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Weissman resistance

Kum Ja Lee, Vivian Chow, Ashley Weissman, Sunil Tulpule, Ibrahim Aldoss, Mojtaba Akhtari
Adults with relapsed or refractory B-cell acute lymphoblastic leukemia have a dismal prognosis with a short median overall survival that can be measured in months. Because most patients will have chemotherapy-resistant disease, allogeneic hematopoietic stem cell transplantation remains the only potentially curative treatment. Despite advances in current management, patients continue to have poor outcomes and lack of durable responses. Thus, new therapies with alternative modes of actions are currently being investigated...
2016: Therapeutics and Clinical Risk Management
Yoko Kojima, Jens-Peter Volkmer, Kelly McKenna, Mete Civelek, Aldons Jake Lusis, Clint L Miller, Daniel Direnzo, Vivek Nanda, Jianqin Ye, Andrew J Connolly, Eric E Schadt, Thomas Quertermous, Paola Betancur, Lars Maegdefessel, Ljubica Perisic Matic, Ulf Hedin, Irving L Weissman, Nicholas J Leeper
Atherosclerosis is the disease process that underlies heart attack and stroke. Advanced lesions at risk of rupture are characterized by the pathological accumulation of diseased vascular cells and apoptotic cellular debris. Why these cells are not cleared remains unknown. Here we show that atherogenesis is associated with upregulation of CD47, a key anti-phagocytic molecule that is known to render malignant cells resistant to programmed cell removal, or 'efferocytosis'. We find that administration of CD47-blocking antibodies reverses this defect in efferocytosis, normalizes the clearance of diseased vascular tissue, and ameliorates atherosclerosis in multiple mouse models...
August 4, 2016: Nature
M Earth Hasassri, Thomas G Boyce, Andrew Norgan, Scott A Cunningham, Patricio R Jeraldo, Scott Weissman, Robin Patel, Ritu Banerjee, Jason M Pogue, Keith S Kaye
We describe a 16-year-old neutropenic patient from the Middle East with bloodstream infection caused by two carbapenemase-producing Escherichia coli isolates that we characterized by whole-genome sequencing. While one displayed meropenem resistance and was blaNDM positive, the other demonstrated meropenem susceptibility yet harbored blaOXA181 (which encodes a blaOXA48-like enzyme). This report highlights the challenge of laboratory detection of blaOXA48-like enzymes and the clinical implications of genotypic resistance detection in carbapenemase-producing Enterobacteriaceae...
June 2016: Antimicrobial Agents and Chemotherapy
Monika Jelic, Amanda L Adler, Arianna Miles-Jay, Scott J Weissman, Matthew P Kronman, Danielle M Zerr
We used the Pediatric Health Information System database to assess the use of antibiotics reserved for the treatment of resistant Gram-negative infections in children from 2004 to 2014. Overall, use of these agents increased in children from 2004 to 2007 and subsequently decreased. Infect Control Hosp Epidemiol 2016:37:967-970.
August 2016: Infection Control and Hospital Epidemiology
Danielle M Zerr, Arianna Miles-Jay, Matthew P Kronman, Chuan Zhou, Amanda L Adler, Wren Haaland, Scott J Weissman, Alexis Elward, Jason G Newland, Theoklis Zaoutis, Xuan Qin
The objective of this study was to determine whether antibiotic exposure is associated with extended-spectrum-beta-lactamase- or AmpC-producing Escherichia coli or Klebsiella pneumoniae infections in children. We collected extended-spectrum-beta-lactamase- or AmpC-producing E. coli or K. pneumoniae isolates and same-species susceptible controls from normally sterile sites of patients aged ≤21 years, along with associated clinical data, at four free-standing pediatric centers. After controlling for potential confounders, the relative risk of having an extended-spectrum-beta-lactamase-producing isolate rather than a susceptible isolate was 2...
July 2016: Antimicrobial Agents and Chemotherapy
M Argyelan, T Lencz, S Kaliora, D K Sarpal, N Weissman, P B Kingsley, A K Malhotra, G Petrides
Electroconvulsive therapy (ECT) is the most effective treatment for depression, yet its mechanism of action is unknown. Our goal was to investigate the neurobiological underpinnings of ECT response using longitudinally collected resting-state functional magnetic resonance imaging (rs-fMRI) in 16 patients with treatment-resistant depression and 10 healthy controls. Patients received bifrontal ECT 3 times a week under general anesthesia. We acquired rs-fMRI at three time points: at baseline, after the 1st ECT administration and after the course of the ECT treatment; depression was assessed with the Hamilton Depression Rating Scale (HAM-D)...
2016: Translational Psychiatry
James R Johnson, Paul Thuras, Brian D Johnston, Scott J Weissman, Ajit P Limaye, Kim Riddell, Delia Scholes, Veronika Tchesnokova, Evgeni Sokurenko
BACKGROUND: The H30 subclone within Escherichia coli sequence type 131 (ST131-H30) has emerged rapidly to become the leading antibiotic-resistant E. coli strain. Hypervirulence, multidrug resistance, and opportunism have been proposed as explanations for its epidemic success. METHODS: We assessed 1133 consecutive unique E. coli clinical isolates from 5 medical centers (2010-2011) for H30 genotype, which we compared with epidemiological and clinical data extracted from medical records by blinded reviewers...
June 15, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Sara Ahmed, Thomas E Besser, Douglas R Call, Scott J Weissman, Lisa P Jones, Margaret A Davis
Multi-locus sequence typing (MLST) is a useful system for phylogenetic and epidemiological studies of multidrug-resistant Escherichiacoli. Most studies utilize a seven-locus MLST, but an alternate two-locus typing method (fumC and fimH; CH typing) has been proposed that may offer a similar degree of discrimination at lower cost. Herein, we compare CH typing to the standard seven-locus method for typing commensal E. coli isolates from dairy cattle. In addition, we evaluated alternative combinations of eight loci to identify combinations that maximize discrimination and congruence with standard seven-locus MLST among commensal E...
May 2016: Journal of Microbiological Methods
Genjiro Suzuki, Jonathan S Weissman, Motomasa Tanaka
Eukaryotic cells are targeted by pathogenic viruses and have developed cell defense mechanisms against viral infection. In yeast, the cellular extrachromosomal genetic element [KIL-d] alters killer activity of M double-stranded RNA killer virus and confers cell resistance against the killer virus. However, its underlying mechanism and the molecular nature of [KIL-d] are unknown. Here, we demonstrate that [KIL-d] is a proteinaceous prion-like aggregate with non-Mendelian cytoplasmic transmission. Deep sequencing analyses revealed that [KIL-d] selectively increases the rate of de novo mutation in the killer toxin gene of the viral genome, producing yeast harboring a defective mutant killer virus with a selective growth advantage over those with WT killer virus...
November 19, 2015: Molecular Cell
Terri Stillwell, Michael Green, Karen Barbadora, Juliet G Ferrelli, Terri L Roberts, Scott J Weissman, Andrew Nowalk
BACKGROUND: The increase in carbapenem-resistant Enterobacteriaceae (CRE) infections is a critical public health issue. We recently experienced the largest single-center pediatric outbreak of carbapenem-resistant Klebsiella pneumoniae (CRKP) at our hospital. The objective of this study was to describe the molecular epidemiology of this outbreak before and after infection-prevention interventions. METHODS: All positive cultures and associated clinical conditions were reviewed to determine whether health care-associated infections (HAIs) exist...
December 2015: Journal of the Pediatric Infectious Diseases Society
Scott J Weissman, Nellie I Hansen, Kristen Zaterka-Baxter, Rosemary D Higgins, Barbara J Stoll
BACKGROUND: Escherichia coli associated with early-onset sepsis (EOS) have historically been antibiotic-susceptible and K1-encapsulated. In the era of emerging antibiotic resistance, however, the clonal makeup of E coli associated with EOS has not been well characterized. METHODS: Escherichia coli isolates were collected from 28 cases of EOS and early-onset meningitis (EOM) from April 2008 through December 2009, during a parent study conducted at National Institute of Child Health and Human Development Neonatal Research Network centers from February 2006 through December 2009...
September 2016: Journal of the Pediatric Infectious Diseases Society
Diego Acosta-Alvear, Min Y Cho, Thomas Wild, Tonia J Buchholz, Alana G Lerner, Olga Simakova, Jamie Hahn, Neha Korde, Ola Landgren, Irina Maric, Chunaram Choudhary, Peter Walter, Jonathan S Weissman, Martin Kampmann
Hallmarks of cancer, including rapid growth and aneuploidy, can result in non-oncogene addiction to the proteostasis network that can be exploited clinically. The defining example is the exquisite sensitivity of multiple myeloma (MM) to 20S proteasome inhibitors, such as carfilzomib. However, MM patients invariably acquire resistance to these drugs. Using a next-generation shRNA platform, we found that proteostasis factors, including chaperones and stress-response regulators, controlled the response to carfilzomib...
2015: ELife
E Pazarentzos, P Giannikopoulos, G Hrustanovic, J St John, V R Olivas, M A Gubens, R Balassanian, J Weissman, W Polkinghorn, T G Bivona
Activation of the phosphoinositide 3-kinase (PI3K) pathway occurs widely in human cancers. Although somatic mutations in the PI3K pathway genes PIK3CA and PTEN are known to drive PI3K pathway activation and cancer growth, the significance of somatic mutations in other PI3K pathway genes is less clear. Here, we establish the signaling and oncogenic properties of a recurrent somatic mutation in the PI3K p110β isoform that resides within its kinase domain (PIK3Cβ(D1067V)). We initially observed PIK3Cβ(D1067V) by exome sequencing analysis of an EGFR-mutant non-small cell lung cancer (NSCLC) tumor biopsy from a patient with acquired erlotinib resistance...
March 3, 2016: Oncogene
Kristen A Wendorf, Meagan Kay, Christopher Baliga, Scott J Weissman, Michael Gluck, Punam Verma, Marisa D'Angeli, Jennifer Swoveland, Mi-Gyeong Kang, Kaye Eckmann, Andrew S Ross, Jeffrey Duchin
BACKGROUND: We identified an outbreak of AmpC-producing Escherichia coli infections resistant to third-generation cephalosporins and carbapenems (CR) among 7 patients who had undergone endoscopic retrograde cholangiopancreatography at hospital A during November 2012-August 2013. Gene sequencing revealed a shared novel mutation in a bla CMY gene and a distinctive fumC/ fimH typing profile. OBJECTIVE: To determine the extent and epidemiologic characteristics of the outbreak, identify potential sources of transmission, design and implement infection control measures, and determine the association between the CR E...
June 2015: Infection Control and Hospital Epidemiology
Minghong Li, Veronica Holmes, Houping Ni, Jenine K Sanzari, Ana L Romero-Weaver, Liyong Lin, Alejandro Carabe-Fernandez, Eric S Diffenderfer, Ann R Kennedy, Drew Weissman
A major risk for astronauts during prolonged space flight is infection as a result of the combined effects of microgravity, situational and confinement stress, alterations in food intake, altered circadian rhythm, and radiation that can significantly impair the immune system and the body's defense systems. We previously reported a massive increase in morbidity with a decrease in the ability to control a bacterial challenge when mice were maintained under hindlimb suspension (HS) conditions and exposed to solar particle event (SPE)-like radiation...
2015: PloS One
D G Dillon, T Wiecki, P Pechtel, C Webb, F Goer, L Murray, M Trivedi, M Fava, P J McGrath, M Weissman, R Parsey, B Kurian, P Adams, T Carmody, S Weyandt, K Shores-Wilson, M Toups, M McInnis, M A Oquendo, C Cusin, P Deldin, G Bruder, D A Pizzagalli
BACKGROUND: Depression is characterized by poor executive function, but - counterintuitively - in some studies, it has been associated with highly accurate performance on certain cognitively demanding tasks. The psychological mechanisms responsible for this paradoxical finding are unclear. To address this issue, we applied a drift diffusion model (DDM) to flanker task data from depressed and healthy adults participating in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study...
August 2015: Psychological Medicine
Wajid Siddiqui, Yasir Ahmed, Helmut Albrecht, Sharon Weissman
Pseudozyma spp are amorphic yeasts. They are commonly plant pathogens, but rarely cause invasive fungal disease in humans. Only three cases of central venous catheter (CVC)-associated blood stream infections due to this organism have been reported in the literature. Main underlying risk factors for Pseudozyma spp infection are bowel surgery, CVC and total parenteral nutrition. We present a rare case of Pseudozyma spp catheter-associated blood stream infection that was successfully treated with antifungal therapy and removal of CVC...
2014: BMJ Case Reports
Jared M Jaynes, Timothy B Edrington, Barry A Weissman
BACKGROUND/PURPOSE: Over the past decade, utilization of scleral gas permeable (GP) contact lenses has steadily increased. Scleral GP lenses offer yet another option for patients suffering from visually debilitating corneal and tear conditions. Oxygen delivery to the cornea in the presence of a contact lens system continues to be a subject of interest, and scleral GP lenses are no exception. This paper utilizes an existing model based on simultaneous two lens systems (piggyback lenses) as a resistance to oxygen in series, and applies this model to scleral GP lens systems...
February 2015: Contact Lens & Anterior Eye: the Journal of the British Contact Lens Association
Olivier Julien, Martin Kampmann, Michael C Bassik, Julie A Zorn, Vincent J Venditto, Kazutaka Shimbo, Nicholas J Agard, Kenichi Shimada, Arnold L Rheingold, Brent R Stockwell, Jonathan S Weissman, James A Wells
We previously discovered a small-molecule inducer of cell death, named 1541, that noncovalently self-assembles into chemical fibrils ('chemi-fibrils') and activates procaspase-3 in vitro. We report here that 1541-induced cell death is caused by the fibrillar rather than the soluble form of the drug. A short hairpin RNA screen reveals that knockdown of genes involved in endocytosis, vesicle trafficking and lysosomal acidification causes partial 1541 resistance. We confirm the role of these pathways using pharmacological inhibitors...
November 2014: Nature Chemical Biology
Pia S Pannaraj, Jennifer Dien Bard, Chiara Cerini, Scott J Weissman
BACKGROUND: Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are on the rise worldwide but are not well described in pediatric populations. This study characterizes the clinical, phenotypic and genotypic characteristics of CRE infections at a free-standing US children's hospital. METHODS: CRE were defined as any clinical Enterobacteriaceae isolate non-susceptible to either imipenem or meropenem and resistant to ceftriaxone, cefotaxime and ceftazidime determined by routine antimicrobial susceptibility testing...
January 2015: Pediatric Infectious Disease Journal
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