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1
Abualhin, Mohammad <1987>. "Does Aorto-Iliac Anatomy Affect Endovascular Aortic Aneurysm Repair Durability With The New Generation Endografts?" Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2021. http://amsdottorato.unibo.it/9611/1/PhD%20Thesis.%20Abualhin%20Final.pdf.
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Introduction:
Endovascular aneurysm repair(EVAR) has become the main treatment for abdominal aortic aneurysm(AAA). Anatomical features of the AAA are pivotal in EVAR success. The aim of this study was to evaluate known anatomical features as risk factors for the freedom from reintervention(FFR) taking into account the new-generation endografts.
Materials and Methods:
This study was a retrospective monocentric study including consecutive patients treated by EVAR from 2012 to 2018 in elective setting. All currently reported anatomic factors including aortic neck and iliac arteries proprieties were examined using the pre-operative AngioCT-imaging. The primary endpoint was to define the anatomical risk factors affecting the FFR.
Results:
A total of 653 patients treated by standard EVAR were included. The mean age was 75.6±8 years. The mean follow-up was 34±11 months. FFR was 98.4%,97.4%,96% and 87.3% at 6,12,24 and 48 months, respectively.
Larger aortic neck diameter was significant risk factor for FFR(P=0.001). Aortic neck severe angulation >60° was correlated to the need for reintervention(P=0.001). Larger aneurysm diameter was associated with higher incidence of reinterventions(P<0.001). Infrarenal aortic length(IRAL) measured as distance between renal artery and aortic bifurcation level, was associated with lower FFR(P=0.002). Similarly, the mean aorto-iliac length(MAIL) measured as the sum of distance between the most distal renal artery and iliac bifurcation in both sides divided by two, resulted a negative factor for FFR (P=0.002). At the multivariate analysis of anatomical features, aortic neck diameter (HR1.18;CI:1.02-1.37,P=0.03) and MAIL (HR1.02;CI:1.01-1.04,P=0.01) were confirmed as significant risk factors for FFR.
Conclusion:
This 7-years real-world study focused on the analysis of anatomic risk factors predisposing for graft-related reinterventions at mid-term. Patient survival and FFR are satisfactory and compatible with other studies results. Aortic neck diameter and MAIL resulted the main risk factors for FFR. IRAL and MAIL resulting significant factors are not described before and need further investigations.
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Landorf, Karl B. "Effectiveness of foot orthoses in the treatment of plantar fasciitis." Thesis, View thesis, 2004. http://handle.uws.edu.au:8081/1959.7/696.
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The aim of this thesis is to evaluate the short and long term effectiveness of foot orthoses in the treatment of plantar fasciitis.Three studies were undertaken, the first two informing the third. The aim of the first study was to establish prescription habits of Australian and New Zealand podiatrists in order to ascertain the most commonly prescribed foot orthoses. The second study was conducted to establish the most appropriate outcome measure to assess the effectiveness of foot orthoses in the treatment of plantar faciitis. The main study, a pragmatic single-blind randomised control trial, was conducted to evaluate the effectiveness of three types of foot orthoses in the treatment of plantar fasciitis. The research concluded that provision of appropriate foot orthoses produces small short-term benefits in function for people with plantar fasciitis, but no effect is apparent at twelve months.
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McNamara, Diana L. "The anatomy of an environmental decision : the case of recycling." Thesis, University of Aberdeen, 2015. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=228206.
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The human race has always faced environmental challenges. What differs at present, however, are the scale and entrenched social structures (e.g., capitalism, man/nature duality, a dominant social paradigm) that are contributing to these problems and our own irrationality when it comes to possible solutions. Implicit testing methodologies, borrowed from experimental psychology, may be able to bypass some of these issues and provide a means to identify simple 'point of decision' interventions to effect change in behavior on an individual level. The approach adopted in the current thesis was to explore the extent to which movement dynamics (measured using MouseTracker) can inform the decisional anatomy of an important pro-environmental activity — recycling. MouseTracker is a useful methodology as it assesses the real-time conflict that people experience when confronted with the decision to recycle a particular item or not. There were three stages to the progression of this research: (1) using focus groups to gain knowledge of undergraduates' beliefs and opinions towards recycling (Study 1); (2) assessing the utility of MouseTracker as an implicit tool to explore recycling decisions (Expts. 1 & 2); and (3) establishing the extent to which personal (i.e, Social Value Orientation) and situational factors (i.e., environmental primes) influence the anatomy of recycling decisions (Expts. 3-6). Results from the focus groups confirmed that university undergraduates hold widely held societal beliefs about recycling, thereby justifying their inclusion in the current investigation. Experiments 1 and 2 confirmed the utility of MouseTracker as a methodology to explore recycling decisions. Overall, participants displayed a stronger attraction to putting recyclable items in the rubbish bin than garbage in the recycle bin, a tendency that was reduced with increasing levels of environmental concern. Results in the subsequent experiments were mixed. An important individual difference variable (i.e., Social Value Orientation) failed to show an influence on recycling behavior (Expt. 3), and subtle environmental primes produced a collection of modest effects (Expts. 4 & 5). Most notably, a messy environment improved recycling performance (Expt. 5). Compelling results were observed, however, when self-directed attention was manipulated (Expt. 6). In particular, recycling performance was enhanced in the presence of a mirror, thereby confirming the relation between self-focus and normative behavior (the efficient disposal of waste). Discussion centers on the theoretical and practical implications of the current findings, limitations with the methodology employed, and consideration is given to future research on this important societal topic.
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Bollmann, Christof. "Quantification of intact quadriceps tendon, and suprapatellar fat pad : MR-arthrography, anatomy, and cryosections in the sagittal plane /." [S.l.] : [s.n.], 2000. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Ditschun, Tanya Louise. "6-n-Propylthiouracil (PROP) taster status determination and its relation to tongue anatomy, food liking and intake /." Connect to Digital dissertations. Restricted to UC campuses. Access is free to UC campus dissertations, 2002. http://uclibs.org/PID/11984.
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Vase, Hollie Francesca. "Interrogating therapeutic manipulation of the endocannabinoid system in the human colon." Thesis, University of Aberdeen, 2013. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=203798.
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The endocannabinoid system (ECS) is known to be involved in key aspects of cell maintenance within the human colon, as well as being dysregulated in pathophysiological conditions, including colon inflammation and cancer. However, the contribution of the ECS within each of these conditions has not been fully elucidated. This indicates that the current identification of key targets within the ECS that are involved in gut pathology could be used as potential novel therapeutics. Two experimental approaches were designed and optimised to give an insight into ECS signal regulation within the human colon and to screen ECS therapeutics, tetrahydrocannabinol (THC) and cannabidiol (CBD); a human colon ex vivo explant culture model and an innovative multiplexed quantitative gene expression technology, the GenomeLab GeXP system (Beckman Coulter). Gene targets were identified that are known markers of regulation and function in cells of healthy tissue. An assay, the hCellMarkerPlex was designed that incorporated twenty-three of these gene targets, epithelial (EZR, KRT18, SLC9A2), proliferation (PCNA, CCND1, MS4A12), differentiation (B4GANLT2, CDX1, CDX2), apoptotic (CASP3, NOX1, NTN1), fibroblast (FSP1, COL1A1), structural (ACTG2, CNN1, DES), gene transcription (HDAC1), stem cell (LGR5), endothelial (VWF) and mucin production (MUC2). The hCellMarkerPlex identified gene signatures which distinguished between normal, adenoma and carcinoma tissue, identifying cellular processes showing abnormal activity associated with pathological status. The resulting biomarker profiles were used to establish a human colon explant culture system. The human colon explant culture presents a novel model to study modulation of the ECS and screen ECS therapeutics. Combined with the GenomeLab GeXP System multiple components of the ECS were assessed at the gene regulatory level. A custom designed GeXP assay, the hECSplex, was developed. hECSplex gene expression signatures of EC receptors (CNR1, CNR2, GPR55 and TRPV1), ECS enzymes (NAPE-PLD, GDE1, DAGLA, DAGLB, FAAH, FAAH2 and PTGS2), inflammatory (IL1B, IL10, IL6, LEP, TNF and SOCS3), signalling pathway (ID1, BCL2, CFL1, BIRC5, TP53, MYC and KRAS), lipid production (SREBF1, ACACA), and plasma-membrane (OCLN) markers revealed altered expression of ECS components in carcinogenesis compared to normal tissue. Abstract vi . The hECSplex gene expression signature of colon explants showed that ECS was not altered during culture, emphasising the explant models capability as a pharmaceutical tool to test current and novel therapeutics. Applications of both THC and CBD to normal colon explants at different concentrations do not lead to any significant changes. Indicating the current pharmacological use of phytocannabinoids is causing no adverse effects in surrounding healthy colon tissue. The GenomeLab System presents new opportunities to interrogate multiple components of the endocannabinoid signalling system in small colon explant tissue samples, and in response to ECS therapeutics.
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Fernandes, Patricio Tatiana Marisa <1987>. "Novel, Bio-Inspired Superparamagnetic Hybrid Microspheres for Bone Tissue Engineering." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2017. http://amsdottorato.unibo.it/7906/1/PhD%20thesis_Tatiana%20Patr%C3%ADcio.pdf.
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The available strategies for the treatment of complex bone defects are limited and do not effectively promote bone tissue regeneration. Smart biomaterials have been investigated and designed as a suitable tool for application in degenerative diseases. In particular, magnetic materials are a class of smart biomaterials that showed promising results in bone tissue regeneration or as a diagnostic use. Therefore, the development of biomaterials with magnetic properties is an emerging field of research. The present work describes the application of biomineralisation process, to develop novel biocompatible and bioactive hybrid biomaterials with superparamagnetic properties. Collagen type I-like peptide matrix (RCP) was mineralised with Fe+2/Fe3+-doped hydroxyapatite and engineered into hybrid microspheres (RCPFeHA) by using an appositely developed and optimized emulsification process. Thorough investigation of physicochemical, morphological, thermal, magnetic and biologic properties of the new hybrid microspheres, as induced by the presence of the inorganic nanophase and controlled iron substitution into hydroxyapatite lattice, revealed bone-like composition, designed shape and size, tailored magnetization, good cytocompatibility and significant activity in inducing osteogenic differentiation and expression of genes relevant for bone tissue formation. Microspheres were stable in physiological and inflammatory-mimicking conditions and delivered calcium and iron ions, which could be related to the osteogenic differentiation of murine pre-osteoblasts cells and human mesenchymal stem cells. On the other hand, the effect of microspheres composition on the release of important growth factor in bone tissue regeneration (i.e. rhBMP-2) was studied under static and pulsed electromagnetic field, and bioactive and slow release over the time was obtained.
The unique features exhibited by the new hybrid magnetic microspheres are interesting and promising for application as new biomaterials with ability of remote activation and control by using external magnetic fields, that might be addressed to smart and personalized applications in medicine, particularly in bone tissue regeneration or smart drug delivery systems.
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Ghetti, Martina <1988>. "New Frontiers of Skin Tissue Engineering: from the Laboratory to Clinical Practice." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2017. http://amsdottorato.unibo.it/8061/1/PhD%20thesis%20Martina%20Ghetti.pdf.
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This thesis is focused on the key role of extracellular matrix in skin tissue engineering. Firstly, I presented three dimensional structures derived through the physiological secretion of extracellular matrix (ECM), that may be a bioinspired scaffold. I performed a biological characterization of cell-assembled ECMs from three different sub-populations of skin fibroblasts; papillary fibroblasts (Pfi), reticular fibroblasts (Rfi), and dermal papilla fibroblasts (DPfi). Fibroblast sub-populations were cultured with ascorbic acid to promote cell-assembled matrix production for 10 days. Cells were removed and the remaining matrices were characterized. I found that the ECM assembled by Pfi exhibited randomly oriented fibers, associated with highest interfibrillar space, reflecting ECM characteristics which are physiologically present within the papillary dermis. Mass spectrometry followed by immunofluorescence analysis showed that Thrombospondin is preferentially expressed within the DPfi ECM. In another experiment, keratinocytes were seeded on the top of cell depleted ECMs to generate epidermal skin constructs. I found that epidermal constructs grown on DPfi or Pfi matrices exhibited normal basement membrane formation, while Rfi matrices were unable to support membrane formation. Thus, inspiration should be taken from these different ECMs, to design therapeutic biomaterials in skin engineering applications. In the second part, I focused on human decellularized matrix for soft tissue repair and I investigated the biological interaction post-implant of this scaffold. The aims of this second part were to show the clinical results after the application of human decellularized matrix in patients suffering from abdominal hernia and to evaluate the response one year post implant, through morphological analysis of biopsy specimens. Clinical results showed that all the patients revealed a well tolerability of human decellularized matrix. Post-implant morphological results showed cellular repopulation, neo-angiogenesis, minimal inflammatory response and a well-organized collagen matrix in all biopsies. This scaffold can be considered a safe product to treat large abdominal defects.
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Alnabulsi, Abdo. "Identification and characterisation of novel protein biomarkers for colorectal cancer prognosis." Thesis, University of Aberdeen, 2018. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=237661.
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Thomson, Alison Kathryn. "Organ developmental and maturational defects in Spinal Muscular Atrophy." Thesis, University of Aberdeen, 2016. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=231849.
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Spinal Muscular Atrophy (SMA), traditionally described as a predominantly childhood form of motor neuron disease, is a leading genetic cause of infant mortality. Although motor neurons are undoubtedly the primary affected cell type, SMA is now widely recognised as a multisystem disorder, where a variety of organs and systems in the body are also affected. Vascular perfusion abnormalities have previously been reported in both patients and mouse models of SMA, however it remains unclear whether these defects are secondary to the motor neuron pathology for which this disease is known. Through analysis of the 'Taiwanese' murine model of severe SMA (Smn-/-;SMN2tg/0, Smn-/+) we report significant vascular defects in the retinas of SMA mice, a tissue devoid of motor neurons, thus providing strong evidence that these vascular defects are independent of motor neuron pathologies. We show that restoration of Smn levels by antisense oligonucleotide treatment at birth significantly ameliorates retinal vascular defects. Next, we report defects in the neural retina, with a significant decrease in key neural cells in SMA mice. A similar vascular pathology was expected in the spleen of SMA mice given that the spleen is small and pale in appearance; however, the density of the intrinsic vasculature remained unchanged. We report that the spleen is disproportionately small in SMA mice, correlated to low levels of cell proliferation, increased cell death, and multiple lacunae. The SMA spleen lacks its distinctive red appearance and presents with a degenerated capsule and a disorganized fibrotic architecture. Histologically distinct white pulp fails to form and this is reflected in an almost complete absence of B lymphocytes necessary for normal immune function. Taken together, these results highlight both the vascular and immune systems as key targets of SMA pathology that should be considered during treatment of this disease.
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Nadal, Catala Gema. "The differential ability of methylated folate and folic acid to maintain DNA stability and normal characteristics in human colon cells in vitro." Thesis, University of Aberdeen, 2017. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=231796.
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Folates are water-soluble B vitamins, which maintain DNA stability by regulating nucleotide synthesis and DNA methylation. Folates influence CRC risk and their ability to prevent or promote carcinogenesis may be dependent on several variables here investigated. No in vitro study has yet modelled the physiological folate status that human colon cells are exposed to in vivo. This study evaluates the ability of different forms and concentrations of folate to maintain DNA stability and normal cell function in folate-sufficient and stable human colonocytes and to modify DNA instability and the acquisition of abnormal characteristics in folate-deficient and genomically-unstable colonocytes. Non-malignant human NCM460 colonocytes cultured at physiologically-relevant concentrations of 5-methyl-THF or FA, representing the average deficient (2.5 ng/mL), sufficient (10 ng/mL) or highest post-supplementation (100 ng/mL) folate levels found in human plasma were used in this study as a model of colon-folate interaction. This work established that FA is taken up and/or retained to a lesser extent than 5-methylTHF and is less efficient at maintaining DNA stability and normal cellular characteristics in folate-sufficient and genomically-stable colonocytes at baseline, particularly at deficient and sufficient concentrations in the medium to longer term (14-21 days). During repletion of folate-deficient and genomically-unstable cells, sufficient concentrations of FA do not increase intracellular folate status and worsen the unstable phenotype, by perpetuating DNA instability and enabling the acquisition of a more pro-malignant protein expression. On the contrary, employing 5-methyl-THF sufficiency for repletion positively modifies the abnormal protein profile and morphological features of folate-deficient cells, mitigating potential progression to malignant transformation. When high post-supplementation concentrations are employed, both folate forms increase intracellular folate status, but drive a more promalignant and stress-induced proteome profile and, in the case of 5-methyl-THF, promote abnormal cell morphologies. In conclusion, the folate type, concentration employed, baseline folate status and timing of exposure to folate supplementation are important variables that should be taken into account by future studies evaluating the potential impact of mandatory FA fortification on CRC.
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Alsaid, Bayan. "L’innervation intra-pelvienne : étude anatomique et immuno-histochimique avec reconstruction tridimensionnelle." Thesis, Paris 11, 2011. http://www.theses.fr/2011PA11T015.
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Introduction : L’utilisation des méthodes anatomiques classiques rend difficile la localisationprécise des micro-fibres nerveuses et ne permet pas de déterminer leur nature ni leur fonction.La chirurgie pelvienne est associée à des séquelles urinaires et sexuelles fréquentes causéespar lésion iatrogène des nerfs pelviens. La connaissance de l’anatomie et de la physiologie del’innervation intra-pelvienne est fondamentale pour tenter de réduire le taux de troublesfonctionnels postopératoires.Objectifs : i) étudier l’anatomie topographique et la nature de fibres nerveuses intrapelvienneen utilisant la reconstruction tridimensionnelle des coupes histologiques immunomarquéesii) standardiser la technique de Dissection Anatomique Assistée par Ordinateur(DAAO) et vérifier sa faisabilité sur des sujets adultes et iii) établir grâce à cette technique deDAAO des modèles pédagogiques tridimensionnels afin d’améliorer la compréhension desdysfonctions sphinctériennes et sexuelles survenant après la chirurgie (rectale et prostatique)et d’adapter éventuellement la technique opératoire.Matériel et méthodes : Des coupes histologiques sériées de pelvis ont été réalisées chez septfoetus masculins, sept foetus féminins et six cadavres adultes masculins. Les coupes ont ététraitées par des méthodes histologiques (Hématoxyline-Eosine et trichrome de Masson) etimmuno-histochimiques pour détecter les fibres nerveuses (anti-S100), les fibres somatiques(anti-PMP22), les fibres adrénergiques (anti-TH), cholinergiques (anti-VAChT), sensitives(anti-SP/CGRP) et nitrergiques (anti-nNOS) ainsi que l’actine lisse des sphincters. Les lamesont ensuite été numérisées par un scanner de haute résolution optique et les imagesbidimensionnelles ont été reconstruites en trois dimensions grâce au logiciel WinSurf.Résultats: La reconstruction tri-dimensionnelle des coupes histologiques immuno-marquéesa permis d'identifier l’anatomie topographique et structurelle de l’innervation intra-pelvienne.Les structures nerveuses afférentes du plexus hypogastrique inférieur (PHI) : nerfssplanchniques pelviens (NSP) et nerfs hypogastriques (NH) véhiculent de façon mixte l’influxsympathique et parasympathique pelvien.Les fibres nerveuses issues de la partie distale du PHI sont responsables de la continenceurinaire et de la fonction sexuelle. Elles sont regroupées et associées au pédicule vasculairepour former la bandelette neuro-vasculaire (BNV). Trois efférences principales sont issues decette BNV : i) des fibres antérieures destinées au sphincter urétral, ii) des fibres antérolatérales,par rapport à la prostate et au vagin, constituant le nerf caverneux destiné aux corpscaverneux du pénis/clitoris et iii) des fibres nerveuses postéro-latérales, par rapport à laprostate et au vagin, formant le « nerf spongieux » destiné aux corps spongieux/bulbesvestibulaires.Les communications autonomiques-somatiques entre le PHI supra-lévatorien et le nerfpudendal infra-lévatorien existent à trois niveaux ; proximal, intermédiaire et distal. Lacommunication distale caverno-pudendale est responsable de l’activité érectile segmentaireobservée au sein du nerf dorsal du pénis/clitoris.Conclusion: La DAAO est une méthode originale de recherche anatomique qui a étéprogressivement améliorée au sein de notre unité de recherche. Cette évolution illustre le faitque l'anatomie descriptive est encore une science dynamique. Notre étude a permis dedévelopper des modèles anatomo-physiologiques d’innervation pelvienne contribuant àaméliorer du point de vue morphologique, chirurgical et pédagogique la compréhension derégions anatomiques complexes comme le petit bassin<br>Introduction: Classic anatomical methods have limitations in micro determination of nervefibre location. Furthermore, the precise detection of the nerve fibres nature is not possible bymeans of dissection. Pelvic surgery is associated with urinary and sexual consequence causedby iatrogenic damage of the pelvic nerves. Anatomic and physiologic knowledge of the intrapelvicinnervation is essential to reduce the rate of postoperative functional complication.Objectives: i) to study the topographic anatomy and the nature of intra-pelvic nerve fibersusing three-dimensional reconstruction of histological immuno-labeled sections ii)standardize the technique of Computer-Assisted Anatomic Dissection (CAAD) and check itsfeasibility on adult subjects iii) reconstructe three dimensional teaching models to improveunderstanding of urinary and sexual dysfunction occurring after surgery (of rectal and ofprostate) to ameliorate the operative technique.Materials and methods: serial histological sections of pelvic portion were performed inseven male foetuses, seven female foetuses and six adult male cadavers. The sections weretraited by histological methods (Hematoxylin-Eosin and Masson's trichrome) and immunohistochemicalmarker of the nerve fibers (anti-S100), the somatic fibers (anti-PMP22), theadrenergic (anti-TH), cholinergic (anti-VAChT), sensory (anti-SP/CGRP) and nitrergic (antinNOS)fibers and the actin smooth muscles. The slides were then digitized by a scanner ofhigh optical resolution and two-dimensional images were reconstructed in three dimensionsusing WinSurf software.Results: The three dimensional reconstruction of histological immuno-labelled sectionsidentified structural and topographic anatomy of intra-pelvic innervation. The afferencenerves of the inferior hypogastric plexus (IHP): pelvic splanchnic nerves (PSN) andhypogastric nerves (HN) contain both sympathetic and parasympathetic fibers.The nerve fibers from the distal part of the IHP is responsible for urinary continence andsexual function. They are grouped and associated with the vascular pedicle to form theneurovascular bundles (NVB). Efferences of this NVB are distributed in three maindirections: i) anterior fibers the urethral sphincter, ii) anterolateral fibers, compared withprostate / vagina, which constitute the cavernous nerve for the corpora cavernosa of the penis/ clitoris and iii) " spongious nerve”, which is the continuity of posterior-lateral nerve fibers,compared with prostate / vagina, for the corpus spongiosum / vestibular bulbs.Autonomic-somatic communications between supra-lavator IHP and infra-levator pudendalnerve are present at three levels; proximal, intermediate and distal communications. Cavernopudendaldistal communication provides segmental erectile activity of the dorsal nerve of thepenis / clitoris.Conclusion: The CAAD is an original method in anatomical research which has beenprogressively improved. This illustrates the fact that descriptive anatomy is still a dynamicscience. Our study has developed anatomico-physiological models of intra-pelvic innervationcontributing to a better understanding of complex anatomical
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Basavaraju, Umesh. "Inflammatory biomarkers of colorectal neoplasia and their manipulation by an anti-inflammatory diet." Thesis, University of Aberdeen, 2011. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=182290.
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Colorectal neoplasia (CRN) continues to be a leading cause of morbidity and mortality in the developed world and with westernisation, similar trends are now emerging in the developing world. Although secondary prevention through screening programmes has reduced mortality, uptake remains poor due to the invasive nature of colonoscopy, which also exerts increased costs to the health care system. Primary prevention remains the ultimate aim to reduce the morbidity and mortality associated with CRN. In this regard, chemoprevention strategies through regular use of aspirin and other NSAIDS have showed great promise but the associated significant side-effects of these drugs has prevented their routine clinical application for this purpose. Hence there is an urgent need for the identification of safer alternatives for primary prevention of CRN. In parallel to this search, better understanding of the molecular pathogenesis of CRN to identify biomarkers that aid in stratification of at risk individuals would also help. In this regard, the role of chronic inflammation and the influence of host genetics in the pathogenesis of CRN has been the focus of extensive research in recent years. However there is a lack of studies which have investigated these associations in an exclusively screened population, which confers some advantages for this type of investigation. Firstly, most of the screened subjects are relatively healthy, asymptomatic and with no significant co-morbidities, the factors which could otherwise influence the levels of inflammatory markers. Secondly, the screened population is in the 50 to74 year age group which represents the group with a high prevalence of CRN and hence increasing the possibility of finding associations which would be more relevant and generalisable. Thirdly, the selected controls match the cases in all important respects, apart from having CRN, thus increasing the validity of the findings in this population. The Grampian region was one of the first in the UK to participate in the National Colorectal Cancer Screening Programme and this resource gave the ideal opportunity to conduct research involving an exclusively screened population. Utilising this cohort, the current thesis addressed three important aspects of the association between inflammation and CRN. Firstly the investigation of the association of inflammatory genotype, inflammatory phenotype and CRN risk. Secondly the impact of environmental factors, specifically dietary antiinflammatory salicylic acid intakes on CRN risk. And finally assessing if inflammation, and hence in the long term risk of CRN, could be attenuated through a comprehensive anti-inflammatory dietary supplementation in the form of a randomised dietary intervention clinical trial. The study of the association of polymorphisms in key inflammatory genes (IL1B- 31, IL8-251, IL6-174, TNFα-308, IL10-1082, IL10-592, PTGS2-765, and IL1RN VNTR) and CRN risk showed some significant findings. A novel finding was that the homozygous IL1B-31C*C genotype was associated with statistically significant increased risk of CRN, OR 1.63 (95% CI 1.06-2.50) whilst the IL8-251 A*A genotype increased the propensity of having high risk lesions by two-fold (OR 2.04; 95% CI 1.02-4.07). The study of circulating inflammatory marker levels in subjects in whom the CRN was in-situ showed that increased CRP levels were associated with increased risk of CRN, OR 1.55 (95% CI 1.00-2.39). Increased levels of IL8 were associated with increased risk of having a high risk lesion, OR 2.57 (95% CI 1.03-6.44). In a sub group of subjects, it was observed that levels IL8 and CRP decreased following polypectomy (mean IL8 20.3 pg/ml to 14.9 pg/ml, p=0.05 and mean CRP 5.99 mg/l to 3.82 mg/l, p=0.07) raising an important question regarding the sequence of the inflammation-neoplasia cascade, “Is inflammation the cause or the effect of neoplasia?” The study of the association of dietary salicylic acid (SA) and CRN using the newly constructed SA database showed that high levels of total SA (aspirin and dietary SA) intakes were associated with a 75% and moderate levels with a 67% decreased risk of CRN. But dietary SA on its own showed no significant effect on CRN risk probably because of low intake levels in the current cohort. Applying the SA database to populations with higher dietary SA intake would help to further explore its association with CRN risk. The randomised clinical trial examining the effect of a combined antiinflammatory dietary supplement (curcumin, omega-3 PUFA and polyphenols rich fruit smoothie) on markers of inflammation in subjects who had adenomatous colorectal polyps removed showed that the inflammatory marker levels in the control group who just continued their habitual diet remained stable without any statistically significant changes at 6 weeks compared to the baseline. Whereas following 6 weeks of dietary intervention, there was marginally significant increase in IL8 and IL1B levels. One of the possible mechanisms for increase in pro-inflammatory marker levels in the intervention group was the weight gain seen in the intervention group. In the intervention group, the post-intervention mean weight (86.80kgs) was significantly higher than the pre-intervention mean weight (85.38 kgs). In summary, the findings from these investigations suggest that a proinflammatory genotype (IL1B-31C*C and IL8-251 A*A) and elevated circulating inflammatory marker levels (CRP and IL8) are associated with increased risk of CRN. And along with the findings that regular NSAID use and total dietary SA are associated with decreased risk of CRN, our data point to inflammation as an underlying pathogenetic mechanism in CRN. The pilot clinical trial has demonstrated that a clinical trial with combined dietary supplementation is feasible, but challenging. The anti-inflammatory dietary intervention strategy employed to reduce the inflammatory markers did not achieve the desired effect and hence more research is required to establish the ideal delivery strategy of the anti-inflammatory dietary agents. Once this is established, dietary chemoprevention of CRN as a safe alternative should be a realistic achievable goal in the future.
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Diamond, Alexandra Jane. "An investigation into the roles of slits and roundabouts during vertebrate limb development." Thesis, University of Aberdeen, 2016. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=231142.
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Slits and their Roundabout (Robo) receptors were identified based on their role in regulating axon guidance, but are known to play multiple roles in development, including regulating heart development and myoblast migration. There are 3 vertebrate Slits (Slit1 – 3) and 4 Robos (Robo1 – 4), and previous work has demonstrated expression of Slit and Robo family members in and around developing joints where their function is unclear. Mutations in human Robo3 have been linked to degenerative joint disorders, such as scoliosis and rheumatoid arthritis. Misregulation of other members of the Slit/Robo signalling pathway is also reported in cells from arthritic joints. This suggests that Slit/Robo signalling is required for normal joint development and/or maintenance, though our understanding of their roles in these processes is rudimentary. The central question of my thesis is to determine the role/s of Slit/Robo signalling in limb and joint development. In situ hybridisation confirmed strong expression of Slits and Robos throughout mouse limb and joint development, though no expression of Slit1 or Robo3 was detected. Analysis of Slit1/2, Slit3 and Robo1 mutant (loss-of-function) mice revealed normal limb development, however misexpression of dominant-negative Robo2 during chicken limb development caused shortening of cartilage elements. To begin to identify molecular changes that may compensate for the loss of Slit/Robo signalling I demonstrated members of the Sema3/PlexinA/Nrp axon guidance family are expressed in patterns comparable to those of Robo1, Robo2 and Slit3. I discovered that PlexinA1 is downregulated in Slit3 mutant mouse limbs. My results suggest the role for Silt/Robo signalling may be more complex than previously thought and do not define a clear role for signalling during limb development. My results suggest the role for Silt/Robo signalling may be more complex than previously thought and do not define a clear role for signalling during limb development. Previous work has linked Slit/Robo signalling to development of degenerative joint disorders, and I propose some hypotheses as to how Slit/Robo signalling could cause bone and joint defects.
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Thapa, Dinesh. "Studies on the influence of essential oils on human gut bacteria and colonic cells." Thesis, University of Aberdeen, 2015. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=225962.
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The ability of essential oils (EO) to manipulate the intestinal microbiota may potentiate their application in food as nutraceutical and as prophylactic agents for colonic disease. Little is known about the influence of EO on gut bacteria, the mechanism of their antibacterial action and genotoxicity to the host. Here, the antibacterial activities of EO in pure and in a mixed faecal culture were investigated. These antibacterial activities were further studied to compare the selective nature of EO and their effects on membrane integrity. The growth of gut pathogens and commensals was inhibited in a dose-dependent manner in pure culture, with most of the pathogens, Escherichia coli O157:H7, Clostridium difficile, C. perfringens and Salmonella typhimurium are sensitive to nerolidol, thymol, eugenol and geraniol at a half maximal inhibitory concentration (IC50) of 50-500 ppm. These concentrations of EO and mainly nerolidol were also inhibitory to some gut commensals, in particular affecting Faecalibacterium prausnitzii adversely in pure culture. In contrast, in the mixed culture system beneficial groups of bacteria, including F. prausnitzii, as determined by qPCR of 16S rRNA genes were not affected. Thymol and geraniol at 500 ppm suppressed the growth of total bacteria, resulting in minimal fermentation. A lower dose of 100 ppm of EO compounds was effective in suppressing the pathogen, C. difficile with no concern for commensal bacteria or their fermentation products, acetate, propionate and butyrate. This study also discovered that the proteome of commensal, Faecalibacterium prausnitzii and pathogenic gut bacteria, Escherichia coli, in response to EO compounds are affected differently. Thymol and eugenol down-regulated virulence factors in E. coli. The tested EO compounds were not genotoxic in the comet assay at non-toxic doses. Differential effects of EO compounds on gut pathogens and commensals and their non-toxicity but geno-protective properties could be applicable in improving gut health in man.
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Xian, Jie <1989>. "From clinic to laboratory: Signal transduction analysis and future applications." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2020. http://amsdottorato.unibo.it/9535/1/PHD%20Thesis%20Jie%20Xian%20new%20.pdf.
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Abstract
Background: Epithelioid hemangioma (EH) of bone is a vascular neoplasm with a ubiquitous distribution, including bone and soft tissue. The clinical behavior of EH is complicated because of its multifocal presentation and rare lymph node involvement. To date, up to 25% EH of bone presents synchronous bone lesions and specific gene alterations. Recently, a novel and recurrent FOS gene rearrangement was present in nearly one third of EH across a variety of locations. Before the discovery of gene rearrangements specific to this rare entity, EH was often misdiagnosed as epithelioid hemangioendothelioma (EHE) or angiosarcoma. Acute Myeloid Leukemia (AML) is characterized by an increase in the number of myeloid cells in the bone marrow and an arrest in their maturation, frequently resulting in impaired hematopoietic differentiation that results in granulocytopenia, thrombocytopenia or anemia, with or without leukocytosis. Currently, Azacitidine is the first-line clinical drug for both MDS and AML, whereas Venetoclax is mainly used for chronic lymphocytic leukemia (CLL) patients with or without 17p deletion. The combination of Venetoclax with Azacitidine is being tested with positive clinical results in AML therapy. However, the molecular mechanisms underlying the effect of this combination therapy are still unclear. Therefore, in this study we analyzed the molecular effects of Azacitidine and Venetoclax combination on the nuclear inositide-dependent pathways, mainly focus on PLC-β1.
Aim: This study aimed at describing for the first time a metachronous multifocal lesions case of EH with fatal outcome and analyze the role of inositide pathways in AML.<br>Results: Here we reported the first case of EH with multifocal metachronous bone lesions. This case shows the possible existence of multifocal metachronous EH without producing a fatal outcome. FOS gene rearrangement is critical to assistant the diagnosis of EH. On the other hand, we studied inositide signalling in AML, confirming the IC50 of MOLM-13, HL-60, THP-1 and U-937 hematopoietic cell lines when exposed to Azacitidine and Venetoclax. Moreover, Azacitidine and Venetoclax treatment could induce an increase of the Sub-G0/G1 phase, as well as a G0/G1 arrest in MOLM-13 cells and HL-60 cells. At the same time, it seems to prolong the S phase in U-937 cells. Furthermore, the combination therapy was also able to specifically induce myelopoiesis, as MOLM-13 and THP-1 cells showed an increased expression of CD14. Finally, the combined treatment triggers a higher expression of PLC-β1, which activates the signaling pathway to degrade PKCα.
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Garner, Austin Michael. "Examining the Relationships between Form, Function, Environment, and Behavior in Adhesive Pad-bearing Lizards." University of Akron / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=akron1626363948177358.
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Saunders, Fiona R. "An investigation of non-steroidal anti-inflammatory drug mediated modulation of the polyamine pathway in an in vitro model of colorectal cancer." Thesis, University of Aberdeen, 2008. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=53328.
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Our hypothesis is that the polyamine biosynthetic pathway, a pathway essential in many cellular functions, is modulated by NSAIDs and that this is, at least in part, how NSAID chemoprevention is mediated. An <i>in vitro </i>model of colorectal cancer was used: two cell lines one of which is COX positive and one COX negative to determine the effects of a range of selective and non-selective NSAIDs on various reactions within the polyamine pathway. NSAIDs are cytotoxic to colorectal cancer cells regardless of their COX expression. NSAID-mediated inhibition of cell growth is accompanied by inhibition of ODC activity, partial depletion of polyamine concentrations and up-regulation of polyamine catabolism. In order to investigate the importance of polyamine metabolism, a specific polyamine inhibitor α-difluoromethylornithine (DFMO) was used in combination with the NSAIDs. DFMO <i>per se </i>is not toxic to cells and it does not enhance NSAID mediated toxicity. DFMO in combination with the NSAIDs did cause increased catabolic activity and more sustained polyamine depletion than either alone, however no additional decrease in ODC activity was observed. This suggests that NSAID toxicity is not enhanced by DFMO in this <i>in vitro </i>model. Analysis of the mode of death indicated that the NSAIDs caused apoptotic cell death, confirmed through biochemical and morphological studies and that the NSAIDs affected gene expression of key enzymes in the polyamine biosynthetic pathway. Our findings suggest that modulation of the polyamine pathway by NSAIDs is at least part of the mechanism of action involved in cancer chemoprevention. Therefore modulation of the polyamine pathway may be useful for design of new chemopreventative drugs.
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Almulhim, Zayed. "Imaging hypoxia in colorectal cancer and gastroesophageal cancer with positron emission tomography." Thesis, University of Aberdeen, 2017. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=232243.
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Purpose: Hypoxia in colorectal cancer (CRC) and gastroesophageal cancer (GEC) decreases tumour responsiveness to radio and chemotherapy leading to cancer progression and poor prognosis. This is the first study to utilise [18F]FAZA hypoxia radiotracer in patients with CRC and GEC. Methods: Six patients (mean age 68±8 years, 2 males and 4 females) with CRC and 4 patients diagnosed with GEC (mean age 65 years, 3 males and 1 female) were included in the study. [18F]FAZA was synthesised at the John Mallard Scottish PET Centre. After injection with 370 MBq of [18F]FAZA, PET/CT images with 60 min dynamic scan were acquired. In addition, 15 min static scans 2 hr post injection were performed. 3D PET images were reconstructed iteratively using an ordered subset expectation maximization (OSEM) method and fused to the corresponding low-dose CT images. [18F]FAZA uptake parameters including maximum standard uptake value (SUVmax), tumour-to-muscle ratio (T/M), tumour-to-bowel ratio (T/B) and volume of interest (VOI) were measured. Results: 4 out 6 patients with CRC (66%) showed clear uptake of [18F]FAZA in the primary tumour. The mean tumour SUVmax was 2.2±0.91 (range 1.12 - 3.71). The tumour SUVmax was significantly higher compared with muscle and bowel (t(5) =3.11, P=0.03), (t(5) =3.08, P=0.03), respectively. However, tumour SUVmean didn't differ significantly compared with muscle and bowel (t(5) =2.41 , P=0.06), (t(5) =2.46 , P=0.06) respectively. The mean tumour to muscle ratio (T/M) ratio was 1.89±0.64 (range 1.10 - 2.87), while the mean tumour to normal bowel (T/B) was 1.92±0.64 (range 1.08 - 2.74). However, [18F]FAZA did not accumulate in any of the tumours found in patients with GEC. Conclusions: [18F]FAZA PET/CT imaging is suitable and feasible for detecting CRC hypoxic tumour regions with image quality that can be used in clinical practice.
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Keller, Elizabeth Greer. "Novel chemotherapeutics against lung and colon cancer." Click here for download, 2010. http://proquest.umi.com.ps2.villanova.edu/pqdweb?did=1961333981&sid=1&Fmt=2&clientId=3260&RQT=309&VName=PQD.
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Obradors, Cherta Albert. "Anàlisi completa d'aneuploïdies d'origen femení i de malalties monogèniques en embrions: el diagnòstic genètic preimplantacional de doble factor (DF-PGD)." Doctoral thesis, Universitat Autònoma de Barcelona, 2009. http://hdl.handle.net/10803/3820.
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El Diagnòstic Genètic Preimplantacional (o DGP) és un conjunt de metodologies, que s'apliquen en el transcurs d'un cicle de reproducció assistida, i que permeten la selecció d'embrions sans en parelles afectes de malalties genètiques hereditàries com la fibrosi quística o l'hemofília, entre moltes altres.<br/>A més, també s'utilitza per realitzar un cribatge d'alteracions cromosòmiques (o aneuploïdies) que puguin afectar l'embrió, ja que s'ha evidenciat que aquestes són molt abundants en avortaments. S'ha postulat que una selecció positiva dels embrions lliures de aneuploïdies (és a dir, euploides) hauria d'augmentar la taxa d'embaràs dels embrions transferits al pacient. Publicacions recents, però, han demostrat que encara que es seleccionin els embrions euploides, la taxa d'embaràs no millora significativament, essent al voltant del 13%, mentre que en pacients als quals no s'aplica el DGP és del 30%. <br/>Un dels motius per aquest reduït èxit bé pot ser la tècnica utilitzada per realitzar el cribatge de aneuploïdies, la FISH, que limita l'estudi a només nou dels 23 cromosomes de l'embrió, quedant doncs més de la meitat sense diagnosticar. Per tant, els embrions que es transfereixen com euploides utilitzant la FISH poden contenir aneuploïdies per a qualsevol dels cromosomes restants no analitzats, fet que implica que l'embrió no implanti o que no generi un embaràs viable. <br/>Alternativament a la FISH, existeix la CGH que permet la detecció de tots els 23 cromosomes de l'embrió. La CGH s'ha aplicat prèviament en el DGP, però té l'inconvenient del temps necessari per realitzar la metodologia, que és de tres dies i que implica que no hi ha prou temps per diagnosticar els embrions abans de transferir-los a la pacient. Així doncs, els embrions s'han de congelar a l'espera d'obtenir els resultats de la CGH, per a ser transferits els que siguin euploides en un altre cicle de reproducció assistida. Aquest procés té apart de la desavantatge de les molèsties que implica la necessitat d'aplicar dos cicles de reproducció assistida contigus a la pacient, el fet que entre el 20-40% dels embrions no sobreviuen al procés de congelació / descongelació. Això pot suposar que encara que un embrió hagi estat diagnosticat com euploide per a tots els cromosomes mitjançant CGH, no es pugui arribar a transferir degut a no sobreviure a la congelació / descongelació. <br/>Per tal de solucionar aquestes desavantatges, una proposta metodològica alternativa és analitzar indirectament el ovòcit mitjançant estudi del corresponent 1er corpuscle polar (1CP). Amb aquesta alternativa, consistent en biopsiar el 1CP a després de la fecundació (o Dia 0), es disposa de fins a 4 dies per obtenir el resultat de la CGH. Això possibilita poder transferir en el mateix cicle de reproducció assistida els embrions derivats d'oòcits potencialment euploides, sense necessitat de congelar i descongelar. Aquesta proposta té el desavantatge, de quedar fora d'anàlisi les anomalies cromosòmiques d'origen masculí o les produïdes en el propi embrió durant les primeres divisions. Malgrat aquesta limitació, i atès que el 80% de les aneuploïdies l'embrió s'originen en l'ovòcit, l'anàlisi amb CGH de l'ovòcit permet detectar la majoria d'embrions aneuploides. Per això aquesta aproximació metodològica és molt adequada per al DGP. <br/>En aquesta tesi doctoral, s'ha aplicat un protocol de DGP per evitar malalties genètiques conjuntament amb un cribatge de aneuploïdies d'origen femení mitjançant la CGH aplicada al 1CP. Aquest doble diagnòstic genètic s'ha definit com diagnòstic genètic preimplantacional de doble factor (o DF-PGD) i ha estat aplicat, durant aquesta tesi doctoral per primera vegada en tot el món. <br/>Concretament, el DF-PGD s'ha aplicat a embrions de deu famílies afectes de Fibrosi Quística, la Síndrome d'Angelman o bé de Von Hippel-Lindau, aconseguint incrementar la taxa d'embaràs fins al 33%, respecte del 12,5% que és la que s'obté quan no es realitza aquest doble anàlisi. S'ha produït el naixement de quatre nadons sans per les respectives malalties familiars. Tot i admetent que aquests resultats són preliminars, apunten que el procediment del DF-PGD és útil per diagnosticar les malalties genètiques hereditàries i a la vegada, permet un augment considerable de la taxa d'embaràs en aquest grup de pacients. <br/>Amb l'objectiu de constatar si el DF-PGD indicat no només a dones d'edat avançada, sinó també en dones joves, aquesta tesi inclou un estudi citogenètic complet d'ovòcits de dones joves, analitzant mitjançant la CGH ambdues cèl·lules constituent del ovòcit madur: el 1CP i la corresponent MII. S'han inclòs en l'estudi dels 84 oòcits de dones joves (de 24 a 26 anys) que participen en programes de donació d'ovòcits en centres de reproducció assistida. S'ha evidenciat que un 40% dels ovòcits contenen aneuploïdies. Així doncs, el DF-PGD pot ser una bona opció per millorar l'actual taxa d'embaràs en pacients amb malalties genètiques hereditàries, independentment de l'edat de la pacient. <br/>En conclusió, en aquesta tesi doctoral s'ha evidenciat que el DF-PGD és una variant de DGP que no només és molt recomanada per a parelles en les quals la dona té una edat reproductiva avançada (més de 35 anys) sinó també per a parelles joves, i que pot resultar molt útil per incrementar les actuals taxa d'embaràs.<br>Preimplantation genetic diagnosis (or PGD) is a set of methodologies that is applied during a cycle of assisted reproduction, allowing the selection of healthy embryos in couples suffering from inherited genetic diseases as cystic fibrosis, haemophilia and many others. <br/>It also is used to perform a screening for chromosomal abnormalities (or aneuploidy) that may affect the embryo, as it has become clear that these are very abundant in abortions. It has been postulated that a positive selection of embryos free of aneuploidy (i.e. euploid embryos) should increase the pregnancy rate of embryos transferred to the patient. Recent publications, however, have shown that although the selection of euploid embryos, the pregnancy rate does not improve significantly, with about 13%, whereas patients who did not apply the DGP are 30%. <br/>One reason for this limited success may well be the technique used for screening for aneuploidy, the FISH, which limits the study to only nine of the 23 chromosomes of the embryo, thus leaving more than half undiagnosed. Therefore, the embryos are transferred as euploid using FISH may contain aneuploidy of the other chromosomes not analyzed, which implies that either a failure of the embryo implantation.<br/>Alternatively to the FISH, the CGH technique allows the detection of all 23 chromosomes of the embryo. The CGH has been applied previously in the PGD, but has the disadvantage of the time required for the methodology, which is three days and that means that there is not enough time to diagnose embryos before transferring them to the patient. Thus, embryos must be frozen to await the results of the CGH to be transferred. This process has the disadvantage of being apart from the discomfort that implies the need to implement two cycles of assisted reproduction to the patient, the fact that between 20-40% of embryos do not survive the process of freezing / thawing. This may mean that while an embryo has been diagnosed as euploide for all chromosomes by CGH, can not be transferred due to not surviving the freezing / thawing process.<br/>To overcome these disadvantages, an alternative methodology is to analyze indirectly through study of the corresponding oocyte corpuscle 1st Polar (1PB). With this alternative, consisting of the biopsy in 1PB after fertilization (or Day 0), it is up to 4 days for the result of the CGH. This enables transfer in the same cycle of assisted reproduction embryos derived from oocytes euploides potentially without the need to freeze and thaw. This proposal has the disadvantage of being left out of the analysis of chromosomal abnormalities or male origins were produced in the embryo during the first division. Despite this limitation, given that 80% of embryo aneuploidy originates in the oocyte, the CGH analysis of oocytes can detect the majority of aneuploid embryos. Therefore the methodological approach is very suitable for the DGP. <br/>In this thesis, we have implemented a protocol for PGD to avoid disease with a genetic screening for aneuploidy in female origin by CGH applied to 1PB. This dual genetic diagnosis has been defined as preimplantation genetic diagnosis of double-factor (or DF-PGD) and has been applied during this thesis for the first time around the world. <br/>Specifically, the DF-PGD has been applied to embryos of ten families affected by cystic fibrosis, Angelman syndrome or von Hippel-Lindau, achieving pregnancy rate increased to 33% on the 12.5% which is obtained when the DF-PGD is not analysis. There was the birth of four healthy babies by their illness relatives. Even accepting that these results are preliminary, it suggests that the proceedings of the DF-PGD is useful for diagnosing hereditary genetic diseases and also allows an increase in pregnancy rate in this group of patients. <br/>Aiming to establish whether the DF-PGD indicated not only older women but also young women, this thesis includes a comprehensive cytogenetic study of oocytes from young women looking through CGH both constituent cells of mature oocyte, the 1CP and the corresponding MII. We performed a study of young women 84 oocytes (24 to 26 years) involved in egg donation programs in assisted reproduction centres. After its analysis, we concluded that 40% of the oocytes contain aneuploidy. Thus, the DF-PGD may be a good option to improve the current pregnancy rate in patients with inherited genetic diseases, regardless of the age of the patient.<br/>In conclusion, this thesis has shown that the DF-PGD is a variant of PGD is not only highly recommended for couples where the woman has an advanced age (over 35 years) but also for young couples and that can be useful to increase the current rate of pregnancy.
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Phyu, Su Myat. "Targeting of the PI3K/AKT/mTOR signalling pathway and associated kinases in breast and colon cancer cells and response evaluation by molecular imaging techniques." Thesis, University of Aberdeen, 2018. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=238576.
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The phosphatidylinositol-3-kinase/AKT (Protein Kinase B)/mammalian target of rapamycin (PI3K/AKT/mTOR) signalling pathway, downstream of tyrosine kinase receptors, is upregulated in human cancers including breast and colon cancers. Glycogen synthase kinase 3 (GSK 3) is a serine/threonine protein kinase plays important role in various cellular processes including glycogen synthesis mediated by insulin signalling pathway. Moreover, 5' adenosine monophosphate activated protein kinase (AMPK), a crucial cellular energy sensor, has regulatory role in cell growth and proliferation through mTOR pathway. Phosphatidylcholine (PtdCho) is the major phospholipid in the mammalian cell membranes and is mainly synthesized by the CDP-choline pathway. Malignant transformation has been reported to be associated with altered choline metabolism. Hyperactivation of the PI3K/AKT signalling pathway upregulates the key enzymes of phospholipid metabolism. The first line antidiabetic drug, metformin, modulates glucose and concomitant lipid metabolism through AMPK activation. Studies suggest phosphatidylcholine biosynthesis and breakdown through CDP-choline pathway are modulated by glucose metabolism and de novo fatty acid synthesis. Cancer cell growth inhibitory effect of PI3K/AKT/mTOR/GSK3 pathway inhibitors and metformin were investigated by cytotoxic assay, western blot and cell cycle analysis in breast and colon cancer cells. IC50 values of anticancer drugs and combination indices between drug combinations were determined. 31P-NMR was carried out on cell extracts after drug treatments. [14C (U)] glucose and [3H] choline incorporation into lipids were also determined. All inhibitors targeting PI3K/AKT/mTOR signaling pathway, GSK3 and metformin have cancer cell growth inhibition. By 31P-NMR, PI3K/AKT/mTOR pathway inhibition induced agent-specific changes in PCho intensity. Increased UDP-sugars observed in breast and colon cancer cell extracts treated with LY294002 and AZD8055, an effect abrogated by inclusion of a GSK3 inhibitor. A link between glycolytic intermediates and phosphatidylcholine biosynthesis was investigated by metformin and GSK3 inhibitor in breast and colon cancer cells.
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Ogren, Jennifer Anne. "Mapping anatomic correlates of pathological activity in the epileptic human hippocampus." Diss., Restricted to subscribing institutions, 2008. http://proquest.umi.com/pqdweb?did=1666117471&sid=3&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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FERRI, NICOLETTA. "EMBODIED TEACHING: PROSPETTIVE DI RICERCA A SCUOLA ATTRAVERSO L'ANATOMIA ESPERIENZIALE." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2018. http://hdl.handle.net/10281/241227.
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Questo lavoro di ricerca nasce dal desiderio di indagare il potenziale riflessivo, euristico e trasformativo della dimensione embodied nei processi di insegnamento/apprendimento. Per farlo ha interrogato un gruppo di insegnanti della scuola primaria, coinvolgendole in una ricerca partecipativa sulle proprie pratiche di insegnamento e sul loro modo unico di incarnarle (embodied teaching), a partire da un’attivazione corporea specifica (Anatomia Esperienziale).
La mia domanda di ricerca si è orientata in due direzioni. Ad un livello metodologico potrebbe essere formulata nel seguente modo: come interrogare l’embodied teaching (Bresler, 2014) di professionisti della scuola, cioè il modo incarnato di interpretare il processo di insegnamento/apprendimento? Ad un livello tematico, invece, l’interrogativo di fondo potrebbe essere così posto: cosa emerge quando si va ad attivare un processo di riflessione sulla pratica professionale di un gruppo di insegnanti della scuola primaria a partire da un’interrogazione che passa dalla percezione e dall’attivazione corporea?
Collocandomi nell’area di ricerca della Pedagogia del corpo (Gamelli, 2011), il macro-paradigma dell’embodiment ha rappresentato un riferimento epistemologico importante per il lavoro. In esso ho trovato un fertile incontro di studi, ricerche e pratiche provenienti da ambiti molto distanti, tra cui le scienze cognitive (l’enactive embodiment di Varela, Thompson, Rosch, 1991), l’ambito performativo (Farnell, 1995; Sheets-Johnstone, 1999; Bresler, 2014) e quello più legato all’educazione (Gamelli, 2011; Rossi, 2017). È precisamente all’incontro di queste tre aree che si colloca la prospettiva di ricerca del presente lavoro.
La parte empirica della ricerca si è svolta con un gruppo di sette insegnanti di una scuola primaria milanese, su adesione volontaria, in sei incontri di tre ore circa ciascuno. Il setting di ricerca è stato strutturato in modo che ci fosse una stratificazione dell’esperienza corporea proposta affinchè ognuna delle partecipanti potesse contattare il proprio embodied teaching nel rispetto del proprio stile personale e corporeo di insegnamento. La metodologia della “co-operative-inquiry” (Heron, Reason, 1997) e la successiva interpretazione di Formenti nella “spirale della conoscenza” (Formenti, 2009), oltre che fornirmi un riferimento epistemologico in termini di dimensione partecipata della conoscenza, mi hanno fornito riferimenti importanti per disegnare la struttura interna degli incontri in modo coerente con i miei presupposti teorici.
L’anatomia esperienziale del Body-Mind Centering è stata la pratica somatica che ho utilizzato per la ricerca empirica. Tutti gli incontri sono stati audioregistrati e trascritti. Dopo una prima analisi tematica attraverso NVivo, è maturata la decisione di andare verso una svolta più performativa della mia ricerca. Questo cambio di prospettiva ha richiesto l’ideazione e la costruzione di un dettagliato – e inedito – metodo di ricerca embodied. Si tratta di uno dei passaggi più originali della mia ricerca di dottorato, che ha visto l’inizio di un lavoro di analisi corporea e performativa dei dati attraverso segmenti audio e testuali che ho selezionato dalle trascrizioni e dai materiali audio degli incontri con le insegnanti.
Questa analisi performativa, documentata in 160 riprese video, si è poi direzionata verso la creazione di una video-performance utilizzata come restituzione alle insegnanti rilanciandolo e aprendo nuovi interrogativi e così possibili sviluppi per ricerche future legate alla dimensione corporea della professione insegnante.<br>This thesis is deeply connected with the will of investigating the reflective, heuristic and transformative potential of the embodied dimension in teaching and learning processes. For this purpose, I engaged a group of Primary School teachers in a participatory research focused on their personal way of embodying teaching practices (embodied teaching) starting from a specific body activation (Experiential Anatomy).
My research question was twofold. At a methodological level I was interested in interrogating the embodied teaching (Bresler 2014) of school professionals, namely their own way of performing the teaching/learning processes. At a thematic level the question was: what does it happen when a researcher activate a reflective process on professional practices of a group of primary school teachers through body activations?
My main theoretical frame is represented by Embodied Pedagogy (Gamelli, 2011) and my fundamental epistemological reference is the so-called “embodiment paradigm”. This paradigm is a generative common ground for studies and practices connected to heterogeneous fields as cognitive sciences (Varela, Thompson and Rosch, 1991), performative disciplines (Farnell, 1995; Sheets-Johnstone, 1999; Bresler, 2014) and education (Gamelli, 2011; Rossi, 2017). My research perspective lies exactly at the crossroads of these three main areas.
The empirical part of my research took place in a Primary School of Milan. I addressed a group of teachers with a research proposal structured on six meetings of three hours each. The research setting was designed in a way that allowed a multi-layered experience of the body activations in order to let each participant explore her own embodied teaching, namely her own personal way of performing teaching. The “co-operative inquiry” theorized by Heron and Reason (1997) and Formenti’s “Spyral of knowledge” (2009) were the two main epistemological pivots in reflecting on the research objectives, as they both advance the idea of research as a co-construction of participatory knowledge. They were also fundamental in order to design the internal structure of each meeting consistently with my theoretical assumptions.
Experiental Anatomy of Body-Mind Centering was the somatic practice that I used for the empirical part. Each meeting was audio-recorded and transcribed. After a first thematic analysis with Nvivo I decided to turn my research in a performative direction. This change of perspective required the creation of a detailed embodied research method. This is the most original part of my thesis that consisted in a performative analysis of a selection of collected data (originated in the six meetings with the participants) in the form of textual and audio excerpts.
This performative analysis, documented by 160 video shootings, ended in the creation of a video-performance that was used as a starting point of the final meeting with research participants. The use of this aestethic and performative object in the research setting revealed itself as a powerful tool in order to trigger an high level of participation in the group. The final meeting, in fact, was a fundamental moment as the participants’ reflections transformed “my” performative composition in a shared knowledge connected with all the research process. The results were very interesting both in terms of new questions raised by the teachers and of future research possibilities in the direction of embodied teaching.
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Cheng, Bo. "Passive rotational damping in flapping flight." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 89 p, 2009. http://proquest.umi.com/pqdweb?did=1889090361&sid=9&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Chellappa, Karthikeyani. "Functional analysis of Tyrosine residues in human hepatocyte nuclear factor 4alpha." Diss., UC access only, 2009. http://proquest.umi.com/pqdweb?index=72&did=1790348311&SrchMode=1&sid=1&Fmt=7&retrieveGroup=0&VType=PQD&VInst=PROD&RQT=309&VName=PQD&TS=1270229827&clientId=48051.
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Thesis (Ph. D.)--University of California, Riverside, 2009.<br>Includes abstract. Includes bibliographical references (leaves 293-348). Issued in print and online. Available via ProQuest Digital Dissertations.
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Shojaeian-Zanjani, Mohammad-Hadi. "Etude en cytologie quantitative de l'olive bulbaire des rongeurs : relation entre mort neuronale et elimination synaptique au cours du developpement et role des cellules cibles dans la regulation du nombre des neurones olivaires." Paris 6, 1987. http://www.theses.fr/1987PA066211.
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"Atypical anatomy in children and adults with persistent developmental stuttering." Tulane University, 2007.
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A larger right prefrontal and a larger left occipital lobe (lobar asymmetry) and a larger left planum temporale (PT) are consistent asymmetries found in the human brain. Reduced or reversed asymmetries from these typical configurations are considered atypical and may be markers of atypical function. Atypical lobar and PT asymmetries have been found in adults with persistent developmental stuttering (PDS). These atypical asymmetries may represent a neural risk for developing PDS. To further understand the development of these asymmetries; volumes, ratios and asymmetry quotients were investigated in three groups: (1) healthy right-handed boys and girls ages 8--13 (2) righthanded boys with PDS and matched controls ages 8--13 (3) right-handed adult men with PDS and matched controls ages 21--49. The healthy boys and girls displayed sex-linked differences. Boys had larger total brain and total gray matter volumes than girls. Due to sex-linked gray matter differences, boys had larger right prefrontal and left occipital volumes which lead to a greater magnitude of brain torque. The PT was leftward in both sexes. The boys with PDS differed in multiple anatomical areas compared to controls. The PDS group had more total white matter and a smaller gray-to-white matter ratio in the right hemisphere compared to controls. The PDS group had a smaller right prefrontal region due to decreased prefrontal inferior gray matter. The occipital volume and asymmetry patterns also differed between groups. Controls had the expected leftward asymmetry while the PDS group was more atypical. Thus, the overall brain torque was more symmetrical in the PDS group. The stuttering severity scores positively correlated with right prefrontal white matter volume. The PT was leftward in the boys with no group difference. Right-handed men with PDS and controls did not differ in lobar volumes and asymmetries. The PT was more symmetrical in the PDS group than controls. Interestingly, in all PDS subjects and controls, the prefrontal and occipital white matter asymmetries followed the typical brain torque configuration while the gray matter asymmetries were more variable. This observation indicates that white matter volumes may be responsible for the typical brain torque configuration<br>acase@tulane.edu
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"Sex differences in the anatomy of human perisylvian regions: Frontal and temporal cortical language areas." Tulane University, 2003.
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The left hemisphere plays a predominant role in speech-language functions. Anatomical asymmetries of perisylvian speech-language regions have been found with evidence that leftward asymmetries are associated with language dominance. There is also evidence that sex-linked differences in the functional organization of language exist, although sex-linked anatomical differences have not been extensively studied and results have been conflicting. For example, developmental language disorders are male predominate, and women may have more bilaterally represented language functions. Given the controversy in the literature and the need to learn more about sex-linked anatomical differences in healthy adults, a series of experiments were designed to study the anatomy and function of perisylvian language related cortex. Volumetric MRI was used to measure gray matter volumes of posterior language areas, including Heschl's gyrus (HG), planum temporale (PT), and posterior superior temporal gyrus (pSTG) in 48 right-handed men and women, matched for age and education and frontal regions, including the pars triangularis (PTR), pars opercularis (POP), and diagonal sulcus (DS) in 60 right-handed men and women, matched for age and education. Language tests were administered to a subsample of subjects. There were no consistent HG asymmetries and no sex differences. There was a leftward PT asymmetry (L > R), but no sex differences. For the pSTG, men had rightward asymmetry (R > L), while women were as likely to have R > L as L > R. For the temporal areas together, in men about equal numbers had L > R as R > L, whereas women had L > R. There were no asymmetries or sex differences for any frontal language areas. When a measure of listening comprehension was examined, there was a trend for a significant PT asymmetry direction-by-sex interaction. Women with rightward PT asymmetry performed better, whereas men with leftward PT scored better. These results are interesting because the PT mediates auditory processing and atypical (R > L) PT anatomy has been found in individuals with dyslexia. Although speculative, it may be that atypical PT anatomy in women is not associated with aberrant function, whereas in men atypical anatomy may be a neural risk for dysfunctional language development. Future studies should explore these important relationships in neurodevelopmental and acquired language disorders<br>acase@tulane.edu
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"Mechanics and quantitative morphology of the carotid baroreceptor region of normotensive and spontaneously hypertensive rats." Tulane University, 1987.
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An in vivo mechanical analysis and a detailed quantitative morphological study of the arteries in the carotid baroreceptor region from normotensive (NTR) and spontaneously hypertensive (SHR) adult (9-10 month old) male rats were completed The morphological studies incorporated a newly developed vascular perfusion technique (Engle and Kirby, 1986) that allowed for the preservation of vascular dimensions at distending pressures equivalent to the physiological mean arterial pressures (PMAP) obtained under normal resting conditions for each individual animal. The following changes in the carotid arteries were documented and quantified. (1) There is a generalized thickening of the tunica intima which is primarily associated with an expansion of the subendothelial space and which resembles the early atherosclerotic lesions developed in man. (2) The internal elastic lamina contains a greater number of fenestration profiles. (3) The volume of the tunica media is increased due to a proportional increase in the absolute amounts of collagen, elastin, and smooth muscle A new index of vessel wall distensibility, defined as the incremental mechanical sensitivity $({\rm S\sb{m}})$, has been developed. Using this parameter, it was demonstrated that the distensibility functions of the carotid arterial walls from both NTRs and SHRs exhibit a distinct peak value $({\rm S\sb{m}MAX})$ which occurs consistently at or near PMAP. The vessel walls are stiffer at pressures both above and below PMAP. The pressure at which ${\rm S\sb{m}MAX}$ occurs (PMAX) is strongly correlated with PMAP, being nearly equal with it. The magnitude of the peak value of ${\rm S\sb{m}}$ decreases as a function of increasing PMAP. These functional relationships are so strong that they indicate physiological significance. The fact that the carotid arterial wall is maximally distensible at PMAP demonstrates the existence of a physiological mechanism for optimizing baroreflex efficiency about the defined set-point pressure. The strong functional relationship between PMAX and PMAP indicates a mechanical mechanism for the long-term resetting of the carotid sinus baroreceptors. Finally, the observed mechanical resetting and decreased sensitivity of the carotid sinus baroreceptors in adult SHRs appear to be the result of a stress induced growth adaptation phenomenon associated with the hypertensive disease state.(Abstract shortened with permission of author.)<br>acase@tulane.edu
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"Corticotropin-releasing factor and dopamine in the central amygdaloid nucleus of the rat: Localization and interactions." Tulane University, 1990.
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Light microscopic immunocytochemistry (ICC) of the central nucleus (CA) of the rat amygdaloid complex revealed two populations of corticotropin releasing factor (CRF) immunoreactive (IR) neuronal perikarya and terminals. Perikarya were isolated within the centrolateral (CL) subdivision of the CA (76.6% of all CRF-IR perikarya in the CA) and the centromedial subdivision of the CA (23.4% of total). CRF-IR fibers were occasionally observed within the stria terminals (ST) while a dense population of CRF-IR terminals was located in the central lateral capsular (CLC) subdivision of CA. In the CLC, CRF-IR terminals were observed to gather around clear circular areas suggesting an association with immunonegative neurons. Tyrosine hydroxylase (TH) IR in the CA was restricted to terminals. These terminals were virtually absent from the CLC, but densely accumulated in the CL where the greatest number of CRF-IR cell bodies were located. In the CL and CM, TH-IR terminals were observed in close association with clear areas that appeared to be unstained neurons. Double ICC for CRF and TH revealed that many of the TH-IR terminals were closely associated with CRF-IR neurons suggesting that synaptic contact might be present Electron microscopic ICC of the CA revealed that CRF-IR neuronal processes were spineless and were contacted by many asymmetric axodendritic synapses which occasionally contained dense cored vesicles while CRF-IR neurons were contacted by numerous mostly symmetric terminals. In the CLC, CRF-IR terminals were observed making numerous synaptic contact with immunonegative structures. Many of these terminals contained clear round vesicles of 50nm diameter and occasional dense cored vesicles that were approximately 100nm in diameter. Double EM ICC for CRF and TH revealed TH-IR terminals making both symmetric and asymmetric synaptic contacts with CRF-IR perikarya and denerites. TH-IR terminals contained 50nm clear round vesicles and 100 nm dense cored vesicles The origin or significance of intracentral amygdaloid CRF-IR connections could not be determined in the present study. However, through interconnections with several brainstem autonomic centers as well as the A10 and A9 mesencephalic dopaminergic cell groups, it is possible that the TH to CRF connections described in this work play an important role in directing autonomic responses to stress<br>acase@tulane.edu
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"Expression of an estrogen receptor variant with transcriptional regulatory activity in human breast cancer cell lines: A possible model system for the development of hormone resistance." Tulane University, 1993.
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Accurate identification of prognostic markers in primary breast cancer is critical for selecting the most beneficial mode of therapy for the affected patients. The estrogen receptor (ER) is a major prognostic marker, indicating the estrogen-responsive nature of breast tumors and the likelihood of response to hormonal therapy. Estrogen receptor variants may possess outlaw functions, acting in a dominant-positive (transcriptionally active in the absence of estrogen) or dominant-negative (transcriptionally inactive, while inhibiting the function of wild-type ER) manner. Developing a strong correlation between particular ER variants and altered estrogen-responsiveness suggests that over-expression of these ER variants or an altered expression ratio of these variants to the wild-type ER may be an important biologic event leading to the formation of hormone-independent, antiestrogen-resistant breast cancer Using a variety of approaches including RNase protection analysis and RT-PCR followed by cloning and sequencing, variant ER mRNAs with complete deletions of exons 5 and 7, in addition to the wild-type ER transcript, have been identified in the ER-negative BT-20 and ER-positive MCF-7 breast tumor cell lines. We have also been able to identify these two variant ER transcripts in a number of breast tumor cell lines both ER-positive and ER-negative. It appears that the exon 5 deletion variant $(\Delta 5)$ is expressed at higher levels than the exon 7 deletion variant $(\Delta 7)$ in each cell line, and the ratio of expression of variant to wild-type ER transcript differed among the cell lines examined. Immunoprecipitation of ER followed by Western blot analysis revealed a truncated receptor in the BT-20 cell line that is the expected size of the purported $\Delta 5$ variant ER protein and which possesses constitutive transcriptional regulatory activity in a yeast expression system. RNase protection analysis also demonstrated a variation in the levels of expression of $\Delta 5$ variant transcripts among stocks of MCF-7 cell lines obtained from different sources. Perhaps more importantly, a preliminary study has suggested that the expression of the $\Delta 5$ variant is modulated in culture by the presence or absence of estradiol<br>acase@tulane.edu
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"Modulation of estrogen receptor expression and the estrogen response pathway by the pineal hormone melatonin in MCF-7 human breast cancer cells." Tulane University, 1994.
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Melatonin, the hormonal product of the pineal gland, has been shown to inhibit the development of mammary tumors in vivo and the proliferation of MCF-7 cells in vitro by mechanisms not yet identified. Previous studies have demonstrated that only human breast cancer cells which express estrogen receptor (ER) are responsive to the antimitogenic effects of melatonin, suggesting a link between the effects of melatonin and the estrogen-response pathway. MCF-7 human breast cancer cells, which are ER-positive and responsive to the mitogenic actions of estrogen, were used to examine the possible association between the antiproliferative activity of melatonin and its ability to modulate the estrogen-response pathway at the level of ER expression. In order to determine the mechanism(s) by which melatonin regulates ER expression in MCF-7 cells, the relationship between ER protein expression, estrogen binding activity, steady-state levels of ER mRNA, the level of ER gene transcription, and the stability of the ER transcript were examined in response to melatonin Physiologic concentrations of melatonin significantly decreased estrogen binding activity, expression of immunoreactive ER protein, and steady-state levels of ER mRNA in a dose-specific and time-dependent manner in both complete and estrogen-depleted media. However, melatonin did not alter receptor affinity and was unable to compete with estrogen for binding to the ER. Studies in a yeast transcriptional assay system confirmed that melatonin does not directly bind to the ER to modulate ER expression. The decreased expression of ER protein in response to melatonin appears to be directly related to both suppressed ER gene transcription and decreased half-life of the ER message. This regulation is independent of the synthesis of new proteins since cycloheximide did not block the melatonin-induced decrease in ER mRNA. The expression of several estrogen-induced genes were differentially regulated by melatonin, suggestive of the interplay of early versus late events in the action of melatonin. Thus, it appears that the antiproliferative actions of melatonin may be mediated, at least in part, through the suppression of the estrogen-response pathway of MCF-7 cells<br>acase@tulane.edu
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"Localization and status of hypothalamic releasing factors in normal (DF/?) and in prolactin- and growth hormone- deficient dwarf (df/df) mice: Vasoactive intestinal peptide (VIP) and growth hormone releasing hormone (GHRH)." Tulane University, 1993.
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This study examined the stimulating factors for prolactin (PRL) and growth hormone (GH). One aim of the study was to establish an anatomical basis for a proposed releasing factor for PRL, vasoactive intestinal peptide (VIP). Ames dwarf mice, which manifest a spontaneous mutation which, when present in homozygous form (df/df), results in absence of PRL and GH, were used in the present study. Immunoreactive VIP and growth hormone releasing hormone (GHRH) were examined and compared between brains of normal and PRL and GH-deficient dwarf mice in order to see whether there is a response of VIP and GHRH neurons to the absence of target hormones, PRL for VIP and GH for GHRH The anatomical source of the hypophysial portal VIP, and the response of the hypothalamic VIP-containing neurons to PRL deficiency was investigated. VIP immunoreactivity was detected in parvocellular paraventricular nucleus neurons. Groups of VIP-containing neurons in the parvocellular paraventricular nucleus project to the median eminence, which contains portal blood vessels that transport hypophysiotropic factors to the pituitary gland. VIP immunoreactivity was also located in axon terminals in both the external and internal zone of the median eminence. Immunoreactive VIP in the cortex, amygdala, bed nucleus of the stria terminalis, and in the suprachiasmatic nucleus were qualitatively comparable between normal and dwarf mice. Qualitative increases in the fiber immunostaining in the external layer of the median eminence and perikaryal immunoreactivity in PVN of the dwarf mouse were detected. The presence of median eminence-afferent VIP neurons in the paraventricular nucleus and fiber immunostaining in the external layer of the median eminence suggest that parvocellular paraventricular neurons may be involved in PRL regulation Studies of the stimulatory factor GHRH in mice have been hampered by the lack of antiserum directed against the mouse-specific peptide. GHRH-containing cell bodies were found to be primarily concentrated in the arcuate nucleus. In addition, new localizations of GHRH-containing cell bodies were demonstrated, such as in the medial preoptic area, anterior hypothalamic area, and in the area lateral to anterior hypothalamic area. It is not known whether these neurons participate in GH regulation. In addition, GHRH-immunoreactive perikarya in the hypothalamic ventromedial nucleus of dwarf mice were noted. Whether these neurons project to median eminence is not known. The number of the GHRH-containing cell bodies in the dwarf arcuate nucleus was increased compared to the number in normals. The increased number of cell bodies was located in the ventral and medial areas of the arcuate nucleus. (Abstract shortened by UMI.)<br>acase@tulane.edu
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"Adrenal corticosteroids: Central nervous system targets, mechanisms of action, and glucocorticoid regulation of preproenkephalin-gene expression." Tulane University, 1992.
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Adrenal corticosteroids have diverse effects on central nervous system (CNS) function. These include regulation of the activity of neurotransmitters-modulators, neuro- and gliogenesis, learning and behavior and neuronal and glial survival. Many of these actions are thought to be mediated at least in part, by intracellular corticosteroid receptors. A Type I receptor, which acts as a mineralocorticoid receptor in the peripheral tissues, is selective for endogenous glucocorticoids in most regions of the CNS. A Type II receptor, also known as the classical glucocorticoid receptor has a low affinity and high capacity for endogenous glucocorticoids in the CNS. We mapped corticosteroid targets in the rat CNS using immunocytochemical detection of corticosteroid receptors. Contrary to previous reports of a restricted distribution of Type I receptors, we found that both types of corticosteroid receptors show widespread expression in neurons, and may indeed be coexpressed by some neurons. However, most glia expressed only Type II receptors. The intracellular location of corticosteroid receptors was regulated by corticosterone and aldosterone, the principle glucocorticoid and mineralocorticoid in rats. In the presence of these steroids, both Type I and II receptors showed a predominantly nuclear location, although cytoplasmic receptor was often present. This suggests a largely genomic role for these receptors in the CNS. We also demonstrated regulation of nuclear Type II receptor immunoreactivity (ir) by progesterone and androgenic-anabolic steroids. Our findings corroborated recent reports on cross-regulation of the Type II receptor by these steroids, based largely on binding studies Using double-labeling immunocytochemical techniques, we demonstrated for the first time, colocalization of Type II receptors by subpopulations of GABA-ir cerebellar Purkinje cells and LHRH-neurons. These cells regulate motor and neuroendocrine processes which are affected by circulating glucocorticoids. Most investigators have suggested that effects of glucocorticoids on these systems are largely indirect. By showing that some Purkinje and LHRH cells are potential direct targets for glucocorticoids, we have broadened the scope of possible mechanisms underlying the effects of glucocorticoids. Finally we examined the regulation expression of preproenkephalin (PPE) gene in the forebrain by glucocorticoids. PPE gene has been used as model, especially in vitro, to study direct regulation by glucocorticoids (i.e. corticosteroid receptor-mediated). We extended this concept in vivo, by examining glucocorticoid regulation of PPE gene expression in forebrain regions, which show an overlap in the distribution of PPE and corticosteroid receptors. In all regions analyzed, we found that circulating glucocorticoids were required for basal expression of PPE. Chronically elevated levels increased expression in selected regions, notably the striatum. We suggest that as in in vitro systems, PPE expression in vivo is regulated directly, at least in part, by glucocorticoids<br>acase@tulane.edu
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"Expression and regulation of Pitx genes during vertebrate organogenesis." Tulane University, 1999.
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Pitx1 and Pitx2 define a new family of bicoid related homeobox genes. The respective expression patterns of these two genes suggests their importance during vertebrate embryo development. Of particular interest is the expression and regulation of these genes during murine tooth development. The expression patterns of both Pitx1 and Pitx2 in the tooth forming region as well as the tooth defect found in patients with Rieger syndrome suggest that both Pitx1 and Pitx2 play a role in the early stages of odontogenesis. Studies show that overlapping domains of Fgf8 and Bmp4 signaling regulate the expression of both Pitx1 and Pitx2 in the tooth forming region Since Pitx2 is an early marker for the dental epithelium, the chicken homologue of Pitx2 (cPitx2) was cloned in an effort to search for molecular markers for the presumptive tooth germ in Aves. Interestingly, in addition to the expression of this gene in the chick mandible, cPitx2 was also asymmetrically expressed relative to the left-right axis of the developing embryo. Studies show that regulation of this gene in the left-lateral plate mesoderm is regulated by the well documented shh-nodal pathway. In addition, expression of cPitx2 in the left half of the fused heart tube appears to be regulated by retinoic acid as demonstrated by the reduced expression of cPitx2 in vitamin A-deficient quail embryos. Finally, upon cloning the chicken homologue of Pitx2 , two isoforms of this gene were isolated, isoform A (cPitx2A ) and isoform B (cPitx2B). However, Northern blot analyses indicates that at least 3, possibly more, isoforms are expressed and may correspond to the various expression patterns of cPitx2 throughout embryogenesis. The expression of antisense cPitx2 transcripts was also detected. The presence of antisense cPitx2 transcripts through development in vivo, as confirmed by Northern blot and RNase Protection Assay (RPA) analysis, suggest yet another mechanism for the regulation of cPitx2 activity. The complementary expression pattern of sense and antisense cPitx2 in the endothelial and hematopoietic cells of the embryonic vasculature, respectively, suggest that these two genes may be involved in regulating the differentiation of the endothelial and hematopoietic cell lineages respectively<br>acase@tulane.edu
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"Modulation of ROR-alpha receptor activity and the calcium/calmodulin signaling pathway by melatonin in MCF-7 human breast cancer cells." Tulane University, 2000.
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The pineal hormone, melatonin has repeatedly been shown to inhibit the proliferation of estrogen receptor alpha (ERalpha)-positive MCF-7 human breast cancer cells. Previous reports have suggested that the actions of melatonin can be mediated either through G protein-coupled membrane receptors, or via retinoid orphan receptors (RORalpha), which constitutively activate gene transcription through their corresponding response elements termed ROREs. Transient transfection assays using an RORE-luciferase reporter construct have shown that the endogenous (RORalpha), receptors expressed in MCF-7 breast cancer cells exhibited a high basal level of transcriptional activity, which was further stimulated by serum. In the presence of serum, both the transcriptional activity and DNA binding ability of (RORalpha), were repressed by melatonin treatment, even though melatonin had no effect on RORalpha protein levels. Although RORalphas were originally proposed as nuclear receptors for melatonin, the direct binding of melatonin to these receptors can not be repeated. Therefore, it is not clear how melatonin can modulate (RORalpha), functions in MCF-7 cells. Consistent with the results from other systems, RORalpha transcriptional activity in MCF-7 cells was found to be responsive to intracellular calcium concentration ([Ca2+]i), calmodulin (CaM), and Ca2+/CaM-dependent protein kinases. Meanwhile, melatonin not only affected CaM subcellular distribution, but also modulated [Ca2+]i change induced by another known calcium stimulator, ATP, indicating that melatonin may regulate RORalpha transcriptional activity via its modulation of the Ca2+/CaM signaling pathway in MCF-7 cells. In exploring the biological functions of (RORalpha), receptors, we found that the decrease in RORalpha protein levels by an (RORalpha), antisense oligonucleotide con-elated with growth inhibition in MCF-7 cells. Our data suggest that RORalpha receptors may play a role in stimulating the proliferation of MCF-7 cells, and thus, the repressive effect of melatonin on these receptors may, at least in part, mediates melatonin's antiproliferative effects on breast cancer cells<br>acase@tulane.edu
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"Proenkephalin gene expression during rat basal ganglia development and the effects of chronic morphine exposure." Tulane University, 1993.
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Proenkephalin is one of the three genes known to encode endogenous opioid peptides. An antibody directed against a unique peptide sequence within proenkephalin that is not found in any other known peptide sequence was characterized and compared to a methionine enkephalin antibody. This antibody was found to be specific for enkephalinergic cell bodies, fibers and terminals. The development of proenkephalin mRNA in the neostriatum and its derivative peptides in the globus pallidus were found to parallel neurogenetic gradients. Expression was also found early in the central nucleus of the amygdala, late in the nucleus accumbens and olfactory tubercle, and transiently in clusters within the neostriatum. Dopaminergic innervation was found to precede proenkephalin expression in the rostral neostriatum and to follow proenkephalin expression in the caudal neostriatum. Neostriatal cells becoming postmitotic on embryonic day 14 (E14) moved twice during the course of their development: first ventrolaterally and then later dorsomedially in clusters. In contrast, neurons born at E19 were found to migrate only ventrolaterally. Clusters of neurons born at E14 corresponded to substance P immunoreactive patches. At progressively more rostral levels, progressively fewer E14-generated cells were detected in the neostriatum. The development of the two main peptidergic projection neurons of the neostriatum, enkephalin and substance P, began from opposite poles of the neostriatum and adjacent structures of the extended amygdala. During the perinatal period (from E16 to the day of birth), the distribution of neurons expressing proenkephalin spread primarily dorsomedially and rostrally. In contrast, neurons expressing substance P spread primarily dorsomedially and caudally. By the day of birth, there was extensive overlap in the distributions of proenkephalin and substance P in the neostriatum, but little to no coexpression of both peptides was ever found. Chronic opiate exposure in utero resulted in a selective increase in proenkephalin mRNA expression in the patch compartment of the neostriatum. Similarities in the anatomical connections, neurochemistry and development of the extended amygdala and the neostriatal patch compartment suggest that they may form a fundamental forebrain circuitry involved in motivated behavior and fight or flight responses<br>acase@tulane.edu
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Baheti, Ankur R. "Development of an anatomy identification skill set for laparoscopic and robotic minimally invasive procedures." 2008. http://proquest.umi.com/pqdweb?did=1594485631&sid=2&Fmt=2&clientId=39334&RQT=309&VName=PQD.
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Thesis (M.S.)--State University of New York at Buffalo, 2008.<br>Title from PDF title page (viewed on Jan. 14, 2009) Available through UMI ProQuest Digital Dissertations. Thesis adviser: Kesavadas, Thenkurrisi Includes bibliographical references.
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"Microanatomical characterization of Loaina uniformis: A morphologic comparison with Loa loa (Nematoda: Filarioidea)." Tulane University, 1996.
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Zoonotic filarial infections have been reported from most parts of the world. However, the range of species involved, host-parasite interactions and morphologic criteria for the specific identification of the species is still poorly known and understood. Species of Dirofilaria are the most common agents of human infection and the most studied group of zoonotic filariae. Several other groups, including species of Brugia and Onchocerca are being reported with increasing frequency. Loaina uniformis, a common parasite of rabbits in the southeastern United States, represents yet another species recovered from human tissues, although extremely rare. This parasite is of additional interest because its apparent morphologic and possible biologic similarity to Loa loa a common filaria of humans in West and Central Africa. The present study was undertaken to characterize the morphologic features of Loaina uniformis to enable its recognition when encountered in human tissues. This objective additionally permitted comparison of L. uniformis to Loa loa at both, gross and microscopic levels to determine, to whatever extent possible, the relationship of the two parasites. L. uniformis adult worms both living and dead were collected from the tissues of the natural host, the rabbit Sylvilagus floridanus. These were processed for gross examination and histologic study by light microscopy of serially sectioned material. Detailed microscopic observations were recorded for worms of both sexes and full anatomic characterizations were prepared. Emphasis was placed on the structure of the body and detailed features of the cuticle, hypodermis and musculature. The structural features of the digestive and reproductive systems as well as their arrangement within the pseudocoelom have been characterized. Observations indicate that L. uniformis can be distinguished from all other known species of zoonotic filariae available for study on the basis of their microanatomical features. Equivalent material of L. Loa obtained from experimental definitive hosts was compared with L. uniformis. The anatomical features of L. uniformis and L. loa are similar in many respects and they share many biological features suggesting that they are taxonomically closely related<br>acase@tulane.edu
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"Steroid regulation of LHRH in rat brain: Glucocorticoids and androgens." Tulane University, 1994.
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Luteinizing hormone releasing hormone (LHRH), a decapeptide, is synthesized in the central nervous system, released into the portal blood, and transported to the anterior pituitary, where it regulates the secretion of luteinizing hormone (LW) and follicle-stimulating hormone (FSH). Therefore, LHRH is a key integrator between the neural and endocrine systems and plays a pivotal role in promoting reproductive functions. The synthesis and secretion of LHRH are under the exquisite control of different neurotransmitters and steroid hormones, including glucocorticoids and androgens. In this dissertation, the effect of glucocorticoid treatment on the content of LHRH neurons was examined first. It was shown in male, but not in female rats, that corticosterone treatment not only increased the number of detectable LHRH neurons in the region around the organum vasculosum of the lamina terminalis (OVLT), but also increased the average size of the neurons in this region. Double-labeling immunocytochemistry demonstrated that LHRH neurons do not have androgen receptors. Further studies revealed that a certain number of tyrosine hydroxylase (TH) neurons in the hypothalamic periventricular nucleus and P-endorphin neurons in the arcuate nucleus colocalize with androgen receptors, suggesting that both TH neurons and P-endorphin neurons might be involved in the mediation of the effects of androgens on LHRH neurons. Androgenic-anabolic steroid (AAS) treatment increased the colocalization rate of TH neurons with androgen receptors in the periventricular nucleus. In the arcuate nucleus, the colocalization of TH neurons with androgen receptors was significantly greater in the dorsomedial than in ventrolateral portions of the nucleus. Finally, it was demonstrated that about 70% of somatostatin neurons in the periventricular nucleus contain androgen receptors. This result provides an anatomical basis for the possible direct action of androgens on these somostatin neurons. Contrary to what was expected, AAS treatment had no effect on the colocalization rate, suggesting that a subpopulation of somatostatin neurons may not express androgen receptors at all<br>acase@tulane.edu
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Ng, Tiong Weng. "Molecular interactions of polo-like Kinase 1 (PLK1) in colorectal cancer." Thesis, 2017. http://hdl.handle.net/1959.7/uws:46007.
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Colorectal cancer (CRC) is one of the most prevalent cancers in Australia with about a third being rectal cancer. Locally advanced rectal cancer is frequently treated with pre-operative radiotherapy (DXT) in concurrent with chemotherapy to reduce the tumour mass for better surgical access, and therefore improving the treatment outcomes. The response to DXT varies amongst individual patients, raising the need of predictive markers to prevent unnecessary toxic therapy. Polo-like kinase 1 (PLK1) is involved in cell cycling and DNA damage response (DDR) and in view of the latter, it may be a potential marker for patient response to chemoradiotherapy. The relationship between PLK1 expression and radiosensitivity remains controversial, particularly in CRC. In addition, the causes of PLK1 overexpression remain unclear although it is associated with oncogenesis. This thesis aims to study the role of PLK1 in radiosensitivity of CRC, the contribution of mutation and DNA methylation to PLK1 expression and the correlation between PLK1 and p21 expression. CRC cell lines (HCT116 and SW48) that are microsatellite unstable and microsatellite stable (Colo320DM and T84) were chosen for the studies. The CRC cells were treated with PLK1-specific siRNA and ionising radiation (IR) and then subjected to PLK1 expression, cell survival, apoptotic and cell cycling analyses. Data analysis from Catalogue of Somatic Mutations in Cancer (COSMIC) and Sanger sequencing of PLK1 gene were performed in the genetic study. The DNA methylation study involved mass spectrometry analysis and pyrosequencing of DNA from the CRC samples. The correlation between PLK1 and p21 was studied by immunohistochemical (IHC) staining on tissue microarray (TMA) of CRC patient cohort. Depletion of PLK1 additively enhanced the effect of IR on cell survival, apoptosis and cell cycle arrest in HCT116, SW48 and Colo320DM, but did not radiosensitise the cells. COSMIC data showed a low incidence of mutation in CRC, but the mutation c.1010A>G (p.R3370Q) at the motif for ubiquitination and proteasomal degradation of PLK1 may elevate the PLK1 stability. Sanger sequencing detected mutations of PLK1 in HCT116 and SW48 but they are not functionally associated. DNA methylation studies concluded that PLK1 expression is likely to be independent of CpG methylation. IR induced a transient increase of PLK1 expression in all the microsatellite unstable cell lines with HCT116 and SW48 downregulated later. Lastly, IHC of CRC patient cohort TMA demonstrated the weak association between PLK1 and p21 expression.
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Tut, Thein Ga. "Predictive biomarkers of radiation sensitivity in rectal cancer." Thesis, 2016. http://hdl.handle.net/1959.7/uws:38000.
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Colorectal cancer (CRC) is the third most common cancer in the world. Australia, New Zealand, Canada, the United States, and parts of Europe have the highest incidence rates of CRC. China, India, South America and parts of Africa have the lowest risk of CRC. CRC is the second most common cancer in both sexes in Australia. Even though the death rates from CRC involving the colon have diminished, those arising from the rectum have revealed no improvement. The greatest obstacle in attaining a complete surgical resection of large rectal cancers is the close anatomical relation to surrounding structures, as opposed to the free serosal surfaces enfolding the colon. To assist complete resection, pre-operative radiotherapy (DXT) can be applied, but the efficacy of ionising radiation (IR) is extremely variable between individual tumours. Reliable predictive marker/s that enable patient stratification in the application of this otherwise toxic therapy is still not available. Current therapeutic management of rectal cancer can be improved with the availability of better predictive and prognostic biomarkers. Proteins such as Plk1, γH2AX and MMR proteins (MSH2, MSH6, MLH1 and PMS2), involved in DNA damage response (DDR) pathway may be possible biomarkers for radiation response prediction and prognostication of rectal cancer. Serine/threonine protein kinase Plk1 is overexpressed in most of cancers including CRC. Plk1 functional activity is essential in the restoration of DNA damage following IR, which causes DNA double strand break (DSB). The earliest manifestation of this reparative process is histone H2AX phosphorylation at serine 139, leading to γ-H2AX. Colorectal normal mucosa showed the lowest level of γH2AX with gradually increasing levels in early adenoma and then in advanced malignant colorectal tissues, leading to the possibility that γH2AX may be a prospective biomarker in rectal cancer management. There are numerous publications regarding DNA mismatch repair (MMR) proteins, the insufficiency of which is characteristic of CRCs with microsatellite instability (MSI). MSI may enable unlimited replicative potential of malignant cell that leads to radiation injury resistance. Therefore, these proteins were characterized in both CRC cell lines (MMR proteins) and different (core and invasive front) rectal cancer tissues (Plk1, γH2AX and MMR proteins) exposed to radiation. Histopathological grading of tumour regression was performed following radiotherapy in rectal cancer as a marker of radiotherapy response and a surrogate indicator of patient prognosis. Though MMR protein expressions correlated with improved in vitro cell survival following radiation, these findings could only be partially replicated in patient tissue samples. This may not be entirely unexpected, given intratumoural heterogeneity in genetic profiles and oxygenation between individual cancer cells, their interaction with stromal environment and a multitude of other factors that cannot be adequately replicated in cell line experiments. In our rectal cancer patient cohort, histopathological regression following radiotherapy did appear to correlate with better clinical outcome, but certainly no replacement for the routine pTNM staging with which it was compared. Overexpression of Plk1 in the primary rectal cancer also correlates with poor tumour regression and reduced overall survival. High level of γH2AX correlates with higher tumour stage, perineural invasion and vascular invasion. However, interpretation of the results is limited by the small number of positivity amongst the cohort, with respect to γH2AX and MMR proteins. The combined analysis of all the proteins examined in this thesis revealed no interactions, possibly suggesting these biomarkers act individually within the DDR pathway, rather than in a demonstrably interdependent manner. Though our results are mixed, finding biomarkers predictive of radiation response is nonetheless critical. Enhancing the radiosensitivity of cancers through manipulating the functional activity and/or expression of prospective biomarkers could conceivably enhance tumour response to the level that the extent of consequent surgical resection can be minimized.
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Koloadin, Leah S. "Intraspecific and interspecific variation in the xylem functional traits of Callitris species growing along an aridity gradient." Thesis, 2020. http://hdl.handle.net/1959.7/uws:67022.
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More severe and prolonged drought events as a result of climate change, have the potential to cause broad scale forest and woodland dieback worldwide. The Australian continent is primarily comprised of arid biomes. However, rapid climate change-induced desertification threatens these surprisingly diverse ecosystems. Callitris is Australia’s most successful conifer genus, yet they remain they remain vulnerable to drought-induced decline. Given Callitris are the primary structural component of vegetation in many Arid-Australian ecosystems, their persistence is the most important factor preventing the collapse of these ecosystems. Resistance to drought-induced xylem cavitation has emerged as a key physiological trait determining the survival of tree species under water-limited conditions. Under the influence of aridity, Callitris have evolved the world’s most cavitation resistant xylem, yet little is known about the xylem anatomy liable to convey this. The main objective of this thesis was to identify the anatomical xylem traits and attributes associated with cavitation resistance in Callitris. The main body of work in this thesis involved analysis of microscopic anatomical traits through the use and development of several microscopy techniques. An inter-specific study produced a complementary dataset of xylem anatomical traits for branches of 15 Callitris and closely related species, building on the physiological dataset by Larter et al. (2017). An intraspecific study among five C. glaucophylla populations required the physiological and anatomical traits measurements. An intraspecific increase in cavitation resistance with aridity was found among the five populations in both the primary branches and roots. To understand whole plant hydraulic function, variability in xylem anatomical traits in the tertiary branches, secondary branches and trunks, of C. glaucophylla, in relation to the primary branches and roots was also explored. A greenhouse experiment tested the plasticity of anatomical traits in C. glaucophylla seedlings grown under contrasting water treatments. Mainly, among seedlings grown under well-watered conditions, height growth and more hydraulically efficient roots are prioritised, while more mechanically reinforced tracheids and safer but less efficient pit traits are favoured among seedling grown under water deficit.
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Fong, Sheri F. T. "The LOX and LOXL2 amine oxidases in colon and esophageal cancer." 2003. http://proquest.umi.com/pqdweb?index=0&did=765084641&SrchMode=1&sid=3&Fmt=2&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1233165331&clientId=23440.
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"Gonadal steroid regulation of NADPH-diaphorase histochemistry in the male and female rat brain." Tulane University, 1996.
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The present series of experiments examined selected brain regions to determine the effects of the gonadal steroids, estrogen and testosterone, on the reactivity of the nitric oxide synthase, NADPH-diaphorase. The results of the first experiment indicated that estrogen administration significantly increased NADPH-diaphorase reactivity 29% in the horizontal limb of the diagonal band of Broca, while testosterone administration significantly reduced NADPH-diaphorase reactivity 27% in the vertical limb of the diagonal band of Broca. The results of the second experiment indicated that 11.8% of NADPH-diaphorase neurons in the vertical limb of the diagonal band of Broca also were immunoreactive for the androgen receptor, while 7.8% of NADPH-diaphorase neurons in the horizontal limb of the diagonal band of Broca additionally were immunoreactive for the androgen receptor. In the ventromedial nucleus of the hypothalamus, however, 90.7% of NADPH-diaphorase also were immunoreactive for the androgen receptor. The results of a third experiment indicated that NADPH-diaphorase reactivity in the ventromedial nucleus of the hypothalamus was significantly increased by 40% in intact female rats sacrificed during proestrus when compared to gonadectomized female rats. NADPH-diaphorase reactivity in either the vertical limb or horizontal limb of the diagonal band of Broca did not significantly fluctuate over the estrous cycle in intact female rats sacrificed during diestrus, proestrus, or estrus. The results of a fourth experiment indicated that NADPH-diaphorase reactivity was not significantly decreased in the diagonal band of Broca of intact male rats when compared to castrated male rats. Collectively, these results indicate that experimental titers of the steroid hormone, testosterone, reduce the reactivity of the nitric oxide synthase, NADPH-diaphorase, in the diagonal band of Broca of male rats. Physiological titers of testosterone, however, do not significantly reduce the reactivity of NADPH-diaphorase in the diagonal band of Broca of male rats. Testosterone may affect NADPH-diaphorase reactivity by a genomic mechanism, as a population of NADPH-diaphorase neurons also were immunoreactive for the androgen receptor. In addition, the present results indicate that experimental titers of the steroid hormone, estrogen, increase the reactivity of NADPH-diaphorase in the diagonal band of Broca of female rats. Alternatively, physiological titers of estrogen do not significantly increase the reactivity of NADPH-diaphorase in the diagonal band of Broca of female rats. However, physiological titers of estrogen do significantly increase the reactivity of NADPH-diaphorase in the ventromedial nucleus of the hypothalamus. These results are in general agreement with previous reports that indicate experimental titers of estrogen increase the reactivity of NADPH-diaphorase, and additionally indicate that NADPH-diaphorase reactivity in the ventromedial nucleus of the hypothalamus is significantly increased during the estrous cycle of intact cycling female rats<br>acase@tulane.edu
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"Neuronal reorganization and glial neuroimmune responses to injury in organotypic slice cultures of neonatal mouse hippocampus." Tulane University, 1996.
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The hippocampal organotypic slice culture was used to study injury in the CNS. Studies characterized factors that influenced regenerative events in the hippocampal dentate gyrus, concomitant changes in glial cell populations, and examined the role of neuroglia in repair of damaged neural tissues Deafferentation of the hippocampus causes dentate granule cell axons, known as the mossy fibers, to initiate collateral neurite sprouting. Following axonal degeneration, mossy fibers form collaterals that invade the dental molecular layer, which contains denervated granule cell dendrites (Zimmer and Gahwiler, 1987) Factors influencing mossy fiber collateral sprouting were identified and found to include time in culture, positional origin of the slice culture along the septo-temporal axis of the hippocampus, and the presence of attached subicular-entorhinal cortical tissues. Additionally, differential damage to mossy fibers was not the basis for the differences in collateral sprouting along the septo-temporal axis Slice cultures were used to investigate glial cell responses to lesion-induced injury in the hippocampus. These experiments demonstrated a temporal correlation between reactive microglia, IL-1$\beta$, and astrocytic hypertrophy over a period of 10 days in vitro (DIV). Microglia were identified using lectin histochemistry, astrocytes and IL-1$\beta$ expressing cells were identified using immunocytochemical markers Reactive microglia steadily decreased as resting microglia increased over 10 DIV. IL-1$\beta$ (+) cells showed a similar pattern of temporal and regional distribution as reactive and resting microglial elements. The onset of astroglial hypertrophy in the dentate gyrus correlated closely with the timecourse of mossy fiber collateral sprouting described. Thus, in hippocampal slice cultures a transient and regional distribution of reactive and resting microglia, IL-1$\beta$ (+) cells and astrocytes occurs within the dentate gyrus during the first 10DIV Excessive numbers of reactive microglia have been correlated with the development and progression of neurodegenerative disease (Dickson, 1990). Experiments were conducted to identify activated and resting microglia, and their reactions to damage incurred during culture preparation. Spontaneous neurodegenerative sites were observed within the first 6DIV as well as within specific regions of the slice cultures. The addition of L-leucine methyl ester to slice cultures significantly reduced the frequency and distribution of neurodegeneration within the first 6DIV<br>acase@tulane.edu
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"Effects of a sequential treatment regimen of melatonin and retinoic acid on MCF-7 human breast cancer cells." Tulane University, 1999.
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Neoplastic events can be marked by uncontrolled cell proliferation, and thus, one major focus of cancer research has been to identify treatments which reduce or inhibit cell growth. Over the years, various compounds, both naturally occurring and chemically synthesized, have been utilized to inhibit neoplastic cell proliferation. Two such oncostatic agents, melatonin and retinoic acid, have been shown to suppress the growth of hormone-responsive breast cancer in a similar time-course. Currently, separate clinical protocols exist for the administration of retinoids and melatonin as adjuvant therapies for cancer. In vitro studies were conducted to examine effects of a sequential treatment regimen of melatonin followed 24 hours later by retinoic acid (RA) on the proliferation of the estrogen receptor (ER)-positive MCF-7 human breast tumor cells line Incubation of hormonally-responsive MCF-7 and T47D cells with melatonin (10--9 M) followed 24 hours later by RA (10--9 M) resulted in the complete cessation of cell proliferation and induction of apoptosis as was evidenced by the formation of a ladder of nucleosomal oligomers when viewed by agarose gel electrophoresis. The apoptotic effect of this sequential treatment with melatonin and RA appears to be both cell and regimen specific since (a) ER-negative MDA-MB-231 and BT-20 breast tumor cells were unaffected, and (b) the simultaneous administration of melatonin and RA was not associated with apoptosis in any of the breast cancer cell lines studied. Furthermore, no induction of a cytocidal effect is observed in cells pre-treated with RA followed by melatonin, suggesting that melatonin is priming the cells to the effects of RA. There also appears to be a minimum pre-treatment time with melatonin of 12 h necessary in order to induce the apoptotic effect. It has been shown also that pre-treatment of MCF-7 cells for 24 hours with melatonin sensitizes the cells to the effects of RA, and that a much lower concentration of RA can be used to induce an apoptotic effect. This sensitization of the cells to RA is not due to up-regulation of RAR or RXR expression since Western blot analysis demonstrated no change in expression of RAR or RXR in response to treatment with melatonin and RA. The sequential treatment regimen of melatonin followed by RA induced cytocidal effects in MCF-7 cells by activating pathways leading to apoptosis. This was evidenced by decreased ER and Bcl-2 as well as increased Bak and Bax expression. Taken together, the results suggest that use of an appropriate regimen of melatonin and RA inhibits the proliferation and induces apoptosis in ER-positive human breast cancer, and should be considered for pre-clinical and clinical evaluation against ER-positive human breast cancer<br>acase@tulane.edu
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Zhao, Hui Fu Yun-Xin. "A coalescent analysis for modeling the mutation process in colorectal cancer /." 2007. http://proquest.umi.com/pqdweb?did=1436357001&sid=1&Fmt=2&clientId=68716&RQT=309&VName=PQD.
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Gebremedhn, Endale G. "Exploring the incidence and variability of oxaliplatin-induced neuropathic pain symptoms in colorectal cancer patients, comparative in vivo / in vitro modelling of oxaliplatin/ 56MESS(IV) as an alternative cancer treatment, and minocycline administration as a prophylactic agent for chemotherapy-induced neuropathic pain." Thesis, 2021. http://hdl.handle.net/1959.7/uws:68146.
Full textAbstract:
Oxaliplatin is commonly used for the treatment of advanced and recurrent colorectal cancer (CRC). However, oxaliplatin-induced neuropathic pain remains a challenge for the healthcare systems worldwide. In chapter II, the incidence and impact of acute oxaliplatin-induced neuropathic pain on chemotherapy treatment in colorectal cancer patients in the first cycle from the published research literature was explored. In chapter III, the variability of oxaliplatin-induced neuropathic pain symptoms from the Southwestern Sydney Local Health District Hospitals (SWLHDHs) database of patients who received oxaliplatin based chemotherapy treatment (2011-2015) and the implications for the management of colorectal cancer patients was assessed. In chapter IV, it was explored whether oxaliplatin can induce behavioural hypersensitivity in healthy rats using the dosing regimen that mimics the standard clinical protocols (oxaliplatin 2.5 mg/kg i.p every two weeks). In chapter V, the effects of oxaliplatin and 56MESS(IV) on the viability, PI staining (cell death) and activation (nitrite production) of RAW264.7 (macrophages) and N11 (microglia) cell lines were explored in vitro. In summary, oxaliplatin-induced neuropathic pain remains a big problem as it affects treatment compliance in quarter of CRC patients during cycle 1 and as neuropathic pain symptoms oscillate across cycles for individual patients. This warrants further detailed patient-by-patient analysis of pain symptoms in future clinical trials. Additionally, the in vivo and in vitro data showed that minocycline pre-treatment has a potential to ameliorate oxaliplatin and 56MESS(IV) induced production of pro-inflammatory chemical mediators such as nitrite in vitro cell lines, which may be relevant to in vivo models of chemotherapy-induced neuropathic pain. However, oxaliplatin-induced neuropathic pain is more likely multifactorial and research should be continued on the mechanisms of neuropathy and potential therapeutic drugs.