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2018

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Full-Text Articles in Medical Sciences

การตรวจหาเชื้อแบคทีเรียก่อโรคในเหาโคจาก 3 จังหวัดของประเทศไทย, จุฬาลักษณ์ พรมรังษ์ Jan 2018

การตรวจหาเชื้อแบคทีเรียก่อโรคในเหาโคจาก 3 จังหวัดของประเทศไทย, จุฬาลักษณ์ พรมรังษ์

Chulalongkorn University Theses and Dissertations (Chula ETD)

เหาโค (Cattle lice) เป็นแมลงดูดเลือดชนิดหนึ่งซึ่งเป็นสาเหตุหลักของปัญหาสุขภาพสัตว์ทั่วโลก หลายงานวิจัยได้เปิดเผยข้อมูลการตรวจพบเชื้อแบคทีเรียก่อโรคในเหาโคและเหาโคอาจมีศักยภาพที่สามารถทำหน้าที่เป็นพาหะนำโรคต่าง ๆ ที่สามารถติดต่อโดยเหา และการศึกษาชนิดของเหาโคโดยใช้เทคนิคทางอณูชีววิทยาและการตรวจหาเชื้อแบคทีเรียก่อโรคในประเทศไทยยังไม่มีการรายงาน งานวิจัยนี้มีวัตถุประสงค์เพื่อตรวจหาเชื้อแบคทีเรียก่อโรคในเหาโคและจำแนกชนิดของเหาโคที่เก็บจากพื้นที่ 3 จังหวัดของประเทศไทย โดยตัวอย่างเหาโคทั้งหมด 109 ตัวอย่าง จะนำมาสกัดดีเอ็นเอและใช้เทคนิค PCR ศึกษาบนตำแหน่งยีน 18S rRNA ที่ได้ทำการพัฒนาออกแบบขึ้นเพื่อระบุชนิดของเหาโค และตรวจหาเชื้อ Bartonella spp., Acinetobacter spp. และ Rickettsia spp. จากนั้นนำมาวิเคราะห์หาลำดับนิวคลีโอไทด์และสร้างแผนภูมิวิวัฒนาการ จากผลลำดับนิวคลีโอไทด์ของยีน 18S rRNA แสดงให้เห็นว่าชนิดของเหาโคในงานวิจัยนี้แบ่งออกเป็น 2 กลุ่ม คือ Haematopinus quadripertusus และ Haematopinus spp. ที่มีความสัมพันธ์ใกล้ชิดกับ H. tuberculatus และสามารถตรวจพบเชื้อ Bartonella spp. ทั้งยีน gltA และ rpoB ทั้งหมด 25 ตัวอย่างจาก 109 ตัวอย่าง (22.93%) พบทั้งในระยะไข่และตัวเต็มวัย เมื่อทำการวิเคราะห์ลำดับนิวคลีโอไทด์และศึกษาแผนภูมิวิวัฒนาการของยีน gltA และ rpoB พบว่าเชื้อ Bartonella spp. ในงานวิจัยนี้มีความใกล้ชิดกับสายพันธุ์ B. bovis งานวิจัยนี้เป็นการรายงานครั้งแรกของการตรวจพบเชื้อ Bartonella spp. ในเหาโคที่เก็บจากพื้นที่ 3 จังหวัดของประเทศไทย และทำให้ทราบถึงข้อมูลชนิดของเหาโคในประเทศไทยโดยใช้เทคนิคทางอณูชีววิทยา ซึ่งข้อมูลเหล่านี้อาจนำมาใช้เพื่อระบุศักยภาพของเหาโคที่จะทำหน้าที่เป็นพาหะนำโรคและอาจถ่ายทอดเชื้อแบคทีเรียก่อโรคเหล่านี้จากสัตว์มาสู่มนุษย์


Deep Coverage Whole Genome Sequences And Plasma Lipoprotein(A) In Individuals Of European And African Ancestries, Seyedeh M. Zekavat, Sanni Ruotsalainen, Robert E. Handsaker, Maris Alver, Jonathan Bloom, Timothy Poterba, Laura Almasy, John Blangero, Joanne E. Curran, Ravindranath Duggirala, Juan M. Peralta, Harald H. H. Goring Jan 2018

Deep Coverage Whole Genome Sequences And Plasma Lipoprotein(A) In Individuals Of European And African Ancestries, Seyedeh M. Zekavat, Sanni Ruotsalainen, Robert E. Handsaker, Maris Alver, Jonathan Bloom, Timothy Poterba, Laura Almasy, John Blangero, Joanne E. Curran, Ravindranath Duggirala, Juan M. Peralta, Harald H. H. Goring

School of Medicine Publications

Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding …


Nano-Pulse Stimulation Ablates Orthotopic Rat Hepatocellular Carcinoma And Induces Innate And Adaptive Memory Immune Mechanisms That Prevent Recurrence, Brittany P. Lassiter, Siqi Guo, Stephen J. Beebe Jan 2018

Nano-Pulse Stimulation Ablates Orthotopic Rat Hepatocellular Carcinoma And Induces Innate And Adaptive Memory Immune Mechanisms That Prevent Recurrence, Brittany P. Lassiter, Siqi Guo, Stephen J. Beebe

Bioelectrics Publications

Nano-pulse stimulation (NPS), previously called nsPEFs, induced a vaccine-like effect after ablation of orthotopic N1-S1 hepatocellular carcinoma (HCC), protecting rats from subsequent challenges with N1-S1 cells. To determine immunity, immune cell phenotypes were analyzed in naïve, treated and protected rats. NPS provides a positive, post-ablation immuno-therapeutic outcome by alleviating immunosuppressive T regulatory cells (Treg) in the tumor microenvironment (TME), allowing dendritic cell influx and inducing dynamic changes in natural killer cells (NKs), NKT-cells and T-lymphocytes in blood, spleen and liver. NPS induced specific increases in NKs and NKT-cells expressing CD8 and activation receptors CD314-NKG2D and CD161 (NK1.1) in the TME …


Cold Atmospheric Plasma As A Potential Tool For Multiple Myeloma Treatment, Dehui Xu, Yujing Xu, Qingjie Cui, Dingxin Liu, Zhijie Liu, Xiaohua Wang, Yanjie Yang, Niaojuan Feng, Rong Liang, Hailan Chen, Kai Ye, Michael G. Kong Jan 2018

Cold Atmospheric Plasma As A Potential Tool For Multiple Myeloma Treatment, Dehui Xu, Yujing Xu, Qingjie Cui, Dingxin Liu, Zhijie Liu, Xiaohua Wang, Yanjie Yang, Niaojuan Feng, Rong Liang, Hailan Chen, Kai Ye, Michael G. Kong

Bioelectrics Publications

Multiple myeloma (MM) is a fatal and incurable hematological malignancy thus new therapy need to be developed. Cold atmospheric plasma, a new technology that could generate various active species, could efficiently induce various tumor cells apoptosis. More details about the interaction of plasma and tumor cells need to be addressed before the application of gas plasma in clinical cancer treatment. In this study, we demonstrate that He+O2 plasma could efficiently induce myeloma cell apoptosis through the activation of CD95 and downstream caspase cascades. Extracellular and intracellular reactive oxygen species (ROS) accumulation is essential for CD95-mediated cell apoptosis in response …


Tumor Cell Death After Electrotransfer Of Plasmid Dna Is Associated With Cytosolic Dna Sensor Upregulation, Katarina Znidar, Masa Bosnjak, Nina Semenova, Olga N. Pakhomova, Loree Heller, Maja Cemazar Jan 2018

Tumor Cell Death After Electrotransfer Of Plasmid Dna Is Associated With Cytosolic Dna Sensor Upregulation, Katarina Znidar, Masa Bosnjak, Nina Semenova, Olga N. Pakhomova, Loree Heller, Maja Cemazar

Bioelectrics Publications

Cytosolic DNA sensors are a subgroup of pattern recognition receptors (PRRs) and are activated by the abnormal presence of the DNA in the cytosol. Their activation leads to the upregulation of pro-inflammatory cytokines and chemokines and can also induce cell death. The presence of cytosolic DNA sensors and inflammatory cytokines in TS/A murine mammary adenocarcinoma and WEHI 164 fibrosarcoma cells was demonstrated using real time reverse transcription polymerase chain reaction (RT-PCR), western blotting and enzyme-linked immunosorbent assay (ELISA). After electrotransfer of plasmid DNA (pDNA) using two pulse protocols, the upregulation of DNA-depended activator of interferon regulatory factor or Z-DNA binding …


Investigating The Role Of Nicotinic Acetylcholine Receptor Agonists In Lung Cancer Progression And Chemosensitivity In The Context Of Treating Chemotherapy-Induced Peripheral Neuropathy, Sarah L. Kyte Jan 2018

Investigating The Role Of Nicotinic Acetylcholine Receptor Agonists In Lung Cancer Progression And Chemosensitivity In The Context Of Treating Chemotherapy-Induced Peripheral Neuropathy, Sarah L. Kyte

Theses and Dissertations

While cancer chemotherapy continues to significantly contribute to the number of cancer survivors, exposure to these drugs can often result in chemotherapy-induced peripheral neuropathy (CIPN), a consequence of peripheral nerve fiber dysfunction or degeneration. CIPN is characterized by sensory symptoms in the hands and feet, such as numbness, burning, and allodynia, resulting in an overall decrease in quality of life. Paclitaxel (Taxol), a microtubule poison that is commonly used to treat breast, lung, and ovarian cancers, has been found to cause CIPN in 59-78% of cancer patients. There is currently no effective preventative or therapeutic treatment for this side effect, …


Evaluation And Adaptation Of Live-Cell Interferometry For Applications In Basic, Translational, And Clinical Research, Kevin A. Leslie Jan 2018

Evaluation And Adaptation Of Live-Cell Interferometry For Applications In Basic, Translational, And Clinical Research, Kevin A. Leslie

Theses and Dissertations

Cell mass is an important indicator of cell health and status. A diverse set of techniques have been developed to precisely measure the masses of single cells, with varying degrees of technical complexity and throughput. Here, the development of a non-invasive, label-free optical technique, termed Live-Cell Interferometry (LCI), is described. Several applications are presented, including an evaluation of LCI’s utility for assessing drug response heterogeneity in patient-derived melanoma lines and the measurement of CD3+ T cell kinetics during hematopoietic stem cell transplantation. The characterization of mast cells during degranulation, the measurement of viral reactivation kinetics in Kaposi’s Sarcoma, and drug …


Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh Jan 2018

Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh

Theses and Dissertations

Cellular senescence a specialized form of growth arrest that contributes to the pathogenesis of several aging-related disorders including cancer. While by definition tumor cells are considered immortalized, they can undergo senescence when exposed to conventional and targeted cancer therapy. Therapy-Induced Senescence (TIS) represents a fundamental response to therapy and impacts its outcomes. However, TIS has been considered a positive therapeutic goal since senescent tumor cells are expected to enter a state of permanent growth abrogation. In this work we examined the hypothesis that a subpopulation of senescent cells can re-acquire proliferative potential after a state of senescent dormancy, indicating that …


Alternative Splicing Of Cytoplasmic Polyadenylation Element Binding Protein 2 Is Modulated Via Serine Arginine Splicing Factor 3 In Cancer Metastasis, James T. Deligio, James Thomas Deligio Jan 2018

Alternative Splicing Of Cytoplasmic Polyadenylation Element Binding Protein 2 Is Modulated Via Serine Arginine Splicing Factor 3 In Cancer Metastasis, James T. Deligio, James Thomas Deligio

Theses and Dissertations

Our laboratory delineated a role for alternative pre-mRNA splicing (AS) in triple negative breast cancer (TNBC). We found the translational regulator cytosolic polyadenylation element binding protein 2 (CPEB2) which has two isoforms, CPEB2A and CPEB2B, is alternatively spliced during acquisition of anoikis resistance (AnR) and metastasis. The splicing event which determines the CPEB2 isoform is via inclusion/ exclusion of exon four in the mature mRNA transcript. The loss of CPEB2A with a concomitant increase in CPEB2B is required for TNBC cells to metastasize in vivo. We examined RNAseq profiles of TNBC cells which had CPEB2 isoforms specifically downregulated to …


Age-Dependent Changes In Oxygen Supply And Demand Of Rat Spinotrapezius Muscle, Sami C. Dodhy Jan 2018

Age-Dependent Changes In Oxygen Supply And Demand Of Rat Spinotrapezius Muscle, Sami C. Dodhy

Theses and Dissertations

Because of the aerobic nature of cellular metabolism in mammalian organisms, a continuous supply of oxygen is necessary to maintain normal physiological function. As organisms age, their metabolic rates generally decline and there are accompanying alterations in the structure and function of the microcirculation, as this part of the cardiovascular system is especially important for oxygen exchange. The overall Oxygen Transport System can be considered as being composed of two complementary components: one for Oxygen Demand and one for Oxygen Supply. The purpose of the current work is to describe the age-dependent changes in both oxygen demand and oxygen supply …


The Role Of Adam10 And Adam17 In Humoral And Type 2 Immunity, Joseph C. Lownik Jan 2018

The Role Of Adam10 And Adam17 In Humoral And Type 2 Immunity, Joseph C. Lownik

Theses and Dissertations

The proper regulation of inducible costimulator (ICOS) and its ligand (ICOSL) have been shown to be essential for maintaining immune homeostasis. Loss of either protein results in defective humoral immunity, and overexpression of ICOS results in aberrant antibody production resembling lupus. How ICOSL is regulated in response to ICOS interaction is still unclear. We demonstrate that ADAM10 is the primary physiological sheddase of ICOSL in both mouse and human. Using an in vivo system in which ADAM10 is deleted only on B cells (ADAM10B-/-), elevated levels of ICOSL were seen. This increase is also seen when ADAM10 is …


Glycosaminoglycan Lyases In The Preparation Of Oligosaccharides, Alhumaidi B. Alabbas Jan 2018

Glycosaminoglycan Lyases In The Preparation Of Oligosaccharides, Alhumaidi B. Alabbas

Theses and Dissertations

Glycosaminoglycans are heterogeneous polysaccharides that mediate important biological functions. There has been considerable interest in deciphering the precise GAG sequences that are responsible for protein interactions. In fact, several GAG oligosaccharides have been discovered to date as targeting proteins with higher level of specificity. Yet, it has been difficult to develop GAG oligosaccharides as drugs. One of the key reasons for this state of art is that GAG synthesis is extremely challenging and is highly structure-specific. Thus, much of the biology and pharmacology of GAG remains unknown and unexploited to date.

An alternative approach is to prepare GAG oligosaccharides using …


Gastrointestinal Microbiota Modulate Antinociceptive Tolerance Development In Mice With Chronic Morphine Exposure, Ryan A. Mischel Jan 2018

Gastrointestinal Microbiota Modulate Antinociceptive Tolerance Development In Mice With Chronic Morphine Exposure, Ryan A. Mischel

Theses and Dissertations

In October 2017, the United States government declared a state of public health emergency in response to the burgeoning prescription opioid epidemic. Opioid analgesics are the gold standard of therapy for moderate to severe pain, but their clinical utility is greatly limited by analgesic tolerance – a primary driver of diminished pain control and opioid dose escalations. Integral in this process are primary afferent sensory neurons in dorsal root ganglia (DRG), the first-order components of nociceptive sensation. With surmounting evidence that morphine and other narcotics can alter gut microbial composition and promote bacterial translocation to other tissues, a question arises …


The Contribution Of Sarm1 To Axonal Degeneration In Cns Inflammatory Disorders, Daniel C. Njoku Jan 2018

The Contribution Of Sarm1 To Axonal Degeneration In Cns Inflammatory Disorders, Daniel C. Njoku

Theses and Dissertations

BACKGROUND: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) that results in demyelination and axonal loss. Efficiently targeting mechanisms of axonal degeneration in MS has the potential to reduce disability but remains an unmet need. Prior research has identified the protein sterile alpha and TIR motif containing 1 (SARM1) as a critical factor that promotes axonal destruction in the program of axonal degeneration known as Wallerian degeneration. SARM1 inactivation reduces axonal degeneration in a variety of contexts including traumatic and toxic injury, but it remains unknown to what extent SARM1 is involved in axonal degeneration …


Effects Of The Na-Cl Co-Transporter (Ncc) In Western Diet Induced Metabolic And Cardiac Dysfunction, Zachary S. Cutter Jan 2018

Effects Of The Na-Cl Co-Transporter (Ncc) In Western Diet Induced Metabolic And Cardiac Dysfunction, Zachary S. Cutter

Theses and Dissertations

Interleukin-18 (IL-18) is a pro-inflammatory cytokine known to be involved in maintaining metabolic homeostasis; however, also capable of inducing cardiac dysfunction. Additionally, IL-18, has been shown to bind to a novel receptor, the Na-Cl Co-transporter (NCC). We hypothesized that NCC mediates IL-18 metabolic and cardiac signaling in mice. Using male C57BL/6J mice, we compared the metabolic and cardiac function changes after at least 8 weeks of high-saturated fat high sugar diet (Western Diet) in NCC knockout (NCCKO), IL-18 knockout (IL-18KO), and wild-type mice. We show that NCCKO mice have significantly increased body weight gain from baseline, no difference in fasting …


Advances In Dual-Energy Computed Tomography Imaging Of Radiological Properties, Dong Han Jan 2018

Advances In Dual-Energy Computed Tomography Imaging Of Radiological Properties, Dong Han

Theses and Dissertations

Dual-energy computed tomography (DECT) has shown great potential in the reduction of uncertainties of proton ranges and low energy photon cross section estimation used in radiation therapy planning. The work presented herein investigated three contributions for advancing DECT applications. 1) A linear and separable two-parameter DECT, the basis vector model (BVM) was used to estimate proton stopping power. Compared to other nonlinear two-parameter models in the literature, the BVM model shows a comparable accuracy achieved for typical human tissues. This model outperforms other nonlinear models in estimations of linear attenuation coefficients. This is the first study to clearly illustrate the …


Development And Validation Of A Semi-Physiological Pharmacokinetic (Pbpk) Model To Predict Systemic And Pulmonary Exposures After Intravenous, Oral Administration And Pulmonary Inhalation Of Selected Drugs, Budesonide, Tobramycin And Ciprofloxacin, In Humans, Bishoy Hanna Jan 2018

Development And Validation Of A Semi-Physiological Pharmacokinetic (Pbpk) Model To Predict Systemic And Pulmonary Exposures After Intravenous, Oral Administration And Pulmonary Inhalation Of Selected Drugs, Budesonide, Tobramycin And Ciprofloxacin, In Humans, Bishoy Hanna

Theses and Dissertations

Using a semi-PBPK modeling/quantitative meta-analysis approach, this project investigated what factors affect pulmonary and systemic exposures of Budesonide (BUD), Tobramycin (TOB), and Ciprofloxacin (CIP) after inhalation:

Three structurally different pulmonary disposition models were developed for each drug, including pulmonary absorption (all three), excretion (TOB and CIP) and sequestration (TOB) in a peripheral and central lung compartment. Systemic disposition parameters were estimated using available human mean plasma (cp(t)) and sputum (cs(t)) concentration profiles after IV administration, and GI absorption parameters were estimated from these profiles after oral administration. Pulmonary disposition parameters were estimated from cp(t) …


Understanding The Role Of Phosphoinositide 3-Kinase And Its Function As A Driving Force Behind The Er Stress Response In Fibrostenotic Crohn’S Disease-Affected Ileal Smooth Muscle Cells, Prashant Yadav Jan 2018

Understanding The Role Of Phosphoinositide 3-Kinase And Its Function As A Driving Force Behind The Er Stress Response In Fibrostenotic Crohn’S Disease-Affected Ileal Smooth Muscle Cells, Prashant Yadav

Theses and Dissertations

Crohn’s disease (CD) affects about 780,000 people in the United States alone, and it is estimated that 6-15 per 100,000 persons will receive a diagnosis of this disease each year. There currently is no cure for Crohn’s disease, and available medical therapies simply serve to alleviate the inflammation. This does not help treat fibrostenosis that Crohn’s disease patients may develop, which can only be treated surgically. Finding alternatives to treat CD requires an understanding of mechanisms at the biochemical level. In this thesis, we attempted to gain a better understanding of certain pathways found to be active in Crohn’s disease-affected …


Branched Short Chain Fatty Acid Isovaleric Acid Causes Smooth Muscle Relaxation Via Camp/Pka Pathway, Inhibits Gastrointestinal Motility, And Disrupts Peristaltic Movement, Bryan Adam Blakeney Jan 2018

Branched Short Chain Fatty Acid Isovaleric Acid Causes Smooth Muscle Relaxation Via Camp/Pka Pathway, Inhibits Gastrointestinal Motility, And Disrupts Peristaltic Movement, Bryan Adam Blakeney

Theses and Dissertations

Isovaleric Acid (IVA) is a 5-carbon branched chain fatty acid present in fermented foods and produced by the fermentation of leucine by colonic bacteria. IVA activates G-protein coupled receptors such as FFAR2, FFAR3, and OR51E1 known to be expressed on enteric neurons and enteroendocrine cells. We previously reported that the shorter, straight chain fatty acids acetate, propionate and butyrate, differentially affect colonic propulsion; however, the effect of branched chain fatty acids on gastrointestinal motility is unknown. We hypothesize that IVA relaxes smooth muscle in a cAMP/PKA dependent manner by direct action on smooth muscle cells. IVA will also decrease peristalsis …


S100b As A Potential Biomarker For Concussion In Male And Female Collegiate Rugby Athletes, Monica L. Ortiz Jan 2018

S100b As A Potential Biomarker For Concussion In Male And Female Collegiate Rugby Athletes, Monica L. Ortiz

Cal Poly Humboldt theses and projects

Sport related concussions are among the top ten most common sport injuries. Substantial and mounting evidence points to extensive short and long term negative consequences from mismanaged sport related concussions. Consequently, researchers have called for better diagnostic concussion tests that are rapid, reliable, sensitive, specific and objective. The purpose of this research was to determine the ability of salivary S100B to detect concussions, predict concussion symptom resolution time, and correlate with changes in neurocognitive performance over the course of one athletic season. A repeated measures of salivary S100B and neurocognitive performance using the ImPACT test and a concussion symptom questionnaire …