Browsing by Author "Green, Francis H. Y."

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    Analyzing the Nanomechanical Oscillations of Brain Tumor Cells using Optical Tweezers
    (2019-01-02) Ghandorah, Salim; Amrein, Matthias; Ghasemloonia, Ahmad; Green, Francis H. Y.; Mahoney, Douglas J.
    Under the microscope, cells manifest nanomechanical oscillations (also known as vibrations and fluctuations). While the exact source of these oscillations is unknown, they may reflect the numerous inherent active processes of living cells. The sum of these active processes of cell characterizes its phenotype and function. Therefore, we hypothesize that the oscillation spectrum is unique for each cell type, and reflective of its functional state, allowing phenotypically-different cell types to be differentiated and functional changes in the cells to be followed. To test this hypothesis, we employed a novel, highly sensitive tool, optical tweezers, to record the oscillations of two brain tumor cells and applied advanced multivariate analysis to statistically evaluate the difference between the oscillation spectra. Two main sub aims were addressed; (1) To find optimal conditions for the optical tweezers setup for single cell oscillation measurements, and (2) To establish statistical methods to differentiate cells based on their oscillation patterns. Our results showed feature-rich spectra of different cell types over a frequency range from a few Hertz (Hz) to 50 kHz. The multivariate analysis generated two separate clusters for each cell type. The analysis also allowed evaluation of the spectra for features that are strongly associated with differences and the features that are common among cells. My thesis expands the current knowledge of cellular oscillations. While previous studies demonstrated a correlation between the metabolic activity of cells and overall magnitude of oscillations, spectral decomposition was either not reported or showed few, if any, cell-specific frequencies. In conclusion, the recording of oscillation spectra of single cells using optical tweezers, followed by multivariate statistical analysis is a promising method to differentiate cell types and follow cellular functions in real-time.
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    Efficacy of a Peruvian Botanical Remedy (Sabell A4+) for Treating Liver Disease and Protecting Gastric Mucosal Integrity
    (2019-10-24) Swain, Mark G.; Wallace, John L.; Tyrrell, D. Lorne; Cabanillas, José; Aung, Steven K. H.; Liu, Hongqun; Finnie-Carvalho, Lindsay; Shrestha, Grishma; Semple, Hugh A.; Green, Francis H. Y.
    The purpose of this study was to determine the efficacy of a Peruvian botanical formulation for treating disorders of hepatic function and gastric mucosal integrity. The formulation A4+ (Sabell Corporation) contains extracts of Curcuma longa rhizome, Cordia lutea flower, and Annona muricata leaf. Individually these plants have been used as traditional remedies for liver disease. We report the efficacy of A4+ and its components using a variety of in vitro and in vivo disease models. The methods used included tests for antioxidant, anti-inflammatory, and antiviral activity as well as mouse models of liver disease, including Concanavalin A-induced immune-mediated hepatitis and a bile duct ligation model for evaluating sickness behaviour associated with liver disease. Rat models were used to evaluate the gastric mucosal protective property of A4+ following indomethacin challenge and to evaluate its anti-inflammatory action in an “air pouch” model. In all tests, A4+ proved to be more effective than placebo. A4+ was antioxidant and anti-inflammatory and diminished Hepatitis C virus replication in vitro. In animal models, A4+ was shown to protect the liver from immune-mediated hepatitis, improve behavioural function in animals with late stage liver disease, and protect the rat gastric mucosa from ulceration following NSAID exposure. We conclude that A4+ ameliorated many aspects of liver injury, inhibited hepatitis C virus replication, and protected the gastric mucosa from NSAIDs. These varied beneficial properties appear to result from positive interactions between the three constituent herbs.
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    Vibrational Profiling of Brain Cells and Tumours using Atomic Force Microscopy
    (2018-03-08) Nelson, Sultan; Amrein, Matthias; Green, Francis H. Y.; Sutherland, Garnette Roy
    Nanoscopic mechanical vibration is observed as a periodic plasma-membrane fluctuation in living cells. The study of this physiological phenomenon is an emerging field of research. All prior experimental work has been limited to single cell study, including erythrocytes (1,2), leukocytes (3), and cardiomyocytes (4). Moreover, the intensity of fluctuation has been shown to be indicative of cells’ overall metabolic activity (5,6). The fluctuation can be modulated using pharmacological blockers (7,8), thus excluding stochastic Brownian motion as the sole explanation. Given our main interest in the potential clinical application of this phenomenon for qualitative and efficient brain tumor identification, we examined vibration waves emanating from cultured cells, and tissues harvested from the brains of newborn rats, as well as from brain tumors and neocortex specimens. In this research project, we first developed a novel atomic force microscope-based (AFM-based) mechanical vibration detection method and a custom-written MATLAB vibration signal analysis algorithm. The AFM system used in this report utilized sensitive cantilevers (probes) to enhance the signal-to-noise ratio, and to improve overall performance. The method was also designed to detect cellular vibration without direct physical contact between the sample and the cantilever probe. Using this unique method, we recorded vibrations emitted from newborn rat hippocampus and cerebellum samples; these brain regions showed distinct vibration profiles. The effect of pharmacological agents on the tissue samples examined suggested synaptic activity is the major contributor to the subtle vibrations observed. For assessment of potential clinical applications of the method, we examined human surgical brain biopsy samples. Malignant astrocytoma tissue samples vibrated with markedly different frequency peaks and amplitude, compared to tissue from meningioma or normal lateral temporal cortex, thus providing a quantifiable measurement to accurately distinguish the three types of tissues. Lastly, we developed a method to convert cellular oscillation signals into sound within the frequency range of normal human hearing to provide medical specialists with a way to differentiate tumors from healthy brain tissue without the need for extensive, complex vibration, spectral analysis training. Evidence attested through this project has shown that vibrational profiling of cells and tissues can be adopted for simultaneous mapping of neuronal and metabolic activity in the brain. Further, the results of this research may have translational clinical implications as a prompt diagnostic technique, which may aid clinicians in discerning between healthy and cancerous tissues in real-time.