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The efficiency of acoustic radiation force impulse imaging for the staging of graft fibrosis after liver transplantation / acoustic radiation force impulseを用いた肝硬度測定による移植後肝グラフトの線維化予測Yoshino, Kenji 25 March 2019 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21643号 / 医博第4449号 / 新制||医||1034(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 川口 義弥, 教授 坂井 義治, 教授 羽賀 博典 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM
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Real-time quantitative PCR analysis of endoscopic biopsies for diagnosing CMV gastrointestinal disease in non-HIV immunocompromised patients: a diagnostic accuracy study / 非HIV免疫抑制患者におけるサイトメガロウイルス消化管疾患の診断に対する内視鏡的生検組織のリアルタイム定量PCR:診断精度研究Tsuchido, Yasuhiro 25 March 2019 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21667号 / 医博第4473号 / 新制||医||1035(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 小柳 義夫, 教授 中川 一路, 教授 長船 健二 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM
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Feasibility of combined upper and lower gastrointestinal endoscopic biopsy in the common marmoset (Callithrix jacchus) to evaluate gastrointestinal diseasesHeilmann, Romy M., McIntosh, Jenny, Acke, Els, Reitemeier, Susanne, Pfannkuche, Helga, Erdmann, Sabrina, Roedler, Frauke S., Einspanier, Almuth 27 July 2023 (has links)
Background: Chronic gastroenteropathies, including gluten sensitivity and marmoset
wasting syndrome, frequently occur in captive colonies of common marmosets
(Callithrix jacchus). Early identification and diagnosis of affected animals are desirable.
Endoscopic examination of the colon in marmosets is described, but the small
intestine can harbor significant mucosal lesions not representing those in the colon.
Evaluating the small intestine currently requires invasive surgical biopsies due to the
small patient size, carrying a risk of severe complications.
Methods: Endoscopic intubation and multisite biopsy of the duodenum/proximal jejunum
are demonstrated in 10 marmosets under general anesthesia.
Results: Esophagogastroduodenoscopy with colonoscopy efficiently aid in examining
the gastrointestinal tract and obtaining an antemortem histologic diagnosis in marmosets
with chronic gastrointestinal signs.
Conclusions: This minimally invasive technique is feasible in marmosets. Future investigations
into the pathogenesis of chronic gastroenteropathies will benefit from these
data, leading to improved animal welfare and better individual and colony health
management.
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Differences in histologic response between early and late antibody mediated rejection therapy: assessment by Banff component scoringSadaka, Basma 14 October 2013 (has links)
No description available.
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Feasibility of combined upper and lower gastrointestinal endoscopic biopsy in the common marmoset (Callithrix jacchus) to evaluate gastrointestinal diseasesHeilmann, Romy M., McIntosh, Jenny, Acke, Els, Reitemeier, Susanne, Pfannkuche, Helga Pfannkuche, Erdmann, Sabrina, Roedler, Frauke S., Einspanier, Almuth 28 August 2023 (has links)
Background: Chronic gastroenteropathies, including gluten sensitivity and marmoset
wasting syndrome, frequently occur in captive colonies of common marmosets
(Callithrix jacchus). Early identification and diagnosis of affected animals are desirable.
Endoscopic examination of the colon in marmosets is described, but the small
intestine can harbor significant mucosal lesions not representing those in the colon.
Evaluating the small intestine currently requires invasive surgical biopsies due to the
small patient size, carrying a risk of severe complications.
Methods: Endoscopic intubation and multisite biopsy of the duodenum/proximal jejunum
are demonstrated in 10 marmosets under general anesthesia.
Results: Esophagogastroduodenoscopy with colonoscopy efficiently aid in examining
the gastrointestinal tract and obtaining an antemortem histologic diagnosis in marmosets
with chronic gastrointestinal signs.
Conclusions: This minimally invasive technique is feasible in marmosets. Future investigations
into the pathogenesis of chronic gastroenteropathies will benefit from these
data, leading to improved animal welfare and better individual and colony health
management
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The DNA methylation landscape of metastatic prostate cancer: from characterization to liquid biopsy applicationsFranceschini, Gian Marco 23 January 2023 (has links)
Epigenetic alterations are observed in virtually all cancer types, yet there is limited understanding of their role in tumorigenesis and evolution. The role of DNA methylation has been particularly elusive in this context. While this epigenetic mark has been extensively profiled in healthy and cancerous samples, our ability to understand its relationship with underlying biological processes is still limited. Moreover, recent advancements in the profiling of cell-free DNA in circulation have sparked renowned attention toward tissue-specific and cancer-specific DNA methylation patterns. In this thesis, I present results to improve and refine the computational characterization of DNA methylation in cancer, focusing on metastatic castration-resistant prostate cancer. The first contribution is the development and performance assessment of Rockermeth, a computational methodology to leverage large-scale DNA methylation profiling data to nominate robust differentially methylated regions (DMRs). Rocker-meth can retrieve biologically relevant DNA methylation changes, as demonstrated by extensive integrative analyses with gene expression, chromatin states, and genomic annotations. The second contribution is the generation of a map of DNA methylation changes across prostate cancer progression. The application of Rockermeth and other tailored methodologies can be used to trace the critical evolutionary steps of this disease, from the healthy tissue to the most lethal metastatic AR-independent counterpart. The main result is the evidence of the ability of DNA methylation to capture a snapshot of the active transcription factors in each state of the disease, offering orthogonal information compared to standard genomic sequencing. The third contribution is the design and development of NEMO, a tailored liquid biopsy sequencing panel approach to allow non-invasive neuroendocrine castration-resistant prostate cancer detection in patients with metastatic disease. Based on previous results and the comprehensive analysis of multiple datasets, I designed a set of informative genomic regions to estimate disease burden and evidence of neuroendocrine transdifferentiation. The actual implementation of the NEMO panel produced a scalable and cost-effective strategy, which has been extensively benchmarked using both in silico and in vitro approaches. The application of NEMO to patient-derived cfDNA samples demonstrated accurate tumor content estimation and robust detection of neuroendocrine disease, making it a promising instance of liquid biopsy for CRPC.
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Unleashing the potential of liquid biopsy: allele-informed evaluation of plasma samples for cancer patients managementOrlando, Francesco 23 January 2023 (has links)
Liquid biopsy and next-generation sequencing of cell-free DNA (cfDNA) in cancer patients’ plasma offer a minimally-invasive solution to detect tumor cell genomic information to aid real-time clinical decision-making. Reliability and sensitivity in the detection of genomic alterations is crucial for patient management and it is particularly relevant in the context of targeted therapies. However, biological and technical factors, such as low cfDNA tumor fraction and sequencing errors, affect the correct interpretation of genomic data limiting the utility of non-invasive cfDNA-based tumor profiling. To address these issues, we designed a prostate cancer bespoke assay, PCF_SELECT, that includes an innovative sequencing panel covering ∼25 000 high minor allele frequency SNPs and tailored analytical solutions to enable allele-informed evaluation of patients’ tumor. The framework also implements ABEMUS, an ad-hoc computational procedure we specifically designed for cfDNA samples to accurately detect somatic point mutations that could emerge under treatment pressure and as drug resistance mechanism. When applied on serial plasma samples from three patients receiving PARP inhibition harboring DNA repair gene aberrations, PCF_SELECT demonstrated high sensitivity in detecting BRCA2 allelic imbalance with decreasing tumor fractions resultant from treatment and identified complex ATM genomic states that may be incongruent with protein losses. As a step towards a more sensitive detection of tumor features in circulation of cancer patients, we next hypothesized that recent WGS-based approaches exploiting cfDNA fragments characteristics could be extrapolated for targeted sequencing data and that gene-region specific measures could improve detection metrics. Preliminary results suggest an increased sensitivity compared to copy-number-based methods supporting the integration at no extra cost in our targeted assay. Overall, this work is relevant to the context of precision oncology. It provides an innovative platform for the management of cancer patients, delivering detailed patient-specific molecular information which could be applied to guide treatment and improve clinical outcomes.
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Soluble ST2 Receptor: Biomarker of Left Ventricular Impairment and Functional Status in Patients with Inflammatory CardiomyopathyObradovic, Danilo Momira, Büttner, Petra, Rommel, Karl-Philipp, Blazek, Stephan, Loncar, Goran, von Haehling, Stephan, von Roeder, Maximilian, Lücke, Christian, Gutberlet, Matthias, Thiele, Holger, Lurz, Philipp, Besler, Christian 02 June 2023 (has links)
Introduction: Inflammatory cardiomyopathy (ICM) frequently leads to myocardial fibrosis, resulting in permanent deterioration of the left ventricular function and an unfavorable outcome. Soluble suppression of tumorigenicity 2 receptor (sST2) is a novel marker of inflammation and fibrosis in cardiovascular tissues. sST2 was found to be helpful in predicting adverse outcomes in heart failure patients with reduced ejection fraction. The aim of this study was to determine the association of sST2 plasma levels with cardiac magnetic resonance (CMR) and echocardiography imaging features of left ventricular impairment in ICM patients, as well as to evaluate the applicability of sST2 as a prognosticator of the clinical status in patients suffering from ICM. Methods: We used plasma samples of 89 patients presenting to the Heart Center Leipzig with clinically suspected myocardial inflammation. According to immunohistochemical findings in endomyocardial biopsies (EMB) conducted in the context of patients’ diagnostic work-up, inflammatory cardiomyopathy was diagnosed in 60 patients (ICM group), and dilated cardiomyopathy in 29 patients (DCM group). All patients underwent cardiac catheterization for exclusion of coronary artery disease and CMR imaging on 1.5 or 3 Tesla. sST2 plasma concentration was determined using ELISA. Results: Mean plasma concentration of sST2 in the whole patient cohort was 45.8 ± 26.4 ng/mL (IQR 27.5 ng/mL). In both study groups, patients within the highest quartile of sST2 plasma concentration had a significantly lower left ventricular ejection fraction (LV-EF) compared to patients within the lowest sST2 plasma concentration quartile (26 ± 11% vs. 40 ± 13%, p = 0.05 for ICM and 24 ± 13% vs. 51 ± 10%, p = 0.004 for DCM). sST2 predicted New York Heart Association (NYHA) class III/IV at 12 months follow-up more efficiently in ICM compared to DCM patients (AUC 0.85 vs. 0.61, p = 0.02) and was in these terms superior to NT-proBNP and cardiac troponin T. ICM patients with sST2 plasma concentration higher than 44 ng/mL at baseline had a significantly higher probability of being assigned to NYHA class III/IV at 12 months follow-up (hazard ratio 2.8, 95% confidence interval 1.01–7.6, log rank p = 0.05). Conclusion: Plasma sST2 levels in ICM patients reflect the degree of LV functional impairment at hospital admission and predict functional NYHA class at mid-term follow-up. Hence, ST2 may be helpful in the evaluation of disease severity and in the prediction of the clinical status in ICM patients.
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Accuracy of a magnetic resonance imaging-based 3D printed stereotactic brain biopsy device in dogsGutmann, Sarah, Winkler, Dirk, Müller, Marcel, Möbius, Robert, Fischer, Jean-Pierre, Böttcher, Peter, Kiefer, Ingmar, Grunert, Ronny, Flegel, Thomas 05 June 2023 (has links)
Background
Brain biopsy of intracranial lesions is often necessary to determine specific therapy. The cost of the currently used stereotactic rigid frame and optical tracking systems for brain biopsy in dogs is often prohibitive or accuracy is not sufficient for all types of lesion.
Objectives
To evaluate the application accuracy of an inexpensive magnetic resonance imaging-based personalized, 3D printed brain biopsy device.
Animals
Twenty-two dog heads from cadavers were separated into 2 groups according to body weight (<15 kg, >20 kg).
Methods
Experimental study. Two target points in each cadaver head were used (target point 1: caudate nucleus, target point 2: piriform lobe). Comparison between groups was performed using the independent Student's t test or the nonparametric Mann-Whitney U Test.
Results
The total median target point deviation was 0.83 mm (range 0.09-2.76 mm). The separate median target point deviations for target points 1 and 2 in all dogs were 0.57 mm (range: 0.09-1.25 mm) and 0.85 mm (range: 0.14-2.76 mm), respectively.
Conclusion and Clinical Importance
This magnetic resonance imaging-based 3D printed stereotactic brain biopsy device achieved an application accuracy that was better than the accuracy of most brain biopsy systems that are currently used in veterinary medicine. The device can be applied to every size and shape of skull and allows precise positioning of brain biopsy needles in dogs.
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Proteomic profiling of matched normal and tumour tongue biopsies from smokers and non-smokers. Oncoproteomic applications for oral tongue squamous cell carcinoma biomarker discoverySaeed, Sidra January 2021 (has links)
Despite considerable development in the therapeutic repertoire for managing cancer-related malignancies, head and neck cancer mortality has not significantly improved. The burden of HNSCC fluctuates across countries and has been associated with exposure to tobacco-derived carcinogens, excessive alcohol consumption or combinations. Due to late detection, patients often present with oral pre-malignant lesions which have progressed to an advanced stage of HNSCC. In this study, the samples were from a male cohort as generally, men are at two to four-fold higher risk than women with over 90% of HNSCCs arising in the upper aerodigestive tract. Therefore, the purpose of this thesis was to identify HNSCC biomarkers in males associated within defined anatomical region (tongue) and causative agents, specific to smoking.
An iTRAQ proteomic approach was used to profile protein changes in matched normal and tumour samples from male non-smoking (n=6) and smoking patients (n=6) with tongue carcinomas revealing identification of potential targets specific to cancer. Samples were subjected to liquid nitrogen cryo-pulverisation and protein determination. Protein extracts from the same category were pooled, trypsin digested and iTRAQ 4-plex labelled. Data was generated by 2D-LC/MS on an Orbitrap Fusion and significantly changed proteins (median ± SD) were subject to bioinformatics appraisal. A total of 3426 proteins were identified and quantified by proteomic analysis. Comparison of non-smoker tumour (NS:T) with smoker tumour (S:T) distinguished 64 proteins that were upregulated and 62 downregulated, S:T vs S:N categorised 349 proteins up- and 395 down-regulated respectively and NS:T vs NS:N identified 469 proteins up- and 431 down-regulated, respectively. Arginase-1 (ARG1), Keratin Type-2 Cytoskeletal 8 (KRT8), Lipocalin-1 (LCN1) and DNA replication licensing factor MCM2 (MCM2) were identified as biologically associated with smoking compared to non-smoking, providing viable targets for verification by immunochemical methods which further supported the proteomic data.
Overall, the project demonstrated the importance of using matched biopsies with good clinicopathological data for experimental design and provided a set of unique targets for a more expanded verification study.
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