation of the facet orientation and surface area by Rhinoceros software. The surface area was increased towards the inferior vertebral levels, while the orientation became less sagittal inferiorly. The investigations suggest that the coronally oriented facet protects and supports the facet joint, while the sagittal orientation may predispose the facet joint to degenerative spondylisthesis. Gross observation of the thoracolumbar fascia documented the superficial myofascial thickenings, decussation and connections. The posterior and middle layers of the thoracolumbar fascia were identified. A three dimensional model enabled visualization of the bilaminar layers of the fascia which was reconstructed in a virtual space. The morphological measurements of the lumbar multifidus, longissimus and iliocostalis muscles were taken. The cross sectional area of the multifidus muscle was increased gradually towards the L5 level. The foot prints of the multifidus, longissimus, iliocostalis lumborum and inter-spinalis muscles enabled the measurement of the surface areas of the attachments of these muscles. The histological study revealed the fibrous enthesis of the iliocostalis muscle and its indirect attachment to the transverse process of the lumbar spine. The multifidus muscle is attached by a fibrocartilaginous enthesis to the articular process and the facet joint capsule. This study suggests that multifidus muscle supports and stabilizes the facet joints. The lumbar enthesis investigation should receive more attention in future studies. The clinical implications of different lumbar structures and functions may provide insight about the lumbar dysfunction. The ability to identify such differences in situ may facilitate varied clinical management of the various types of lumbar disorders.

The effects of sane anabolic and naturally-occuring sex steroids on intestinal transport of leucine have been studied in rainbow trout (Sallno gairdneri), in vivo (gut perfusion), and in vitro (everted gut sacs or intestinal strips). Administration of 17a-methyltestosterone (Mr) by injection for a prolo03ed period of time, enhanced intestinal transport and accumulation of leucine. 11-ketotestosterone (KT) or MT treatment in vitro, by direct addition to incubation media, elicited significant short-term increases in active transport of leucine, without effecting intestinal accumulation. Luminal administration of Mr in vivo similarly elicited short-term responses, without effecting leucine accumulation in the intestine or other peripheral tissues. However; neither MT nor KT significantly affected intestinal transport of water in trout. Although long term injection of oestradiol (E2) enhanced intestinal transport and accumulation of leucine, E2 treatment in vitro was without effect. Addition of ouabain or 2,4,dinitrophenol in the presence of MT abolished steroid-stimulated leucine transform, in vitro. No significant differences were observed between immature male or female trout with respect to either transport of leucine and water, or intestinal granular cell density. However, 'apparent' Na+ absorption and percentage fold height were higher in females, while total intestinal thickness and enterocyte heights were greater in males. These sex differences were essentially abolished. after gonadectany. It is suggested that the short-term effects of the androgenic steroids might be partly mediated through increased activity of Na+,K+,ATPase, and that steroid-induced growth promotion in fish may,to sane extent, be a consequence of enhanced efficiency of intestinal function.

No description available.

Diabetic nephropathy is associated with secondary hypertension arising from aberrant sodium reabsorption in the kidney. This thesis characterises a novel human cell line derived from the human cortical collecting duct (HCD) to assess glucoseevoked changes in key elements, such as the serum and glucocorticoid inducible kinase (SGKI) and the epithelial sodium channel (ENaC), involved in the regulation of sodium transport. In addition I have also examined the effects of TGF-f3I and [Ci+]i on SGKI and ENaC expression. RT-PCR, western blot analysis, immunocytochemistry and single cell imaging were employed to determine presence, localisation and function of these elements under various glycaemic conditions. Our data suggest that high glucose, TGF-f3I and [Cl+]i up-regulate both SGKI and [alpha]ENaC protein expression, which in turn stimulates Na+ transport. In pathological conditions associated with aberrant Na + reabsorption, excessive levels of Na + may further exacerbate the state of hypertrophy, a common manifestation associated with diabetic nephropathy. Mechanical stress evoked TRPV4 m~diated changes in [Ca2+]i. Propagation of this Ca2+ signal via the gap junction protein connexin 43 (Cx-43) was enhanced following glucose treatment, as was Cx-43 expression. Under pathophysiological conditions these changes and the increased expression levels of our key signaling elements, may lead to deranged Na+ handling and inhibition of cell volume recovery mechanisms which together may further enhance the condition of diabetic nephropathy in Type 11 diabetes.

Thesis (M.Sc.), Faculty of Science, University of the Witwatersrand, 2011 / General descriptions of the fascia lata as a structure could be found in all major anatomy textbooks. However, there is a paucity of information on the fascia lata and its surrounding structures in scientific literature. This study investigates how fascia and muscle relate in the extensor compartment of the thigh – i.e. as the muscle epimysium or as a separate fascial layer. Using detailed dissections of ten cadaver lower limbs and axial Magnetic Resonance Imaging and Ultrasonography in four volunteers, findings were compared to correlate all observed features. Results highlighted anatomical aspects and relationships not previously documented. The fascia lata demonstrated a single, epimysial relationship to the tensor fascia lata, upper sartorius and parts of the vastus medialis muscles, while forming a separate fascial layer over the lower sartorius, rectus femoris and vastus lateralis muscles. Findings suggest the fascia lata may function as more than containment of musculature and allude to functional implications for surgery and rehabilitation.