Browsing by Subject "disease"

Now showing 1 - 7 of 7
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    Antimicrobial Resistance Incidence and Risk Factors among Helicobacter pylori–Infected Persons, United States
    (Center for Disease Control and Prevention, 2004-06) Duck, William M.; Sobel, Jeremy; Pruckler, Janet M.; Song, Qunsheng; Swerdlow, David; Friedman, Cindy; Sulka, Alana; Swaminathan, Balasubra; Taylor, Tom; Hoekstra, Mike; Griffin, Patricia; Smoot, Duane; Peek, Rick; Metz, David C.; Bloom, Peter B.; Goldschmid, Steven; Parsonnet, Julie; Triadafilopoulos, George; Perez-Perez, Guillermo I.; Vakil, Nimish; Ernst, Peter; Czinn, Steve; Dunne, Donald; Gold, Ben D.; Medicine, School of Medicine
    Helicobacter pylori is the primary cause of peptic ulcer disease and an etiologic agent in the development of gastric cancer. H. pylori infection is curable with regimens of multiple antimicrobial agents, and antimicrobial resistance is a leading cause of treatment failure. The Helicobacter pylori Antimicrobial Resistance Monitoring Program (HARP) is a prospective, multicenter U.S. network that tracks national prevalence rates of H. pylori antimicrobial resistance. Of 347 clinical H. pylori isolates collected from December 1998 through 2002, 101 (29.1%) were resistant to one antimicrobial agent, and 17 (4.8%) were resistant to two or more antimicrobial agents. Eighty-seven (25.1%) isolates were resistant to metronidazole, 45 (12.9%) to clarithromycin, and 3 (0.9%) to amoxicillin. On multivariate analysis, black race was the only significant risk factor (p < 0.01, hazard ratio 2.04) for infection with a resistant H. pylori strain. Formulating pretreatment screening strategies or providing alternative therapeutic regimens for high-risk populations may be important for future clinical practice.
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    Automatic Detection of Associatons Among Terms Related to Alzheimer's Disease from Medline Abstracts
    Lai, Dongbing; Mukhopadhyay, Snehasis
    Alzheimer's disease is a progressive, age-related, degenerative brain disorder, which is one of the most serious diseases in old people. The patients' memory is lost and their personality and behavior are changed gradually; furthermore, this process is irreversible until the patients die [1]. Alzheimer's disease first attacks the entorhinal cortex; then to the hippocampus, which help to control short-term memory; then to other regions, especially the cerebral cortex, which is very important in using language and reasoning [1 , 2]. After its attack, the neurons degenerate and lose synapses and eventually die [1 , 2]. According to the age of having this disease, Alzheimer's disease can be divided to early-onset (usually at age 30 to 60) and late-onset (at age of 65 or older) [1]. About 5% to 10% of Alzheimer's disease cases are early onset [1 ]. Another way to describe Alzheimer's disease is according to the inheritance pattern. In this way, Alzheimer's disease also can be divided to: sporadic Alzheimer's disease, which has no certain inheritance pattern; and familial Alzheimer's disease (FAD), which has certain inheritance pattern [1]. All FAD are early onset [1 ]. Alzheimer's disease is a progressive disease and the progression of symptoms can be divided into mild, moderate and severe phases [2, 3]. The symptoms of mild Alzheimer's disease include loss of memory, disorientation, and difficulty of performing routine tasks. [2]. Patients in this phase can live independently [3]. The moderate symptoms include having great difficulty in daily living, wandering, personality changes, agitation and anxiety [2]. Patients in this phase should be cared by other people. People in severe phase lose all communication functions, almost cannot think, and need total care [2].
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    Dissecting the expression dynamics of RNA-binding proteins in posttranscriptional regulatory networks
    (2009-12) Mittal, Nitish; Roy, Nilanjan; Babu, M. Madan; Janga, Sarath Chandra
    In eukaryotic organisms, gene expression requires an additional level of coordination that links transcriptional and posttranslational processes. Messenger RNAs have traditionally been viewed as passive molecules in the pathway from transcription to translation. However, it is now clear that RNA-binding proteins (RBPs) play an important role in cellular homeostasis by controlling gene expression at the posttranscriptional level. Here, we show that RBPs, as a class of proteins, show distinct gene expression dynamics compared to other protein coding genes in the eukaryote Sacchoromyces cerevisiae. We find that RBPs generally exhibit high protein stability, translational efficiency, and protein abundance but their encoding transcripts tend to have a low half-life. We show that RBPs are also most often posttranslationally modified, indicating their potential for regulation at the protein level to control diverse cellular processes. Further analysis of the RBP-RNA interaction network showed that the number of distinct targets bound by an RBP (connectivity) is strongly correlated with its protein stability, translational efficiency, and abundance. We also note that RBPs show less noise in their expression in a population of cells, with highly connected RBPs showing significantly lower noise. Our results indicate that highly connected RBPs are likely to be tightly regulated at the protein level as significant changes in their expression may bring about large-scale changes in global expression levels by affecting their targets. These observations might explain the molecular basis behind the cause of a number of disorders associated with misexpression or mutation in RBPs. Future studies uncovering the posttranscriptional networks in higher eukaryotes can help our understanding of the link between different levels of regulation and their role in pathological conditions.
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    Focal Adhesion Kinases in Adhesion Structures and Disease
    (2012-05) Eleniste, Pierre P; Bruzzaniti, Angela
    Cell adhesion to the extracellular matrix (ECM) is essential for cell migration, proliferation, and embryonic development. Cells can contact the ECM through a wide range of matrix contact structures such as focal adhesions, podosomes, and invadopodia. Although they are different in structural design and basic function, they share common remodeling proteins such as integrins, talin, paxillin, and the tyrosine kinases FAK, Pyk2, and Src. In this paper, we compare and contrast the basic organization and role of focal adhesions, podosomes, and invadopodia in different cells. In addition, we discuss the role of the tyrosine kinases, FAK, Pyk2, and Src, which are critical for the function of the different adhesion structures. Finally, we discuss the essential role of these tyrosine kinases from the perspective of human diseases.
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    PRMTs and miRNAs: functional cooperation in cancer and beyond
    (Taylor & Francis, 2019-06-24) Jin, Jiamin; Martin, Matthew; Hartley, Antja-Voy; Lu, Tao; Pharmacology and Toxicology, School of Medicine
    Epigenetic modulators play pivotal roles in directing gene expression for the maintenance of normal cellular functions. However, when these modulators are aberrantly regulated, this can result in a variety of disease states, including cancer. One class of epigenetic regulators, protein arginine methyltransferases (PRMTs), have been shown to play critical roles in disease through methylation of arginine residues (R) on histone or non-histone proteins. Quite different from PRMTs, microRNAs (miRNAs) belong to the family of modulators known as noncoding RNAs (ncRNA) that act to regulate gene expression via RNA-mediated gene silencing. Importantly, miRNAs are frequently dysregulated and contribute to the progression of cancer and other conditions, including neurological and cardiovascular diseases. Recently, numerous studies have shown that miRNAs and other epigenetic enzymes can co-regulate each other. This review highlights multiple nodes of interaction between miRNAs and PRMTs and also discusses how this interplay might open up promising opportunities for drug development for the treatment of cancer and other diseases.
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    Retinal Ganglion Cells With a Glaucoma OPTN(E50K) Mutation Exhibit Neurodegenerative Phenotypes when Derived from Three-Dimensional Retinal Organoids
    (Elsevier, 2020-07-14) VanderWall, Kirstin B.; Huang, Kang-Chieh; Pan, Yanling; Lavekar, Sailee S.; Fligor, Clarisse M.; Allsop, Anna R.; Lentsch, Kelly A.; Dang, Pengtao; Zhang, Chi; Tseng, Henry C.; Cummins, Theodore R.; Meyer, Jason S.; Medical and Molecular Genetics, School of Medicine
    Retinal ganglion cells (RGCs) serve as the connection between the eye and the brain, with this connection disrupted in glaucoma. Numerous cellular mechanisms have been associated with glaucomatous neurodegeneration, and useful cellular models of glaucoma allow for the precise analysis of degenerative phenotypes. Human pluripotent stem cells (hPSCs) serve as powerful tools for studying human disease, particularly cellular mechanisms underlying neurodegeneration. Thus, efforts focused upon hPSCs with an E50K mutation in the Optineurin (OPTN) gene, a leading cause of inherited forms of glaucoma. CRISPR/Cas9 gene editing introduced the OPTN(E50K) mutation into existing lines of hPSCs, as well as generating isogenic controls from patient-derived lines. RGCs differentiated from OPTN(E50K) hPSCs exhibited numerous neurodegenerative deficits, including neurite retraction, autophagy dysfunction, apoptosis, and increased excitability. These results demonstrate the utility of OPTN(E50K) RGCs as an in vitro model of neurodegeneration, with the opportunity to develop novel therapeutic approaches for glaucoma.
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    Some basic facts on combination therapy
    (Association of Kenya Physicians, 2007) Kokwaro, Gilbert; Association of Kenya Physicians Scientific Conference (11th : Mar. 2007 : Eldoret, Kenya)
    What are the problems with malaria? • The disease • The drugs • The policies • The finance COMBINATION THERAPY: DEFINITION • CT is the simultaneous use of two or more blood schizonticidal drugs with independent modes of action and different biochemical targets in the parasites • • CTs can be either fixed ratio combinations or multiple-drug therapy, in which components are co-administered in separate tablets or capsules.