bacteremia is rarely encountered in clinical practice. When it is, patients usually have underlying periodontal disease or colorectal carcinoma. To the best of our knowledge, this is the first case of bacteremia in a patient without the predisposing risk factors listed above.
View Article and Find Full Text PDFPrimary T-cell non-Hodgkin lymphoma (NHL) of the gastrointestinal tract (GIT) is a rare, poorly-characterized clinical entity. A well-known complication of intestinal NHL is perforation due to chemotherapy, but perforation as a presenting sign of GIT lymphoma is extremely rare. Here we present a case of spontaneous intestinal perforation secondary to primary intestinal T-cell lymphoma and highlight the importance of early recognition of this uncommon cause of perforation as a crucial step to ensure expedited hematology referral and initiation of appropriate treatment.
View Article and Find Full Text PDFCase Rep Gastroenterol
December 2022
Lemmel syndrome is a rare clinical entity characterized by the presence of a periampullary duodenal diverticulum resulting in compression and dilatation of the pancreatic and common bile ducts, accompanied by obstructive jaundice. Gastric outlet obstruction is not a known complication of this syndrome, and there are no standardized approaches to its treatment. We present the first case of Lemmel syndrome presenting as gastric outlet obstruction and provide the results of a systematic literature review.
View Article and Find Full Text PDFSpontaneous pneumothorax (PTX) is a rare but life-threatening complication of lung injuries sustained from severe COVID-19 infection, most commonly associated with mechanical ventilation. Development of spontaneous PTX in patients after only mild COVID-19 infections not requiring hospitalization is even rarer. Here, we present the case of a 37-year-old male with spontaneous PTX secondary to a mild COVID-19 infection diagnosed one-month prior.
View Article and Find Full Text PDFVery long chain fatty acids (VLCFAs) are essential building blocks for the synthesis of ceramides and sphingolipids. The first step in the fatty acid elongation cycle is catalyzed by the 3-keto acyl-coenzyme A (CoA) synthases (in mammals, ELOVL elongases). Although ELOVLs are implicated in common diseases, including insulin resistance, hepatic steatosis and Parkinson's, their underlying molecular mechanisms are unknown.
View Article and Find Full Text PDFAn amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDFThe B7 family represents one of the best-studied subgroups within the Ig superfamily, yet new interactions continue to be discovered. However, this binding promiscuity represents a major challenge for defining the biological contribution of each specific interaction. We developed a strategy for addressing these challenges by combining cell microarray and high-throughput FACS methods to screen for promiscuous binding events, map binding interfaces, and generate functionally selective reagents.
View Article and Find Full Text PDFMembranes in cells have defined distributions of lipids in each leaflet, controlled by lipid scramblases and flip/floppases. However, for some intracellular membranes such as the endoplasmic reticulum (ER) the scramblases have not been identified. Members of the TMEM16 family have either lipid scramblase or chloride channel activity.
View Article and Find Full Text PDFBackground: Allogeneic hematopoietic stem-cell transplantation for X-linked severe combined immunodeficiency (SCID-X1) often fails to reconstitute immunity associated with T cells, B cells, and natural killer (NK) cells when matched sibling donors are unavailable unless high-dose chemotherapy is given. In previous studies, autologous gene therapy with γ-retroviral vectors failed to reconstitute B-cell and NK-cell immunity and was complicated by vector-related leukemia.
Methods: We performed a dual-center, phase 1-2 safety and efficacy study of a lentiviral vector to transfer complementary DNA to bone marrow stem cells after low-exposure, targeted busulfan conditioning in eight infants with newly diagnosed SCID-X1.
Importance: Pharmaceutical manufacturers can receive 6 additional months of market exclusivity for performing pediatric clinical trials of brand-name drugs widely used in adults. Congress created this incentive in 1997 because these drugs were being used off-label in children without such trials.
Objective: To review updates to drug labeling and the cost to consumers of extending market exclusivity related to the pediatric exclusivity program.
Change history: In the HTML version of this Letter, Extended Data Fig. 4 incorrectly corresponded to Fig. 4 (the PDF version of the figure was correct).
View Article and Find Full Text PDFViral infections continue to represent major challenges to public health, and an enhanced mechanistic understanding of the processes that contribute to viral life cycles is necessary for the development of new therapeutic strategies . Viperin, a member of the radical S-adenosyl-L-methionine (SAM) superfamily of enzymes, is an interferon-inducible protein implicated in the inhibition of replication of a broad range of RNA and DNA viruses, including dengue virus, West Nile virus, hepatitis C virus, influenza A virus, rabies virus and HIV. Viperin has been suggested to elicit these broad antiviral activities through interactions with a large number of functionally unrelated host and viral proteins.
View Article and Find Full Text PDFSulfur, most abundantly found in the environment as sulfate (SO), is an essential element in metabolites required by all living cells, including amino acids, co-factors and vitamins. However, current understanding of the cellular delivery of SO at the molecular level is limited. CysZ has been described as a SO permease, but its sequence family is without known structural precedent.
View Article and Find Full Text PDFHistorically, entities with a vested interest in a product that critics have suggested is harmful have consistently used research to back their claims that the product is safe. Prominent examples are: tobacco, lead, bisphenol A, and atrazine. Research literature indicates that about 80-90% of studies with industry affiliation found no harm from the product, while only about 10-20% of studies without industry affiliation found no harm.
View Article and Find Full Text PDFProduction of prokaryotic membrane proteins for structural and functional studies in E. coli can be parallelized and miniaturized. All stages from cloning, expression, purification to detergent selection can be investigated using high-throughput techniques to rapidly and economically find tractable targets.
View Article and Find Full Text PDFWhile excessive tensile strain can be detrimental to nerve function, strain can be a positive regulator of neuronal outgrowth. We used an in vivo rat model of sciatic nerve strain to investigate signaling mechanisms underlying peripheral nerve response to deformation. Nerves were deformed by 11% and did not demonstrate deficits in compound action potential latency or amplitude during or after 6 h of strain.
View Article and Find Full Text PDFIn a cadaveric model, we evaluated thumb metacarpal subsidence, indicated by a decreased metacarpal-to-scaphoid distance, after 2 surgical procedures used to treat thumb carpometacarpal (CMC) osteoarthritis (OA): partial trapeziectomy with capsular interposition (PTCI), which involves removal of 2 mm of both the distal trapezium and base of the metacarpal; and total trapeziectomy with capsular interposition (TTCI). Nine matched pairs of cadaveric hands were randomly assigned to undergo either PTCI or TTCI. Preoperatively, physiologic forces were applied across the thumb CMC joint by loading 6 tendons, simulating lateral pinch.
View Article and Find Full Text PDFUnbiased binding assays involving small-molecule microarrays were used to identify compounds that display unique patterns of selectivity among members of the zinc-dependent histone deacetylase family of enzymes. A novel, hydroxyquinoline-containing compound, BRD4354, was shown to preferentially inhibit activity of HDAC5 and HDAC9 in vitro. Inhibition of deacetylase activity appears to be time-dependent and reversible.
View Article and Find Full Text PDFFront Cell Neurosci
September 2015
Local synthesis of proteins within the Schwann cell periphery is extremely important for efficient process extension and myelination, when cells undergo dramatic changes in polarity and geometry. Still, it is unclear how ribosomal distributions are developed and maintained within Schwann cell projections to sustain local translation. In this multi-disciplinary study, we expressed a plasmid encoding a fluorescently labeled ribosomal subunit (L4-GFP) in cultured primary rat Schwann cells.
View Article and Find Full Text PDFPlants synthesize carotenoids, which are essential for plant development and survival. These metabolites also serve as essential nutrients for human health. The biosynthetic pathway for all plant carotenoids occurs in chloroplasts and other plastids and requires 15-cis-ζ-carotene isomerase (Z-ISO).
View Article and Find Full Text PDFCell Mol Life Sci
November 2015
Local and long-distance transport of cytoskeletal proteins is vital to neuronal maintenance and growth. Though recent progress has provided insight into the movement of microtubules and neurofilaments, mechanisms underlying the movement of actin remain elusive, in large part due to rapid transitions between its filament states and its diverse cellular localization and function. In this work, we integrated live imaging of rat sensory neurons, image processing, multiple regression analysis, and mathematical modeling to perform the first quantitative, high-resolution investigation of GFP-actin identity and movement in individual axons.
View Article and Find Full Text PDFCoxiella burnetii is a highly infectious bacterium and potential agent of bioterrorism. However, it has not been studied as extensively as other biological agents, and very few of its proteins have been structurally characterized. To address this situation, we undertook a study of critical metabolic enzymes in C.
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