The aim of this dissertation was to research the field of production design as a sustainable heterotopic image during the various phases of film production. As production topic, The Lorax (Seuss 1971) was explored for its continuing relevant message of warnings against avarice. To provide the production with zeitgeist, the local Pretoria context was implemented to portray this universal narrative message. Information on production design is limited and inadequate. Sources ignore the influences and potential of production design behind the camera lens, which can be quite profound. Production design is influenced by the location and the location is influenced by the production design. Filmic structure and the traditional production design process were researched to provide a structure for the design process. To design the production, film industry conventions were employed with influences from the field of interior architecture. The result of the research is the first step to an inclusive look at production design and its place in the film industry, as well as in society. The result of the design process is a preproduction design package that can be handed over to production companies for further development. In order to complete a production design, the production designer needs a support network of various departments and resources. This dissertation, as the attempt of an individual, is a step to recognize the full potential of the field of production design, by means of a practical example – The Heterotopic Production Design for The Lorax. / Dissertation (MInt(Prof))--University of Pretoria, 2009. / Architecture / unrestricted

Faculty of Health sciences School of Medicine 0420338r juneteare@yahoo.co.uk / This study, in non-human primates (Papio ursinus), evaluated the healing potential of recombinant human transforming growth factor-3 (rhTGF-3) when implanted in exposed periodontal furcation defects either by direct application to the defect or by transplantation of rhTGF-3-instigated heterotopic bone as source of autogenous bone. Class II furcation defects were surgically created bilaterally in the first and second molars of both the mandible and the maxilla of four clinically healthy adult baboons. Simultaneously, autogenous bone was induced bilaterally within the rectus abdominis muscle of the baboons using rhTGF-3. Forty days later, the periodontal defects were implanted with rhTGF-3 in Matrigel® as delivery system, or rhTGF-3 plus muscle tissue in Matrigel®, or with the harvested rhTGF-3-induced autogenous bone. Sixty days after periodontal implantation, the animals were euthanased and the molars harvested together with the surrounding tissue. Histological analysis was performed by light microscopy and digital imaging computer software. The extent of regeneration was assessed by measuring area and volume of new alveolar bone, height of new alveolar bone and height of new cementum. The results, compared to controls, showed pronounced periodontal tissue regeneration in experimental defects. The most noteworthy healing was observed in defects implanted with heterotopically induced autogenous bone as well as those implanted with rhTGF-3 plus muscle tissue. The findings of this study suggest that rhTGF-3 applied directly to a defect, or rhTGF-3-induced autogenous bone, transplanted to a defect, have significant regenerative capabilities in periodontal tissue regeneration of nonhuman primates Papio ursinus.

Helicobacter pylori (HP), known to cause active chronic gastritis, has primarily been found in gastric-type mucosa. Even in the duodenum, the organism was detected in islands of metaplastic gastric mucosa. HP has also been found in gastric metaplasia of Barrett's esophagus in 15-50%. The aim of our study was to determine: (1) the frequency with which HP is found on histopathological sections of heterotopic gastric mucosa (HGM) patch(es) at the upper esophagus, as compared to that of the stomach proper, and (2) the histopathological significance of infection in the HGM patches. From 63 patients with HGM patches at the upper esophagus, 48 patients were found to have concurrent adequate specimen from the stomach for modified Steiner's stain. In 22 patients (45.8%), pair sections from HGM and stomach were negative for HP. Of 26 patients (54.1%) HP-positive on sections from the antrum and/or body (both in 21 cases) nine patients (18.7%) demonstrated HP in the HGM patches. Whereas focal acute inflammatory changes on the HandE section of HGM was present in six patients, HP was detected in HGM only in one. Chronic inflammatory cell infiltration was detected in all nine HP-positive HGM patches and in 37 of 39 HP-negative patches. A mixed acute and chronic inflammatory cell infiltration was found in five of these 37 patients. Our data demonstrate that HP infection of HGM patches at the upper esophagus is part of the HP gastritis and an independent colonization of HGM patches without gastric infection does not occur. No correlation was found between the presence of acute and chronic inflammatory changes in HandE-stained section and positivity of HP in modified Steiner's section of HGM.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23058号 / 医博第4685号 / 新制||医||1048(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 妻木 範行, 教授 浅野 雅秀, 教授 別所 和久 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

国立情報学研究所で電子化したコンテンツを使用している。

Please read the abstract in die section front of this document. / Dissertation (MChD)--University of Pretoria, 2009. / Oral Pathology and Oral Biology / unrestricted

Olaudah Equiano or Gustavas Vassa may have had abolitionist motivations when writing The Interesting Narrative of the Life of Olaudah Equiano or Gustavas Vassa, the African, Written by Himself, but the function of the text is much different and self-serving. Specifically, in looking closely at the wording of the text, with its language of we versus they, in group versus out group, ours versus theirs, Equiano clearly feels he at no time belongs fully to any specific group or place; rather, he only partially belongs anywhere, and thus, creates this work of autobiography and appropriation of fiction and oral tradition to negotiate and cultivate his own liminal, or even heterotopic, space. In other words, I suggest he may have used the writing of this text to define his sense of self, creating a space in which he was both in control and fully belonged.

Η ετερότοπη οστεοποίηση είναι ένα όχι σπάνιο φαινόμενο που οδηγεί σε δημιουργία οστικών δομών σε σημεία που φυσιολογικά υπάρχουν μαλακά μόρια. Ετερότοπη οστεοποίηση μπορεί να προκληθεί κατόπιν τοπικού τραύματος, κατόπιν νευρολογικού τραύματος, ύστερα από χειρουργική επέμβαση σε περιοχές όπως τα ισχία και οι αγκώνες, λόγω γενετικού υποστρώματος σε ασθενείς πολύ μικρών ηλικιών και τέλος αντιδραστικές ετερότοπες οστεοοποιήσεις άνω ή κάτω άκρων. Στην παρούσα διατριβή προσεγγίστηκε η νευρογενούς αιτιολογίας ετερότοπη οστεοποίηση, κυρίως κατόπιν ΚΕΚ. Ο παθοφυσιολογικός μηχανισμός του φαινομένου είναι εν πολλοίς άγνωστος και αυτό που θεωρείται δεδομένο είναι η διαταραχή του ισοζυγίου οστεοβλαστικής – οστεοκλαστικής δραστικότητας κατόπιν της δράσης του επαγωγικού παράγοντα. Ύστερα από τη δράση του επαγωγικού παράγοντα –στη συγκεκριμένη περίπτωση της ΚΕΚ – αυξάνεται η οστεοβλαστική δραστηριότητα τοπικά. Κατά το σχηματισμό του οστού λοιπόν, παράγονται και εκκρίνονται πρωτεογλυκάνες στις αλυσίδες των οποίων προσκολλώνται οι γλυκοζαμινογλυκάνες. Πρωτεογλυκάνες και γλυκοζαμινογλυκάνες συναποτελούν μαζί με τις κολλαγονικές και μη κολλαγονικές πρωτεΐνες, τα τρία κύρια είδη μακρομορίων του εξωκυττάριου δικτύου του οστού. Σκοπός της μελέτης μας ήταν αφενός η μελέτη των πρωτεογλυκανών και γλυκοζαμινογλυκανών στο ετερότοπο οστό σε αντιδιαστολή με φυσιολογικό-ορθότοπο οστό προκειμένου να διερευνηθεί ο ρόλος τους στην δημιουργία του φαινομένου της ετρότοπης οστεοποίησης. Αφετέρου για να διερευνηθεί καλύτερα ο παθοφυσιολογικός μηχανισμός του φαινομένου, μελετήθηκαν κυτταρικοί πληθυσμοί με οστεοβλαστική δραστηριότητα στο περιφερικό αίμα ασθενών που είχαν υποστεί ΚΕΚ και νοσηλεύονταν στη ΜΕΘ, καθώς και πειραματοζώων κατόπιν τεχνητής επαγωγής Κρανιοεγκεφαλικής Βλάβης. Η θειική χονδροϊτίνη και το υαλουρονικό οξύ είναι οι μοναδικοί τύποι γλυκοζαμινογλυκανών στο εξωκυττάριο δίκτυο ετερότοπου οστού όπως και στο φυσιολογικό. Εντούτοις, το ολικό ποσό τους είναι κατά 70% μικρότερο σε σύγκριση με αυτό του φυσιολογικού οστού. Διαφορετική είναι και η εκατοστιαία αναλογία αυτών των μακρομορίων. Η επικρατούσα μορφή δισακχαρίτη θειικής χονδροϊτίνης είναι η θειωμένη στην θέση 6. Ωστόσο η ποσοτική διαφοροποίηση από το φυσιολογικό οστό τόσο στους 4 θειωμένους όσο και στους μη θειωμένους δισακχαρίτες είναι υπαρκτή σε όλα τα ετερότοπα δείγματα. Από πλευράς πρωτεογλυκανών η αγγρικάνη και η διακοσμητίνη είναι ποιοτικά παρούσες στο εξωκυττάριο δίκτυο οστίτη ιστού. Επομένως, ποσοτικές διαφοροποιήσεις στο ετερότοπο οστό σε αντιδιαστολή με το φυσιολογικό είναι υπαρκτές και αυτή η διαφοροποίηση πιθανώς αντικατοπτρίζει διαφορετικές ενζυμικές δραστηριότητες στο φαινόμενο της ετερότοπης οστεοποίησης. Στη μελέτη των κυτταρικών πληθυσμών με οστεοβλαστική δραστηριότητα στο περιφερικό αίμα διαπιστώνονται τα ακόλουθα: Αυξημένη οστεοβλαστική δραστηριότητα στους πληθυσμούς CD-63(+) η οποία εμφανίζει κορυφή στις 6-10 ημέρες μετά την ΚΕΚ. Αυξανόμενη οστεοβλαστική δραστηριότητα πληθυσμών κυττάρων osteocalcin (+) σε όλες τις μετρήσεις μετά την ΚΕΚ. Το σύστημα οστεοπροτεγερίνης – sRANKL εμφανίζει τα εξής χαρακτηριστικά: η osteoprotegerin είναι μετρήσιμη και αυξάνει προς το τέλος των μετρήσεων. Το sRANKL απεναντίας δεν είναι μετρήσιμο σε καμία χρονική στιγμή κατόπιν της ΚΕΚ. Τα παραπάνω συνεπάγονται ότι η ΚΕΚ είναι παράγων επαγωγής οστεοβλαστικής δραστηριότητας όχι μόνο τοπικά αλλά και συστηματικά. Η εκτροπή της οστεοβλαστικής δραστηριότητας προς δημιουργία ετερότοπης οστεοποίησης χρήζει μελέτης μεγαλυτέρου δείγματος ασθενών και πιθανότατα και σε επίπεδα γονιδιακής έκφρασης κυτταρικών καλλιεργειών ασθενών κατόπιν ΚΕΚ. / Ηeterotopic ossification is a relatively frequent phenomenon that leads to the formation of heterotopic osseous structures at points where soft molecules normally do exist. Heterotopic ossification can be induced after local lesion, neurological lesion, after surgical intervention in regions as the hips and the elbows, due to genetic causes in patients of very small ages and, finally, the phenomenon has been observed as distinct, reactive cases in upper or lower limbs. In this Thesis, pathophysiology and mechanisms of neurogenic heterotopic ossification were studied. Pathways of the phenomenon still unknown to date. What is thaught to be the case in the formation of HO, is the disturbance of balance of osteoblastic to osteoclastic activities, after the induction-Head injury in this situation. After Traumatic Brain Injury, osteoblastic activity is induced locally. During bone formation proteoglycans are produced and secreted. Glucozaminoglycans are attached on the side chains of Proteoglycans. Proteoglycans and Glycozaminoglycans constitute along with collageneous and non-collageneous proteins the major macromolecules of extracellular matrix. The purpose of our study was the characterization of proteoglycans and glycozaminoglycans of the heterotopic bone versus the normotopic bone towards the elucidation of their role in the heterotopic bone formation. On the other hand, a more detailed approach to the pathophysiology of the phenomenon requires cellular populations expressing osteoblastic activities to be observed and studied. This is done in peripheral blood of patients that had sustained traumatic brain injuries and being hospitalized within IC units. Same studies on cellular populations have been conducted in a rabbit animal model of traumatic brain injury. Chondroitin-Sulfate and Hyaluronate are the only glycozaminoglycans that have been observed in extracellular matrix of heterotopic bone as well as in normotopic one. Quantitative analyses, however, revealed that their total amount is 70% less compared to normotopic bone. The commonest form of dissacharites of chondroitin-sulfate is the one sulfated at 6-O. However, there is a significant quantitative difference between normotopic and heterotopic bone in 4-O sulfated as well as in non sulfated dissacharites. With regards to proteoglycans, aggrecan and decorin are present in extracellular matrix. Quantitative differences between normotopic and heterotopic bone do exist and reflect a possible alternative pathway of bone formation in the HO phenomenon. The studies on osteoblastic activities of peripheral blood after traumatic brain injury revealed that there is increased osteoblastic activity in CD-63 (+) population that peaks 6-10 days after the inciting event. Osteocalcin (+) population do excibit increased osteoblastic activity as well which increases along with time. The system osteoprotegerin - sRANKL presents the following characteristics: osteoprotegerin is measurable and increases towards the end of measurements. sRANKL on the contrary is not measurable at any time following traumatic brain injury. Consequently, Traumatic Brain Injury do induce osteoblastic activity not only locally but also systemically. The deviation of osteoblastic activity towards heterotopic ossification requires studies of bigger sample of patients, probably to the level of differential gene expression of cellular cultures derived from patients having sustained neurotrauma.

BACKGROUND: Inflammation is a key regulator in skeletal homeostasis during normal growth and tissue repair. However, the role that inflammation plays in skeletal processes is not well understood. Previous studies showed that damage associated molecular pattern (DAMP) molecules released after injury may contribute to immune activation and subsequent fibrosis. OBJECTIVE: This project aims to elucidate the link between tissue damage caused by trauma and the subsequent inflammatory response in a genetic condition of bone morphogenetic protein (BMP) pathway over activation. METHODS: We investigated this potential link by examining immune cells from patients with fibrodysplasia ossificans progressiva (FOP), a genetic condition of endochondral heterotopic ossification caused by activating mutations in the Activin A type I receptor (ACVR1). Patients with FOP show sensitivity to trauma, elevated serum cytokines and abnormal cytokine/chemokine secretion from monocytes and macrophages when stimulated with lipopolysaccharide in vitro. This suggested that BMP pathway activation may alter immune responses in patients with FOP. We studied macrophages derived from peripheral blood monocytes or created from human induced pluripotent stem cells (iPSC) from FOP and control subjects. Macrophages were evaluated by gene expression and culture media by multiplex cytokine analysis after stimulation with key DAMPs that were previously identified to be released after tissue injury. These DAMPs act as endogenous activators of inflammation. RESULTS: Monocyte derived macrophages from control subjects showed increased expression of pro-inflammatory cytokines in response to stimulation with DAMPs, HMGB1 and S100A8/A9. FOP monocyte-derived macrophages treated with each DAMP showed elevated production of CCL22, IL-8, CCL3, and CCL8 when compared to control macrophages. However, both control and FOP macrophages showed increased production of pro-inflammatory cytokines in response to DAMPs compared to non-stimulated conditions. RNA expression profiles of FOP iPSC derived macrophages did not show significantly increased responsiveness to DAMPs compared to control. Surprisingly, control patient iPSC derived macrophages show elevated expression of TNF-a and IL-1B CONCLUSIONS: Macrophages derived from peripheral blood monocytes show that DAMPs may be responsible for macrophage activation and the development of inflammatory complications in patients with FOP. Control iPSC derived macrophages showed similarity to monocyte derived macrophages in their response to DAMPs, suggesting that our iPSC derived macrophages are an applicable model for investigating the human immune system. The dissimilarity in FOP macrophage responsiveness to endogenous activators of our two macrophage models, suggest that iPSC derived macrophages may be affected by the different differentiation and polarization methods, and needs to be characterized further. Similarly, RNA expression profiles may not reflect cytokine production patterns of stimulated iPSC macrophages and warrants further studies. / 2021-06-07T00:00:00Z

京都大学 / 新制・課程博士 / 博士(医学) / 甲第25499号 / 医博第5099号 / 新制||医||1074(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 尾野 亘, 教授 浅野 雅秀, 教授 平井 豊博 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM