Treatment of Theiler's virus-induced demyelinating disease with teriflunomide.

Teriflunomide is an oral therapy approved for the treatment of relapsing remitting multiple sclerosis (MS), showing both anti-inflammatory and antiviral properties. Currently, it is uncertain whether one or both of these properties may explain teriflunomide's beneficial effect in MS. Thus, to learn more about its mechanisms of action, we evaluated the effect of teriflunomide in the Theiler's encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) model, which is both a viral infection and an excellent model of the progressive disability of MS.

The effect of B-cell depletion in the Theiler's model of multiple sclerosis.

B cell depletion (BCD) is being considered as a treatment for multiple sclerosis (MS), but there are many uncertainties surrounding the use of this therapy, such as its potential effect in individuals with concurrent viral infections. We sought to discover what effect BCD, induced by an anti-CD20 monoclonal antibody, would have on Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). Mice were injected with the anti-CD20 monoclonal antibody 5D2, 14 days before or 14 days after infection with TMEV.

The immune response in the CNS in Theiler's virus induced demyelinating disease switches from an early adaptive response to a chronic innate-like response.

Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is an important model of the progressive disability caused by irreversible CNS tissue injury, and provides an example of how a CNS pathogen can cause inflammation, demyelination, and neuronal damage. We were interested in which molecules, especially inflammatory mediators, might be upregulated in the CNS throughout TMEV-IDD. We quantitated by a real-time RT-PCR multi-gene system the expression of a pathway-focused panel of genes at 30 and 165 days post infection, characterizing both the early inflammatory and the late neurodegenerative stages of TMEV-IDD.

Chemokine biomarkers in central nervous system tissue and cerebrospinal fluid in the Theiler's virus model mirror those in multiple sclerosis.

Chemokines have increasingly been implicated in inflammatory and infectious disease of the central nervous system, both as biomarkers and as molecules important in pathogenesis. Multiple sclerosis is a disabling disease of unknown etiology, and recently chemokines have been identified as being upregulated molecules in the disease. We were interested in how the chemokine expression patterns in the central nervous system of a viral model of multiple sclerosis, Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), compared to that in humans with multiple sclerosis.

Sensitivity of endoscopic retrograde cholangiopancreatography standard cytology: 10-y review of the literature.

Background: Biliary strictures present a unique diagnostic challenge to clinicians as they can be caused by both benign and malignant conditions. With the high mortalities associated with hepatopancreaticobiliary malignancies, accurate and rapid tissue diagnosis is imperative and typically done before initiation of treatment. However, the exact sensitivity of standard cytology from endoscopic retrograde cholangiopancreatography (ERCP) to diagnose malignancy remains unclear because of wide distribution of reported values in the literature.

Chromatin immunoprecipitation and microarray analysis reveal that TFIIB occupies the SL RNA gene promoter region in Trypanosoma brucei chromosomes.

RNA polymerase II (RNAP-II) synthesizes the m(7)G-capped Spliced Leader (SL) RNA and most protein-coding mRNAs in trypanosomes. RNAP-II recruitment to DNA usually requires a set of transcription factors that make sequence-specific contacts near transcriptional start sites within chromosomes. In trypanosomes, the transcription factor TFIIB is necessary for RNAP-II-dependent SL RNA transcription.

Cervical spondylotic myelopathy: factors in choosing the surgical approach.

Cervical spondylotic myelopathy is a progressive disease and a common cause of acquired disability in the elderly. A variety of surgical interventions are available to halt or improve progression of the disease. Surgical options include anterior or posterior approaches with and without fusion.

SIRT1: new avenues of discovery for disorders of oxidative stress.

Introduction: The sirtuin SIRT1 is expressed throughout the body, has broad biological effects and can significantly affect both cellular survival and longevity during acute and long-term injuries, which involve both oxidative stress and cell metabolism.

Areas Covered: SIRT1 has an intricate role in the pathology, progression, and treatment of several disease entities, including neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, tumorigenesis, cardiovascular disease with myocardial injury and atherosclerosis, metabolic disease, and aging-related disease. New areas of study in these disciplines, with discussion of the cellular biology, are highlighted.

A rare presentation of nephrogenic adenoma: multiple upper tract lesions in a female patient.

Nephrogenic adenomas are rare benign lesions of the urinary tract occurring most frequently in the bladder of male patients. We report the case of a female patient presenting with gross hematuria, which lateralized to the left ureter on cystoscopy. At the time of ureteroscopy, two polypoid lesions were identified in an upper and lower pole calyx, which were found on biopsy to be nephrogenic adenomas.

Systemic in vivo lentiviral delivery of miR-15a/16 reduces malignancy in the NZB de novo mouse model of chronic lymphocytic leukemia.

Similar to human chronic lymphocytic leukemia (CLL), the de novo New Zealand Black (NZB) mouse model has a genetically determined age-associated increase in malignant B-1 clones and decreased expression of microRNAs miR-15a and miR-16 in B-1 cells. In the present study, lentiviral vectors were employed in vivo to restore miR-15a/16, and both the short-term single injection and long-term multiple injection effects of this delivery were observed in NZB. Control lentivirus without the mir-15a/16 sequence was used for comparison.

PolyA-specific ribonuclease (PARN-1) function in stage-specific mRNA turnover in Trypanosoma brucei.

Deadenylation is often the rate-limiting event in regulating the turnover of cellular mRNAs in eukaryotes. Removal of the poly(A) tail initiates mRNA degradation by one of several decay pathways, including deadenylation-dependent decapping, followed by 5' to 3' exonuclease decay or 3' to 5' exosome-mediated decay. In trypanosomatids, mRNA degradation is important in controlling the expression of differentially expressed genes.

EPO relies upon novel signaling of Wnt1 that requires Akt1, FoxO3a, GSK-3β, and β-catenin to foster vascular integrity during experimental diabetes.

Multiple complications can ensue in the cardiovascular, renal, and nervous systems during diabetes mellitus (DM). Given that endothelial cells (ECs) are susceptible targets to elevated serum D-glucose, identification of novel cellular mechanisms that can protect ECs may foster the development of unique strategies for the prevention and treatment of DM complications. Erythropoietin (EPO) represents one of these novel strategies but the dependence of EPO upon Wnt1 and its downstream signaling in a clinically relevant model of DM with elevated D-glucose has not been elucidated.

Mammalian target of rapamycin: hitting the bull's-eye for neurological disorders.

The mammalian target of rapamycin (mTOR) and its associated cell signaling pathways have garnered significant attention for their roles in cell biology and oncology. Interestingly, the explosion of information in this field has linked mTOR to neurological diseases with promising initial studies. mTOR, a 289 kDa serine/threonine protein kinase, plays an important role in cell growth and proliferation and is activated through phosphorylation in response to growth factors, mitogens, and hormones.

Skull base defect in a patient with ozena undergoing dacryocystorhinostomy.

Ozena, which is often used interchangeably with atrophic rhinitis or empty nose syndrome, is a progressive and chronically debilitating nasal disease that results in atrophy of the nasal mucosa, nasal crusting, fetor, and destruction of submucosal structures. Although the etiology is not completely understood, infection with Klebsiella ozaenae is widely believed to contribute to the destructive changes. We present a case of a patient with ozena secondary to K.

The New Zealand black mouse as a model for the development and progression of chronic lymphocytic leukemia.

Background: Similar to a subset of human patients who progress from monoclonal B lymphocytosis (MBL) to chronic lymphocytic leukemia (CLL), New Zealand Black (NZB) mice have an age-associated progression to CLL. The murine disease is linked to a genetic abnormality in microRNA mir-15a/16-1 locus, resulting in decreased mature miR-15a/16.

Methods: Spleens of aging NZB were analyzed for the presence of B-1 cells via flow cytometry and for the presence of a side population (SP) via the ability of cells to exclude Hoechst 33342 dye.

Readability of spine-related patient education materials from subspecialty organization and spine practitioner websites.

Study Design: Analysis of spine-related websites available to the general public.

Objective: To assess the readability of spine-related patient educational materials available on professional society and individual surgeon or practice based websites.

Summary Of Background Data: The Internet has become a valuable source of patient education material.

The non-canonical CTD of RNAP-II is essential for productive RNA synthesis in Trypanosoma brucei.

The carboxy-terminal domain (CTD) of the largest subunit (RPB1) of RNA polymerase II (RNAP-II) is essential for gene expression in metazoa and yeast. The canonical CTD is characterized by heptapeptide repeats. Differential phosphorylation of canonical CTD orchestrates transcriptional and co-transcriptional maturation of mRNA and snRNA.

Identification of the HIT-45 protein from Trypanosoma brucei as an FHIT protein/dinucleoside triphosphatase: substrate specificity studies on the recombinant and endogenous proteins.

A new member of the FHIT protein family, designated HIT-45, has been identified in the African trypanosome Trypanosoma brucei. Recombinant HIT-45 proteins were purified from trypanosomal and bacterial protein expression systems and analyzed for substrate specificity using various dinucleoside polyphosphates, including those that contain the 5'-mRNA cap, i.e.

Microinjections of alpha-melanocyte stimulating hormone into the nucleus ambiguus of the rat elicit vagally mediated bradycardia.

Neurons that immunostain for alpha-melanocyte stimulating hormone (alpha-MSH) have been identified in the nucleus ambiguus (nAmb). The presence of mRNA for melanocortin type 4 receptors (MC4Rs) has also been reported in this nucleus. On the basis of this information, it was hypothesized that activation of MC4Rs in the nAmb may play a role in the regulation of cardiac function.

Ischemic preconditioning of the liver: a few perspectives from the bench to bedside translation.

Utilization of ischemic preconditioning to ameliorate ischemia/reperfusion injury has been extensively studied in various organs and species for the past two decades. While hepatic ischemic preconditioning in animals has been largely beneficial, translational efforts in the two clinical contexts--liver resection and decreased donor liver transplantation--have yielded mixed results. This review is intended to critically examine the translational data and identify some potential reasons for the disparate clinical results, and highlight some issues for further studies.

Adnexal torsion leading to death of an infant.

Background: Torsion of the uterine adnexa is an uncommon occurrence in infants, but when it does occur, the consequences may be catastrophic.

Case: A 4-month-old female presented with sudden cardiac and respiratory arrest. There were no prior signs of illness.

Spinal injuries in pedestrians struck by motor vehicles.

Study Design: Retrospective study of consecutive patients that were struck by motor vehicles and sustained spinal injuries over a 6-year period from 1997 to 2003.

Objective: To determine spinal injury patterns and associated injuries in pedestrians struck by motor vehicles.

Summary Of Background Data: Motor vehicle accidents involving pedestrians are associated with high morbidity and mortality rates.

Characterization of clinically-attenuated Burkholderia mallei by whole genome sequencing: candidate strain for exclusion from Select Agent lists.

Background: Burkholderia mallei is an understudied biothreat agent responsible for glanders which can be lethal in humans and animals. Research with this pathogen has been hampered in part by constraints of Select Agent regulations for safety reasons. Whole genomic sequencing (WGS) is an apt approach to characterize newly discovered or poorly understood microbial pathogens.

Case report: elevated serum beta human chorionic gonadotropin in a woman with osteosarcoma.

Human chorionic gonadotropin is a glycoprotein hormone normally synthesized by placental syncytiotrophoblast cells. It also is secreted by gestational trophoblastic tumors, gonadal tumors, and even various nongonadal tumors, including bone and soft tissue sarcomas, as a paraneoplastic syndrome. The literature contains one case report of beta human chorionic gonadotropin production from a primary bone sarcoma occurring in a male patient.