Showing papers by "Mark D. Johnson published in 2012"
Stony Brook University1, Washington University in St. Louis2, Emory University3, Oregon Health & Science University4, University of Florida5, University at Buffalo6, University of Alabama at Birmingham7, Houston Methodist Hospital8, St. Joseph's Hospital and Medical Center9, University of Texas Southwestern Medical Center10, Medical College of Wisconsin11, Medical University of South Carolina12, Mayo Clinic13, National Institutes of Health14
TL;DR: Periprocedural strokes in SAMMPRIS had multiple causes with the most common being perforator occlusion, and excluding patients with these features from undergoing percutaneous transluminal angioplasty and stenting to lower the procedural risk would limit per cutaneous translumsinal angio-stenting and stent selection to a small subset of patients.
Abstract: Background and Purpose—Enrollment in the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial was halted due to the high risk of stroke or death within 30 days of enrollment in the percutaneous transluminal angioplasty and stenting arm relative to the medical arm. This analysis focuses on the patient and procedural factors that may have been associated with periprocedural cerebrovascular events in the trial. Methods—Bivariate and multivariate analyses were performed to evaluate whether patient and procedural variables were associated with cerebral ischemic or hemorrhagic events occurring within 30 days of enrollment (termed periprocedural) in the percutaneous transluminal angioplasty and stenting arm. Results—Of 224 patients randomized to percutaneous transluminal angioplasty and stenting, 213 underwent angioplasty alone (n=5) or with stenting (n=208). Of these, 13 had hemorrhagic strokes (7 parenchymal, 6 subarachnoid), 19 had ischemic strok...
155 citations
TL;DR: The National Institutes of Health Genetic Testing Registry (GTR) maintains comprehensive information about testing offered worldwide for disorders with a genetic basis through basic information maintained in National Center for Biotechnology Information’s databases.
Abstract: The National Institutes of Health Genetic Testing Registry (GTR; available online at http://www.ncbi.nlm.nih.gov/gtr/) maintains comprehensive information about testing offered worldwide for disorders with a genetic basis. Information is voluntarily submitted by test providers. The database provides details of each test (e.g. its purpose, target populations, methods, what it measures, analytical validity, clinical validity, clinical utility, ordering information) and laboratory (e.g. location, contact information, certifications and licenses). Each test is assigned a stable identifier of the format GTR000000000, which is versioned when the submitter updates information. Data submitted by test providers are integrated with basic information maintained in National Center for Biotechnology Information's databases and presented on the web and through FTP (ftp.ncbi.nih.gov/pub/GTR/_README.html).
153 citations
TL;DR: In this article, the manifestations of CMV infection within the luminal gastrointestinal tract are reviewed and the options for diagnosis and management are discussed.
Abstract: Cytomegalovirus (CMV) infection is common worldwide, but the majority are asymptomatic. However, during initial infection or reactivation, CMV can cause tissue-invasive end-organ damage including in the gastrointestinal tract, especially in immunocompromised individuals. Gastrointestinal CMV disease can present with myriad of symptoms and be highly variable endoscopically. In this article we review the manifestations of CMV infection within the luminal gastrointestinal tract and discuss the options for diagnosis and management.
71 citations
TL;DR: It is shown that asymmetric Numb localization specifies glioblastoma stem‐like cell (GSC) fate in a manner that does not require Notch inhibition, and both Numb isoforms decrease epidermal growth factor receptor (EGFR) expression, thereby regulating GSC fate.
Abstract: Glioblastoma contains a hierarchy of stem-like cancer cells, but how this hierarchy is established is unclear. Here, we show that asymmetric Numb localization specifies glioblastoma stem-like cell (GSC) fate in a manner that does not require Notch inhibition. Numb is asymmetrically localized to CD133-hi GSCs. The predominant Numb isoform, Numb4, decreases Notch and promotes a CD133-hi, radial glial-like phenotype. However, upregulation of a novel Numb isoform, Numb4 delta 7 (Numb4d7), increases Notch and AKT activation while nevertheless maintaining CD133-hi fate specification. Numb knockdown increases Notch and promotes growth while favoring a CD133-lo, glial progenitor-like phenotype. We report the novel finding that Numb4 (but not Numb4d7) promotes SCFFbw7 ubiquitin ligase assembly and activation to increase Notch degradation. However, both Numb isoforms decrease epidermal growth factor receptor (EGFR) expression, thereby regulating GSC fate. Small molecule inhibition of EGFR activity phenocopies the effect of Numb on CD133 and Pax6. Clinically, homozygous NUMB deletions and low Numb mRNA expression occur primarily in a subgroup of proneural glioblastomas. Higher Numb expression is found in classical and mesenchymal glioblastomas and correlates with decreased survival. Thus, decreased Numb promotes glioblastoma growth, but the remaining Numb establishes a phenotypically diverse stem-like cell hierarchy that increases tumor aggressiveness and therapeutic resistance. STEM CELLS2012;30:1313–1326
57 citations
TL;DR: A patient with severe Crohn’s colitis and refractory CDC in whom FBT successfully averted colectomy is described, which suggests unrecognized risk factors, which may include factors contributing to the maintenance of pathogenic microbiomes, are being considered.
Abstract: Human intestinal microbiomes (mutualistic, commensal intestinal fecal flora and its genomic composition) [1] are complex ecosystems which serve protective, trophic, and metabolic functions influencing immune regulation, colonization resistance (preventing pathogenic microorganism colonization), and the production of essential short-chain fatty acids (SCFAs). Pyro-sequencing performed on human fecal flora (comprising some 10 trillion microbes) [2] reveals[5,600 bacterial taxa [3] dominated by Bacteroides ([90% of the composition of normal microbiomes), and Firmicutes, executing distinct, redundant, and complementary roles integral to human physiology. Perhaps only 300–500 species can be cultured in vitro [2]. Microbiomes reveal stability, durability, functional redundancy, and resiliency, despite dynamic compositional perturbations. However, our microbiome’s stability erodes when exposed to antibiotics and/or infections, wherein pathogenic microbiomes (fecal flora encompassing enteric pathogens) supersede [3, 4], perpetuated under host genetic and immune restriction [5]. Modernization has exposed our microbiome to altered diet (processed foods), sanitation/ hygiene, and antibiotics, changing its composition. This may engender pathogenic local intestinal immunologic priming, activation, and immune bias. This immune dysregulation, loss of microbiome diversity, and colonization with enteric pathogens, termed ‘‘dysbiosis’’, may potentiate chronic intestinal and extra-intestinal diseases, including inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) [1, 6]. Pathologic microbiomes may dominate the fecal flora within days of an adverse exposure, stabilizing with an altered flora (deviating from the host’s original flora) [7–9]. Once established, antibiotic-resistant flora may persist for years in the absence of further antibiotic exposure. The protean deleterious pathophysiological repercussions manifest from persistent perturbation and/or shifts in composition, diversity, and ecological equilibrium of our coevolved microbiomes are becoming increasingly appreciated. These include refractory Clostridium difficile colitis (CDC; loss of colonization resistance to C. difficile and other enteric pathogens), IBD, and IBS. Recurrent CDC occurs in 20% of cases caused by the re-growth of vegetative/germinative organisms from residual spores (sequestered in diverticula), which are resistant to antibiotics [7]. The organism persistence coupled to repeated antibiotic exposure exacerbates maladaptive microbiome diversity, potentiating the refractoriness to re-establishing healthy microbiomes, which can ultimately foster colonization resistance [8]. Risk factors for recurrent CDC and/or refractoriness to therapy include poor adaptive/anamnestic immune responses (low anti-toxin A IgG) and maintaining pathogenic microbiomes (including exposure to antibiotics and/or enteric infections) [9]. The proportion of community-onset versus hospital-derived C. difficile infections is increasing, associated with younger individuals and fewer antibiotic exposures [10]. This suggests unrecognized risk factors, which may include factors contributing to the maintenance of pathogenic microbiomes. Fecal bacteriotherapy (FBT) has gained momentum as salvage treatment for severe/refractory CDC. We describe a patient with severe Crohn’s colitis and refractory CDC in whom FBT successfully averted colectomy. The patient was a 33-year-old female diagnosed with Crohn’s colitis several months preceding the hospitalization for CDC. She failed multiple courses of oral/rectal C. A. Duplessis (&) D. You M. Johnson A. Speziale Naval Medical Center San Diego, 34800 Bob Wilson Drive, Ste. 5, San Diego, CA 92134-1005, USA e-mail: christopher.duplessis@med.navy.mil
31 citations
TL;DR: Data indicate that alternative splicing and frequent codeletion of CHEK2 and NF2 contribute to the genomic instability and associated development of aggressive biologic behavior in meningiomas.
31 citations
TL;DR: Methotrexate can be infused into the fourth ventricle in nonhuman primates without clinical or radiographic evidence of injury and may have pharmacokinetic advantages over current treatment paradigms.
Abstract: Object The authors hypothesized that chemotherapy infusions directly into the fourth ventricle might potentially play a role in treating malignant fourth ventricular tumors. The study tested the safety and pharmacokinetics of short- and long-term infusions of methotrexate into the fourth ventricle in a new nonhuman primate model. Methods Six rhesus monkeys underwent posterior fossa craniectomy and catheter insertion into the fourth ventricle. In Group I (3 animals), catheters were externalized, and lumbar drain catheters were placed simultaneously to assess CSF distribution after short-term methotrexate infusions. In 2 animals, methotrexate (0.5 mg) was infused into the fourth ventricle daily for 5 days. Serial CSF and serum methotrexate levels were measured. The third animal had a postoperative neurological deficit, and the experiment was aborted prior to methotrexate administration. In Group II (3 animals), catheters were connected to a subcutaneously placed port for subsequent long-term methotrexate in...
7 citations
TL;DR: Ex-vivo imaging confirmed the presence of bacteria within the colonic epithelium and fluorescent in-situ hybridization with the Cy3- to verify this finding.
4 citations