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1
Hall, Leon Lorenzo. "Glomerular disease : an investigation of gene expression in single human glomeruli." Thesis, University of Leicester, 1998. http://hdl.handle.net/2381/29566.
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Glomerular disease commonly presents with microscopic haematuria. Holes must be present in the glomerular basement membrane to allow erythrocytes through to the urinary space. The development of these holes possibly involves the decreased synthesis and/or increased degradation of the glomerular basement membrane. Glomerulosclerosis may be viewed as the reverse scenario to that of haematuria involving the increased synthesis and decreased degradation of the mesangial matrix. In this study semi-quantitative RT-PCR based methods have been applied to single glomeruli from IgA nephropathy, thin membrane disease, and control cases. The results of these studies found decreased levels of mRNA for PDGF, MT1-MMP, TIMP1, TIMP2, and collagen type IV 2 (p values equaled 0.0026, 0.0013, 0.0119, 0.0438, and 0.015 respectively) in thin membrane disease. In IgA nephropathy decreased levels of mRNA for MT1-MMP (p=0.007) were detected. Increased mRNA for TIMP1 was seen only in IgA cases with time dependent increases in serum creatinine levels (p=0.0106). The immunocytochemistry investigation of MMP2, MMP9, collagen type III, and tenascin found increased levels of tenascin in IgA nephropathy (p=0.004). In situ zymography was used for the detection of matrix metalloproteinase activity in frozen sections. This investigation identified a 15 % decrease in metalloproteinase activity in IgA nephropathy cases. The finding of decreased MT1-MMP and TIMP1 mRNA in IgA nephropathy possibly relates to the decreased activation of MMP2 and increased inhibition of MMP9, respectively. These findings along with increased levels of tenascin protein support the proposed involvement of an imbalance in matrix synthesis and degradation as a cause of the accumulation of mesangial matrix in IgA nephropathy. Decreased levels of PDGF, MT1-MMP, TIMP1, TIMP2, and collagen type IV 2 mRNA in thin membrane disease suggest the involvement of a complex mechanism of disease involving decreased synthesis and increased degradation of the glomerular basement membrane.
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Mitsner, Vladimir. "Modeling diffusion in cerebellar glomeruli." Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2007. http://wwwlib.umi.com/cr/ucsd/fullcit?p3284167.
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Thesis (Ph. D.)--University of California, San Diego, 2007.Title from first page of PDF file (viewed January 14, 2008). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 88-96).
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Murphy, Gabe J. "Synaptic processing in olfactory bulb glomeruli /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2004. http://wwwlib.umi.com/cr/ucsd/fullcit?p3137220.
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Roux, Lisa. "Neuroglial network interactions in the olfactory glomeruli." Paris 6, 2011. http://www.theses.fr/2011PA066400.
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Une des propriétés caractéristiques des astrocytes est leur niveau d'expression élevé en connexines, les protéines constitutives des jonctions communicantes, à la base de leur organisation en réseaux. L'objectif de cette thèse a été de comprendre comment les neurones et les astrocytes interagissent non pas à l'échelle cellulaire, comme cela a généralement été étudié, mais au niveau des réseaux multicellulaires. Cette étude a été menée dans les glomérules olfactifs où les circuits neuronaux forment des unités fonctionnelles bien définies. Des expériences de «dye coupling» réalisées sur des tranche aigues de bulbe olfactif de souris, ont tout d'abord permis d'établir que (1) l'organisation spatiale des réseaux astrocytaires reflète les unités fonctionnelles glomérulaires et (2) qu'ils sont régulés par l'activité neuronale ainsi que l'expérience olfactive. La contribution des réseaux astrocytaires à l'activité de réseau du bulbe olfactif a ensuite été étudiée in vitro. Une activité rythmique (<1Hz), dépendante des interactions neuronales au sein du glomérule, a été observée dans les cellules mitrales. Ses caractéristiques s'apparentent aux oscillations lentes enregistrées pendant le sommeil dans le système thalamo-cortical. Des souris transgéniques dépourvues de connexines astrocytaires ont permis de montrer que les astrocytes modulent cette activité de réseau via ces protéines. Ces résultats mettent en évidence une boucle d'interactions réciproques entre réseaux neuronaux et astrocytaires. Ils suggèrent qu'un tel dialogue pourrait jouer un rôle dans les relations bulbe olfactif - cortex qui, à la différence des autres systèmes sensoriels, sont dépourvues de relais thalamique
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Rado, Anita 1967. "Mathematical models of ionic diffusion in olfactory glomeruli." Diss., The University of Arizona, 1998. http://hdl.handle.net/10150/282741.
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Many vertebrate and invertebrate olfactory systems are similar in the organization of their synaptic neuropil into glomeruli, structures surrounded by an incomplete layer of glial processes. Within glomeruli, the axons of olfactory receptor neurons synapse with the dendrites of their target brain neurons. Glomeruli are likely to be odor specific in that each glomerulus processes information from a subset of axons about a particular chemical feature of odorant molecules. Therefore, a large proportion of the neurons within a glomerulus may be excited simultaneously in response to a particular odor. The resulting release of potassium ions from neurons may be sufficient to cause a substantial increase in the extracellular concentration of potassium ions and thus affect the excitability of neighboring neurons. The goal of this study is to develop theoretical models for the diffusion of potassium ions in the extracellular space, and to predict how the glial border affects the spread of potassium ions following the activation of olfactory sensory neurons. Observations of the morphology of the interior and border of the glomerulus were used to estimate the porosity and effective diffusivity of these regions, and the size of the "mouth" region where there is no glial covering. Potassium was assumed to be released into the extracellular space during an initial 0.5 seconds. The time-dependent diffusion equation was solved in spherical coordinates using a finite-difference method. The results indicated that the glial envelope forms a partial barrier to the diffusion of potassium ions, and greatly reduces the spread of potassium ions to neighboring glomeruli following release. According to the model, the decline in potassium concentration within the glomerulus due to the leakage from the mouth and glial boundaries is relatively slow, taking more than 10 seconds to approach its resting level. These findings support the hypothesis that the characteristic distribution of glial cells around glomeruli could play a significant role in olfactory information processing.
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Imabayashi, Takeshi. "Expression of basic helix-loop-helix proteins in the glomeruli." Kyoto University, 2001. http://hdl.handle.net/2433/150563.
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Semmelhack, Julia L. "Individual glomeruli mediate innate olfactory attraction and aversion in Drosophila." Diss., [La Jolla] : University of California, San Diego, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p3369174.
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Thesis (Ph. D.)--University of California, San Diego, 2009.Title from first page of PDF file (viewed September 15, 2009). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.
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Krull, Catherine Ellen. "A role for tenascin-like molecules in developing olfactory glomeruli." Diss., The University of Arizona, 1993. http://hdl.handle.net/10150/186434.
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The distribution and potential functions of extracellular matrix and cell-surface molecules during neural development were explored, using an insect olfactory system as a model. Immunocytochemical and biochemical experiments were performed to examine the cellular localization and temporal pattern of expression of molecules similar to the vertebrate extracellular matrix molecule tenascin. These studies showed that tenascin-like molecules were associated with glial cells that form borders around distinct units of neuropil called glomeruli. These molecules were present at critical times during the glomerulus formation. In vitro assays, performed to examine the effects of tenascin on the morphological development of moth CNS neurons, indicated that the growth of these neurons was inhibited by tenascin. Taken together, these results suggest that glial cells decorated with tenascin-like molecules could contribute to the patterning of the olfactory neuropil by constraining neurite outgrowth within developing glomeruli. The distribution of other glycosylated molecules that could play important developmental roles was examined using the lectin peanut agglutinin. This lectin labeled the tips of dendrites as they grow into developing glomeruli to interact with glial cells or sensory axons. Four lectin-labeled proteins were shown to be developmentally regulated and thus could participate in neurite outgrowth, synapse formation or the stabilization of glomerular units. Future experiments to further explore molecular mechanisms underlying the development of neural architecture are proposed. The results of this study are discussed in the context of dynamic interactions between neurons and glial cells.
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Gao, Xiang. "Local Purinergic Control of Arteriolar Reactivity in Pancreatic Islets and Renal Glomeruli." Doctoral thesis, Uppsala universitet, Institutionen för medicinsk cellbiologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-230770.
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Local control of regional blood flow is exerted mainly through the arterioles. An adequate minute-to-minute regulation of blood perfusion of the kidney and the pancreas is obtained by the modulation of arteriolar reactivity, which will influence the organ function. The importance of purinergic signaling in this concept has been addressed, with special emphasis on the role of the adenosine A1 receptor. The effects of adenosine on two specialized vascular beds, namely the renal glomerulus and the pancreatic islets, have been examined. Characteristic for these regional circulations is their very high basal blood flow, but with somewhat different responses to vasoconstrictor and vasodilator stimuli. By adapting a unique microperfusion technique it was possible to separately perfuse isolated single mouse arterioles with attached glomeruli or pancreatic islets ex vivo. Microvascular responses were investigated following different additions to the perfusion fluid to directly examine the degree of dilation or constriction of the arterioles. This has been performed on transgenic animals in this thesis, e.g. A1 receptor knockout mice. Also effects of P2Y receptors on islet arterioles were examined in both normoglycemic and type 2 diabetic rats. Furthermore, interference with adenosine transport in glomerular arterioles were examined.. Our studies demonstrate important, yet complex, effects of adenosine and nucleotide signaling on renal and islet microvascular function, which in turn may influence both cardiovascular and metabolic regulations. They highlight the need for further studies of other purinergic receptors in this context, studies that are at currently being investigated.
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Heinbockel, Thomas 1963. "Functional organization of male-specific olfactory glomeruli in the sphinx moth Manduca sexta." Diss., The University of Arizona, 1997. http://hdl.handle.net/10150/288800.
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The macroglomerular complex (MGC) in the antennal lobe of the sphinx moth Manduca sexta is the first brain region for processing sex-pheromonal information. How is the MGC is functionally organized, and how are chemical and physical features of the pheromone encoded by projection neurons (PNs) innervating the MGC (MGC-PNs). For some MGC-PNs with arborizations in the toroid, one of the two major glomeruli of the MGC, bombykal (a key pheromone component) can evoke a mixed (inhibitory/excitatory/inhibitory) response similar to that evoked by the pheromone blend. Likewise, for some neurons with arborizations in the cumulus, C-15 (a mimic of the second key component) can evoke a similar mixed response. The maximal pulse frequency encoded by these component-specific neurons was not increased in the presence of the blend, but seemed to arise through the convergence of two parallel pathways, one excitatory and one inhibitory, both activated by the same olfactory stimulus. Convergence of different synaptic pathways allowed MGC-PNs to resolve intermittent stimuli and thus to relay the temporal structure of the pheromonal signal to higher brain centers. In a subset of MGC-PNs that was excited by antennal stimulation with either of the two components (bombykal-C-15 cells, blend neurons), the ability to encode intermittent stimuli was improved when stimulating with the blend. The temporal character of the responses was dependent on the ratio of the two key components in the blend. Component-specific MGC-PNs responded over a range of increasing pheromone concentration with stronger inhibitory and excitatory postsynaptic potentials and more impulses but the responses were not affected by changing the blend ratio. Two basic response patterns emerged when the ipsilateral antennal flagellum was stimulated at different zones along its proximo-distal axis while the activity of MGC-PNs was recorded. A subset of neurons with broad receptive fields was excited regardless of the zone of the antenna stimulated, whereas another subset responded selectively to stimulation of the basal region of the antenna. A diverse array of MGC-PNs forms a heterogeneous group of parallel output channels that encode features of the pheromone signal that the moth is likely to encounter in the natural stimulus situation.
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Davidson, Gary. "FGF2 requirement for podocyte maturation in-vitro." Thesis, University of Aberdeen, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.311157.
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FGF2 is expressed in renal podocytes as they differentiate in-vivo, as demonstrated by specific antibody staining within developing glomeruli of chicken metanephros. Mice lacking FGF2 have been generated in the laboratory by targeted deletion and kidneys of Fgf2 deficient mice appear to develop normally. Detailed histological analysis of adult kidneys from these mice however has revealed low frequency glomerular abnormalities. Additionally, a few obvious cases of glomerulosclerosis with severe podocyte damage were observed specifically in mutant mice. Taken together these observations indicate FGF2 plays a role in podocyte development and/or function. A novel culture system that allows the induction of podocyte cell differentiation in-vivo has recently been developed. The system is based on isolation of conditionally immortalised podocyte cells derived from H-2KbtsA58 transgenic (immorto) mice. Isolation of podocyte cells from renal glomeruli of wild-type and FGF2 deficient immorto mice was performed to address the functional relevance of FGF2 in podocyte development. Conditionally immortalised wild-type podocyte cells (wild-type MPCs) display characteristic features of podocytes in-vivo, however Fgf2 null MPCs show striking morphological and molecular abnormalities. Mutant podocyte cells do not undergo the epithelial-to-mesenchymal transformation (EMT) associated with normal podocyte maturation and, correspondingly, fail to differentiate. The EMT mediator Slug is up-regulated as wild-type cells differentiate but is missing in mutant cells, suggesting this transcription factor acts downstream of FGF signalling to mediate EMT associate maturation of podocytes. Fgf7 and Fgf10 expressions are lost in Fgf2 deficient MPC cells, but not in Fgf2 deficient kidney cortex, affording an explanation to the emergence of a stronger defect in-vitro.
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Kuwabara, Takashige. "Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal and distal nephrons." Kyoto University, 2009. http://hdl.handle.net/2433/124312.
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Block, Carolin. "Differential proteomic analysis of isolated glomeruli from two murine nephropathy models at early stages of glomerulosclerosis." Diss., lmu, 2008. http://nbn-resolving.de/urn:nbn:de:bvb:19-90585.
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Block, Carolin. "Differential proteomic analysis of isolated glomeruli from two murine nephropathy models at early stages of glomerulosclerosis." kostenfrei, 2007. http://edoc.ub.uni-muenchen.de/9058/.
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De, León Héctor. "Characterization of atrial natriuretic factor and angiotensin II receptors in rat renal glomeruli, preglomerular vessels and mesentery." Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=41280.
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Atrial natriuretic factor (ANF) and angiotensin II (ANG-II) have multiple biological actions, most of them related, directly or indirectly, to blood pressure regulation and fluid homeostasis. The present work was undertaken to study the regulation of renal glomerular ANF receptors by renal sympathetic nerves and ANG-II, to characterize ANF and ANG-II receptor subtypes in rat renal preglomerular vessels, and to define the precise localization of these receptors in the rat mesentery. Using radioligand binding techniques, we demonstrated that renal denervation up-regulated glomerular ANF receptors, and ANG-II blunted this effect, independently of modifications in plasma ANF levels. Receptor characterization studies showed that rat renal preglomerular vessels and glomeruli do not express detectable amounts of ANP-B receptors, and that they have a different proportion of ANP-A and ANP-C receptors. In glomeruli, 85% of receptors are ANP-C and 15% are ANP-A. In preglomerular vessels, ANP-A receptors represented 60% whereas ANP-C accounted for 40%. The large majority of ANG-II receptors in rat renal preglomerular vessels corresponds to the AT$ sb1$ subtype. In the rat mesentery, saturation binding experiments demonstrated that all ANF and most ANG-II receptors (90%) were localized not in the arteries, but in the surrounding perivascular adipose tissue. Most ANF receptors were ANP-C, and a minor fraction were ANP-A and ANP-B. Competition studies with selective ANG-II antagonists revealed that only the AT$ sb1$ receptor subtype is expressed in mesenteric adipose tissue. We expect our studies may contribute to the understanding of the physiological significance of tissue-specific distribution of receptors for ANF and ANG-II in intrarenal structures and within the entire vascular tree. Further studies are required to comprehend the challenging role of ANF and ANG-II in adipose tissue.
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Schröder, Alexandra. "Genexpressionsanalyse mesangialer Proliferationen unter Anwendung der entzündlichen und proliferativen Marker in Laser-mikrodissezierten, Formalin-fixierten und Paraffin-eingebetteten Glomeruli der menschlichen Nierenbiopsien /." Köln, 2008. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000253689.
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Lillevoll, Siri Corneliussen. "Mapping projection neurons originating from male-specific versus ordinary antennal lobe glomeruli in the central olfactory pathway of the moth Heliothis virescens." Thesis, Norges teknisk-naturvitenskapelige universitet, Psykologisk institutt, 2013. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-23566.
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Fylogenetisk sett, er de kjemiske sansene de eldste, og alle organismer har utviklet en evne til å detektere kjemisk stimuli fra det eksterne miljøet. Insekter har lange antenner med sensoriske luktenevroner som kan detektere flyktige odoranter fra det omkringliggende miljøet – både feromoner og plantedufter. Lukt-informasjonen blir omformet til nerveimpulser som sendes til det primære luktsenter i insekthjernen, antenneloben. Seksualresponsen til hann-møll er direkte knyttet til luktesansen; å kunne følge duft-sporet sendt ut av en mottakelig hunn-møll, er en forutsetning for hannens reproduktive suksess. De to segregerte, men parallelle luktebanene som man finner i hann-møllens luktesystem, ett for feromoner og ett for plantedufter, gjør nettopp denne skapningen til et velegnet modellobjekt for den som søker å forstå luktesystemets kodingsmekanismer. Ved å sette inn én type fargestoff (dextran tetramethylrodamine/biotin) i det området av antenneloben som er ansvarlig for å prosessere feromoninformasjon og et annet fargestoff (dextran fluorescein/biotin eller Alexa 488) i det området av antenneloben som er ansvarlig for å prosessere planteduftinformasjon, ble de antenno-protocerebrale trakter knyttet til de to systemene visualisert i dette prosjektet. De antenno-protocerebrale traktene består av projeksjonsnevroner som forbinder antenneloben med høyere integrasjonsområder, heriblant mushroom body calyces og det laterale protocerebrum. Resultatene viste fargede projeksjonsnevroner knyttet til både feromon- og planteduftsystemet i alle de tre hovedtraktene. De to nevrontypene viste til dels ulike projiseringsmønstre både i mushroom body calyces og i det laterale protocerebrum. I tillegg til de tre hovedtraktene som er beskrevet før, ble en ny antenno-protocerebral trakt funnet, den såkalte 2nd medio-lateral antennoprotocerebral tract.Phylogenetically, the chemical senses are considered to be the oldest and all organisms have developed a system for detecting chemical molecules from the external environment. Insects possess long antennae which are covered with olfactory receptor neurons (ORNs) capable of detecting volatile odors from the surroundings environment – both pheromones and plant odors alike. The olfactory information is transduced to nerve impulses that are carried to the primary olfactory center in the insect brain, the antennal lobe. The sexual response of the male moth is directly linked to the olfactory sense; being able to detect the pheromone trail emitted by a calling female, is a prerequisite for reproductive success of the male. The two segregated but parallel olfactory pathways which are found in the male moth, dedicated to pheromones and plant odors, respectively, makes this organism an excellent mini-model for studying the olfactory system. By inserting one dye (dextran tetramethylrodamine/biotin) into the antennal lobe area that is responsible for processing pheromone information and another dye (dextran fluorescein/biotin or Alexa 488) into the area processing plant odor signals, the antenno-protocerebral tracts linked to the two odor systems were visualized in the current project. The antenno-protocerebral tracts connect the antennal lobe to higher integration areas, particularly to the mushroom body calyces and the lateral protocerebrum. The results demonstrate that projection neurons linked to the two olfactory sub-systems, dedicated to pheromones and plant odors, respectively, are present in all the three main tracts. The antennal lobe output neurons tuned to pheromones showed a partly different projection pattern from that displayed by plant odor neuron, both in the calyces and in the lateral protocerebrum. In addition to the three main antenno-protocerebral tracts previously described, a new tract, not formerly found, was discovered – the so-called 2nd medio-lateral antenno-protocerebral tract.
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Chen, Hsiang-Hsin. "Imagerie IRTF tridimensionnelle pour l'étude de l'insuffisance rénale chronique." Thesis, Bordeaux, 2015. http://www.theses.fr/2015BORD0448/document.
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L’insuffisance rénale chronique (IRC) et l’une des pires maladies chroniques dans les pays développés. Les grades de l’IRC sont principalement basés sur la mesure ou l’estimation du taux de filtration rénale (GFR). Cependant, cette méthode est peu sensible sur les premiers stades de la pathologie et n’apporte donc pas de valeur diagnostique. La détection de la pathologie à des stades précoces et son traitement peuvent éviter ou limiter les effets délétères de la chronicité. Cette thèse se penche sur le développement de la microscopie IRTF en tant qu’outil diagnostic pour l’identification par histopathologie à l’échelle du glomérule dans un modèle d’IRC. Nous avons développé la technique de reconstruction 3D pour l’imagerie IRTF des modifications biochimiques à l’échelle du glomérule pour déterminer des marqueurs de l’IRC. La déconvolution spectrale et le clustering sont appliqués après analyses IRTF pour distinguer les modèles sains et pathologiques. Ensuite, la microvasculature glomérulaire est révélée par agent de contraste pour en déterminer les anomalies morphologiques. Grâce aux résultats obtenus en 3D et l’utilisation de méthodes statistiques avancées, la microscopie IRTF est utilisée comme une technique fonctionnelle pour déterminer les modifications morphologiques et moléculaires apparaissant au cours du développement de l’IRCCKD (Chronic Kidney Disease) is one of the worst public diseases in developing countries. The stages of CKD are mainly based on measured or estimated GFR (Glomerular Filtration Rate). However, this method is not sensitive enough on early stages of the pathology and thus do not offer accurate diagnostic value. Early detection and treatment can often limit or avoid the chronicity effects of the disease. This thesis focuses on the development of FTIR microscopy as a diagnostic tool for the identification by histopathology at glomerulus level of the kidney in CKD model. We developed a technique of 3D reconstruction for the FTIR imaging of biochemical components changes in glomeruli for identifying the pathological marker of CKD. The curve-fitting and spectral clustering are applied on the FTIR microscopy analysis to distinguish between healthy and pathological glomeruli of a kidney. Then, the glomerular microvasculatureis highlighted to reveal the morphological abnormalities by perfusing contrast agents into blood vessels. With advanced 3D statistical methods and 3D image visualization by microscopy, FTIR spectro-imaging can be used as a functional technique to determine the morphological and molecular changes occurring along CKD development
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Dei, Cas Alessandra. "Inducible soluble VEGF receptor overexpression in Glomeruli: implication for the physiological role of VEGF in the kidney (Generation of animal model and preliminary data)." Thesis, King's College London (University of London), 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.582575.
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VEGF plays an important role during nephrogenesis and glomeulogenesis. In most adult tissues VEGF is downregulated but it remains constitutively expressed in capillaries with fenestrated endothelium such as in the glomeruli. In the kidney, VEGF is expressed and secreted by podocytes and its receptors are expressed on endothelial cells. The role of constitutive VEGF expression in the adult glomerulus is only partially understood. The aim of this study was to generate an in vivo system whereby VEGF action could be inhibited specifically in the kidney and selectively in the adult fully developed glomeruli. Our working hypothesis was that VEGF could be responsible for the maintenance of endothelial fenestration in glomerular capillaries and possibly playing a role in the filtration or water and solutes. Using a transgenic approach, we over-expressed, with an inducible system, specifically in the glomeruli the soluble truncated VEGF receptor (sFlt-I). By over-expressing sFlt-l in our system, we obtained some preliminary results that suggest a critical role ofVEGF in the functionality of the glomerular filtration barrier.
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Christner, Sarah [Verfasser], and Ulrich [Akademischer Betreuer] Schraermeyer. "The effects of a single intravitreal injection of the VEGF-A-inhibitors aflibercept and ranibizumab on glomeruli of monkeys / Sarah Christner ; Betreuer: Ulrich Schraermeyer." Tübingen : Universitätsbibliothek Tübingen, 2017. http://d-nb.info/1199470090/34.
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Milica, Milojković. "Uticaj darbepoetina alfa na broj glomerula novorođenih miševa sa intrauterusnom restrikcijom rasta." Phd thesis, Univerzitet u Novom Sadu, Medicinski fakultet u Novom Sadu, 2017. https://www.cris.uns.ac.rs/record.jsf?recordId=102330&source=NDLTD&language=en.
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Intrauterusna restrikcija rasta (IUGR) se odnosi na stanje u kojem fetus nije u mogućnosti da ostvari svoj genetski potencijal za rast. IUGR je ozbiljan klinički problem i nedavno je povezan sa bolestima odraslog doba kao što su hipertenzija, insulin nezavistan diabetes melitus, dislipidemije i ishemijske bolesti srca. Eritropoetin je glavni regulator proliferacije i diferencijacije eritroidnih progenitorskih ćelija zahvaljujući svojoj antiapoptotičkoj aktivnosti. Cilj istraživanja je bio da se ispita uticaj IUGR na bubrege, kao i uticaj eritropotina na bubrege sa IUGR. Eksperimentalna studija je sprovedena u gajilištu Pasterovog zavoda u Novom Sadu na 60 miševa rase NMRI. IUGR je izazivana aplikacijom deksametazona gravidnim ženkama. Po rođenju su mladunci bili podeljeni u sedam grupa. Mladuncima je u 1. i 7. danu života davan darbepoetin alfa (DA) u dozama od 1, 4 i 10μg/kg. Dve grupe su predstavljale potomke majki koje su tokom trudnoće dobile DA. Nakon 4 nedelje su uzimani uzorci bubrega i vršena je morfološka i stereološka analiza glomerula. Aplikacija deksametazona (100 μg/kg) trudnim mišicama dovodi do potomstva sa IUGR. Primena DA kod novorođenih miševa sa IUGR dovodi do bržeg porasta telesne mase u prvih 7 dana života („catch-up― rasta). Miševi rođeni sa IUGR imaju manju površinu glomerula bubrega. Primena DA nakon rođenja i u 7. danu života (4 i 10 μg/kg) kod novorođenih miševa sa IUGR dovodi do hipertrofije glomerula bubrega. IUGR nema uticaja na broj glomerula bubrega miševa. Primena DA nema uticaja na broj glomerula bubrega miševa. Miševi rođeni sa IUGR imaju manju debljinu korteksa bubrega. Primena DA (4 i 10 μg/kg) kod miševa rođenih sa IUGR dovodi do povećanja debljine korteksa bubrega. Davanje DA kod IUGR značajno povećava površinu glomerula i debljinu korteksa bubrega.Intrauterine growth restriction (IUGR) refers to a condition in which a foetus is not able to achieve its genetic potential for growth. IUGR is a serious clinical problem, and has recently been linked with diseases of adulthood, such as hypertension, insulin-independent diabetes mellitus, dyslipidemia, and ischemic heart disease. Erythropoietin is the major regulator of proliferation and differentiation of erythroid progenitor cells, thanks to its anti-apoptotic activities. The aim of this study was to investigate the effect of IUGR on the kidneys, and the impact of erythropoietin on the kidneys with IUGR. The experimental study was conducted in Pasteur Institute of Novi Sad on 60 mice of NMRI race. IUGR has been imposed with the application of dexamethasone to pregnant females. After birth, the pups were divided into seven groups. DA was administered to the pups on the 1st and 7th day of life (dose 1, 4 and 10 μg/kg). Two groups represented the offspring of the mothers who during pregnancy received DA. After 4 weeks, kidney samples were taken and morphological and stereological analysis of the glomeruli was performed. The application of dexamethasone (100 μg/kg) to pregnant mice leads to their offspring with IUGR. Application of DA to newborn mice with IUGR leads to faster weight gain in the first 7 days of life ("catch-up" growth). Mice born with IUGR have a reduced glomerular surface. Application of DA after birth and on the 7th day of life (4 and 10 μg/kg) in mice with IUGR leads to hypertrophy of the kidney glomeruli. IUGR has no effect on the number of kidney glomeruli. Application of DA has no effect on the number of kidney glomeruli. Mice born with IUGR have a reduced cortical thickness. Application of DA (4 and 10 μg/kg) in mice born with IUGR leads to increased thickness of the kidney cortex. Application of DA to mice with IUGR significantly increases the surface area of the kidney glomeruli and cortical thickness.
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Junior, Alvaro Martins Batista. "Efeito do treinamento aeróbico sobre o remodelamento glomerular e marcadores inflamatórios em ratos hipertensos." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5160/tde-20052013-101451/.
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Sabendo que o aumento da pressão arterial (PA) é importante no desencadeamento de uma resposta inflamatória e alterações estruturais como forma adaptativa, a hipótese desse estudo é a de que o treinamento aeróbio (TA) pode causar um remodelamento glomerular benéfico e agir sobre a expressão de citocinas inflamatórias. Para responder a esta hipótese, foram considerados como objetivos: 1) Avaliar se o curso temporal do TA leva a melhora morfológica; 2) Avaliar a expressão de marcadores inflamatórios no curso temporal do TA. Foram usados ratos machos normotensos (WKY) e espontaneamente hipertensos (SHR). Os animais foram divididos em quatorze grupos, entre hipertensos e normotensos, treinados e sedentários. As avaliações de teste de esforço máximo (TEM) foram feitas nas semanas 0, 6 e 12, de forma a avaliar o desempenho físico e a permitir ajustar o protocolo de TA. Nos períodos das semanas 0, 1, 2, 4, 8 e 12, grupos de animais foram submetidos à cateterização da artéria femoral para a medida de PA e frequência cardíaca (FC). Em seguida, os animais foram eutanasiados e os rins foram coletados para análise histológica, usando as técnicas: Ácido Periódico de Schiff (APS) e Picrossirius, e detecção por imunohistoquímica (IHQ) de marcadores inflamatórios (IL-1?, IL-6). Os resultados obtidos foram avaliados estatisticamente comparando-se os grupos por análise de variância (ANOVA) Fatorial, complementada por teste post hoc de Bonferroni. Para todas as análises foi adotado o nível de significância de p<=0,05. Tanto SHR quanto WKY apresentaram melhora no desempenho físico. Ao final do TA, somente os SHR apresentaram queda de pressão arterial média (PAM) e tanto SHR quanto WKY apresentaram queda de FC. A análise morfométrica glomerular mostrou que o TA induziu um aumento da área do glomérulo no WKY, e um aumento da área da cápsula de Bowman e da área do glomérulo no SHR. Também observamos diminuição na deposição de fibras de colágeno, proteoglicanos, IL-1? e IL-6 glomerulares, induzida pelo TA. Concluindo, os dados indicam que o TA induziu um remodelamento glomerular benéfico e uma redução na expressão de IL-1? e IL-6 nos animais hipertensos, o que possivelmente está associado à queda de PAM observadaConsidering that the increase in blood pressure (BP) is an important trigger for inflammatory response and structural changes as adaptive way, the hypothesis of this study is that aerobic training (TA) may induce a beneficial glomerular remodeling and act on the expression of inflammatory cytokines. To address this hypothesis, we considered the following objectives: 1) to assess the time course of TA that leads to morphological improvement, 2) evaluate the expression of inflammatory markers in the temporal course of TA. We used male normotensive (WKY) and spontaneously hypertensive rats (SHR). The animals were divided into fourteen groups, among hypertensive and normotensive trained and sedentary. Evaluations of maximum effort test (TEM) were taken at weeks 0, 6 and 12, in order to evaluate the physical performance and permit adjustments in the protocol of TA. At weeks 0, 1, 2, 4, 8 and 12, the rats underwent femoral artery catheterization for measurement of BP and heart rate (HR). After then, the animals were euthanized and kidneys were collected for histological analysis, using the techniques of periodic acid-Schiff (APS) and picrosirius, and detection by immunohistochemistry (IHC) of inflammatory markers (IL-1? and IL-6). The results were statistically evaluated by comparing the groups by analysis of variance (ANOVA) Factorial, complemented by Bonferroni\'s post hoc test. For all analyzes was adopted significance level of p <= 0.05. Both SHR as WKY showed improvement in physical performance. At the end of the TA, only SHR decreased mean arterial pressure (MAP), when both SHR and WKY decreased HR. The glomerular morphometric analysis revealed that TA induced an increase in the glomerular area in WKY and an increase in the area of Bowman\'s capsule and of glomerulus in SHR. We also observed a decrease in the deposition of collagen fibers and proteoglycans in glomerulus, and IL-1? and IL-6 IHQ staining in glomerulus induced by TA. In conclusion, our data suggests that TA induces a beneficial glomerular remodeling and a reduction in the glomerular expression of IL-1? and IL-6 in hypertensive animals, which is possibly associated with the reduction observed in MAP
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Almeida, Gilsirene Scantelbury de [UNESP]. "Comparação entre as diferentes formas de avaliar a taxa da Filtração Glomerular na população idosa atendida no Centro de Atenção Integrada de Melhor Idade – CAIMI na cidade de Manaus." Universidade Estadual Paulista (UNESP), 2013. http://hdl.handle.net/11449/108403.
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000733099.pdf: 472916 bytes, checksum: 1c725a43faa2e29a92740f18a4a9cef2 (MD5)A doença renal crônica (DRC) representa um problema de saúde pública global. Os idosos têm diminuição progressiva da função renal e os hipertensos e diabéticos apresentam maior risco de lesão renal. Essas doenças crônicas são comuns aos idosos favorecendo o comprometimento de lesão renal. Com base neste fato, o objetivo do estudo foi identificar o melhor método para avaliar precocemente a filtração glomerular (FG) em indivíduos idosos. Comparando-se as fórmulas baseadas na creatinina sérica, bem como o Clearance de Creatinina de 24h com a fórmula baseada nos níveis séricos de Cistatina C, eleita como padrão ouro. Foi realizado um estudo observacional, analítico, de delineamento transversal sobre a filtração glomerular e o desenvolvimento da doença renal, com base nos resultados obtidos na avaliação clínica e nos exames laboratoriais de bioquímica e urinálise. Participaram do estudo 180 idosos de ambos os sexos, com idade igual ou superior a 60 anos, do Centro de Atenção Integrada da Melhor Idade (CAIMI), da cidade de Manaus-AM. Foram construídos gráficos de dispersão, calculado o coeficiente de correlação, bem como traçados diagramas de Bland Altman e curvas ROC. A média de idade dos 180 idosos foi de 67 anos - 68,8% do sexo feminino, e 31,1% do sexo masculino. Hipertensos representaram 43,5% do total. Renais crônicos representaram 19%. Portadores de diabetes mellitus chegaram a 38,3%. Ao observar a equação de regressão, quando o CKD-epiCys for zero, o Clearance de Creatinina (ClCr) valerá 62,07 ml/min/1,73m2, o que caracteriza uma superestimação do valor real da FG. A média avaliada pelo ClCr e CKD-epiCys foi de 28,8 ml/min/1,73m2. Este valor é bem superior à zero, que seria o ideal. Isto mostra que o ClCr superestima a FG avaliada pelo CKD-epiCys. A curva ROC para o ClCr na discriminação da presença de FG< 60 ml/min avaliada pelo padrão foi de 0,65, com ...
Chronic kidney disease (CKD) is a global public health problem. The elderly have progressive decrease of renal function, and those with hypertension and diabetes are at increased risk of kidney damage. These chronic diseases are common to the elderly and promote renal injury. This study aimed to identify the best method to assess early glomerular filtration (GF) in elderly subjects. Formulas based on serum creatinine and creatinine clearance of 24 hours were compared with the formula based on serum cystatin C chosen as gold standard. We conducted an observational, analytical, cross-sectional design of the glomerular filtration rate and the development of kidney disease, through results obtained in clinical evaluation, and biochemistry and urinalysis laboratory tests. Participants were 180 patients of both sexes, aged over 60 years, from the Centro de Atenção Integrada da Melhor Idade [Center for Integrated Management of the Elderly], in the city of Manaus, State of Amazonas, Brazil. Scatter plots were constructed by calculating the correlation coefficient, as well as Bland Altman plotted diagrams and ROC curves. The average age of the elderly participants was 67 years; 68.8% were female and 31.1% male; 43.5% had hypertension; 19%, chronic renal failure; and 38.83%, diabetes mellitus. By observing the regression equation, when the CKD-epiCys was zero, creatinine clearance (CrCl) was 62.07 ml/min/1.73m2, which means overestimation of the real FG rate. The average assessed by CrCl. and CKD-epiCys was 28.8 ml/min/1,73m2, a value above zero, which would be ideal. This shows that CrCl. overestimates FR assessed by CKD-epiCys. The ROC curve for CrCl to discriminate the presence of FG <60 ml / min measured by the standard was 0.65, with 95% confidence interval from 0.56 to 0.76 (p = 0.006). The CrCl had statistically significant predictive power concerning the presence of KD. The regression was assessed by ...
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Menezes, Karolina Martins Ferreira. "Reconstrução tridimensional do lobo olfativo do carrapato Amblyomma sculptum (Acari: Ixodidae)." Universidade Federal de Goiás, 2017. http://repositorio.bc.ufg.br/tede/handle/tede/7088.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Amblyomma sculptum belongs to Amblyomma cajennense complex and parasites human beings as well domestic and wild animals. This tick species has a world recognized importance in public and animal health due blood expoliation and transmission of some pathogens such as Rickettsia rickettsia, causal agent of Rocky Mountain Spotted Fever in Brazil. Ticks oriented themselves using chemical stimuli perceived by their sensorial organs. The Haller organ, which is localized in the first leg, has olfactory sensilla which perceive volatile molecules, as the odors. Inside of the sensilla there are neurones that project themselves to olfactory lobes in the synganglion, the central nervous system. In ticks, there is a gap in how the perception of the olfactory information is integrated in the synganglion and this comprehension would allow obtain details that could be used to the development of new control strategies. This work aims to verify the integration between the Haller organ and the synganglion by determining its neuronal projection patterns until the olfactory lobes as well accomplish its three-dimensional reconstruction. Males and females of A. sculptum were immobilized and the Haller organ was excised. The olfactory nerves were filled with one drop of dextran tetramethylrhodamine 1%. The synganglions were dissected in saline, fixed in 4% paraformaldehyde, washed in saline and triton X-100, dehydrated in alcohol series and mounted in glicerol. The synganlions were examined in a fluorescence microscope (Axio Scope.A1) to confirm filling from the peripheral neurons to the synganglion. The olfactory lobes stained were digitalized in a confocal microscope TCS SP8 (Leica) and the series were examined in the Reconstruct software. The olfactory lobes of one male and three females were selected to tracing the edges of each glomerulus in successive optical sessions in order to obtain the 3D reconstruction. The volume was calculated using the same software and their correlation was analyzed by Pearson correlation. The neuronal projections from the Haller organ were confined in the olfactory lobes, which were organized in glomeruli. The number of glomeruli in the males was 26 and 30 in each olfactory lobe examined and in the females varied between 24 and 29. Male and females showed similar glomeruli in both olfactory lobes, meaning they are homologues, when compared intra and intersexually, with a positive correlation between 72% and 95%. Considering the volume, the glomeruli were also similar and no macroglomerulus was identified, as any glomerulus in the male and female were two times bigger than the average volume. The number of specimens evaluated does not allow inferring if the lower number of glomeruli in the females was statistically significant. This work shows, for the first time, the 3D reconstruction of the olfactory lobe in a tick species. The results obtained contribute to understand how ticks process their olfactory information.
Amblyomma sculptum, pertencente ao complexo A. cajennense, parasita humanos, animais domésticos e silvestres. Apresenta importância mundialmente reconhecida na saúde pública e animal por espoliar seus hospedeiros e transmitir patógenos causadores de doenças, como Rickettsia rickettsii agente de Febre Maculosa no Brasil. Os carrapatos orientam-se por estímulos químicos detectados por seus órgãos sensoriais, como o órgão de Haller, localizado no primeiro par de patas, que possui sensilas olfativas capazes de detectarem moléculas voláteis, como os odores. No interior destas sensilas há neurônios que se projetam para os lobos olfativos, organizados em glomérulos, no interior do singânglio, o sistema nervoso central. Em carrapatos, pouco se sabe sobre como a percepção da informação olfativa é integrada no singânglio e esta compreensão permitiria obter mais detalhes sobre a biologia, contribuindo para o desenvolvimento de novas tecnologias de controle. Objetivou-se verificar a integração entre o órgão de Haller e o singânglio por meio da determinação dos padrões de projeção neuronal das sensilas olfativas aos lobos olfativos e da reconstrução tridimensional dos glomérulos. Machos e fêmeas adultos de A. sculptum foram imobilizados, o órgão de Haller seccionado e o nervos olfativos corados com dextran tetrametilrodamina 1%. Os singânglios foram dissecados em PBS, fixados em paraformaldeído 4%, lavados em PBST e PBS, desidratados em séries ascendente de etanol e montados em lâminas com glicerol. Os singânglios foram observados em microscópio de fluorescência Axio Scope.A1 para determinar aqueles onde houve projeção. Os lobos olfativos corados foram digitalizados em microscópio confocal a laser TCS SP8 e as séries de imagens confocais foram avaliadas no programa Reconstruct. Selecionaram-se os lobos olfativos de um macho e três fêmeas para identificação dos glomérulos, marcação manual e numeração, com posterior reconstrução 3D. O programa permitiu o cálculo dos volumes glomerulares que foram analisados por correlação de Pearson. As projeções neuronais originadas nas sensilas olfativas do órgão de Haller estiveram confinadas estritamente aos lobos olfativos, organizados em glomérulos. Os glomérulos no macho variaram entre 26 e 30 e nas fêmeas, entre 24 e 29. Macho e fêmeas apresentaram glomérulos similares, denominados homólogos, nos dois lobos olfativos quando comparados intra- e intersexualmente, com correlação positiva entre 72% e 95%. Com relação aos tamanhos e formas, os glomérulos foram similares e não foram identificados macroglomérulos, uma vez que os glomérulos com maiores volumes no macho e nas fêmeas não apresentaram valores superiores a duas vezes o valor da média. O número de indivíduos avaliados não permitiu inferir se a menor quantidade de glomérulo nas fêmeas foi estatisticamente significativa e, portanto, não se pode afirmar se há dimorfismo sexual. Em carrapatos este foi o primeiro trabalho em que se realizou a reconstrução tridimensional dos lobos olfativos. Os resultados obtidos contribuem para o conhecimento do processamento central da informação olfativa em carrapatos.
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Brittain, Alison Louise. "Growth Hormone (GH) and the Glomerular Podocyte." Ohio University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1554208861914841.
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Lemos, Carla Cavalheiro da Silva. "Alterações renais gênero-dependentes em ratos com insuficiência renal crônica." Universidade do Estado do Rio de Janeiro, 2011. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=5817.
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A insuficiência renal crônica (IRC) é caracterizada por alterações glomerulares secundárias aos mecanismos adaptativos ocasionados por perda de néfrons funcionantes. Alterações na hemodinâmica glomerular, proliferação celular, influxo de células inflamatórias, desequilíbrio na síntese de proteínas da matriz extracelular glomerular (MECG) e perda da seletividade de carga e/ou tamanho da membrana basal glomerular têm sido apontados como mecanismos envolvidos na expansão mesangial e conseqüente glomeruloesclerose. A participação dos hormônios sexuais na função renal e na evolução da insuficiência renal crônica tem sido sugerida. Os glicosaminoglicanos, especialmente o heparan sulfato (HS), têm sido associados à seletividade glomerular de macromoléculas. O remodelamento podocitário precoce e a proteinuria (PTN) se relacionam com a progressão da IRC. Neste contexto, o acúmulo de MECG, proliferação de miofibroblastos e PTN têm sido apontados como mediadores precoces que precedem as lesões glomerulares e túbulo-intersticiais. Neste estudo, avaliamos as alterações renais precoces (30 dias de IRC) gênero-dependentes em ratos (M) e ratas (F) Wistar submetidos à redução de 5/6 da massa renal (IRC) e à castração (c). Os animais foram divididos em 10 grupos: Controles (C) (CM, CF, CMc, CFc) e sham (CM sham, CF sham); e aqueles submetidos à nefrectomia 5/6: IRCM, IRCF, IRCMc, IRCFc. Os animais foram castrados com 5 semanas e submetidos à nefrectomia 5/6 com 7 semanas de idade. Resultados significativos mostraram que os machos com IRC apresentaram maior PTN, acompanhada de maior comprometimento mesangial, imunomarcação positiva para α-actina e maior concentração de heparan sulfato (HS) comparados com as fêmeas IRC (p<0,05). Estas alterações foram reduzidas nos machos castrados. A análise da morfologia podocitária mostrou raras regiões onde ocorreram alterações podocitárias nos grupos IRC. O conjunto de dados sugere que o hormônio masculino pode participar na manutenção do equilíbrio mesangial e que a PTN participa do processo de expansão mesangial. Adicionalmente, a maior concentração de HS nos machos com IRC sugere que durante o processo de remodelação da MEG, tenha ocorrido geração de HS de novo, funcionalmente defeituoso, comprometendo a barreira de filtração glomerular, corroborando com a perda de seletividade da mesma e, contribuindo para maior PTN neste grupo. As fêmeas com IRC apresentaram alterações mais discretas quando comparadas aos machos; apresentaram decréscimo de HS renal associado a PTN e a castração não alterou este perfil. Em resumo, a PTN ocorre precocemente na IRC, contribuindo para o desequilíbrio da MECG. Os mecanismos envolvidos nestes processos parecem sofrer influência dos hormônios sexuais; e os hormônios masculinos parecem agravar estas alterações, contribuindo possivelmente para um pior prognóstico da doença renal nos machos.Chronic renal failure (CRF) is characterized by adaptive mechanisms secondary to the loss of functioning nephrons. Glomerular hemodynamics alterations, cellular proliferation, inflammatory cells influx, imbalance between synthesis and degradation of the glomerular extracellular matrix (GECM) and loss of charge and/or size selectivity of the glomerular basal membrane are pointed as mechanisms leading to mesangial expansion and glomerulosclerosis. Additionally, participation of gender related hormones on renal function and progression of CRF have been suggested. We evaluated the effect of castration in renal alterations in males (M) and females (F) Wistar rats, after 30 days of 5/6 reduction of renal mass (CRF). The animals were castrated (c) at 5 weeks old and 7 weeks old 5/6 and sham nephrectomy were done. Groups: Control (C) CM, CM sham, CMc, CF, CF sham, CFc, CRFM, CRFMc, CRFF, CRFFc. CRFM group showed higher proteinuria followed by increased mesangial expansion and α-actin immunostaining. Concomitant higher concentration of heparan sulfate (HS) was also observed when compared to CRFF (p<0.05). These alterations were reduced in CRFMc group. Podocyte morphology analysis through electronic microscopy showed few disorders of foot processes in CRF groups Overall, CRFF group showed fewer alterations compared to males, and a reduction of HS was observed in association with PTN. Castration did not change this profile in female rats. Data suggest that male hormones may participate in the maintenance of the mesangial equilibrium and that PTN collaborated with the mesangial expansion process. Additionally, the higher concentration of HS in CRFM suggest that the remodeling process of the GECM, included a synthesis of de novo HS, that presented a functioning defect, compromising the glomerular filtration barrier and, ultimately corroborated with the loss of its selectivity and consequently with a higher PTN. This set of results leads us to conclude that PTN appears early in the course of CRF, may contribute to renal GECM imbalance and, the mechanisms involved in these processes seem to be influenced by gender-related hormones. In addition, male hormones seem to aggravate renal alterations contributing to a poor prognosis of CRF progression in male rats.
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Chavele, Konstantia-Marie. "The role of Mannose receptor in glomerul." Thesis, Imperial College London, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.508459.
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Rahman, E. U. "Interaction of monocytes with glomerular mesangial cell matrix in the pathogenesis of glomerular injury." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1306802/.
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Acute inflammatory kidney diseases may resolve, leaving limited residual damage or progress to cause chronic renal scarring characterized by glomerulosclerosis and interstitial fibrosis. Understanding the mechanisms that control inflammation within the kidney may facilitate the development of treatment strategies to prevent irreversible kidney damage and slow progression of chronic kidney disease. Infiltration of mononuclear cells is recognized as an early event in many different conditions that may ultimately lead to kidney injury. Having extravasated from blood vessels at sites of injury, these multifunctional cells differentiate into tissue macrophages, which depending on their phenotype, have the potential to both promote resolution of inflammation or to cause scarring, making them an attractive target for therapy. Having left the glomerular capillary lumen, mononuclear cells are very likely to encounter the mesangial matrix. It was therefore hypothesized that interactions between monocytes and matrix components might modify the behavior of the infiltrating cells and thereby modify the outcome of the inflammatory process. The work presented in this thesis demonstrates that mesangial matrix activates monocytes leading to expression of peroxisome proliferators activated receptor γ and the CD36 scavenger receptor, both markers of macrophage differentiation. Since LDL accumulation in the mesangium may contribute to glomerular injury, the interaction between this lipoprotein and the matrix was also examined. These studies demonstrated that LDL becomes oxidized when exposed to matrix components, possibly due to loss of protective antioxidants. The presence of oxidized LDL has the potential to induce mesangial cell chemokine production, which is likely to promote further monocyte influx into the glomerulus. Furthermore, matrix-activated monocytes internalized oxidized LDL via CD36 scavenger receptor, leading to foam cell formation, a recognized characteristic feature of glomerular injury. Foam cell formation may in turn amplify and perpetuate the disease process by driving further production of cytokines and growth factors. Finally, to establish that these observations were relevant to human glomerular disease, the presence of macrophages expressing PPAR-γ and the CD36 scavenger receptor in human kidney biopsy samples taken from patients with inflammatory glomerular disease was demonstrated, using sections from non-inflamed kidneys as controls. These observations imply that monocyte-matrix interactions are important in the context of glomerular disease and may represent a potential target for therapies designed to limit injury resulting from glomerular inflammation.
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CORDA, VALENTINA. "Electrophysiological and morphological analyses in two species of insects, Protophormia terraenovae and Ceratitis capitata." Doctoral thesis, Università degli Studi di Cagliari, 2014. http://hdl.handle.net/11584/266415.
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Chemoreception represents one of the most important sensory modality to guarantee animals survival, and it plays a fundamental role also in an insect life. In fact, the detection of food sources and proper sites of ovoposition, the identification of conspecifics for mating or aggregation, the recognition of prey or predators are all behaviors resulting from the activation of different processes after the exposure to the wide range of soluble and volatile chemical molecules in the environment. In this respect, insects present clearly separate senses of taste and olfaction comparable to those of vertebrates, and they represent an excellent experimental model to investigate the complexity of gustative and olfactory systems also thanks to the relative simple organization of their neuronal circuits, as well as the feasibility of the breeding. On the basis of these considerations, aim of my work was to give a contribution on our understanding of chemoreceptive mechanisms. In particular, I investigated two main aspects of chemoreception in insects, divided in two separate sections.
Section 1: The spike generator in the labellar taste receptors of the blowfly is differently affected by 4-aminopyridine and 5-hydroxytryptamine In taste chemoreception of invertebrates the interaction of taste stimuli with specific membrane receptors and/or ion channels located in the apical membrane of taste receptor cells results in the generation of a receptor potential which, in turn, activates the ‘encoder’ region to produce action potentials which propagate to the CNS.
This study investigates, in the labellar chemosensilla of the blowfly, Protophormia terraenovae, the voltage-gated K+ currents involved in the action potential repolarization and repetitive firing of the neurons by way of the Kv channel inhibitors, 4-aminopyridine and 5-hydroxytryptamine.
The receptor potential and the spike activity were simultaneously recorded from the ‘salt’, ‘sugar’ and ‘deterrent’ cells, by means of the extracellular side-wall technique, in response to 150 mM NaCl, 100 mM sucrose and 1 mM quinine HCl, before, 0-10 min after apical administration of 4-AP (0.01–10 mM) or 5-HT (0.1–100 mM).
The results show that the receptor potential in all three cells is neither affected by 4-AP nor by 5-HT. Instead, spike activity is significantly decreased, by way of blocking different Kv channel types: an inactivating A-type K+ current (KA) modulating repetitive firing of the cells and responsible for the after hyperpolarization, and a sustained K+ current that resembles the delayed rectifier (DKR) and contributes to action potential repolarization.
Section 2: Morphological characterization of the antennal lobes in the Mediterranean fruit fly Ceratitis capitata
The medfly (Ceratitis capitata Wied.) is one of the most important pest for horticulture, targeting a great variety of fruit and vegetables species worldwide. Due to its commercial relevance, many studies focused on the development and improvement of control strategies based on olfactory chemoreception. A complete knowledge of the anatomical and functional properties of the olfactory system is still lacking. Aim of this work is to give a morphological characterization based on the three-dimensional reconstruction of the antennal lobes (ALs) in adult medfly brains.
In order to reach this goal, we performed unilateral antennal backfills of olfactory receptor neurons (ORNs) in adult males and females by means of the neuronal tracer neurobiotin, revealed by streptavidin-Cy3 or Avidin-Alexafluor 488 conjugated. In association with the anterograde staining, immunohistochemistry was applied in some brains. Confocal stacks acquired from whole-mount specimens were analyzed with the AMIRA software, using the Segmentation tool.
Unilateral neurobiotin and immunohistochemical stainings successfully revealed the AL structure of the adult medfly in all the specimens tested. As in other insects, the ALs of C. capitata are organized in glomeruli, more tightly packed in the anterior part than the posterior one. Axons of ORNs innervate a bilateral pair of homologous glomeruli and form a commissure between the two ALs, which is a typical feature of Diptera. We counted systematically a number of 53 glomeruli in each AL studied, with few exception. Our results provide a basis for future investigations on the interactions with host plants of this important agricultural pest.
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Philip, Brian. "Development of an In-Vitro Glomerulus." Thesis, State University of New York at Binghamton, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10620956.
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Our lab previously characterized the use of a multi-channel microfluidic glomerular device containing both biological (Human Umbilical Vein Endothelial Cells (HUVECs)) and artificial physical (8nm polyethersulferone (PES) membranes) mechanisms of filtration. This model was found to filter 71% BSA-FITC in solution. However, in-vivo, cells are responsible for filtration through vein endothelial cells and podocytes, cells fundamental to filtration due to slit diaphragms, within the glomerulus.
Our current focus is on improving this glomerular device by the addition of conditionally immortalized human podocyte cells (CIHP-1) and use of larger pore size membranes incapable of filtering to create a more realistic model. Before doing so, membranes were exposed to flow and found to maintain shape, cells were identified by light microscopy and immunohistochemistry, and coatings were optimized to keep cells on membranes during flow. Podocytes’ slit diaphragms allow them to filter small to large molecules ranging from 3 kDa to around 150 kDa. Previous work found 30nm polyethersulferone membranes seeded with HUVECs unable to filter BSA-FITC, a medium sized molecule at 65 kDa. With the inclusion of podocytes, a 70% filtration of BSA conjugated with AlexaFluor 488 was achieved. However, the small molecule Ovalbumin conjugated with AlexaFluor 488 (45 kDa) and the larger molecule Rabbit IgG-FITC (160 kDa) were not filtered. While the model has regions to improve itself, it certainly contains prospects for providing better analysis of disease progression, reduction in nephrotoxicity of drugs, and improved treatment for renal diseases.
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Wootton, Andrew. "The glomerular basement membrane and nephritis /." Title page, contents and abstract only, 1985. http://web4.library.adelaide.edu.au/theses/09PH/09phw918.pdf.
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Feehally, J. "Immunological studies in human glomerular disease." Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.371526.
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McKay, Neil G. "Glomerular mesangial cell synthesis of fibronectin." Thesis, University of Aberdeen, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317941.
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Many forms of human glomerulonephritis share the common features of mesangial proliferation and the deposition of extracellular matrix. It is thought that mesangial cells make a significant contribution to the accumulation of extracellular matrix. The factors involved in regulating matrix accumulation are not clearly defined but cytokines particularly TGF-β1 are thought to be involved. One of the matrix components shown to accumulate in such diseases is fibronectin. Fibronectin exists in two forms; 1. a soluble dimer which circulates in the blood stream, and 2. as an insoluble multimer which is incorporated into extracellular matrix as linked dimers. The incorporation of fibronectin into extracellular matrix is mediated by the fibronectin receptors. There are three known receptors for fibronectin, VLA3, VLA4 and VLA5. The differences between the two types of fibronectin arise by alternative splicing of the fibronectin pre-mRNA. Three regions of alternative splicing are known, two additional cell binding sites are found within the IIICS region of alternative splicing, therefore a possible function of alternative splicing is to alter composition of the extracellular matrix. The expression of the fibronectin gene can be altered by cytokines, particularly transforming-growth factor-Beta-1. The effect of TGF-β1 and PDGF-BB upon fibronectin synthesis in human mesangial cells was determined. Fibronectin gene expression and pre-mRNA splicing as well as the synthesis of fibronectin protein were investigated. The localisation of fibronectin synthesised in response to cytokine stimulation was also determined. In order to test the interaction of these two cytokines in human mesangial cells neutralising antibodies were used to inactivate TGF-β when cells were stimulated with PDGF-BB or PDGF was inactivated upon TGF-β1 stimulation. The results show that TGF-β1 stimulation is independent of PDGF, but that PDGF-BB acts, at least partially, by inducing TGF-β. The results reported in this thesis indicate a central role for TGF-β1 in the development of mesangial sclerosis resulting from excess matrix synthesis and deposition. Furthermore they suggest that clinical regimens aimed at preventing the progression of glomerulonephritis should be targeted at blocking the action of this cytokine.
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Satchell, Simon C. "Angiopoietins and the glomerular endothelial cell." Thesis, University of Bristol, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274753.
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Yu, Mei-Ching. "Biomarkers of glomerular inflammation and fibrosis." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/45431.
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Progression of glomerular diseases to chronic kidney disease or renal failure is a major diagnostic and therapeutic problem. In addition to finding new treatment, more reliable biomarkers, using near patient technology, are needed to improve early detection of patients at risk of progressive renal injury. To achieve this aim, two approaches were applied to study novel biomarkers of glomerular inflammation and fibrosis. Firstly, expression of specific inflammatory cytokines and growth factors, including two members of the CCN protein family which are connective tissue growth factor (CTGF)/CCN2 and nephroblastoma overexpressed gene (NOV)/CCN3, were studied in a rat model of crescentic glomerulonephritis (GN). CCN2/CTGF is now regarded as a major profibrotic growth factor of chronic renal inflammation and fibrosis. On the other hand, recently, emerging evidence suggests that CCN3/NOV acts as an endogenous negative regulator of extracellular matrix accumulation and is capable of counteracting the fibrogenic effect of CCN2/CTGF. This targeted approach may be helpful in providing a novel insight into the pathophysiological activities of these two CCN proteins involved in progressive kidney disease and development of novel therapy. With regard to Fourier transform infrared (FTIR) spectroscopy, it has been increasingly used in biomedical research but so far it has not been investigated for diagnosing and/or screening progressive kidney disease. Thus, the second approach was aimed to investigate whether FTIR technique could be employed as an unbiased method of detecting sensitive renal biomarkers. Using FTIR spectroscopy, several characteristic urinary and plasma spectral markers related to renal inflammation and chronic fibrosis were identified from the rat model of crescentic GN. In particular the urinary 1545 cm-1 spectral marker was also reliable in assessing therapeutic responses in corticosteroid-treated rats with GN and severe lupus nephritis in mice. In addition, this urinary spectral marker was translatable in assessment of crescentic GN in patients. In conclusion, analysis of specific cytokines/growth factors and FTIR spectroscopic technology are likely to improve or assist diagnosis and evaluate progression of glomerulonephritis.
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Zhang, Jie. "Glomerular Hyperfiltration and Hypertension in Diabetes." Scholar Commons, 2017. https://scholarcommons.usf.edu/etd/7455.
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In the present study, we investigated the pathophysiological mechanisms of the hemodynamic alteration in diabetes. Glomerular hyperfiltration occurs in the early stage of diabetes mellitus and has been recognized to promote the pathogenesis of diabetic nephropathy. We determine the role of TGF response and the vascular tone of Af-Art in diabetic hyperfiltration and we found that 1) tubular high glucose directly activates NOS1 and increases NO generation in the macula densa, which inhibits TGF response and increases GFR; 2) high glucose dilates renal Af-Art through GLUT1 and mediated by NOS3-derived NO generation; 3) in diabetes, blunted TGF mediated by NOS1 in the macula densa promotes glomerular hyperfiltration. The prevalence of hypertension is much higher in diabetic subjects than non-diabetic population. We studied the potential mechanisms of blood pressure regulation in diabetes, including TGF response and renal afferent arteriolar response to vasoconstrictors, and we found that 1) inadequate NOS1 in the macula densa enhances TGF, which restricts glomerular hyperfiltration and induces hypertension in diabetes; 2) hemodynamic responses to ANG II is increased in diabetes, which is associated with increased expression and activity of AT1 receptors in the Af-Art; 3) Ang II upregulates the expression and activity of Nox2 and Nox4 in the macula densa, which enhances TGF response.
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Carter, Simon. "Standardised Outcomes in Nephrology – Glomerular Disease (SONG-GD): developing a core outcome set for trials in glomerular disease." Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/28641.
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Glomerular diseases are a major cause of kidney failure worldwide and are responsible for a large burden on patients and health systems. Patients may experience fatigue, reduced mobility, cognitive dysfunction, infertility, bone disease, cancer and impaired psychosocial wellbeing. Trials are the primary means of assessing interventions that may improve health outcomes, however outcomes reported in trials may lack relevance during treatment decision-making or be inconsistently reported which limits the effective comparison of treatments. The aim of the Standardised Outcomes in Nephrology – Glomerular Disease initiative (SONG-GD) was to establish a core outcome set for trials in adults with glomerular disease. The methods included this thesis are: a systematic review to analyse the scope and heterogeneity of reported outcomes for glomerular disease activity; focus groups with nominal group technique to identify and rank patient-important outcomes; an international two-round Delphi survey to develop consensus among diverse stakeholder groups; and two stakeholder workshops to discuss and endorse the proposed core outcomes. SONG-GD established the core outcomes of kidney function, disease activity, death, life participation and cardiovascular disease to be reported in all trials in adults with glomerular disease. Ultimately, this core outcome set will ensure the shared priorities of patients, care partners and health professionals are addressed by trial outcomes and improve the evidence base for shared treatment decision-making.
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松尾, 清一, 信夫 坂本, 征郎 丸山, 由起夫 湯沢, 大裕 水谷, Seiichi Matsuo, Nobuo Sakamoto, Ikuro Maruyama, Yukio Yuzawa, and Motohiro Mizutani. "Glomerular localization of thrombomodulin in human glomerulonephritis." Thesis, the United States and Canadian Academy of Pathology, 1993. http://hdl.handle.net/2237/16374.
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He, Liqun. "Analysis of kidney glomerular and microvascular transcriptomes /." Stockholm : Karolinska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-300-9/.
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Singh, Anurag. "Human glomerular endothelial cell and its glycocalyx." Thesis, University of Exeter, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.497585.
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The endothelium is the primary regulator of microvascular permeability whilst fulfilling other functions by controlling coagulation, inflammation and vascular tone. The glycocalyx covers the luminal side of the endothelia and is an important contributor to the endothelia function. The glomerulus is a highly specialised microcirculation in which the capillary wall, including the endothelium, is uniquely adapted to function as a biological sieve and filters 180 litres of plasma every day. This sieving action of the glomerular capillary is highly efficient and selective: allowing free flow of water and small solutes and highly restrictive to passage of proteins. Alterations in this functions leads to proteinuria and heralds the onset of disease. The glomerular endothelial cells possess transcellular pores or fenestrations to facilitate high hydraulic permeability and like all endothelia, also possess a glycocalyx layer that covers both fenestral, and non-fenestral domains. Unlike the endothelial glycocalyx in systemic vessels, the glomerular endothelial glycocalyx has not been subjected to detailed and direct scientific scrutiny. The aim of this thesis is to examine the role of glomerular endothelial glycocalyx as a barrier to the passage of protein.
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Slater, Sadie. "Engineering the Glomerular Filtration Barrier in Vitro." Thesis, University of Bristol, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.499937.
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Coward, Richard J. M. "Glucose transport in the human glomerular podocyte." Thesis, University of Bristol, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424407.
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Edwards, Aurélie. "Filtration of macromolecules by renal glomerular capillaries." Thesis, Massachusetts Institute of Technology, 1996. http://hdl.handle.net/1721.1/11265.
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Norman, Justine. "The nature of glomerular dysfunction in preeclampsia." Thesis, University of Leicester, 2005. http://hdl.handle.net/2381/29500.
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Normal pregnancy was compared to preeclamptic (PE) pregnancy with respect to glomerular ultrafiltration nitric oxide (NO) activity, derived from the metabolism of L-arginine (L-arg) to citrulline. Two biomathematical models, the "isoporous plus shunt" (mean pore size ro, shunt component wo) and "lognormal" (mean pore size U, standard deviation S), together with fractional dextran clearance (betaD) enabled estimation of glomerular ultrafiltration parameters (Kf~ ultrafiltration coefficient, DP-transglomerular pressure). NO activity was assed from plasma and 24hr urinary NOx (nitrate and nitrite), second messenger cyclic GMP (cGMP) and NO synthase inhibitor asymmetric-D-methyl-arginine 9ADMA). Late pregnant (LP) and post partum (PP) data are presented. As NO might mediate gestational renal vasodilatation, the effects of infused L-arginine (NO precursor) compared to glycine, on ultrafiltration were examined, testing the hypothesis that NO deficiency is important in renal vasoconstriction and hypofiltration of PE.;Normal pregnancy is associated with increased GFR, ERPF, wo and S (p<0.05). PE pregnancy is associated with reduced Kf but increased ro, wo U and S. PE values PP approach controls. From the indices that were utilised, there was no evidence of significant NO deficiency in Preeclampsia and even if there was a relative deficiency the infusion of the NO precursor L-arginine failed to augment the decreased renal haemodynamics of Preeclampsia. In PE the hypofiltration therefore has both a haemodynamic and a structural basis, it recovers PP and L-arg has no ameliorating effect in LP, or PP.
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Huang, Chiu-Ju. "Study of pronephric-glomerular morphogenesis in zebrafish." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/5671.
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Midline convergence of organ primordia is an important mechanism for shaping the vertebrate body-plan at various stages of development, such as the morphogenesis of the heart and endoderm. Down regulation of wnt or noncanonical wnt signalling components, such as dishelleved (Dvl) or RhoA GTPase (RhoA), impairs midline convergence of the heart primordia and endoderm in zebrafish. This suggests that wnt signaling plays an important role in regulating midline convergence. At the early patterning stage of the zebrafish kidney, the two pronephric-glomerular primodia (PGP), which derive from intermediate mesoderm, converge towards the midline and fuse to form a functional pronephros. In contrast, during development of the mammalian kidney, the pronephros degenerates as the mesonephros develops without midline convergence. The hypothesis is thus that there is/are mechanisms underlying midline convergence of PGP in zebrafish, which is/are in addition to the control of the non-canonical wnt/Dvl/RhoA pathway and specific to kidney morphogenesis. In this study, the aim was to identify genetic factors that are specifically involved in the mechanism of PGP midline convergence by establishing a cell lineage tracing transgenic system with Cre-loxP, followed by the analysis of selected mutant embryos using the cell lineage tracing system, whole-mount in situ hybridization (WISH) and immunostaining. The cell lineage tracing system was generated, and tested. Constructs, in which β-actin promoter drives the transcription of the reporter genes, were microinjected into zebrafish embryos at 1- to 4-cell stages. The mRNAs in microinjected embryos (5 dpf) were analyzed by RT-PCR. The results show that the constructs induced indiscriminate alternative splicing. RNA splicing mechanisms were not affected by transcription termination when the polyA signal was located in introns. To provide an alternative approach, three mutants were selected after screening of available ENU zebrafish mutants. These mutants were chosen not only because of their genetic importance in cell adhesion and motility but also because of their respective developmental defects in tissues surrounding the PGP, such as the notochord (no tail, ntl), somite (spadetail, spt), and endodermal tissues (zygotic oneeyed pinhead, Zoep). Spt and ntl are key targets of fibroblast growth factor (FGF) signalling in the trunk and tail respectively. EGP-CFC gene oep is a Nodal signalling cofactor. Firstly, a rapid genotyping technique was developed, which was applied in identifying the mutant alleles. Since the tools for tracing PGP using transgenes were unavailable, the three mutants were analyzed by WISH and immunostaining. Zygotic mutation of Zoep causes a PGP midline convergence phenotype of variable severity due to maternal Oep effects. In more than 90% of Zoep-/- embryos, PGP midline convergence was impaired. Even though the abnormality could be observed as early as 15 hpf, the differentiation of the PGP was not affected. Heart primordial phenotypes were also observed but they did not correlate with that of the PGP phenotypes. Embryos homozygous for mutations in T-box transcription factors, ntl or spt had normal heart midline convergence phenotypes. PGP midline convergence abnormality was observed in spt-/- but not in ntl-/- prior to 36 hpf. In addition the extracellular matrix (ECM) might play a key role in the mechanisms of PGP midline convergence. Furthermore, PGP midline convergence proceeds from 10 hpf (the specification of intermediate mesoderm) to 48 hpf (fused pronephric glomerulus) in wild type zebrafish embryos. The process was quantified by 2D image analysis of the PGP distance. Prior to 18 hpf, PGP midline convergence is closely correlated with the midline convergence of mesoderm but not at later stages in Zoep-/-. Spt is essential for PGP but not for cardiac primordium midline convergence. Data from this research suggests that there is not one universal mechanism, which controls all the midline convergence of organ primordia. Indeed, specific factors, which depend on tissues and development stages, are also required.
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Singh, A. "Human glomerular endothelial cell & its glycocalyx." Thesis, Exeter and Plymouth Peninsula Medical School, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.701080.
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Patterson, Angela M. "Activation antigens on human glomerular mesangial cells." Thesis, University of Aberdeen, 1999. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU532806.
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In the work described in this thesis the expression of activation antigens on human glomerular mesangial cells was investigated by selecting and subcloning hybridomas which secrete putative antibodies towards activated human mesangial cells. The panel of twelve monoclonal antibodies, produced in this way, was characterised to define the target antigens, cytokine receptors or cell adhesion molecules expressed as a result of mesangial cell activation. The twelve monoclonal antibodies were tested against non - stimulated mesangial cells and those stimulated with the growth factors PDGF or TGFβ1. Stimulation of the mesangial cells with PDGF or TGFβ1 was associated with an increase in the activity of the antibodies from tolerised mice. Comparing this significant difference in reactivity by these antibodies against non - stimulated and stimulated mesangial cells indicated that the antibodies were directed towards antigens expressed by stimulated mesangial cells. These antigens may be up - regulated antigens weakly expressed on non - stimulated mesangial cells or activation antigens expressed de novo. The reactivity of antibodies from the mouse immunised with PDGF stimulated mesangial cells against non - stimulated and PDGF stimulated mesangial cells was similar, indicating that the antibodies were directed towards cell surface antigens that are expressed to a similar degree by both non - stimulated and stimulated mesangial cells, that is, native antigens. The pattern of reactivity of antibodies from the mouse immunised with TGFβ1 stimulated mesangial cells, against non - stimulated and TGFβ1 stimulated mesangial cells, were similar to the reactivity shown by the antibodies from the corresponding tolerised mouse, indicating that the technique of tolerisation did not further enhance the specificity of the antibodies towards activation antigens. Seven antibodies of the panel of twelve monoclonal antibodies successfully detected antigens in normal and disease kidney. A striking pattern of reactivity against normal and diseased kidney was observed with three antibodies.
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Kluth, David Charles. "Glomerular gene transfer using genetically modified macrophages." Thesis, University of Aberdeen, 2001. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU534987.
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In this thesis I show that macrophages (both cell lines and primary cultures) can be transfected by recombinant adenoviruses expressing -galactosidase (A-gal/Av1Bng), that the macrophages become activated by the transfection process and can be easily manipulated to localise to inflamed glomeruli after direct injection into the renal artery of rats with an experimentally induced glomerular inflammation caused by nephrotoxic nephritis. The injection of transfected macrophages reduces the severity of injury in this model of glomerulonephritis as shown by a reduction in the degree of albuminuria. This approach provides a favourable system for gene delivery in inflammatory disease and shows that both the functional properties of the transfected macrophage as well the transgene it is engineered to produce are relevant for in vivo gene transfer. This approach has also been used to determine the effect of macrophages expressing active TGF-1 on the development of glomerular inflammation. TGF-1 expressing macrophages localised efficiently to inflamed glomeruli and produced the cytokine in vivo. These cells produced a reduction in the level of albuminuria compared to unmodified disease but not in comparison to injection of macrophages transfected with adenovirus expressing -galactosidase. In addition there was no alteration in the infiltration by ED1 positive macrophages. Thus TGF-1 expressed in this manner appears unable to significantly modulate glomerular inflammatory disease and the potential reasons for this are discussed. The system I have developed of macrophage transfection and delivery provides a valuable approach to study and modulate inflammatory disease.
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Auffarth, Benjamin. "Machine Learning Techniques with Specific Application to the Early Olfactory System." Doctoral thesis, KTH, Beräkningsbiologi, CB, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-90474.
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This thesis deals with machine learning techniques for the extraction of structure and the analysis of the vertebrate olfactory pathway based on related methods. Some of its main contributions are summarized below. We have performed a systematic investigation for classification in biomedical images with the goal of recognizing a material in these images by its texture. This investigation included (i) different measures for evaluating the importance of image descriptors (features), (ii) methods to select a feature set based on these evaluations, and (iii) classification algorithms. Image features were evaluated according to their estimated relevance for the classification task and their redundancy with other features. For this purpose, we proposed a framework for relevance and redundancy measures and, within this framework, we proposed two new measures. These were the value difference metric and the fit criterion. Both measures performed well in comparison with other previously used ones for evaluating features. We also proposed a Hopfield network as a method for feature selection, which in experiments gave one of the best results relative to other previously used approaches. We proposed a genetic algorithm for clustering and tested it on several realworld datasets. This genetic algorithm was novel in several ways, including (i) the use of intra-cluster distance as additional optimization criterion, (ii) an annealing procedure, and (iii) adaptation of mutation rates. As opposed to many conventional clustering algorithms, our optimization framework allowed us to use different cluster validation measures including those which do not rely on cluster centroids. We demonstrated the use of the clustering algorithm experimentally with several cluster validity measures as optimization criteria. We compared the performance of our clustering algorithm to that of the often-used fuzzy c-means algorithm on several standard machine learning datasets from the University of California/Urvine (UCI) and obtained good results. The organization of representations in the brain has been observed at several stages of processing to spatially decompose input from the environment into features that are somehow relevant from a behavioral or perceptual standpoint. For the perception of smells, the analysis of such an organization, however, is not as straightforward because of the missing metric. Some studies report spatial clusters for several combinations of physico-chemical properties in the olfactory bulb at the level of the glomeruli. We performed a systematic study of representations based on a dataset of activity-related images comprising more than 350 odorants and covering the whole spatial array of the first synaptic level in the olfactory system. We found clustered representations for several physico-chemical properties. We compared the relevance of these properties to activations and estimated the size of the coding zones. The results confirmed and extended previous studies on olfactory coding for physico-chemical properties. Particularly of interest was the spatial progression by carbon chain that we found. We discussed our estimates of relevance and coding size in the context of processing strategies. We think that the results obtained in this study could guide the search into olfactory coding primitives and the understanding of the stimulus space. In a second study on representations in the olfactory bulb, we grouped odorants together by perceptual categories, such as floral and fruity. By the application of the same statistical methods as in the previous study, we found clustered zones for these categories. Furthermore, we found that distances between spatial representations were related to perceptual differences in humans as reported in the literature. This was possibly the first time that such an analysis had been done. Apart from pointing towards a spatial decomposition by perceptual dimensions, results indicate that distance relationships between representations could be perceptually meaningful. In a third study, we modeled axon convergence from olfactory receptor neurons to the olfactory bulb. Sensory neurons were stimulated by a set of biologically-relevant odors, which were described by a set of physico-chemical properties that covaried with the neural and glomerular population activity in the olfactory bulb. Convergence was mediated by the covariance between olfactory neurons. In our model, we could replicate the formation of glomeruli and concentration coding as reported in the literature, and further, we found that the spatial relationships between representational zones resulting from our model correlated with reported perceptual differences between odor categories. This shows that natural statistics, including similarity of physico-chemical structure of odorants, can give rise to an ordered arrangement of representations at the olfactory bulb level where the distances between representations are perceptually relevant.QC 20120224
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Ferguson, Joanne Kathryn. "Glomerular and systemic permeability in proteinuric renal impairment." Thesis, University of Bristol, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.535481.
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