To study the influence of the central noradrenergic system on sensitivity to sedative-hypnotic effects mediated by the aminobutyric acid (GABA) system, intact rats were contrasted with rats in which noradrenergic nerves were largely destroyed shortly after birth with the neurotoxin DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine; 50 mg/kg sc x2, P1 and P3]. At 10 weeks, loss of the righting reflex (LORR) was used as an index to study the acute sedative-hypnotic effects of phenobarbital (100 mg/kg ip) and ethanol (4 g/kg ip, 25% v/v). Additionally, GABA concentration in the medial prefrontal cortex (PFC), hippocampus, cerebellum and brainstem was estimated by an HPLC/ED method. Neonatal DSP-4 treatment diminished the sedative-hypnotic effects of both phenobarbital and ethanol in adult rats. While the endogenous GABA content in the PFC, hippocampus, brainstem and cerebellum of DSP-4-treated rats was not altered, phenobarbital significantly decreased GABA content of both intact and DSP-4-lesioned rats by ∼40% in the hippocampus and by ∼20% in other brain regions at 1 h. Ethanol reduced GABA content by ∼15-30% but only in the hippocampus and brainstem of both intact and lesioned rats. These findings indicate that the noradrenergic system exerts a prominent influence on sedative-hypnotics acting via GABAergic systems in the brain without directly altering GABA levels in the brain.

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第20422号 / 農博第2207号 / 新制||農||1047(附属図書館) / 学位論文||H29||N5043(農学部図書室) / 京都大学大学院農学研究科地域環境科学専攻 / (主査)教授 天野 洋, 教授 田中 千尋, 准教授 刑部 正博 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13156号 / 論医博第2143号 / 新制||医||1028(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 林 康紀, 教授 渡邉 大, 教授 影山 龍一郎 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

Patients with a tuberculoma typically present with pulmonary involvement of tuberculosis and have risk factors for tuberculosis (TB). The risk factors for tuberculosis include bacillary load, proximity to infectious case, immunosuppressive conditions, malnutrition, young age, diabetes mellitus, working in healthcare, recent incarceration, alcohol use, and tobacco use. Although rare, it is possible for a patient to present with a tuberculoma despite the absence of risk factors for tuberculosis other than diabetes and without pulmonary involvement.

No description available.

Melanoma is the most deadly form of skin cancer worldwide, which causes the 75% of deaths related to skin cancer. National Cancer Institute estimated that 91,270 new case and 9,320 deaths are expected in 2018 caused by melanoma. Early detection of melanoma is the key for the treatment. The image technique to diagnose skin cancer is dermoscopy, which leads to improved diagnose accuracy compared to traditional ABCD criteria. But reading and examining dermoscopic images is a time-consuming and complex process. Therefore, computerized analysis methods of dermoscopic images have been developed to assist the visual interpretation of dermoscopic images. The automatic segmentation of skin lesion attributes is a key step in computerized analysis of dermoscopic images. The International Skin Imaging Collaboration (ISIC) hosted the 2018 Challenges to help the diagnosis of melanoma based on dermoscopic images. In this thesis, I develop a deep learning based approach to automatically segment the attributes from dermoscopic skin lesion images. The approach described in the thesis achieved the Jaccard index of 0.477 on the official test dataset, which ranked 5th place in the challenge. / Master of Science / Melanoma is the most deadly form of skin cancer worldwide, which causes the 75% of deaths related to skin cancer. Early detection of melanoma is the key for the treatment. The image technique to diagnose skin cancer is called dermoscopy. It has become increasingly conveniently to use dermoscopic device to image the skin in recent years. Dermoscopic lens are available in the market for individual customer. When coupling the dermoscopic lens with smartphones, people are be able to take dermoscopic images of their skin even at home. However, reading and examining dermoscopic images is a time-consuming and complex process. It requires specialists to examine the image, extract the features, and compare with criteria to make clinical diagnosis. The time-consuming image examination process becomes the bottleneck of fast diagnosis of melanoma. Therefore, computerized analysis methods of dermoscopic images have been developed to promote the melanoma diagnosis and to increase the survival rate and save lives eventually. The automatic segmentation of skin lesion attributes is a key step in computerized analysis of dermoscopic images. In this thesis, I developed a deep learning based approach to automatically segment the attributes from dermoscopic skin lesion images. The segmentation result from this approach won 5th place in a public competition. It has the potential to be utilized in clinic application in the future.

No / Recent analysis of the juvenile (≤12 years) human remains from a 19th century site in Wolverhampton, England revealed a relatively high level of nutritional deficiency diseases within the population. Indeed, 41.7% of the 48 juvenile skeletons analysed exhibited a combination of porous and proliferative bone lesions consistent with the pathological alterations associated with nutritional stress. This paper describes a pathological lesion on the inferior surface of the basilar portion of the occipital bone, not previously reported in association with infantile scurvy, but which was exhibited by 90% (N=9) of the 10 scorbutic individuals identified during this study.

The left hemisphere (LH) is accepted as the dominant hemisphere for language processing. There is also evidence confirming the language processing abilities of the right hemisphere (RH), particularly its lexical-semantic processing potential (Chiarello, 1988; Joanette, Goulet, & Hannequin, 1990). The capacity of the RH for language processing is significant to the investigation of language processing following LH lesions. However, the precise neurocognitive mechanisms underlying language processing following lesion remain to be fully elucidated. Subsequently, the overall aim for this thesis is to investigate hemispheric contributions to semantic processing following unilateral lesions, and to explore the significance of the contribution made by the RH. In order to achieve this overall aim, the current thesis firstly explores the hemispheric contributions made to lexical-semantic processing for healthy adults, and then shifts focus to explore the changes in hemispheric processing for participants with unilateral lesions (LH and RH). Comparisons of hemispheric activation between these groups will clarify the underlying hemispheric mechanisms that facilitate language processing following unilateral lesion. This thesis includes four complementary investigations of hemispheric contributions to semantic processing. The first study combined divided visual field (DVF) priming with event-related potentials (ERPs), in order to investigate controlled hemispheric semantic priming for young healthy adults. Two experiments were employed for a between subjects comparison of time-course differences (stimulus onset asynchrony, or SOA, varied between experiments) in hemispheric activation of associated and nonassociated category members. Continuous electroencephalograms were recorded throughout the priming task for each participant, and later analysed with reference to relevant ERP components (N400 and Late Positive Complex). Bilateral N400 priming was revealed for associated category members at both the short and long SOA. There was no significant N400 priming for the nonassociated category member condition. The examination of hemispheric priming of associated and nonassociated category member stimuli over the same time-course was continued in the second study for participants with unilateral LH lesions and matched controls. The second investigation aimed to determine the impact of unilateral LH lesions on controlled hemispheric semantic priming, utilising the DVF priming paradigm with participants following unilateral lesions. This study also aimed to explore associations between hemispheric activation during the online priming task and offline comprehension abilities. Differences in priming were observed between the LH lesion group and the control group, with participants in the LH lesion group requiring the association relationship to elicit priming. Priming also varied for participants as a function of their offline comprehension abilities, with RH priming associated with higher offline scores. The third investigation continued the exploration of hemispheric semantic activation following LH lesion, examining the impact of a LH lesion on interhemispheric control mechanisms, and the modification of hemispheric processing capacities with and without dominant hemisphere control. This investigation again utilised DVF priming with associated and nonassociated category member stimuli, in conjunction with the dual task paradigm. The dual task paradigm is designed to overload one hemisphere’s processing resources in order to remove interhemispheric suppression. Findings indicate that following LH lesions, the RH’s contribution is enhanced under conditions that are designed to overload the LH. The final study shifts from the investigation of participants with LH lesions to the impact of a RH lesion. This exploration of controlled hemispheric semantic priming following RH lesion sought to increase our understanding of the underlying mechanisms for semantic processing following unilateral lesion. The RH’s role in lexical-semantic processing has been documented consistently over approximately the last twenty years, however, there remains limited direct investigation of a RH lesion’s impact on contributions to semantic processing. A single case investigation utilised the same experimental procedure as the second study described. Findings suggest a similar activation pattern between the individual with RH lesion and the control participants, with both exhibiting bilateral activation of the associated and nonassociated category member stimuli. However, a subtle difference was found between the activation of the individual with RH lesion and that of the control group, with the individual with a RH lesion showing increased strategic processing difficulties at the longer SOA. Overall, the current thesis demonstrates the importance of the RH for efficient strategic semantic processing for both healthy adults, and people with unilateral lesions. In addition, this thesis concludes that following a LH lesion, the RH contribution to controlled semantic processing may be associated with successful comprehension, and that RH contributions may be improved with the addition of a secondary task designed to overload LH processing. The present thesis provides evidence to support the use of the DVF priming paradigm in the investigation of hemispheric contributions to semantic processing following unilateral lesion. It is anticipated that these findings will improve the current understanding of the underlying hemispheric contributions to lexical-semantics following a unilateral lesion, and will encourage continuing investigation into the RH’s capacity to impact language recovery.

Anlass der vorliegenden Arbeit war die Suche nach einem geeigneten Sehnendefekt-Modell, das die Untersuchung der Wirkung moderner Therapieansätze unter Standardbedingungen ermöglicht. Die Auswertung der Literatur zeigte, dass eine große Anzahl an Sehnendefekt-Modellen mit sehr unterschiedlichen Fragestellungen sowohl an Großtieren, Kleintieren als auch Labortieren eingesetzt wurde. In der vorliegenden Arbeit wurden bekannte Sehnendefekt-Modelle mit besonderem Augenmerk auf die verwendete Methodik und das damit induzierte Schadmuster untersucht. Die umfassende Literaturauswertung mit präziser pathomorphologischer Charakterisierung der Defekte diente als entscheidende Grundlage für die Entwicklung des eigenen Tiermodells. Beim hier vorgestellten Schafmodell handelt es sich um ein Core Lesion- Modell. Es simuliert die am häufigsten beim Pferd auftretende Sehnenerkrankung und bietet die Möglichkeit der direkten intraläsionalen Injektion eines Therapeutikums. Die Core Lesion stellt ein abgeschlossenes Kompartiment dar, so dass keine Trägermaterialien nötig sind, um ein appliziertes Therapeutikum am Wirkort zu binden. Verschiedene chirurgische Zugänge und Zielsehnen wurden beim Schafmodell untersucht. Als geeignet für ein Core Lesion- Modell erwiesen sich beim Schaf die tiefe Beugesehne distal des Karpalgelenks sowie die oberflächliche Beugesehne im Bereich des Tendo calcaneus communis. Für die Induktion der Läsion wurden in Anlehnung an die von LITTLE und SCHRAMME (2006) bzw. SCHRAMME et al. (2010a) beim Pferd gezeigte Methodik unterschiedliche chirurgische Instrumente verwendet. Dabei wurden der Einsatz einer Knochenmark-Extraktionsnadel sowie verschiedene manuell oder elektrisch betriebene arthroskopische Klingen und Fräsköpfe hinsichtlich ihrer Verwendbarkeit sowie des durch sie verursachten Schadmusters miteinander verglichen. Ein manueller Instrumenteneinsatz führte zu deutlich milderen Schadmustern. Dabei kam es durch die Verwendung des Stiletts einer Knochenmark-Extraktionsnadel in einigen Bereichen zu scharfen Faserdurchtrennungen, in anderen Bereichen wurden die Kollagenfasern nur stumpf auseinander gedehnt. Der Einsatz arthroskopischer Klingen und Fräsköpfe beim Schafmodell ist nur eingeschränkt möglich. Durch die geringe Sehnengröße stehen nur sehr wenige Instrumente mit einem entsprechend kleinen Durchmesser zur Verfügung. Ein Round Burr konnte unter experimentellen Bedingungen eingesetzt werden und führte zu einer hochgradigen Schädigung des kompletten Sehnenquerschnitts. Dabei wurden die Fasern aus ihrer ursprünglichen Orientierung heraus gerissen, zumeist aber nicht vom umgebenden Gewebe abgetrennt. Ein Synovial Resector führte hingegen zu einer scharfen Faserdurchtrennung und dadurch zu einem deutlich abgegrenzten Defektbereich. Weitere Einzelheiten wie die resultierende Einblutung und das Einwandern verschiedener Entzündungszell-Spezies müssen in-vivo untersucht werden, um eine klare Empfehlung für den Einsatz der verschiedenen Instrumente formulieren zu können. Die Auswertung der vorhandenen Sehnendefekt-Modelle sowie die eigenen Ergebnisse führten zu dem Schluss, dass eine Kombination verschiedener Methoden sinnvoll sein könnte. Die Arbeit beschreibt ein sicheres, praktikables Großtiermodell für die Simulation von Core Lesions. Das Modell kann zunächst im Tierversuch eingesetzt werden, um die nach Defektinduktion ablaufenden pathophysiologischen Prozesse zu charakterisieren. Dann steht mit dem Schafmodell ein zeitgemäßes Modell für die Untersuchung verschiedener Therapiekonzepte zur Verfügung, das für die Pferdemedizin eingesetzt werden kann, sich aber auch für Untersuchungen mit humanmedizinischem Hintergrund vielversprechend zeigt. Das Modell stellt damit ein wichtiges Bindeglied zwischen Grundlagenforschung und dem klinischen Einsatz moderner Therapiekonzepte dar.