Το φυλοσύνδετο γονίδιο wiser (CG32711) είναι απαραίτητο για την ανάπτυξη της Drosophila melanogaster. Η μελέτη μιας θερμοευαίσθητης, θανατογόνου μετάλλαξης που ονομάζεται wisertsl αποκάλυψε ότι το γονίδιο wiser εμπλέκεται μεταξύ άλλων στην ανάπτυξη των φτερών. Η μετάλλαξη wisertsl οφείλεται σε ένα P στοιχείο (7E P) που βρίσκεται 490 bp ανοδικά του σημείου έναρξης της μεταγραφής του γονιδίου wiser. 95 bp καθοδικά του 7E P στοιχείου υπάρχει μια P{lacW} ένθεση υπεύθυνη για τη θανατογόνο μετάλλαξη PL26. Οι μεταλλάξεις wisertsl και PL26 είναι αλληλόμορφα του ίδιου γονιδίου ενώ 12000 περίπου βάσεις ανοδικά του γονιδίου wiser και 490 bp ανοδικά του γονιδίου trf2 υπάρχει μια άλλη P{lacW} ένθεση που είναι υπεύθυνη για τη θανατογόνο μετάλλαξη PL28. Οι PL26 και PL28 δεν δείχνουν συμπληρωματικότητα με τη μετάλλαξη wisertsl όσον αφορά το θανατογόνο φαινότυπο στους 29ºC. Όμως το διαγονίδιο UAS-wiser δε διασώζει το θανατογόνο φαινότυπο του PL28. Τα αποτελέσματα της παρούσας εργασίας αποκάλυψαν ότι: 1) Το γονίδιο wiser αλληλεπιδρά με το γονίδιο dpp. Εκτοπική έκφραση του διαγονιδίου (UAS wiser) υπό τον έλεγχο του οδηγού στελέχους apGAL4, μειώνει την έκφραση του dpp στην περιοχή του εμβρυικού δίσκου που θα δώσει τμήμα του θώρακα (notum). 2) Σε ομόζυγα wisertsl άτομα η έκφραση των γονιδίων dpp, dad, omb και salm (όπως αποκαλύπτεται από την έκφραση των αντίστοιχων –lacZ διαγονιδίων) μειώνεται στον εμβρυικό δίσκο του φτερού. Τα παραπάνω γονίδια είναι απαραίτητα για την ανάπτυξη του προσθοπίσθιου άξονα του εμβρυικού δίσκου του φτερού που σημαίνει ότι και το γονίδιο wiser εμπλέκεται στο σχηματισμό του. 3) Το γονίδιο wiser αλληλεπιδρά με το γονίδιο Notch (N) καθώς N wisertsl /wisertsl θηλυκά έχουν εντονότερα φαγωμένα φτερά. 4) Οι μεταλλάξεις wisertsl και PL28 είτε αφορούν και οι δύο το γονίδιο wiser ή η PL28 αφορά το γονίδιο trf2 που σημαίνει ότι και αυτό εμπλέκεται στο σχηματισμό του φτερού. / The X- linked wiser (CG32711) gene is a vital gene for the development of Drosophila melanogaster. The study of a temperature sensitive lethal mutation, named wisertsl, revealed that the wiser gene is implicated among others in the development of wings. The wisertsl mutation is due to a wild P element (7E P) located 490 bp upstream of the presumed transcription start site of the gene wiser at the region 7Ε. 95 bp downstream of the 7E P element is located a P{lacW} responsible for the lethal mutation PL26 and ~ 12000 bp upstream of the gene wiser and 490 bp upstream of the gene trf2 exists another P{lacW} insertion which is responsible of the lethal mutation PL28. The mutations PL26 and PL28 do not show complementation with the wisertsl mutation as regards the lethal phenotype at 29°C. However, while the transgene UAS-wiser saves the lethal phenotypes of wisertsl and PL26 it does not save the lethal phenotype of the mutation PL28. The present data study revealed that: 1) The wiser gene interacts with the dpp gene. Ectoping expression of the UAS wiserCDS construct under the control of apGAL4 driver, reduced the dpp expression (revealed by dpp-lacZ) in the notum territory of the wing imaginal disc. 2) In the homozygous wisertsl individuals the expression of dpp, dad, salm and omb genes (revealed by the corresponding -lacZ strains) is reduced in the wing imaginal disc. The above genes are implicated in the development of the anterior-posterior (A/P) axis of the wing imaginal disc. 3) The wiser gene interacts with the Notch (N) gene. N wisertsl/wisertsl females have stronger notching phenotype. 4) The induction of mitotic clones revealed that the mutation PL28 either concerns an enhancer of the wiser gene or the gene trf2. At the late case the gene trf2 must affect the development of the wings as well.

Πρόκειται για μια προοπτικη, συγκριτική, τυχαιοποιημένη, κλινική και ακτινολογική μελέτη της εξέλιξης της πώρωσης οπισθοπλάγιας σπονδυλοδεσίας με τη χρήση είτε αυτόλογου μοσχευματός είτε κοραλλιογενους υδροξυαπατίτη είτε μιγματος των δύο. Μελετήθηκαν 3 ομάδες ασθενών Α, Β και Γ με 18, 19 και 20 ασθενείς αντιστοιχά. Στην πρώτη ομάδα χρησιμοποιήθηκε μόνο αυτόλογο μόσχευμα, στη δεύτερη κοραλλιογενής υδροξυαπατίτης και αυτόλογο μόσχευμα και στην τρίτη ομάδα μόνο κοραλλιογενής υδροξυαπατίτης. Η εκτίμηση ήταν κλινική και ακτινολογική. Διαπιστώθηκε ότι η ενσωμάτωση του κοραλλιογενούς υδροξυαππατίτη χρειάζεται επααρκή αποφλοιωμένη οστική επιφάνεια και η τοποθετηση του στα οπισθοπλάγια σπονδυλικά στοιχεία δεν οδηγεί σε σπονδυλοδεσία. Όμως η τοποθετησή του κοραλλιογενούς υδροξυαπατίτη στα οπίσθια σπονδυλικά στοιχεία οδηγεί σε σπονδυλοδεσία στον αναμενόμενο χρόνο. / This prospective longitudinal randomized clinical and radiological study compared the evolution of instrumented posterolateral lumbar and lumbosacral fusion using either coralline hydroxyapatite or iliac bone graft or both. Three comparable groups A, B, and C were evaluated. In group A only autograft was used. In group B autograft and coralline hydroxyapatite were used and in group C only coralline hydroxyapatite was used as graft extender. The goups were evaluated clinically and radiologicalý It was found that coralline hydroxyapatite applied in the poserolateral spinal elements does not leed to a spinal fusion because of lack of bleeding osseous surfaces. However if coralline hydroxyapatite is applied in the laminae of the posterior spine it leeds to spinal fusion within the expected time.

Posterior tibial tendon dysfunction (PTTD) is a common degenerative condition leading to a severe impairment of gait. There is currently no effective method to determine whether a patient with advanced PTTD would benefit from several months of bracing and physical therapy or ultimately require surgery. Tendon degeneration is closely associated with irreversible degradation of its collagen structure, leading to changes to its mechanical properties. If these properties could be monitored in vivo, it could be used to quantify the severity of tendonosis and help determine the appropriate treatment. Ultrasound elasticity imaging (UEI) is a real-time, noninvasive technique to objectively measure mechanical properties in soft tissue. It consists of acquiring a sequence of ultrasound frames and applying speckle tracking to estimate displacement and strain at each pixel. The goals of my dissertation were to 1) use acoustic simulations to investigate the performance of UEI during tendon deformation with different geometries; 2) develop and validate UEI as a potentially noninvasive technique for quantifying tendon mechanical properties in human cadaver experiments; 3) design a platform for UEI to measure mechanical properties of the PTT in vivo and determine whether there are detectable and quantifiable differences between healthy and diseased tendons. First, ultrasound simulations of tendon deformation were performed using an acoustic modeling program. The effects of different tendon geometries (cylinder and curved cylinder) on the performance of UEI were investigated. Modeling results indicated that UEI accurately estimated the strain in the cylinder geometry, but underestimated in the curved cylinder. The simulation also predicted that the out-of-the-plane motion of the PTT would cause a non-uniform strain pattern within incompressible homogeneous isotropic material. However, to average within a small region of interest determined by principal component analysis (PCA) would improve the estimation. Next, UEI was performed on five human cadaver feet mounted in a materials testing system (MTS) while the PTT was attached to a force actuator. A portable ultrasound scanner collected 2D data during loading cycles. Young's modulus was calculated from the strain, loading force and cross sectional area of the PTT. Average Young's modulus for the five tendons was (0.45±0.16GPa) using UEI. This was consistent with simultaneous measurements made by the MTS across the whole tendon (0.52±0.18GPa). We also calculated the scaling factor (0.12±0.01) between the load on the PTT and the inversion force at the forefoot, a measurable quantity in vivo. This study suggests that UEI could be a reliable in vivo technique for estimating the mechanical properties of the human PTT. Finally, we built a custom ankle inversion platform for in vivo imaging of human subjects (eight healthy volunteers and nine advanced PTTD patients). We found non-linear elastic properties of the PTTD, which could be quantified by the slope between the elastic modulus (E) and the inversion force (F). This slope (ΔE/ΔF), or Non-linear Elasticity Parameter (NEP), was significantly different for the two groups: 0.16±0.20 MPa/N for healthy tendons and 0.45±0.43 MPa/N for PTTD tendons. A receiver operating characteristic (ROC) curve revealed an area under the curve (AUC) of 0.83±0.07, which indicated that the classifier system is valid. In summary, the acoustic modeling, cadaveric studies, and in vivo experiments together demonstrated that UEI accurately quantifies tendon mechanical properties. As a valuable clinical tool, UEI also has the potential to help guide treatment decisions for advanced PTTD and other tendinopathies.

Rupture of the anterior cruciate ligament (ACL) increases anterior-posterior (AP) laxity. The treatment aims to reduce or teach the patient to control this instability. Altered kinematics due to absent ligament function may result in knee arthrosis. This study evaluated the clinical and functional results of reconstructive surgery. Roentgen stereophotogrammetry (RSA) was used to analyse the stabilising effect of knee braces, reconstructive surgery and the kinematics of the knee with and without weight-bearing. The stability of the knees were assessed in 86 patients with ACL injuries before and/or after reconstructive surgery with the RSA technique and with the KT-1000 arthrometer The KT- 1000 (89 N) recorded smaller side to side differences than the RSA set-up without any correlation between the methods. The effect of three different braces on the AP and rotatory laxity was studied on patients with ACL injuries. The ECKO and the modified Lenox Hill reduced the instability with about one third. The SKB had no significant effect. None of the braces decreased the internal rotatory laxity but the Lenox Hill reduced the external rotatory laxity. Thirty-two patients with old ACL tears were treated with surgical reconstruction using the over the top technique (OTT) with or without augmentation. A small reduction in AP laxity was observed at the 6 month follow-up, The AP laxity was almost the same two years after as before surgery. No correlation was observed between the stability and knee function. Fifty-four patients with old unilateral anterior cruciate ligament injuries were randomised either to the over the top (OTT) or the isometric femoral tunnel position (ISO) at ACL reconstructive surgery. Seven of 24 (ISO) and 9 of 25 (OTT) had "normal" laxity two years after surgery. The patients operated with the ISO technique did not have better subjective knee function, muscle strength, functional performance or knee stability than patients operated with the OTT technique. The knee kinematics in patients with chronic unilateral ACL ruptures were examined during active extension in the supine position (13 patients) and during extension and weight-bearing (13 patients). The tibia displaced at an average 1.9 mm more anteriorly and 0.8 mm distally in the injured than in the intact knees during active extension. During extension and weightbearing the tibia was about 2 mm more posteriorly positioned than in the intact knee. The ACL rupture did not affect tibial rotations. Conclusions: The RSA recorded larger side to side differences in ACL injured and reconstructed patients than the KT-1000 arthrometer. Some knee braces are able to reduce AP laxity in ACL injured knees. No correlation was observed after surgery between knee laxity and functional scoring or tests. ACL reconstructions with isometric graft position on the femoral side did not offer any advantages compared to the over the top placement. Altered knee kinematics in the ACL injured knees were observed during knee extension with and without weight-bearing. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1993, härtill 6 uppsatser</p> / digitalisering@umu

No description available.

Background/Rationale: In addition to their established cardioprotective role, β-adrenergic antagonists also increase the risk of stroke and mortality. We propose that a vascular mechanism could contribute to cerebral tissue ischemia in β-blocked patients. Methods: Cardiac output (CO), mean arterial pressure (MAP) and microvascular brain oxygen tension (PBrmvO2) were measured in anesthesized mice treated with metoprolol (3mg•kg-1, i.v.). Dose-response curves (DRCs) for adrenergic-agonists were generated in mesenteric resistance arteries (MRAs; isoproterenol, clenbuterol) and posterior cerebral arteries (PCAs; phenylephrine, isoproterenol) before and after metoprolol treatment. Results: Metoprolol reduced CO, maintained MAP and increased systemic vascular resistance (SVR) resulting in a decreased PBrmvO2 in mice. Metoprolol attenuated β-adrenergic mediated vasodilation in both MRAs and PCAs. Conclusions: Metoprolol reduced brain perfusion in mice. A decrease in CO contributed however, metoprolol also inhibited β-adrenergic vasodilation of mesenteric and cerebral arteries. This provides evidence in support of a vascular mechanism for cerebral ischemia in β-blocked patients.

Background/Rationale: In addition to their established cardioprotective role, β-adrenergic antagonists also increase the risk of stroke and mortality. We propose that a vascular mechanism could contribute to cerebral tissue ischemia in β-blocked patients. Methods: Cardiac output (CO), mean arterial pressure (MAP) and microvascular brain oxygen tension (PBrmvO2) were measured in anesthesized mice treated with metoprolol (3mg•kg-1, i.v.). Dose-response curves (DRCs) for adrenergic-agonists were generated in mesenteric resistance arteries (MRAs; isoproterenol, clenbuterol) and posterior cerebral arteries (PCAs; phenylephrine, isoproterenol) before and after metoprolol treatment. Results: Metoprolol reduced CO, maintained MAP and increased systemic vascular resistance (SVR) resulting in a decreased PBrmvO2 in mice. Metoprolol attenuated β-adrenergic mediated vasodilation in both MRAs and PCAs. Conclusions: Metoprolol reduced brain perfusion in mice. A decrease in CO contributed however, metoprolol also inhibited β-adrenergic vasodilation of mesenteric and cerebral arteries. This provides evidence in support of a vascular mechanism for cerebral ischemia in β-blocked patients.

Thesis (Ph.D.). / Written for the Dept. of Pharmacology and Therapeutics. Title from title page of PDF (viewed 2009/06/05). Includes bibliographical references.

Made available in DSpace on 2013-08-07T19:04:03Z (GMT). No. of bitstreams: 1 000438181-Texto+Completo-0.pdf: 3961885 bytes, checksum: 1a2e9a9bcf3838013c6755da613f5eb7 (MD5) Previous issue date: 2011 / INTRODUCTION : Posterior Reversible Encephalopathy Syndrome (PRES) is a clinico-radiological entity that presents with headache, altered mental status, seizure and visual disturbance and is associated with a reversible probably vasogenic edema, predominantly in occipital and parietal lobes. The precise physiopathology remains unclear and there isn’t an experimental model of this disorder. OBJECTIVES : The objectives of this paper were (1) the clinical and radiological evaluation of patients with PRES in the Hospital São Lucas-PUCRS and (2) the development of a translational model based on clinical features that mimetize this syndrome in pregnants Wistar rats. METHODS : It was performed a review of clinical data, neuroimage and blood basic test of 25 patients with PRES, that were followed in Hospital São Lucas-PUCRS in the period from March 15 of 2007 to September 15 of 2011. Based on clinical features and neuroimagem findings, we developed a rat model of PRES using pregnant Wistar rats, which were submitted to a reduction of uterine pressure perfusion (RUPP), measurement of arterial blood pressure with an invasive catheter and a brain anatomo-pathologic study, after Evans’s blue venous infusion to verify the permeability of the blood-brain-barrier. RESULTS : Our clinical sample consisted of 25 patients (4 men and 21 women) with mean age of 27,84 years old (range from 2 to 74 years old). The most common causes of PRES reported in this series were associated with pregnant situations that occurred in 11 cases (44%). The symptom more commonly reported was headache in 18 patients (72%). The occipital lobe was the most common topography of the magnetic ressonance abnormality (edema) and occurred in 23 cases (92%). The highest value of the systolic blood pressure presented the mean of 176 mmHg and the highest value of the diastolic blood pressure presented the mean of 95,2 mmHg. Animals submitted to RUPP to simulate the PRES presented increase of the blood-brain-barrier permeability and elevation of blood pressure, when compared with the control animals. CONCLUSION : In our series, PRES occurred predominantly in women and the most frequent triggers were obstetric causes; headache was the most common symptom and the neuroimage findings showed a predominance of posterior alteration suggesting a vasogenic edema due a breakdown of blood brain barrier. The experimental rat model was developed based on these clinical observations, so, we used pregnant rats submitted to reduction of uterine pressure perfusion. We identified in these animals increase of blood pressure and a breakdown of blood brain barrier corroborating to establish an experimental model of PRES. We believe that an experimental model of PRES could be important for future studies allowing a better comprehension of this syndrome. / INTRODUÇÃO : A Síndrome Encefalopatia Reversível Posterior (Posterior Reversible Encephalopathy Syndrome – PRES) é uma entidade clinico-radiológica caracterizada por cefaléia, alteração do nível de consciência, crises convulsivas e alteração visual e está associado a um edema provavelmente vasogênico na substância branca encefálica, predominantemente afetando os lobos occipitais e parietais. A fisiopatogenia do PRES permanece desconhecida e não existe um modelo experimental de tal distúrbio. OBJETIVOS : O objetivo desse trabalho é avaliar apresentação clínica juntamente com os exames de neuroimagem realizados por pacientes com Síndrome da Encefalopatia Reversível Posterior no Hospital São Lucas-PUCRS e baseado nos achados clínicos desenvolver um modelo translacional que mimetize essa síndrome em ratos Wistar.MÉTODOS : Foram revisados os prontuário juntamente com os exames de neuroimagem e laboratoriais de 25 pacientes portadores da síndrome da encefalopatia reversível posterior, os quais foram atendidos no Hospital São Lucas-PUCRS no período de 15 de março de 2007 à 15 de setembro de 2011. A partir das características clínicas e de neuroimagem analisadas nesta pesquisa desenvolvemos modelo experimental de PRES com o uso de ratas Wistar gestantes, as quais foram submetidas à redução da pressão de perfusão uterina (RUPP do inglês Reduction of Uterine Pressure Perfusion), medida de pressão arterial invasiva e estudo anatomopatológico dos encéfalos dos animais, após infusão venosa de azul de Evans para avaliação da permeabilidade da barreira hemato-encefálica. RESULTADOS : Dos 25 pacientes com PRES analisados com idade média de 27,84 anos (variando de 2 anos a 74 anos), 4 eram homens e 21 mulheres. As causas e/ou desencadeadores mais comumente encontrados foram de origem obstétricas em 11 casos (44%). O sintoma mais freqüentemente referido foi cefaléia em 18 pacientes (72%). A topografia mais comumente acometida pelo edema gerado pelo PRES foi occipital em 23 pacientes (92%). O valor da pressão arterial sistólica máxima em média foi de 176 mmHg e a pressão arterial diastólica máxima em média foi de 95,2 mmHg. Os animais submetidos ao modelo experimental proposto através do procedimento RUPP para mimetizar o PRES apresentaram alterações de permeabilidade da barreira hematoencefálica e elevação da pressão arterial quando comparado aos animais controles. CONCLUSÃO : Na nossa casuística o PRES foi nitidamente predominante em mulheres, os fatores desencadeantes/causais mais frequentes foram os de origem obstétrica, predominando a cefaleia como sintoma; os exames de neuro-imagem confirmaram o predomínio posterior das alterações estruturais e sugerem serem decorrentes de edema vasogênico com quebra da barreira hematoencefálica. O modelo experimental em ratos Wistar foi desenvolvido baseado nestas observações clínicas motivo pelo qual utilizamos ratas gestante submetidas a redução da pressão de perfusão uterina. Identificamos nestes animais a quebra da barreira hematoencefálica corroborando para o estabelecimento do modelo experimental do PRES, o qual pensamos que possa ser de fundamental importância para estudos posteriores que permitam uma melhor compreensão desta síndrome.

Un outil fondamental en statistique est le modèle de régression linéaire. Lorsqu'une des covariables est une fonction, on fait face à un problème de statistique en grande dimension. Pour conduire l'inférence dans cette situation, le modèle doit être parcimonieux, par exemple en projetant la covariable fonctionnelle dans des espaces de plus petites dimensions.Dans cette thèse, nous proposons une approche bayésienne nommée Bliss pour ajuster le modèle de régression linéaire fonctionnel. Notre modèle, plus précisément la distribution a priori, suppose que la fonction coefficient est une fonction en escalier. A partir de la distribution a posteriori, nous définissons plusieurs estimateurs bayésiens, à choisir suivant le contexte : un estimateur du support et deux estimateurs, un lisse et un estimateur constant par morceaux. A titre d'exemple, nous considérons un problème de prédiction de la production de truffes noires du Périgord en fonction d'une covariable fonctionnelle représentant l'évolution des précipitations au cours du temps. En terme d'impact sur les productions, la méthode Bliss dégage alors deux périodes de temps importantes pour le développement de la truffe.Un autre atout du paradigme bayésien est de pouvoir inclure de l'information dans la loi a priori, par exemple l'expertise des trufficulteurs et des biologistes sur le développement de la truffe. Dans ce but, nous proposons deux variantes de la méthode Bliss pour prendre en compte ces avis. La première variante récolte de manière indirecte l'avis des experts en leur proposant de construire des données fictives. La loi a priori correspond alors à la distribution a posteriori sachant ces pseudo-données.En outre, un système de poids relativise l'impact de chaque expert ainsi que leurs corrélations. La seconde variante récolte explicitement l'avis des experts sur les périodes de temps les plus influentes sur la production et si cet l'impact est positif ou négatif. La construction de la loi a priori repose alors sur une pénalisation des fonctions coefficients en contradiction avec ces avis.Enfin, ces travaux de thèse s'attachent à l'analyse et la compréhension du comportement de la méthode Bliss. La validité de l'approche est justifiée par une étude asymptotique de la distribution a posteriori. Nous avons construit un jeu d'hypothèses spécifique au modèle Bliss, pour écrire une démonstration efficace d'un théorème de Wald. Une des difficultés est la mauvaise spécification du modèle Bliss, dans le sens où la vraie fonction coefficient n'est sûrement pas une fonction en escalier. Nous montrons que la loi a posteriori se concentre autour d'une fonction coefficient en escalier, obtenue par projection au sens de la divergence de Kullback-Leibler de la vraie fonction coefficient sur un ensemble de fonctions en escalier. Nous caractérisons cette fonction en escalier à partir du design et de la vraie fonction coefficient. / The linear regression model is a common tool for a statistician. If a covariable is a curve, we tackle a high-dimensional issue. In this case, sparse models lead to successful inference, for instance by expanding the functional covariate on a smaller dimensional space.In this thesis, we propose a Bayesian approach, named Bliss, to fit the functional linear regression model. The Bliss model supposes, through the prior, that the coefficient function is a step function. From the posterior, we propose several estimators to be used depending on the context: an estimator of the support and two estimators of the coefficient function: a smooth one and a stewpise one. To illustrate this, we explain the black Périgord truffle yield with the rainfall during the truffle life cycle. The Bliss method succeeds in selecting two relevant periods for truffle development.As another feature of the Bayesian paradigm, the prior distribution enables the integration of preliminary judgments in the statistical inference. For instance, the biologists’ knowledge about the truffles growth is relevant to inform the Bliss model. To this end, we propose two modifications of the Bliss model to take into account preliminary judgments. First, we indirectly collect preliminary judgments using pseudo data provided by experts. The prior distribution proposed corresponds to the posterior distribution given the experts’ pseudo data. Futhermore, the effect of each expert and their correlations are controlled with weighting. Secondly, we collect experts’ judgments about the most influential periods effecting the truffle yield and if the effect is positive or negative. The prior distribution proposed relies on a penalization of coefficient functions which do not conform to these judgments.Lastly, the asymptotic behavior of the Bliss method is studied. We validate the proposed approach by showing the posterior consistency of the Bliss model. Using model-specific assumptions, efficient proof of the Wald theorem is given. The main difficulty is the misspecification of the model since the true coefficient function is surely not a step function. We show that the posterior distribution contracts on a step function which is the Kullback-Leibler projection of the true coefficient function on a set of step functions. This step function is derived from the true parameter and the design.