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https://www.readbyqxmd.com/read/28654435/myasthenia-gravis-new-developments-in-research-and-treatment
#1
Amelia Evoli
PURPOSE OF REVIEW: Myasthenia gravis, a rare disorder of the neuromuscular transmission, is increasingly acknowledged as a syndrome more than as a single disease. This review summarizes recent advances in pathophysiology which confirm the disease heterogeneity, and may help find disease-targeted and patient-targeted therapies. RECENT FINDINGS: Antibodies to the acetylcholine receptor, the muscle-specific tyrosine kinase and the lipoprotein receptor protein 4, characterize disease subtypes with distinct clinical traits and immune-pathogenic mechanisms...
June 24, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28654095/polygenic-risk-has-an-impact-on-the-structural-plasticity-of-hippocampal-subfields-during-aerobic-exercise-combined-with-cognitive-remediation-in-multi-episode-schizophrenia
#2
S Papiol, D Popovic, D Keeser, A Hasan, T Schneider-Axmann, F Degenhardt, M J Rossner, H Bickeböller, A Schmitt, P Falkai, B Malchow
Preliminary studies suggest that, besides improving cognition, aerobic exercise might increase hippocampal volume in schizophrenia patients; however, results are not consistent. Individual mechanisms of volume changes are unknown but might be connected to the load of risk genes. Genome-wide association studies have uncovered the polygenic architecture of schizophrenia. The secondary analysis presented here aimed to determine the modulatory role of schizophrenia polygenic risk scores (PRSs) on volume changes in the total hippocampus and cornu ammonis (CA) 1, CA2/3, CA4/dentate gyrus (DG) and subiculum over time...
June 27, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28654057/murine-aortic-crush-injury-an-efficient-in-vivo-model-of-smooth-muscle-cell-proliferation-and-endothelial-function
#3
Dan Yu, George Makkar, Rajabrata Sarkar, Dudley K Strickland, Thomas S Monahan
Arterial reconstruction, whether angioplasty or bypass surgery, involves iatrogenic trauma causing endothelial disruption and vascular smooth muscle cell (VSMC) proliferation. Common murine models study small vessels such as the carotid and femoral arteries. Herein we describe an in vivo system in which both VSMC proliferation and endothelial barrier function can be simultaneously assessed in a large vessel. We studied the infrarenal aortic response to injury in C57BL/6 mice. The aorta was injured from the left renal vein to the aortic bifurcation by 30 transmural crushes of 5-seconds duration with a cotton-tipped applicator...
June 11, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28654052/flow-sorting-and-exome-sequencing-of-the-reed-sternberg-cells-of-classical-hodgkin-lymphoma
#4
Jonathan B Reichel, Jason McCormick, Jonathan R Fromm, Olivier Elemento, Ethel Cesarman, Mikhail Roshal
The Hodgkin Reed-Sternberg cells of classical Hodgkin lymphoma are sparsely distributed within a background of inflammatory lymphocytes and typically comprise less than 1% of the tumor mass. Material derived from bulk tumor contains tumor content at a concentration insufficient for characterization. Therefore, fluorescence activated cell sorting using eight antibodies, as well as side- and forward-scatter, is described here as a method of rapidly separating and concentrating with high purity thousands of HRS cells from the tumor for subsequent study...
June 10, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28653862/optimal-response-to-dimethyl-fumarate-associates-in-ms-with-a-shift-from-an-inflammatory-to-a-tolerogenic-blood-cell-profile
#5
Silvia Medina, Noelia Villarrubia, Susana Sainz de la Maza, José Lifante, Lucienne Costa-Frossard, Ernesto Roldán, Carmen Picón, José C Álvarez-Cermeño, Luisa M Villar
BACKGROUND: The precise mechanism of action of dimethyl fumarate (DMF) treatment in MS remains unknown. OBJECTIVE: To identify the changes in the blood lymphocyte profile of MS patients predicting no evidence of disease activity (NEDA) status after DMF treatment. METHODS: We studied blood lymphocyte subsets of 64 MS patients treated with DMF at baseline and after 6 months of treatment by flow cytometry. NEDA (41 patients) or ongoing disease activity (ODA, 23 patients) were monitored after a year of follow-up...
June 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28653395/parp14-limits-severity-of-allergic-skin-disease
#6
Purna Krishnamurthy, Sonia Da-Silva-Arnold, Matthew J Turner, Jeffrey B Travers, Mark H Kaplan
Poly-ADP ribose polymerase-14 (PARP14 or ARTD8) was initially identified as a transcriptional co-activator for Stat6, where the presence of IL-4 and activated Stat6 induces the enzymatic activity of PARP14 that promotes Th2 differentiation and allergic airway disease. To further our understanding of PARP14 in allergic disease, we studied the function of PARP14 in allergic inflammation of skin using mice that express constitutively active Stat6 in T cells (Stat6VT) and develop spontaneous inflammation of the skin...
June 27, 2017: Immunology
https://www.readbyqxmd.com/read/28652580/immunological-phenotype-of-the-murine-lrba-knockout
#7
Laura Gámez-Díaz, Julika Neumann, Fiona Jäger, Michele Proietti, Felicitas Felber, Pauline Soulas-Sprauel, Lisa Perruzza, Fabio Grassi, Tamara Kögl, Peter Aichele, Manfred Kilimann, Bodo Grimbacher, Sophie Jung
Biallelic mutations in the human Lipopolysaccharide Responsive Beige-like Anchor (LRBA) gene lead to a primary immunodeficiency known as LRBA deficiency, characterized by a broad range of clinical manifestations including autoimmunity, organomegaly, hypogammaglobulinemia and recurrent infections. Considering the phenotypic heterogeneity in patients and the severity of the disease, our aim was to assess the role of LRBA in immune cells and to understand the underlying pathomechanisms through the study of a Lrba knockout (Lrba(-/-)) mouse model...
June 27, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28652394/lack-of-both-nucleotide-binding-oligomerization-domain-containing-proteins-1-and-2-primes-t-cells-for-activation-induced-cell-death
#8
Sashi G Kasimsetty, Alana A Shigeoka, Andrew A Scheinok, Amanda L Gavin, Richard J Ulevitch, Dianne B McKay
Nucleotide-binding oligomerization domain (Nod)-containing proteins Nod1 and Nod2 play important roles in the innate immune response to pathogenic microbes, but mounting data suggest these pattern recognition receptors might also play key roles in adaptive immune responses. Targeting Nod1 and Nod2 signaling pathways in T cells is likely to provide a new strategy to modify inflammation in a variety of disease states, particularly those that depend on Ag-induced T cell activation. To better understand how Nod1 and Nod2 proteins contribute to adaptive immunity, this study investigated their role in alloantigen-induced T cell activation and asked whether their absence might impact in vivo alloresponses using a severe acute graft versus host disease model...
June 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28652380/immune-escape-in-breast-cancer-during-in-situ-to-invasive-carcinoma-transition
#9
Carlos R Gil Del Alcazar, Sung Jin Huh, Muhammad B Ekram, Anne Trinh, Lin L Liu, Francisco Beca, Xiaoyuan Zi, Minsuk Kwak, Helga Bergholtz, Ying Su, Lina Ding, Hege G Russnes, Andrea L Richardson, Kirsten Babski, Elizabeth Min Hui Kim, Charles McDonnell, Jon Wagner, Ron Rowberry, Gordon J Freeman, Deborah Dillon, Therese Sorlie, Lisa M Coussens, Judy E Garber, Rong Fan, Kristie Bobolis, D Craig Allred, Joon Jeong, So Yeon Park, Franziska Michor, Kornelia Polyak
To investigate immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinoma in situ (DCIS), and invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutrophils. Gene expression profiling of CD45+CD3+ T cells demonstrated a decrease in CD8+ signatures in IDCs. Immunofluorescence analysis showed fewer activated GZMB+CD8+ T cells in IDC than in DCIS, including in matched DCIS recurrent IDC...
June 26, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28652370/small-mitochondrial-arf-smarf-protein-corrects-p53-independent-developmental-defects-of-arf-tumor-suppressor-deficient-mice
#10
Jolieke G van Oosterwijk, Chunliang Li, Xue Yang, Joseph T Opferman, Charles J Sherr
The mouse p19(Arf) (human p14(ARF)) tumor suppressor protein, encoded in part from an alternative reading frame of the Ink4a (Cdkn2a) gene, inhibits the Mdm2 E3 ubiquitin ligase to activate p53. Arf is not expressed in most normal tissues of young mice but is induced by high thresholds of aberrant hyperproliferative signals, thereby activating p53 in incipient tumor cells that have experienced oncogene activation. The single Arf mRNA encodes two distinct polypeptides, including full-length p19(Arf) and N-terminally truncated and unstable p15(smArf) ("small mitochondrial Arf") initiated from an internal in-frame AUG codon specifying methionine-45...
June 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28651603/a-systems-pharmacology-based-approach-to-identify-novel-kv1-3-channel-dependent-mechanisms-in-microglial-activation
#11
Srikant Rangaraju, Syed Ali Raza, Andrea Pennati, Qiudong Deng, Eric B Dammer, Duc Duong, Michael W Pennington, Malu G Tansey, James J Lah, Ranjita Betarbet, Nicholas T Seyfried, Allan I Levey
BACKGROUND: Kv1.3 potassium channels regulate microglial functions and are overexpressed in neuroinflammatory diseases. Kv1.3 blockade may selectively inhibit pro-inflammatory microglia in neurological diseases but the molecular and cellular mechanisms regulated by Kv1.3 channels are poorly defined. METHODS: We performed immunoblotting and flow cytometry to confirm Kv1.3 channel upregulation in lipopolysaccharide (LPS)-activated BV2 microglia and in brain mononuclear phagocytes freshly isolated from LPS-treated mice...
June 26, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28651002/the-n-terminal-domain-of-mycobacterium-tuberculosis-ppe17-rv1168c-protein-plays-a-dominant-role-in-inducing-antibody-responses-in-active-tb-patients
#12
Philip Raj Abraham, Niteen Pathak, Gourango Pradhan, Gaddam Sumanlatha, Sangita Mukhopadhyay
The PPE (proline-proline-glutamic acid) proteins of Mycobacterium tuberculosis are characterized by a conserved N-terminal domain of approximately 180 amino acids and variable C-terminal domain. Since last decade, these proteins have gained much importance in the serodiagnosis of tuberculosis (TB) as they act as a source of antigenic variation. We have demonstrated earlier that one of the PPE proteins PPE17 (Rv1168c) induces strong B-cell and T-cell responses in active TB disease and also displays a higher antibody titer compared to immunodominant antigens such as ESAT-6, Hsp60 and PPD...
2017: PloS One
https://www.readbyqxmd.com/read/28650473/testes-specific-protease-50-promotes-cell-proliferation-via-inhibiting-activin-signaling
#13
Z-B Song, P Wu, J-S Ni, T Liu, C Fan, Y-L Bao, Y Wu, L-G Sun, C-L Yu, Y-X Huang, Y-X Li
Testes-specific protease 50 (TSP50), a novelly identified oncogene, has the capacity to induce cell proliferation, cell invasion and tumor growth. Further studies indicated that CAGA-luc (an activin-responsive reporter construct) reporter activity could be significantly suppressed by TSP50 overexpression, implying that the activin signaling may participate in TSP50-mediated cell proliferation. Here, we reported that TSP50 had an inhibitory effect on activin signaling. Mechanistic studies revealed that TSP50 could interact with ActRIIA, inhibit activin typeIreceptor (ActRIB) phosphorylation, repress Smad2/3 nuclear accumulation and finally promote cell proliferation by reducing the expression of activin signal target gene p27...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28649877/retrospective-cohort-study-and-biobanking-of-patients-treated-for-hemangioma-in-childhood-telomeres-as-biomarker-of-aging-and-radiation-exposure
#14
Monika Frenzel, Michelle Ricoul, Mohamed Amine Benadjaoud, Marion Bellamy, Aude Lenain, Nadia Haddy, Ibrahima Diallo, Christine Mateus, Florent de Vathaire, Laure Sabatier
PURPOSE: Cohorts allowing joint epidemiological and biological analyses are essential for radiation risk assessment. The French Hemangioma Cohort (FHC), studied within the European project EpiRadBio, is one of the rare cohorts suitable for studying the effect of low dose radiation exposure (<100 mGy at organs), with a long-term follow-up. This highly homogeneous cohort consists of healthy individuals belonging to a normal population, except for the presence of skin hemangioma (age at exposure: between 6 months and 3 years of age)...
June 26, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28649848/mogamulizumab-for-the-treatment-of-t-cell-lymphoma
#15
Shinichi Makita, Kensei Tobinai
T-cell lymphoma is a relatively rare hematologic malignancy that accounts for 10-20% of non-Hodgkin lymphomas. Treatment strategies for T-cell lymphomas are different from that for B-cell lymphomas and have poor prognoses. Among various subtypes of T-cell lymphomas, adult T-cell leukemia-lymphoma (ATL) has the worst prognosis. To achieve further improvement in the treatment outcome of T-cell lymphomas, several novel agents such as brentuximab vedotin, lenalidomide, romidepsin, and pralatrexate are actively being studied...
June 24, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28649611/lrrk2-levels-in-immune-cells-are-increased-in-parkinson-s-disease
#16
D A Cook, G T Kannarkat, A F Cintron, Laura M Butkovich, Kyle B Fraser, J Chang, N Grigoryan, S A Factor, Andrew B West, J M Boss, M G Tansey
Mutations associated with leucine-rich repeat kinase 2 are the most common known cause of Parkinson's disease. The known expression of leucine-rich repeat kinase 2 in immune cells and its negative regulatory function of nuclear factor of activated T cells implicates leucine-rich repeat kinase 2 in the development of the inflammatory environment characteristic of Parkinson's disease. The aim of this study was to determine the expression pattern of leucine-rich repeat kinase 2 in immune cell subsets and correlate it with the immunophenotype of cells from Parkinson's disease and healthy subjects...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/28648905/antibodies-against-immune-checkpoint-molecules-restore-functions-of-tumor-infiltrating-t-cells-in-hepatocellular-carcinomas
#17
Guoying Zhou, Dave Sprengers, Patrick P C Boor, Michail Doukas, Hannah Schutz, Shanta Mancham, Alexander Pedroza-Gonzalez, Wojciech G Polak, Jeroen de Jonge, Marcia Gaspersz, Haidong Dong, Kris Thielemans, Qiuwei Pan, Jan N M IJzermans, Marco J Bruno, Jaap Kwekkeboom
BACKGROUND & AIMS: Ligand binding to inhibitory receptors on immune cells, such as programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), downregulates the T-cell-mediated immune response (called immune checkpoints). Antibodies that block these receptors increase anti-tumor immunity in patients with melanoma, non-small cell lung cancer, and renal cell cancer. Tumor-infiltrating CD4(+) and CD8(+) T cells in patients with hepatocellular carcinoma (HCC) have been found to be functionally compromised...
June 22, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28648895/nuclear-factor-erythroid-2-regulates-human-hsc-self-renewal-and-t-cell-differentiation-by-preventing-notch1-activation
#18
Alessandro Di Tullio, Diana Passaro, Kevin Rouault-Pierre, Sukhveer Purewal, Dominique Bonnet
Nuclear factor erythroid-derived 2 (NF-E2) has been associated with megakaryocyte maturation and platelet production. Recently, an increased in NF-E2 activity has been implicated in myeloproliferative neoplasms. Here, we investigate the role of NF-E2 in normal human hematopoiesis. Knockdown of NF-E2 in the hematopoietic stem and progenitor cells (HSPCs) not only reduced the formation of megakaryocytes but also drastically impaired hematopoietic stem cell activity, decreasing human engraftment in immunodeficient (NSG) mice...
June 21, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28648136/two-new-alkaloids-from-the-twigs-of-trigonostemon-filipes
#19
Yu Wang, Pei Wang, Fan-Dong Kong, Jun Wang, Wen-Jian Zuo, Hao Wang, Hao-Fu Dai, Wen-Li Mei
A phytochemical investigation of the alkaloid constituents from Trigonostemon filipes Y. T. Chang et S. L. Mo led to the isolation of two new indole alkaloids, trigonostemine G (1) and trigonostemone J (2), together with two known ones, trigonostemine A (3) and trigonostemine B (4). Their structures were determined by extensive spectroscopic methods. Compounds 1-4 exhibited moderate AChE inhibitory activity with inhibition ratio of 31.6, 31.7, 41.7, and 42.4%, respectively. In addition, compounds 1-2 showed weak cytotoxicity against K562 and BEL-7402 human cancer cell lines...
June 26, 2017: Journal of Asian Natural Products Research
https://www.readbyqxmd.com/read/28648120/long-qt-syndrome-associated-caveolin-3-mutations-differentially-regulate-the-hyperpolarization-activated-cyclic-nucleotide-gated-channel-4
#20
L J Motloch, R Larbig, T Darabi, S Reda, K A Motloch, B Wernly, M Lichtenauer, T Gebing, A Schwaiger, N Zagidullin, M Wolny, U C Hoppe
Background Caveolin-3 (cav-3) mutations are linked to the long-QT syndrome (LQTS) causing distinct clinical symptoms. Hyperpolarization-activated cyclic nucleotide channel 4 (HCN4) underlies the pacemaker current If. It associates with cav-3 and both form a macromolecular complex. Methods To examine the effects of human LQTS-associated cav-3 mutations on HCN4-channel function, HEK293-cells were cotransfected with HCN4 and wild-type (WT) cav-3 or a LQTS-associated cav-3 mutant (T78M, A85T, S141R, or F97C). HCN4 currents were recorded using the whole-cell patch-clamp technique...
June 26, 2017: Physiology International
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