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Cns diseases

Katherine C Pehlivan, Brynn B Duncan, Daniel W Lee
PURPOSE OF REVIEW: Genetically engineered T cells expressing a chimeric antigen receptor (CAR-T) targeting specific antigens present on acute lymphoblastic leukemia (ALL) blasts have generated promising results in children and adults with relapsed and refractory disease. We review the current evidence for CAR-T cell therapy in ALL, associated toxicities, and efforts to improve durable response to therapy. RECENT FINDINGS: CD19-directed CAR-T cells have recently been approved by the FDA for use in children and young adults with ALL and in adults with diffuse large B cell lymphoma (DLBCL) in the relapsed/refractory setting...
August 17, 2018: Current Hematologic Malignancy Reports
Xu Jiang, Palanivel Ganesan, Thamaraiselvan Rengarajan, Dong-Kug Choi, Palanisamy Arulselvan
Pathogenesis of Parkinson's disease (PD) is undoubtedly a multifactorial phenomenon, with diverse etiological agents. Pro-inflammatory mediators act as a skew that directs disease progression during neurodegenerative diseases. Understanding the dynamics of inflammation and inflammatory mediators in preventing or reducing disease progression has recently gained much attention. Inflammatory neuro-degeneration is regulated via cytokines, chemokines, lipid mediators and immune cell subsets; however, individual cellular phenotypes in the Central Nervous System (CNS) acts in diverse ways whose persistent activation leads to unresolving inflammation often causing unfavorable outcomes in neurodegenerative disease like PD...
July 16, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Qianwen Wang, Zhong Zuo
In parallel with the blood-brain barrier (BBB), transporters and enzymes on the blood-cerebrospinal fluid barrier (BCSFB) serve as the first barrier for drug brain uptake. In addition, their expressions on the brain parenchyma are considered as the secondary barrier for central nervous system (CNS) drug delivery. Currently, a lack of information on transporters and enzymes expressed on both BCSFB and brain parenchyma is the major cause of failure in CNS drug development. Areas covered: Transporters and enzymes expressed on BCSFB as well as brain parenchyma and their impact on drug brain uptake was highlighted and compared with that on BBB...
August 17, 2018: Expert Opinion on Drug Metabolism & Toxicology
Jing Wang, Dalong Ni, Zhiwei Shen, Yan Ren, Yanyan Liu, Wenpei Fan, Yue Wu, Guishan Zhang, Hua Zhang, Renhua Wu, Xiaoyuan Feng, Wenbo Bu, Zhenwei Yao
Magnetic resonance spectroscopy (MRS) allows the assessment of metabolic contents and biochemical information in vivo. It provides essential compositional information in the diagnosis and monitoring of central nervous system (CNS) diseases, especially brain tumors. Conventional MRS is usually confined to endogenous metabolites that may lack specificity for certain disease such as differentiating glioma from other tumor and non-tumorous lesions. Therefore, exogenous MRS contrast agents (CAs) that may improve the sensitivity and specificity of MRS are highly desirable for its clinical use...
August 17, 2018: Advanced Healthcare Materials
Cheng-Rong Yu, Jin Kyeong Choi, Anita N Uche, Charles E Egwuagu
IL-10 and IL-35 suppress excessive immune responses and therapeutic strategies are being developed to increase their levels in autoimmune diseases. In this study, we sought to identify major cell types that produce both cytokines in-vivo and to characterize mechanisms that regulate their production. Experimental autoimmune uveitis (EAU) is a CNS autoimmune disease that serves as model of human uveitis. We induced EAU in C57BL/6J mice and investigated whether T cells, B lymphocytes, or myeloid cells are the major producers of IL-10 or IL-35 in blood, lymph nodes (LNs), spleen, and at the site of ocular inflammation, the neuroretina...
August 17, 2018: Journal of Leukocyte Biology
Marios K Georgakis, Georgios Tsivgoulis, Dimitrios Spinos, Nikolaos G Dimitriou, Athanasios P Kyritsis, Ulrich Herrlinger, Eleni Th Petridou
INTRODUCTION: Gliomatosis cerebri (GC) is a rare fatal widespread infiltrating CNS tumor. As consistent disease features have not been established, the tumor comprises a diagnostic challenge. METHODS: We conducted a systematic literature search for published case reports and case series on patients with histologically confirmed GC. Clinical, diagnostic, neuroimaging, histopathological, and molecular data on individual or summary patient level were extracted and analyzed...
August 16, 2018: Journal of Neuro-oncology
Lindsay Joy Spielman, Deanna Lynn Gibson, Andis Klegeris
The number of bacterial cells living within the human body is approximately equal to, or greater than, the total number of human cells. This dynamic population of microorganisms, termed the human microbiota, resides mainly within the gastrointestinal tract. It is widely accepted that highly diverse and stable microbiota promote overall human health. Colonization of the gut with maladaptive and pathogenic microbiota, a state also known as dysbiosis, is associated with a variety of peripheral diseases ranging from type 2 diabetes mellitus to cardiovascular and inflammatory bowel disease...
August 13, 2018: Neurochemistry International
Laura Sedra, Jean-Paul Paluzzi, Angela B Lange
In this study, a long neuropeptide F receptor of the blood-feeding hemipteran, Rhodnius prolixus (RhoprNPFR) has been cloned and characterized. Approximately 70% of the RhoprNPFR deduced protein sequence is identical to that of other hemipteran NPFRs. RhoprNPFR has seven highly-conserved transmembrane domains, two cysteine residues in the 2nd and 3rd extracellular loops that likely form a disulfide bond integral for maintaining the structure of the receptor, and a conserved DRY motif after the third transmembrane domain...
2018: PloS One
Rita Martins, Carlos Casimiro, Ana Valverde, Jose Campillo
We herein report a rare case of a 25-year-old immunocompetent male patient with disseminated tuberculosis of central nervous system (CNS), first presenting as multiple cerebral lesions with no meningeal involvement. Subsequent diagnostic workup disclosed extensive peritoneal involvement. A broad differential diagnosis was considered, including neoplastic and infectious diseases. The diagnosis was confirmed with positive PCR result for Mycobacterium tuberculosis in the biopsied mesenteric tissue. The patient was started on tuberculostatic regimen with favorable outcome...
2018: Case Reports in Neurological Medicine
Patrizia LoPresti
Oligodendrocytes (OLGs), the myelin-forming cells of the central nervous system (CNS), are lifelong partners of neurons. They adjust to the functional demands of neurons over the course of a lifetime to meet the functional needs of a healthy CNS. When this functional interplay breaks down, CNS degeneration follows. OLG processes are essential features for OLGs being able to connect with the neurons. As many as fifty cellular processes from a single OLG reach and wrap an equal number of axonal segments. The cellular processes extend to meet and wrap axonal segments with myelin...
August 15, 2018: International Journal of Molecular Sciences
Juan Li, Zhi-Biao Zhang, Zheng-Rong Liu, Mei Yang, Yan-Xia Nie, Meng-Meng Wu
OBJECTIVE: To explore the factors influencing total complete remission (CR), recurrence, disease-free survival (DFS) rate and overall survival (OS) rate in adults with Philadelphia (Ph) chromosome negative acute lymphoblastic leukemia (ALL) and the effect of subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT) on prognosis. METHODS: The clinical data of 87 adult patients with Ph negative ALL were retrospectively analyzed, the CHOP regimen plus L-asparaginase (L-Asp) was used for the induction therapy, and the CHOP+ modified Hyper-CVAD or methotrexate was set up as the consolidation chemotherapy regimen...
August 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Philippine Lucas, Serge Boulinguez, Vincent Sibaud, Loïc Mourey, Laurence Lamant, Carle Paul, Nicolas Meyer
BACKGROUND: Combined treatment with BRAF-V600 and MEK inhibitors has significantly improved progression-free and overall survival of patients with BRAF-mutated melanoma. Pattern of disease progression and outcomes in patients have not been fully characterized. METHODS: We conducted a single-center, retrospective, descriptive analysis of a cohort of 52 patients treated with BRAF-V600 + MEK inhibitors for advanced melanoma over a 12-month period. The aim of this study was to characterize disease progression, defined as metastatic pattern, disease kinetics, and response to subsequent therapies, in melanoma patients treated with BRAF-V600 + MEK inhibitors...
August 15, 2018: Dermatology: International Journal for Clinical and Investigative Dermatology
Dominic Skinner, Brett S Marro, Thomas E Lane
Chemokines (chemotactic cytokines) are involved in a wide variety of biological processes. Following microbial infection, there is often robust chemokine signaling elicited from infected cells, which contributes to both innate and adaptive immune responses that control growth of the invading pathogen. Infection of the central nervous system (CNS) by the neuroadapted John Howard Mueller (JHM) strain of mouse hepatitis virus (JHMV) provides an excellent example of how chemokines aid in host defense as well as contribute to disease...
August 15, 2018: Viral Immunology
Martina Donadoni, Rahsan Sariyer, Hassen Wollebo, Anna Bellizzi, Ilker Kudret Sariyer
The human neurotropic polyomavirus JC, JC virus (JCV), infects the majority of human population during early childhood and establishes a latent/persistent infection for the rest of the life. JCV is the etiologic agent of the fatal demyelinating disease of the central nervous system, progressive multifocal leukoencephalopathy (PML) that is seen primarily in immunocompromised individuals. In addition to the PML, JCV has also been shown to transform cells in culture systems and cause a variety of tumors in experimental animals...
March 2018: Genes & Cancer
Marissa L Dubbelaar, Laura Kracht, Bart J L Eggen, Erik W G M Boddeke
Gene expression analyses of microglia, the tissue-resident macrophages of the central nervous system (CNS), led to the identification of homeostatic as well as neurological disease-specific gene signatures of microglial phenotypes. Upon alterations in the neural microenvironment, either caused by local insults from within the CNS (during neurodegenerative diseases) or by macroenvironmental incidents, such as social stress, microglia can switch phenotypes-generally referred to as "microglial activation...
2018: Frontiers in Immunology
Letizia Leocani, Simone Guerrieri, Giancarlo Comi
: ABSTRACT:: Multiple sclerosis (MS) is an inflammatory, degenerative disease of the central nervous system (CNS) characterized by progressive neurological decline over time. The need for better "biomarkers" to more precisely capture and track the effects of demyelination, remyelination, and associated neuroaxonal injury is a well-recognized challenge in the field of MS. To this end, visual evoked potentials (VEPs) have a role in assessing the extent of demyelination along the optic nerve, as a functionally eloquent CNS region...
September 2018: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
An Beckers, Annelies Van Dyck, Ilse Bollaerts, Jessie Van Houcke, Evy Lefevere, Lien Andries, Jessica Agostinone, Inge Van Hove, Adriana Di Polo, Kim Lemmens, Lieve Moons
Neural insults and neurodegenerative diseases typically result in permanent functional deficits, making the identification of novel pro-regenerative molecules and mechanisms a primary research topic. Nowadays, neuroregenerative research largely focuses on improving axonal regrowth, leaving the regenerative properties of dendrites largely unstudied. Moreover, whereas developmental studies indicate a strict temporal separation of axogenesis and dendritogenesis and thus suggest a potential interdependency of axonal and dendritic outgrowth, a possible axon-dendrite interaction during regeneration remains unexplored...
August 13, 2018: Molecular Neurobiology
Fiona Costello, Jodie M Burton
Multiple sclerosis (MS) is a progressive neurological disorder characterized by both inflammatory and degenerative components that affect genetically susceptible individuals. Currently, the cause of MS remains unclear, and there is no known cure. Commonly used therapies tend to target inflammatory aspects of MS, but may not halt disease progression, which may be governed by the slow, subclinical accumulation of injury to neuroaxonal structures in the central nervous system (CNS). A recognized challenge in the field of MS relates to the need for better methods of detecting, quantifying, and ameliorating the effects of subclinical disease...
2018: Eye and Brain
Stefan Rutkowski, Piergiorgio Modena, Daniel Williamson, Kornelius Kerl, Karsten Nysom, Barry Pizer, Ute Bartels, Stephanie Puget, François Doz, Antony Michalski, Katja von Hoff, Mathilde Chevignard, Shivaram Avula, Matthew J Murray, Stefan Schönberger, Thomas Czech, Antoinette Y N Schouten-van Meeteren, Uwe Kordes, Christof M Kramm, Dannis G van Vuurden, Esther Hulleman, Geert O Janssens, Guirish A Solanki, Marie-Luise C van Veelen, Ulrich Thomale, Martin U Schuhmann, Chris Jones, Felice Giangaspero, Dominique Figarella-Branger, Torsten Pietsch, Steve C Clifford, Stefan M Pfister, Stefaan W Van Gool
Paediatric CNS tumours are the most common cause of childhood cancer-related morbidity and mortality, and improvements in their diagnosis and treatment are needed. New genetic and epigenetic information about paediatric CNS tumours is transforming the field dramatically. For most paediatric CNS tumour entities, subgroups with distinct biological characteristics have been identified, and these characteristics are increasingly used to facilitate accurate diagnoses and therapeutic recommendations. Future treatments will be further tailored to specific molecular subtypes of disease, specific tumour predisposition syndromes, and other biological criteria...
August 2018: Lancet Oncology
Matthijs van der Meulen, Linda Dirven, Esther J J Habets, Martin J van den Bent, Martin J B Taphoorn, Jacoline E C Bromberg
Incidence of primary CNS lymphoma (PCNSL) is increasing, while prognosis is improving as treatments advance. However, declined cognitive functioning remains a major challenge in the treatment of PCNSL. This cognitive decline, in conjunction with other symptoms caused by the disease or its treatment, or both, can compromise health-related quality of life (HRQOL). The aim of this Review was to give a comprehensive overview on cognitive functioning and HRQOL for patients with PCNSL, including an evaluation of patient-related and treatment-related factors that can influence cognitive functioning and HRQOL...
August 2018: Lancet Oncology
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