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https://www.readbyqxmd.com/read/29031566/high-nrf2-expression-controls-endoplasmic-reticulum-stress-induced-apoptosis-in-multiple-myeloma
#1
Yu Sun, Amina Abdul Aziz, Kristian Bowles, Stuart Rushworth
Multiple myeloma (MM) is an incurable disease characterized by clonal plasma cell proliferation. The stress response transcription factor Nuclear factor erythroid 2 [NF-E2]-related factor 2 (NRF2) is known to be activated in MM in response to proteasome inhibitors (PI). Here, we hypothesize that the transcription factor NRF2 whose physiological role is to protect cells from reactive oxygen species via the regulation of drug metabolism and antioxidant gene plays an important role in MM cells survival and proliferation...
October 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29019745/imaging-of-nonmalignant-adrenal-lesions-in-children
#2
Kiran M Sargar, Geetika Khanna, Rebecca Hulett Bowling
The adrenal glands in children can be affected by a variety of benign lesions. The diagnosis of adrenal lesions can be challenging, but assessment of morphologic changes in correlation with the clinical presentation can lead to an accurate diagnosis. These lesions can be classified by their cause: congenital (eg, discoid adrenal gland, horseshoe adrenal gland, and epithelial cysts), vascular and/or traumatic (eg, adrenal hemorrhage), infectious (eg, granulomatous diseases), enzyme deficiency disorders (eg, congenital adrenal hyperplasia [CAH] and Wolman disease), benign neoplasms (eg, pheochromocytomas, ganglioneuromas, adrenal adenomas, and myelolipomas), and adrenal mass mimics (eg, extralobar sequestration and extramedullary hematopoiesis)...
October 2017: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/28992976/a-mixed-methods-evaluation-of-the-feasibility-and-acceptability-of-an-adapted-cardiac-rehabilitation-program-for-home-care-patients
#3
Jodi L Feinberg, David Russell, Ana Mola, Melissa Trachtenberg, Irene Bick, Terri H Lipman, Kathryn H Bowles
Home care clinicians have an opportunity to improve care for post-hospitalization patients with cardiovascular disease. This mixed methods study examined the feasibility and acceptability of an adapted cardiac rehabilitation (CR) program for the home care setting. Surveys measuring patient self-care and knowledge were administered to patients (n = 46) at baseline and at 30-day follow-up. Semi-structured interviews were conducted with patients (n = 28) and home care clinicians (n = 11) at completion of the program...
October 6, 2017: Geriatric Nursing
https://www.readbyqxmd.com/read/28991134/isolated-testicular-recurrence-of-aml-in-patients-with-chronic-gvhd-1-year-following-allogeneic-stem-cell-transplant
#4
Brian N Dang, Satiro De Oliveira, LaVette Bowles, Theodore B Moore
BACKGROUND: Patients with chronic graft-versus-host disease (cGVHD) following allogeneic transplant for myeloid leukemias seem to experience a reduced risk of relapse than comparable patients without cGVHD. It is unclear to what extent extramedullary sites are impacted by a graft-versus-leukemia effect. DESIGN/METHOD: Case Series and review of the literature. RESULTS: We present 2 cases of pediatric patients with Acute Myelogenous Leukemia who developed isolated testicular relapse more than a year following hematopoietic stem cell transplantation despite having had extensive cGVHD...
October 4, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28980524/structure-of-pink1-and-mechanisms-of-parkinson-s-disease-associated-mutations
#5
Atul Kumar, Jevgenia Tamjar, Andrew D Waddell, Helen I Woodroof, Olawale G Raimi, Andrew M Shaw, Mark Peggie, Miratul Mk Muqit, Daan Mf van Aalten
Mutations in the human kinase PINK1 (hPINK1) are associated with autosomal recessive early-onset Parkinson's disease (PD). hPINK1 activates Parkin E3 ligase activity, involving phosphorylation of ubiquitin and the Parkin ubiquitin-like (Ubl) domain via as yet poorly understood mechanisms. hPINK1 is unusual amongst kinases due to the presence of three loop insertions of unknown function. We report the structure of Tribolium castaneum PINK1 (TcPINK1), revealing several unique extensions to the canonical protein kinase fold...
October 5, 2017: ELife
https://www.readbyqxmd.com/read/28961851/comprehensive-genomic-profiles-of-metastatic-and-relapsed-salivary-gland-carcinomas-are-associated-with-tumor-type-and-reveal-new-routes-to-targeted-therapies
#6
J S Ross, L M Gay, K Wang, J-A Vergilio, J Suh, S Ramkissoon, H Somerset, J M Johnson, J Russell, S Ali, A B Schrock, D Fabrizio, G Frampton, V Miller, P J Stephens, J A Elvin, D W Bowles
Background: Relapsed/metastatic salivary gland carcinomas (SGCs) have a wide diversity of histologic subtypes associated with variable clinical aggressiveness and response to local and systemic therapies. We queried whether comprehensive genomic profiling could define the tumor subtypes and uncover clinically relevant genomic alterations, revealing new routes to targeted therapies for patients with relapsed and metastatic disease. Patients and methods: From a series of 85 686 clinical cases, DNA was extracted from 40 µm of formalin-fixed paraffin embedded (FFPE) sections for 623 consecutive SGC...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28955799/liposomal-delivery-of-phosphodiesterase-5-inhibitors-augments-ut-15c-stimulated-atp-release-from-human-erythrocytes
#7
Elizabeth A Bowles, Dimitri Feys, Nuran Ercal, Randy S Sprague
The use of liposomes to affect targeted delivery of pharmaceutical agents to specific sites may result in the reduction of side effects and an increase in drug efficacy. Since liposomes are delivered intravascularly, erythrocytes, which constitute almost half of the volume of blood, are ideal targets for liposomal drug delivery. In vivo, erythrocytes serve not only in the role of oxygen transport but also as participants in the regulation of vascular diameter through the regulated release of the potent vasodilator, adenosine triphosphate (ATP)...
December 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28942770/the-battle-against-flystrike-past-research-and-new-prospects-through-genomics
#8
Clare A Anstead, Trent Perry, Stephen Richards, Pasi K Korhonen, Neil D Young, Vernon M Bowles, Philip Batterham, Robin B Gasser
Flystrike, or cutaneous myiasis, is caused by blow fly larvae of the genus Lucilia. This disease is a major problem in countries with large sheep populations. In Australia, Lucilia cuprina (Wiedemann, 1830) is the principal fly involved in flystrike. While much research has been conducted on L. cuprina, including physical, chemical, immunological, genetic and biological investigations, the molecular biology of this fly is still poorly understood. The recent sequencing, assembly and annotation of the draft genome and analyses of selected transcriptomes of L...
2017: Advances in Parasitology
https://www.readbyqxmd.com/read/28918511/the-role-of-major-virulence-factors-of-aiec-involved-in-inflammatory-bowl-disease-a-mini-review
#9
REVIEW
Yuqian Yang, Yuexia Liao, Yan Ma, Weijuan Gong, Guoqiang Zhu
Adherent-invasive Escherichia coli (AIEC) has recently attracted more attention because it is closely related to the pathogenicity of human inflammatory bowel disease (IBD). AIEC possesses a multitude of virulence factors. Considering these virulence factors belonging to various virulence groups, including adhesins, invasins, toxins, protectins, and siderophore-mediated iron acquisition, this review summarizes the current knowledge of how the major virulence factors assisting in AIEC survive in, adhere to, and invade host cells...
September 16, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28911205/a-zebrafish-model-of-x-linked-adrenoleukodystrophy-recapitulates-key-disease-features-and-demonstrates-a-developmental-requirement-for-abcd1-in-oligodendrocyte-patterning-and-myelination
#10
Lauren R Strachan, Tamara J Stevenson, Briana Freshner, Matthew D Keefe, D Miranda Bowles, Joshua L Bonkowsky
X-linked adrenoleukodystrophy (ALD) is a devastating inherited neurodegenerative disease caused by defects in the ABCD1 gene and affecting peripheral and central nervous system myelin. ABCD1 encodes a peroxisomal transmembrane protein required for very long chain fatty acid (VLCFA) metabolism. We show that zebrafish (Danio rerio) Abcd1 is highly conserved at the amino acid level with human ABCD1, and during development is expressed in homologous regions including the central nervous system and adrenal glands...
September 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28843971/hard-neck-lumps-a-review-of-uncommon-and-sometimes-overlooked-causes-of-these-worrying-presentations
#11
REVIEW
M I Ammar, R S Oeppen, C Bowles, P A Brennan
While a neck lump is a common presentation that can raise suspicion of a potentially serious underlying disease, a hard lump, though less common, may be even more concerning for the patient, and prompt urgent investigation. Metastatic squamous cell carcinoma is the commonest underlying diagnosis that must be excluded, but other diseases or even normal anatomy of the neck can be associated with lumps that are hard or bony. Many of these presentations are relatively rare and may not be familiar to oral and maxillofacial surgeons (OMFS) (particularly more junior clinicians) as a differential diagnosis of a hard neck mass...
August 23, 2017: British Journal of Oral & Maxillofacial Surgery
https://www.readbyqxmd.com/read/28820718/water-sanitation-and-hygiene-in-rural-health-care-facilities-a-cross-sectional-study-in-ethiopia-kenya-mozambique-rwanda-uganda-and-zambia
#12
Amy Guo, J Michael Bowling, Jamie Bartram, Georgia Kayser
Safe and sufficient water, sanitation, and hygiene (WaSH) prevent the spread of disease in health-care facilities (HCFs). Little research has been conducted on WaSH in HCF in sub-Saharan Africa. We carried out a cross-sectional study of WaSH in 1,318 randomly selected rural HCF (hospitals, health centers, health posts, and clinics) in regions throughout Ethiopia, Kenya, Mozambique, Rwanda, Uganda, and Zambia. Methods included questionnaires with head doctors and nurses to document WaSH access, continuity, quality, quantity and reliability, and analysis of drinking water samples for Escherichia coli...
July 31, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28803248/a-functional-assay-for-sick-sinus-syndrome-genetic-variants
#13
Chuanchau J Jou, Cammon B Arrington, Spencer Barnett, Jiaxiang Shen, Scott Cho, Xiaoming Sheng, Patrick C McCullagh, Neil E Bowles, Chase M Pribble, Elizabeth V Saarel, Thomas A Pilcher, Susan P Etheridge, Martin Tristani-Firouzi
BACKGROUND/AIMS: Congenital Sick Sinus Syndrome (SSS) is a disorder associated with sudden cardiac death due to severe bradycardia and prolonged pauses. Mutations in HCN4, the gene encoding inward Na+/K+ current (If), have been described as a cause of congenital SSS. The objective of this study is to develop an SSS model in embryonic zebrafish, and use zebrafish as a moderate-throughput assay to functionally characterize HCN4 variants. METHODS: To determine the function of hcn4 in zebrafish, embryos were either bathed in the If -specific blocker (ZD-7288), or endogenous hcn4 expression was knocked down using splice-blocking morpholinos...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28801931/immunomodulatory-effects-of-adipose-stromal-vascular-fraction-cells-promote-alternative-activation-macrophages-to-repair-tissue-damage
#14
Annie C Bowles, Rachel M Wise, Brittany Y Gerstein, Robert C Thomas, Roberto Ogelman, Isabella Febbo, Bruce A Bunnell
The pathogenesis of many diseases is driven by the interactions between helper T (TH ) cells and macrophages. The phenotypes of these cells are functional dichotomies that are persuaded according to the surrounding milieu. In both multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, TH 1 and TH 17 cells propagate autoimmune signaling and inflammation in the peripheral lymphoid tissues. In turn, this proinflammatory repertoire promotes the classical activation, formerly the M1-type, macrophages...
August 12, 2017: Stem Cells
https://www.readbyqxmd.com/read/28800031/risk-factors-for-development-of-melanoma-brain-metastasis-and-disease-progression-a-single-center-retrospective-analysis
#15
Laura J Gardner, Morgan Ward, Robert H I Andtbacka, Kenneth M Boucher, Glen M Bowen, Tawnya L Bowles, Adam L Cohen, Kenneth Grossmann, Ying J Hitchcock, Sheri L Holmen, John Hyngstrom, Hung Khong, Martin McMahon, Marcus M Monroe, Carolyn B Ross, Gita Suneja, David Wada, Douglas Grossman
Melanoma metastasis to the brain is associated with a poor prognosis. We sought to determine patient demographics and primary tumor factors associated with the development of brain metastasis (BM) and survival. We also investigated whether the BM detection setting (routine screening vs. symptomatic presentation) affected clinical outcomes. A database of melanoma patients seen from 1999 to 2015 at our institution was reviewed to identify patients who developed BM. Patients with BM were matched by initial stage with patients who did not develop BM as a control group...
October 2017: Melanoma Research
https://www.readbyqxmd.com/read/28798270/a-phase-i-dose-escalation-study-of-the-safety-and-pharmacokinetics-of-pictilisib-in-combination-with-erlotinib-in-patients-with-advanced-solid-tumors
#16
Stephen Leong, Rebecca A Moss, Daniel W Bowles, Joseph A Ware, Jing Zhou, Jill M Spoerke, Mark R Lackner, Geetha Shankar, Jennifer L Schutzman, Ruud van der Noll, Emile E Voest, Jan H M Schellens
BACKGROUND: Epidermal growth factor receptor (EGFR) and phosphatidylinositol 3-kinase (PI3K) are involved in the proliferation and survival of many cancer types. Enhanced antitumor activity may be achieved through combined inhibition of these pathways. We report results for pictilisib (GDC-0941, a class I pan-PI3K inhibitor) plus erlotinib (an EGFR tyrosine kinase inhibitor) in patients with advanced solid tumors. MATERIALS AND METHODS: A 3 + 3 dose-escalation study was carried out at a starting daily dose of 60 mg pictilisib on days 1-21 of a 28-day cycle and 150 mg erlotinib from day 2 of cycle 1...
August 10, 2017: Oncologist
https://www.readbyqxmd.com/read/28794819/upregulation-of-autophagy-genes-and-the-unfolded-protein-response-in-human-heart-failure
#17
Brian C Jensen, Scott J Bultman, Darcy Holley, Wei Tang, Gustaaf de Ridder, Salvatore Pizzo, Dawn Bowles, Monte S Willis
The cellular environment of the mammalian heart constantly is challenged with environmental and intrinsic pathological insults, which affect the proper folding of proteins in heart failure. The effects of damaged or misfolded proteins on the cell can be profound and result in a process termed "proteotoxicity". While proteotoxicity is best known for its role in mediating the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, its role in human heart failure also has been recognized. The UPR involves three branches, including PERK, ATF6, and IRE1...
2017: International Journal of Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/28757165/an-efficient-platform-for-astrocyte-differentiation-from-human-induced-pluripotent-stem-cells
#18
Julia Tcw, Minghui Wang, Anna A Pimenova, Kathryn R Bowles, Brigham J Hartley, Emre Lacin, Saima I Machlovi, Rawan Abdelaal, Celeste M Karch, Hemali Phatnani, Paul A Slesinger, Bin Zhang, Alison M Goate, Kristen J Brennand
Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural progenitor cell (NPC) intermediate. We evaluated this protocol across 42 NPC lines (derived from 30 individuals). Transcriptomic analysis demonstrated that hiPSC-astrocytes from four individuals are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28754123/post-mortem-molecular-profiling-of-three-psychiatric-disorders
#19
Ryne C Ramaker, Kevin M Bowling, Brittany N Lasseigne, Megan H Hagenauer, Andrew A Hardigan, Nicholas S Davis, Jason Gertz, Preston M Cartagena, David M Walsh, Marquis P Vawter, Edward G Jones, Alan F Schatzberg, Jack D Barchas, Stanley J Watson, Blynn G Bunney, Huda Akil, William E Bunney, Jun Z Li, Sara J Cooper, Richard M Myers
BACKGROUND: Psychiatric disorders are multigenic diseases with complex etiology that contribute significantly to human morbidity and mortality. Although clinically distinct, several disorders share many symptoms, suggesting common underlying molecular changes exist that may implicate important regulators of pathogenesis and provide new therapeutic targets. METHODS: We performed RNA sequencing on tissue from the anterior cingulate cortex, dorsolateral prefrontal cortex, and nucleus accumbens from three groups of 24 patients each diagnosed with schizophrenia, bipolar disorder, or major depressive disorder, and from 24 control subjects...
July 28, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28653806/assessment-of-large-copy-number-variants-in-patients-with-apparently-isolated-congenital-left-sided-cardiac-lesions-reveals-clinically-relevant-genomic-events
#20
Neil A Hanchard, Luis A Umana, Lisa D'Alessandro, Mahshid Azamian, Mojisola Poopola, Shaine A Morris, Susan Fernbach, Seema R Lalani, Jeffrey A Towbin, Gloria A Zender, Sara Fitzgerald-Butt, Vidu Garg, Jessica Bowman, Gladys Zapata, Patricia Hernandez, Cammon B Arrington, Dieter Furthner, Siddharth K Prakash, Neil E Bowles, Kim L McBride, John W Belmont
Congenital left-sided cardiac lesions (LSLs) are a significant contributor to the mortality and morbidity of congenital heart disease (CHD). Structural copy number variants (CNVs) have been implicated in LSL without extra-cardiac features; however, non-penetrance and variable expressivity have created uncertainty over the use of CNV analyses in such patients. High-density SNP microarray genotyping data were used to infer large, likely-pathogenic, autosomal CNVs in a cohort of 1,139 probands with LSL and their families...
August 2017: American Journal of Medical Genetics. Part A
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