111 |
The Relationship Between Adult Hippocampal Neurogenesis and Spatial Learning and Memory in Natural Populations of Food-storing Red Squirrels (Tamiasciurus hudsonicus).Johnson, Kristin Margaret 24 February 2009 (has links)
Previous research on the relationship between spatial memory and adult hippocampal neurogenesis has been controversial. In the present study, neurogenesis was compared between two natural populations of the same species that differ in their reliance on spatial memory to cache and retrieve stored food. Western red squirrels store food in a single site whereas eastern red squirrels store food in multiple sites. Neurogenesis was assessed using endogenous markers of the number of proliferating cells (Ki-67) and the number of immature neurons (DCX), and neuronal recruitment was determined by measuring the area of the dentate gyrus of the hippocampus. The number of proliferating cells, immature neurons and neuronal recruitment were enhanced in the eastern compared to the western red squirrels, reflecting the food storing strategies used by the squirrels. This suggests that there is a positive correlation between adult hippocampal neurogenesis and spatial learning and memory.
|
112 |
Chronic Deep Brain Stimulation and Pharmacotherapy for the Treatment of Depression: Effects on Neuroplasticity in RatsIsabella, Silvia 30 May 2011 (has links)
Deep brain stimulation (DBS) is currently being investigated as a therapy for treatment-resistant depression, with promising results. However, it is not clear whether or not DBS works via the same mechanisms as those induced by antidepressant medications. Processes currently implicated in antidepressant effects include neuroplastic changes and promotion of neurogenesis. We investigated the effects of chronic treatment with three different classes of antidepressants and DBS on markers of neuroplasticity (brain-derived neurotrophic factor, (BDNF), and phosphorylated cyclic-AMP regulatory element binding protein, (pCREB)) and neurogenesis (Ki-67, bromodeoxyuridine (BrdU) and doublecortin) in the rat hippocampus. No clear treatment effects were seen on BDNF, pCREB and Ki-67 levels. However all treatments caused increased levels of BrdU (range: 46%-96%) and doublecortin (8%-61%), although these effects were statistically significant only for DBS and amitriptyline, respectively. This overall pattern of results may suggest that diverse antidepressant treatments could possibly share common mechanisms involving cell survival and neuronal differentiation. Potentiated effects of DBS on cell survival may underlie its efficacy in treatment-resistant depression.
|
113 |
Chronic Deep Brain Stimulation and Pharmacotherapy for the Treatment of Depression: Effects on Neuroplasticity in RatsIsabella, Silvia 30 May 2011 (has links)
Deep brain stimulation (DBS) is currently being investigated as a therapy for treatment-resistant depression, with promising results. However, it is not clear whether or not DBS works via the same mechanisms as those induced by antidepressant medications. Processes currently implicated in antidepressant effects include neuroplastic changes and promotion of neurogenesis. We investigated the effects of chronic treatment with three different classes of antidepressants and DBS on markers of neuroplasticity (brain-derived neurotrophic factor, (BDNF), and phosphorylated cyclic-AMP regulatory element binding protein, (pCREB)) and neurogenesis (Ki-67, bromodeoxyuridine (BrdU) and doublecortin) in the rat hippocampus. No clear treatment effects were seen on BDNF, pCREB and Ki-67 levels. However all treatments caused increased levels of BrdU (range: 46%-96%) and doublecortin (8%-61%), although these effects were statistically significant only for DBS and amitriptyline, respectively. This overall pattern of results may suggest that diverse antidepressant treatments could possibly share common mechanisms involving cell survival and neuronal differentiation. Potentiated effects of DBS on cell survival may underlie its efficacy in treatment-resistant depression.
|
114 |
Efeito da hipoxia intermitente em marcadores de progressão de melanoma em um modelo de apneia do sono em camundongosPerini, Silvana January 2013 (has links)
Objetivos do Estudo: O aumento do crescimento de melanoma foi avaliado em camundongos expostos a hipóxia intermitente. As proteínas que caracterizam a agressividade do tumor ainda não foram investigadas. O estudo teve como objetivo verificar se a hipóxia intermitente simulada pela apneia do sono afeta marcadores de melanoma na progressão tumoral. Desenho: Estudo prospectivo controlado em animais. Senário: Hospital Universitário. Participantes: Doze camundongos C57BL/6. Intervenções: Camundongos foram expostos a hipóxia intermitente ou simulada. Durante 8 horas por dia, o grupo hipóxia foi submetido a um total de 480 ciclos de 30 segundos de hipóxia progressiva SpO2 nadir de 8 ± 1%, seguidos por 30 segundos de normóxia. Um milhão de células de melanoma B16F10 foi injetado por via subcutânea. No dia 14, após a eutanásia, os tumores foram removidos, fixados e corados. Médias e resultados: coloração imunohistoquímica de Ki-67, PCNA, S100-B, HMB-45, Melan-A, TGF, Caspase-1 e HIF-1α foi quantificada por dois observadores que utilizaram captura digital e processamento em três lâminas de cada animal para cada marcador. O tamanho e o peso dos tumores foram semelhantes nas experiências de hipóxia e simulada. A percentagem da mediana [25-75 quartis] de área positiva corada para Ki-67 foi de 23% [15-28] no grupo hipóxia e 0,3% [0,2-1,1] no grupo controle (P = 0,02); para PCNA, as percentagens foram 31% [25-38] e 7% [5-18], respectivamente (P = 0,009). As diferenças entre os grupos para os marcadores restantes não foram significativas. Conclusões: Os marcadores da transcrição do RNA ribossomal e da síntese de DNA são mais expressos em tumores de camundongos expostos a hipóxia intermitente do que em controles, indicando que a apneia do sono pode levar a uma maior agressividade do tumor. / Study Objectives: Increased melanoma growth has been reported in mice exposed to intermittent hypoxia. Proteins that characterize tumor aggressiveness have not been investigated. The study aims to verify whether intermittent hypoxia mimicking sleep apnea affects markers of melanoma tumor progression. Design: Prospective controlled animal study. Settings: University hospital. Participants: Twelve C57bl/6 mice. Interventions: Mice were exposed to intermittent or sham hypoxia. During 8 hours per day, the hypoxia group was submitted to a total of 480 cycles of 30 seconds of progressive hypoxia to a nadir FIO2 of 8±1%, followed by 30 seconds of normoxia. One million B16F10 melanoma cells were injected subcutaneously. On the 14th day, after euthanasia, tumors were removed, fixed and stained. Measurements and Results: Immunohistochemistry staining for Ki-67, PCNA, S100-B, HMB-45, Melan-A, TGFβ, Caspase-1 and HIF-1α was quantified by two observers using digital capture and processing in three slides from each animal for each marker. The size and weight of the tumors were similar in hypoxia and simulated experiments. Median [25-75 quartiles] percentage of positive area stained for Ki-67 was 23% [15-28] in the hypoxia group and 0.3% [0.2-1.1] the control group (P=0.02); for PCNA, the percentages were 31% [25-38] e 7% [5-18], respectively (P=0.009). The differences between the groups for the remaining markers were not significant. Conclusions: Markers of ribosomal RNA transcription and of DNA synthesis are more expressed in tumors of mice exposed to intermittent hypoxia than of controls, indicating that sleep apnea can lead to greater tumor aggressiveness.
|
115 |
Efeito da hipoxia intermitente em marcadores de progressão de melanoma em um modelo de apneia do sono em camundongosPerini, Silvana January 2013 (has links)
Objetivos do Estudo: O aumento do crescimento de melanoma foi avaliado em camundongos expostos a hipóxia intermitente. As proteínas que caracterizam a agressividade do tumor ainda não foram investigadas. O estudo teve como objetivo verificar se a hipóxia intermitente simulada pela apneia do sono afeta marcadores de melanoma na progressão tumoral. Desenho: Estudo prospectivo controlado em animais. Senário: Hospital Universitário. Participantes: Doze camundongos C57BL/6. Intervenções: Camundongos foram expostos a hipóxia intermitente ou simulada. Durante 8 horas por dia, o grupo hipóxia foi submetido a um total de 480 ciclos de 30 segundos de hipóxia progressiva SpO2 nadir de 8 ± 1%, seguidos por 30 segundos de normóxia. Um milhão de células de melanoma B16F10 foi injetado por via subcutânea. No dia 14, após a eutanásia, os tumores foram removidos, fixados e corados. Médias e resultados: coloração imunohistoquímica de Ki-67, PCNA, S100-B, HMB-45, Melan-A, TGF, Caspase-1 e HIF-1α foi quantificada por dois observadores que utilizaram captura digital e processamento em três lâminas de cada animal para cada marcador. O tamanho e o peso dos tumores foram semelhantes nas experiências de hipóxia e simulada. A percentagem da mediana [25-75 quartis] de área positiva corada para Ki-67 foi de 23% [15-28] no grupo hipóxia e 0,3% [0,2-1,1] no grupo controle (P = 0,02); para PCNA, as percentagens foram 31% [25-38] e 7% [5-18], respectivamente (P = 0,009). As diferenças entre os grupos para os marcadores restantes não foram significativas. Conclusões: Os marcadores da transcrição do RNA ribossomal e da síntese de DNA são mais expressos em tumores de camundongos expostos a hipóxia intermitente do que em controles, indicando que a apneia do sono pode levar a uma maior agressividade do tumor. / Study Objectives: Increased melanoma growth has been reported in mice exposed to intermittent hypoxia. Proteins that characterize tumor aggressiveness have not been investigated. The study aims to verify whether intermittent hypoxia mimicking sleep apnea affects markers of melanoma tumor progression. Design: Prospective controlled animal study. Settings: University hospital. Participants: Twelve C57bl/6 mice. Interventions: Mice were exposed to intermittent or sham hypoxia. During 8 hours per day, the hypoxia group was submitted to a total of 480 cycles of 30 seconds of progressive hypoxia to a nadir FIO2 of 8±1%, followed by 30 seconds of normoxia. One million B16F10 melanoma cells were injected subcutaneously. On the 14th day, after euthanasia, tumors were removed, fixed and stained. Measurements and Results: Immunohistochemistry staining for Ki-67, PCNA, S100-B, HMB-45, Melan-A, TGFβ, Caspase-1 and HIF-1α was quantified by two observers using digital capture and processing in three slides from each animal for each marker. The size and weight of the tumors were similar in hypoxia and simulated experiments. Median [25-75 quartiles] percentage of positive area stained for Ki-67 was 23% [15-28] in the hypoxia group and 0.3% [0.2-1.1] the control group (P=0.02); for PCNA, the percentages were 31% [25-38] e 7% [5-18], respectively (P=0.009). The differences between the groups for the remaining markers were not significant. Conclusions: Markers of ribosomal RNA transcription and of DNA synthesis are more expressed in tumors of mice exposed to intermittent hypoxia than of controls, indicating that sleep apnea can lead to greater tumor aggressiveness.
|
116 |
Associação da expressão do Ki67 e linfonodos axilares metastáticos com a sobrevida livre de doença no câncer de mama invasivoPAIVA, Carina Batista 23 February 2016 (has links)
Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-08-09T14:09:09Z
No. of bitstreams: 2
license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5)
Dissertaçao_Carina_Paiva_PPG_MESTRADO_PATOLOGIA_TURMA2014-2016.pdf: 7682349 bytes, checksum: 18a47d04a840b2356f9461b6b6d72f96 (MD5) / Made available in DSpace on 2017-08-09T14:09:09Z (GMT). No. of bitstreams: 2
license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5)
Dissertaçao_Carina_Paiva_PPG_MESTRADO_PATOLOGIA_TURMA2014-2016.pdf: 7682349 bytes, checksum: 18a47d04a840b2356f9461b6b6d72f96 (MD5)
Previous issue date: 2016-02-23 / Marcadores biológicos são requeridos para estimar o risco de recorrência da doença em
mulheres com câncer de mama. O Ki67 é um marcador de proliferação celular e seu valor
preditivo e prognóstico tem sido estudado como um importante biomarcador de rotina na
prática clínica. Nosso estudo teve como objetivo avaliar a relação entre a intensidade da
expressão do Ki-67 e o envolvimento de linfonodos axilares com metástases com a sobrevida
livre de doença em mulheres com câncer de mama. Esse estudo foi retrospectivo e 134
pacientes foram elegíveis para o estudo. A associação entre os escores do Ki67 e outros
fatores prognósticos, tais como tamanho do tumor, grau, status dos linfonodos axilares,
invasão perineural e linfovascular, biomarcadores RE, RPg e HER-2 foram avaliados, além da
análise de sobrevivência. Dos 134 pacientes, 53 tiveram recorrência da doença. O valor da
mediana dos escores do Ki67 foi de 30% de todos os pacientes. Um total de 78 (58,25) dos
pacientes tiverm escores alto do Ki67. A associação estatisticamente significante foi entre os
escores altos do Ki67 com o grau histológico (p<0.001), subtipos moleculares (p<0.001),
receptores de estrógeno (p=0.023) e receptores de progesterona (p=0.001). A sobrevida livre
de doença em indivíduos com Ki67 alto e axila clinicamente negativa apresentou um menor
tempo em meses em comparação com os indivíduos com escores do Ki67 baixo (p=0.049). / Biological markers are required to estimate the risk of disease recurrence in women with
breast cancer. The Ki 67 is a cell proliferation marker and its predictive and prognostic value
has been studied as an important marker in routine clinical practice. Our study aimed to
evaluate the relationship between the intensity of Ki67 expression and involvement of axillary
lymph nodes with metastases to the disease-free survival in women with breast cancer. This
was a retrospective study and 134 patients were eligible for the study. The association
between the scores of Ki67 and other prognostic factors such as tumor size, grade, status of
axillary lymph nodes, perineural invasion and lymphovascular, in addition to biomarkers ER,
PgR, and HER2 were evaluated, as well as survival analysis. Of the 134 patients, 53 have had
recurrence of disease. The median value of Ki scores 67 was 30% of all patients. A total of 78
(58.25) of the patients had high scores Ki 67. A statistically significant association was
between high scores of Ki67 with the histological grade, molecular subtypes of progesterone
receptors estrogen receptors. A statistically significant association was between high scores of
Ki67 with the histological grade (p <0.001), molecular subtypes (p <0.001), estrogen receptor
(p = 0.023) and progesterone receptors (p = 0.001). The disease-free survival in patients with
high Ki67 and clinically negative axilla had a shorter time in months compared to individuals
with low Ki67 scores (p = 0.049).
|
117 |
The Keyboard Percussion Trios of Toru Takemitsu and Toshi Ichiyanagi, a Lecture Recital, together with Three Recitals of Selected Works of Cahn, Maslanka, Miki, Miyoshi, Ptaszynska, Schultz, Wesley-Smith, and OthersFinnie, Jimmy W. (Jimmy Wayne) 08 1900 (has links)
The purpose of this study is to examine the various signatures of compositional style as manifested in the keyboard percussion trios Rain Tree by Toru Takemitsu and Wind Trace by Toshi Ichiyanagi. Significant personal interaction between the aforementioned Japanese composers and American composer John Cage justifies an investigation of his influence on their compositional styles. Toru Takemitsu is currently one of the most prolific Japanese composers. In 1981, Takemitsu composed the percussion trio Rain Tree. Three years later (1984) the Japanese concert pianist Toshi Ichiyanagi composed Wind Trace using Rain Tree's identical instrumentation of marimba, vibraphone, and crotales. Rain Tree and Wind Trace are very similar in compositional style. Formally, both works are single-movement compositions employing rhythmic tension, harmonic dissonance, and visual imagery created by the use of polyrhythms, aleatory, nonfunctional harmony, and extra-musical references. This study investigates the Japanese philosophy of ma and its influence in Rain Tree and Wind Trace. Ma is the natural pause or interval between two or more phenomena occurring continuously. According to Takemitsu, ma is living space, more than actual space. Both compositions utilize space as an essential compositional technique to either connect compartmentalized activity or to complement melodic material. With the utmost respect for nature, Toru Takemitsu and Toshi Ichiyanagi have synthesized elements of Oriental and Occidental music into compositional styles that are unique yet universal. Functioning within both composer's strong personal aesthetics, the affective use of aleatoric and polyrhythmic structures reflect John Cage's influence. Takemitsu's decision to reevaluate the qualities of Japanese traditional music, and to consciously attempt to express the qualities of nature within his music, are attributable to his associations with John Cage. Rain Tree and Wind Trace are virtuosic vehicles of musical expression for which an understanding of the subtle elements within the Eastern and Western art forms is essential.
|
118 |
Ki-67 Regulates Cell Cycle Progression and Heterochromatin OrganizationSun, Xiaoming 15 September 2017 (has links)
A subset of eukaryotic heterochromatin is located around the nucleoli, and this localization is correlated with gene silencing. Although there is some evidence for trans-acting factors organizing genomic loci around the nucleolus, the characterization of proteins and /or RNAs involved in perinculeolar heterochromatin localization and maintenance is incomplete. Notably, the mammalian female inactive X chromosome, a well-studied model of facultative heterochromatin, frequently resides in the perinucleolar regions during mid to late S phase. The disruption of the Xi–nucleolus association results in the erosion of heterochromatin compartment and silencing, which renders it a good model to investigate the mechanism and biological relevance of heterochromatin organization around the nucleolus. This dissertation will present evidence showing that Ki-67 regulates inactive X (Xi) chromosome association with nucleoli, maintains Xi heterochromatic structures, and regulates cell cycle progression, in cell-type-specific manner dependent on checkpoint proficiency.
Ki-67 protein plays roles in heterochromatin organization during interphase. Upon Ki-67 depletion, a subset of Xi in human female hTERT-RPE1 moved away from nucleolus and displayed several features of compromised heterochromatin maintenance. These chromatin alterations were limited to Xi chromosomes localized away from the nuclear lamina and were not observed in virally transformed 293T cells upon Ki-67 depletion. Furthermore, I demonstrated that the different Xi heterochromatin alteration responses result from cell-type-specific reduced proportion of cells in S phase upon Ki-67 depletion. In human hTERT-RPE1, WI-38, IMR90, hTERT-BJ cell lines, depletion of Ki-67 slowed entry into S phase and coordinately downregulated genes related to DNA replication. These cell lines are able to induce p21 expression upon Ki-67 depletion. On the contrary, alteration of transcription and cell cycle progression were not observed in tumor-derived HeLa, U2OS and 293T cell lines. These cell lines do not induce p21 expression either. I additionally examined the Ki-67 function in mouse cell cultures. Depletion of Ki-67 neither redistributes inactive X chromosome nor regulates S phase progression in primary female mouse embryonic cells.
|
119 |
Crossover Mixed Analysis in a Convergent Mixed Methods Design Used to Investigate Clinical Dialogues About Cancer Treatment in the Japanese Context / がん医療現場における対話の分析:収斂デサインとクロスオーバー分析を用いた混合型研究Hatta, Taichi 23 January 2019 (has links)
京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13222号 / 論医博第2169号 / 新制||医||1033(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 中山 健夫, 教授 松村 由美, 教授 森田 智視 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM
|
120 |
Automatisierte Erkennung anatomischer Strukturen und Dissektionsebenen im Rahmen der roboterassistierten anterioren Rektumresektion mittels Künstlicher IntelligenzCarstens, Matthias 09 July 2024 (has links)
Als dritthäufigstes Krebsvorkommen und zweithäufigste Krebstodesursache hat das kolorektale Karzinom (KRK) einen hohen Stellenwert für die interdisziplinäre Therapie in der Onkologie. Bei etwa 50% der Patienten befindet sich das KRK im Rektum. Die Behandlung erfolgt kurativ durch die operative Entfernung des Rektums samt der regionären Lymphknoten. Bis heute konnten keine klinischen bzw. onkologischen Vorteile der roboterassistierten Rektumresektion gegenüber der konventionell laparoskopischen Variante bewiesen werden. In dieser Arbeit wurde mithilfe maschineller Lernverfahren (Künstlicher Intelligenz, KI) ein Algorithmus trainiert, welcher bestimmte kritische anatomische Strukturen und Dissektionsebenen automatisch identifizieren kann. Damit soll zukünftig eine Assistenzfunktion etablieren werden, welche dem Chirurgen dabei helfen soll, autonome Nerven und Blutgefäße zu schonen, was das onkologische Outcome verbessern könnte. Insgesamt wurden 29 anteriore Rektumresektionen berücksichtigt, welche je in 5 OP-Phasen eingeteilt wurden (Peritoneale Inzision, Gefäßdissektion, Mediale Mobilisation, Laterale Mobilisation, Mesorektale Exzision). Etwa 500 – 2.500 Bilder wurden von jeder Phase aus den Operationsvideos extrahiert und bestimmte Strukturen wurden semantisch segmentiert. Die Leave-One-Out-Kreuzvalidierung wurde für die Algorithmus-Validierung angewendet. Als maschinelles Lernverfahren diente ein Mask R-CNN basierender Deep Learning-Algorithmus. Um die Prädiktionen evaluieren zu können, wurden die Objekterkennungs-Metriken Intersection over Union (IoU), Precision, Recall, F1 und Specificity berechnet. Gute IoU-Werte konnten bei der Instrumentenerkennung (IoU bis zu 0,82 ± 0,26), bei der Gerota’schen Faszie (IoU: 0,74 ± 0,03) und beim Mesokolon (IoU: 0,65 ± 0,05) während der medialen Mobilisation, bei der Abdominal wall (IoU: 0,78 ± 0,04) und beim Fat (IoU: 0,64 ± 0,10) während der lateralen Mobilisation und beim Peritoneum, welches beim ersten Einschnitt inzidiert wird, erreicht werden (IoU: 0,69 ± 0,22). Eine weniger präzise automatische Erkennung wurde bei der mesorektalen Faszie (IoU: 0,28 ± 0,08), beim Mesorektum (IoU: 0,45 ± 0,08), beim Kolon und Dünndarm (IoU: 0,46 ± 0,09 bzw. 0,33 ± 0,24) und der Vena mesenterica inferior (IoU: 0,25 ± 0,17) berechnet. Unzureichende Werte wurden bei den eigentlichen Dissektionslinien, den Bläschendrüsen und bei der Arteria mesenterica inferior erzielt, mit durchschnittlichen IoU-Werten kleiner 0,01 bis 0,16. Das künstliche neuronale Netzwerk erkannte zudem meist etwas ziemlich gut oder erkannte es gar nicht. Mittelgute Einzelwerte sind selten. Zusammenfassend zeigen diese Ergebnisse, dass eine KI in der Lage ist, anatomische Strukturen in laparoskopischen Aufnahmen bei einer solch komplexen OP zu erkennen. Für die KI ist es schwierig, vor allem kleinere oder hochvariabel aussehende Strukturen wie die Bläschendrüsen, Blutgefäße oder die mesorektale Faszie zu identifizieren. Es ist anzunehmen, dass die Prädiktionen mit einem größeren und diverseren Trainingsdatensatz verbessert werden können. Für Strukturen wie Dissektionslinien, für welche keine wirklichen optischen Abhebungen von anderen Strukturen im Bild bestehen, könnten andere Bereiche für die Einblendung einer Schnittführungslinie in den Bildern von Bedeutung sein. Eine zukünftige Implementierung dieser Methode in den Operationssaal im Rahmen einer Navigationsfunktion für den Chirurgen wäre demzufolge möglich.
|
Page generated in 0.0193 seconds