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https://www.readbyqxmd.com/read/28990497/calr-jak2-and-mpl-mutation-status-in-argentinean-patients-with-bcr-abl1-negative-myeloproliferative-neoplasms
#1
Mara Jorgelina Ojeda, Irma Margarita Bragós, Karina Lucrecia Calvo, Gladis Marcela Williams, María Magdalena Carbonell, Arianna Flavia Pratti
OBJECTIVES: To establish the frequency of JAK2, MPL and CALR mutations in Argentinean patients with BCR-ABL1-negative  myeloproliferative neoplasms (MPN) and to compare their clinical and haematological features. METHODS: Mutations of JAK2V617F, JAK2 exon 12, MPL W515L/K and CALR were analysed in 439 Argentinean patients with BCR-ABL1-negative MPN, including 176 polycythemia vera (PV), 214 essential thrombocythemia (ET) and 49 primary myelofibrosis (PMF). RESULTS: In 94...
October 9, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28979237/identification-of-mpl-r102p-mutation-in-hereditary-thrombocytosis
#2
Christine Bellanné-Chantelot, Matthieu Mosca, Caroline Marty, Rémi Favier, William Vainchenker, Isabelle Plo
The molecular basis of hereditary thrombocytosis is germline mutations affecting the thrombopoietin (TPO)/TPO receptor (MPL)/JAK2 signaling axis. Here, we report one family presenting two cases with a mild thrombocytosis. By sequencing JAK2 and MPL coding exons, we identified a germline MPL R102P heterozygous mutation in the proband and his daughter. Concomitantly, we detected high TPO levels in the serum of these two patients. The mutation was not found in three other unaffected cases from the family except in another proband's daughter who did not present thrombocytosis but had a high TPO level...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28978863/myeloid-neoplasms-in-the-world-health-organization-2016-classification
#3
Norio Asou
In the 2016 revision of the World Health Organization (WHO) classification, the categories of myeloid neoplasms have not been revised significantly from the 2008 fourth edition. However, recent discovery of molecular abnormalities provides a new perspective regarding the diagnostic and prognostic markers. In myeloproliferative neoplasms, the identification of CALR gene mutation, in addition to the JAK2 and MPL mutations, has impacted the diagnostic criteria. In myelodysplastic syndromes and acute myeloid leukemia, in addition to alterations in the transcription factors and signal transduction pathways, discovery of gene mutations in the epigenetic regulators that are involved in DNA methylation, histone modification, cohesin complex, and RNA splicing, by comprehensive genetic analyses, has improved our understanding of the pathobiology of these diseases...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28978835/effect-of-mutation-on-diagnosis-risk-stratification-and-treatment-decisions-in-philadelphia-negative-myeloproliferative-neoplasms
#4
Keita Kirito
Since the discovery of the activating mutation of JAK2, known as JAK2V617F, our understanding of mutation profiles, and the biological significance of this mutation in Philadelphia-negative (Ph-) MPNs has drastically changed over the last decade. Mutations of the thrombopoietin receptor MPL and chaperone protein calreticulin gene also induce aberrant activation of JAK and downstream molecules, including STAT proteins, and contribute to the development of MPNs. Mutations of the genes JAK2, MPL, and calreticulin are referred to as "driver mutations" for MPNs...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28968993/human-papillomavirus-16l1-58l2-chimeric-virus-like-particles-elicit-durable-neutralizing-antibody-responses-against-a-broad-spectrum-of-human-papillomavirus-types
#5
Xue Chen, Hongyang Liu, Zhirong Wang, Shuo Wang, Ting Zhang, Meili Hu, Liang Qiao, Xuemei Xu
The neutralizing antibodies elicited by human papillomavirus (HPV) major capsid protein L1 virus-like particle (VLP)-based vaccines are largely type-specific. An HPV vaccine inducing cross-neutralizing antibodies broadly will be cost-effective and of great value. To this end, we constructed HPV16L1-58L2 chimeric VLP (cVLP) by displaying HPV58 L2 aa.16-37 on the DE surface region of HPV16 L1. We found that vaccination with the HPV16L1-58L2 cVLP formulated with alum plus monophosphoryl lipid A (Alum-MPL) adjuvant elicited robust neutralizing antibodies in both mice and rabbits against all tested HPV types including HPV16/31/33/35/52/58 (genus α9), HPV18/39/45/59/68 (genus α7), HPV6/11 (genus α10), HPV2/27/57 (genus α4), and HPV5 (genus β1)...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28963929/evaluation-of-the-adjuvant-effect-of-agonists-of-toll-like-receptor-4-and-7-8-in-a-vaccine-against-leishmaniasis-in-balb-c-mice
#6
Mosayeb Rostamian, Hamid M Niknam
There is no effective vaccine against human leishmaniasis. Achieving successful vaccines seems to need powerful adjuvants. Separate or combined use of toll like receptor (TLR) agonists as adjuvant is a promising approach in Leishmania vaccine research. In present study, we evaluated adjuvant effect of separate or combined use of a TLR7/8 agonist, R848 and a TLR4 agonist, monophosphoryl lipid A (MPL) beside soluble Leishmania antigen (SLA) in BALB/c mice. Mice were vaccinated three times by SLA with separate or combined TLR7/8 and TLR4 agonists and were then challenged by Leishmania major...
September 27, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28962123/whole-genome-gene-expression-changes-and-hematological-effects-of-rikkunshito-in-patients-with-advanced-non-small-cell-lung-cancer-receiving-first-line-chemotherapy
#7
Yung-Che Chen, An-Shen Lin, Yu-Chiang Hung, Kuang-Den Chen, Ching-Yuan Wu, Chien-Hao Lie, Chang-Chun Hsiao, Chung-Jen Chen, Shih-Feng Liu, Wen-Feng Fang, Jen-Chieh Chang, Ting-Ya Wang, Yi-Hsi Wang, Yu-Hsiu Chung, Tung-Ying Chao, Sum-Yee Leung, Mao-Chang Su, Meng-Chih Lin
It has been demonstrated that the traditional Chinese medicine rikkunshito, ameliorates anorexia in several types of human cancer and attenuates lung injury by inhibiting neutrophil infiltration. The current study investigated the clinical and hematological effects of rikkunshito and its underlying mechanisms of action in the treatment of advanced non-small cell lung cancer (NSCLC). The Illumina microarray BeadChip was used to analyze the whole-genome expression profiles of peripheral blood mononuclear cells in 17 patients with advanced NSCLC...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28955303/genetic-alterations-of-the-thrombopoietin-mpl-jak2-axis-impacting-megakaryopoiesis
#8
REVIEW
Isabelle Plo, Christine Bellanné-Chantelot, Matthieu Mosca, Stefania Mazzi, Caroline Marty, William Vainchenker
Megakaryopoiesis is an original and complex cell process which leads to the formation of platelets. The homeostatic production of platelets is mainly regulated and controlled by thrombopoietin (TPO) and the TPO receptor (MPL)/JAK2 axis. Therefore, any hereditary or acquired abnormality affecting this signaling axis can result in thrombocytosis or thrombocytopenia. Thrombocytosis can be due to genetic alterations that affect either the intrinsic MPL signaling through gain-of-function (GOF) activity (MPL, JAK2, CALR) and loss-of-function (LOF) activity of negative regulators (CBL, LNK) or the extrinsic MPL signaling by THPO GOF mutations leading to increased TPO synthesis...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28948469/dissection-of-signaling-events-downstream-of-the-c-mpl-receptor-in-murine-hematopoietic-stem-cells-via-motif-engineered-chimeric-receptors
#9
Koichiro Saka, Chen-Yi Lai, Masanori Nojima, Masahiro Kawahara, Makoto Otsu, Hiromitsu Nakauchi, Teruyuki Nagamune
Hematopoietic stem cells (HSCs) are a valuable resource in transplantation medicine. Cytokines are often used to culture HSCs aiming at better clinical outcomes through enhancement of HSC reconstitution capability. Roles for each signal molecule downstream of receptors in HSCs, however, remain puzzling due to complexity of the cytokine-signaling network. Engineered receptors that are non-responsive to endogenous cytokines represent an attractive tool for dissection of signaling events. We here tested a previously developed chimeric receptor (CR) system in primary murine HSCs, target cells that are indispensable for analysis of stem cell activity...
September 25, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28948454/molecular-pathogenesis-of-myeloproliferative-neoplasms-influence-of-age-and-gender
#10
REVIEW
Jeffrey Patterson-Fortin, Alison R Moliterno
The myeloproliferative neoplasms polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) display distinct clinical and pathologic features but are characterized by mutations in JAK2, MPL, and CALR leading to activation of the JAK-STAT pathway. This review addresses the pathogenesis and mechanisms of these mutant alleles and the unique interactions of both of age and gender.
September 25, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28941070/non-aqueous-primary-li-air-flow-battery-and-optimization-of-its-cathode-through-experiments-and-modeling
#11
Byoungsu Kim, Kensuke Takechi, Sichao Ma, Sumit Verma, Shiqi Fu, Amit Desai, Ashtamurthy S Pawate, Fuminori Mizuno, Paul Kenis
We develop a primary Li-air battery with a flowing Li-ion free ionic liquid as the recyclable electrolyte, boosting power capability due to promoted superoxide diffusion and enhancing discharge capacity due to separately stored discharge products. Also we use experimental and computational tools to analyze cathode properties leading to a set of parameters that improve the discharge current density of the non-aqueous Li-air flow battery. We systematically modified the structure and configuration of the cathode gas diffusion layers (GDLs) by using different levels of hot-pressing and the presence or absence of a microporous layer (MPL)...
September 22, 2017: ChemSusChem
https://www.readbyqxmd.com/read/28931526/cellubrevin-vesicle-associated-membrane-protein-3-vamp-3-mediated-endocytosis-and-trafficking-regulate-platelet-functions
#12
Meenakshi Banerjee, Smita Joshi, Jinchao Zhang, Carole L Moncman, Shilpi Yadav, Beth A Bouchard, Brian Storrie, Sidney W Whiteheart
Endocytosis is key to fibrinogen (Fg) uptake, trafficking of integrins (αIIbβ3, αvβ3) and purinergic receptors (P2Y1, P2Y12), and thus for normal platelet function. However, the molecular machinery required and possible trafficking routes are still ill-defined. To further identify elements of the platelet endocytic machinery, we examined the role of a vesicle-residing, Soluble N-ethylmaleimide Factor Attachment Protein Receptor (v-SNARE) called Cellubrevin/Vesicle-Associated Membrane Protein-3 (VAMP-3) in platelet function...
September 20, 2017: Blood
https://www.readbyqxmd.com/read/28929531/oral-administration-of-milk-derived-phospholipids-inhibits-penetration-of-cutaneous-nerve-fibres-into-epidermis-in-a-mouse-model-of-acute-dry-skin
#13
A Sakaguchi, Y Kamata, N Takahashi, H Matsuda, R Kosaka, Y Umehara, H Ogawa, M Tominaga, K Takamori
The density of intraepidermal nerve fibres has been shown to be higher in itchy dry skin than in healthy skin, suggesting that epidermal hyperinnervation is at least partly involved in peripheral itch sensitization. We investigated whether oral administration of milk-derived phospholipids (MPLs) would inhibit epidermal hyperinnervation in a mouse model of dry skin. We found that the number of intraepidermal nerve fibres was significantly lower in the MPL group than in the control group. Expression of nerve growth factor (NGF) levels in the epidermis was significantly decreased by oral administration of MPLs, whereas expression of semaphorin (Sema)3A, a nerve repulsion factor, was increased in the MPL group...
September 20, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28922045/monomeric-m2e-antigen-in-vesivax%C3%A2-liposomes-stimulates-protection-against-type-a-strains-of-influenza-comparable-to-liposomes-with-multimeric-forms-of-m2e
#14
J P Adler-Moore, W Ernst, H Kim, N Ward, S M Chiang, T Do, G Fujii
Given the interest in the ectodomain of the matrix 2 (M2e) channel protein as a target for development of a universal influenza vaccine, we examined the role of the antigen configuration of M2e in generating a protective immune response. A series of M2e mutations and a truncated M2e segment were prepared as a means of controlling the formation of monomer, dimer, and higher order multimeric forms of M2e. Each of these M2e peptides was incorporated into a liposome-based vaccine technology platform previously shown to stimulate a protective response to influenza A infection using M2e as a mixture of monomers, dimers and multimers (L-M2e1-HD/MPL)...
September 18, 2017: Journal of Liposome Research
https://www.readbyqxmd.com/read/28903325/cxcl12-cxcr4-pathway-is-activated-by-oncogenic-jak2-in-a-pi3k-dependent-manner
#15
Hadjer Abdelouahab, Yanyan Zhang, Monika Wittner, Shinya Oishi, Nobutaka Fujii, Rodolphe Besancenot, Isabelle Plo, Vincent Ribrag, Eric Solary, William Vainchenker, Giovanni Barosi, Fawzia Louache
JAK2 activation is the driver mechanism in BCR-ABL-negative myeloproliferative neoplasms (MPN). These diseases are characterized by an abnormal retention of hematopoietic stem cells within the bone marrow microenvironment and their increased trafficking to extramedullary sites. The CXCL12/CXCR4 axis plays a central role in hematopoietic stem cell/ progenitor trafficking and retention in hematopoietic sites. The present study explores the crosstalk between JAK2 and CXCL12/CXCR4 signaling pathways in MPN. We show that JAK2, activated by either MPL-W515L expression or cytokine stimulation, cooperates with CXCL12/CXCR4 signaling to increase the chemotactic response of human cell lines and primary CD34(+) cells through an increased phosphatidylinositol-3-kinase (PI3K) signaling...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878043/the-rapid-in-vivo-evolution-of-pseudomonas-aeruginosa-in-ventilator-associated-pneumonia-patients-leads-to-attenuated-virulence
#16
Ke Wang, Yi-Qiang Chen, May M Salido, Gurjeet S Kohli, Jin-Liang Kong, Hong-Jie Liang, Zi-Ting Yao, Yan-Tong Xie, Hua-Yu Wu, Shuang-Qi Cai, Daniela I Drautz-Moses, Aaron E Darling, Stephan C Schuster, Liang Yang, Yichen Ding
Pseudomonas aeruginosa is an opportunistic pathogen that causes severe airway infections in humans. These infections are usually difficult to treat and associated with high mortality rates. While colonizing the human airways, P. aeruginosa could accumulate genetic mutations that often lead to its better adaptability to the host environment. Understanding these evolutionary traits may provide important clues for the development of effective therapies to treat P. aeruginosa infections. In this study, 25 P. aeruginosa isolates were longitudinally sampled from the airways of four ventilator-associated pneumonia (VAP) patients...
September 2017: Open Biology
https://www.readbyqxmd.com/read/28873766/occurrence-and-phenotypic-and-molecular-characterization-of-listeriamonocytogenes-and-salmonella-spp-in-slaughterhouses-in-southern-brazil
#17
Mariana Almeida Iglesias, Isabela Schneid Kroning, Luana Tombini Decol, Bernadette Dora Gombossy de Melo Franco, Wladimir Padilha da Silva
This study addressed the occurrence of Listeriamonocytogenes and Salmonella spp. in bovine carcasses at two slaughterhouses in southern Brazil. Then, the antimicrobial susceptibility profile and the virulence potential of the isolates were evaluated. Two hundred carcasses were sampled at four steps of the slaughter process, with L. monocytogenes being isolated in 12 and Salmonella spp. in 17 carcasses. All L. monocytogenes isolates carried the hlyA, prfA, plcA, plcB, actA, iap, mpl, inlA, inlB, inlC, and inlJ genes, while Salmonella spp...
October 2017: Food Research International
https://www.readbyqxmd.com/read/28871230/comparative-analysis-for-glycopatterns-and-complex-type-n-glycans-of-glycoprotein-in-sera-from-chronic-hepatitis-b-and-c-infected-patients
#18
Xinmin Qin, Yonghong Guo, Haoqi Du, Yaogang Zhong, Jiaxu Zhang, Xuetian Li, Hanjie Yu, Zhiwei Zhang, Zhansheng Jia, Zheng Li
Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients. Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28859041/case-report-clinical-variation-in-children-with-thrombopoietin-receptor-c-mpl-mutations-report-of-2-cases
#19
Clara Lo, Elysia Alvarez, Robert S Ohgami, Michael Jeng
Congenital amegakaryocytic thrombocytopenia (CAMT, MIM# 604498) is a rare congenital bone marrow failure syndrome which presents early in life with abnormal bleeding because of thrombocytopenia. Classically, megakaryocytes are decreased to absent in the bone marrow. The development of aplastic anemia early in childhood has led to the recommendation for early stem cell transplantation. Quantitative or loss-of-function mutations in the myeloproliferative leukemia gene (c-mpl), whose gene product functions as the thrombopoietin receptor, have been identified as causative for CAMT...
August 30, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28853613/lung-endothelial-microrna-1-regulates-tumor-growth-and-angiogenesis
#20
Asawari Korde, Lei Jin, Jian-Ge Zhang, Anuradha Ramaswamy, Buqu Hu, Saeed Kolahian, Brenda Juan Guardela, Jose Herazo-Maya, Jill M Siegfried, Laura Stabile, Margaret A Pisani, Roy S Herbst, Naftali Kaminski, Jack A Elias, Jonathan T Puchalski, Shervin S Takyar
RATIONALE: VEGF down-regulates miR-1 in the lung endothelium, and endothelial cells play a critical role in tumor progression and angiogenesis. OBJECTIVES: To examine the clinical significance of miR-1 in NSCLC and its specific role in tumor endothelium. Method and measurements: MiR-1 levels were measured by Taqman assay. Endothelial cells were isolated by magnetic sorting. We used VE-cadherin promoter to create a vascular-specific miR-1 lentiviral vector and an inducible transgenic mouse...
August 30, 2017: American Journal of Respiratory and Critical Care Medicine
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