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https://www.readbyqxmd.com/read/28336325/allogeneic-hematopoietic-stem-cell-transplantation-is-underutilized-in-older-patients-with-myelodysplastic-syndromes
#1
Bartlomiej M Getta, Ashwin Kishtagari, Patrick Hilden, Martin S Tallman, Molly Maloy, Patrick Gonzales, Hugo Castro-Malaspina, Miguel-Angel Perales, Sergio Giralt, Roni Tamari, Virginia Klimek
Allogeneic hematopoietic stem cell transplantation (HCT) is the only curative treatment for myelodysplastic syndrome (MDS). The proportion of MDS patients referred for transplant evaluation, those undergoing transplantation and the reasons for not undergoing transplant are unknown. In this retrospective analysis, pre-defined HCT eligibility and indications criteria were applied to 362 unselected patients with newly diagnosed MDS seen by Leukemia faculty between 2008 and 2015 at Memorial Sloan Kettering Cancer Center...
March 20, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28333145/the-cryo-thermal-therapy-eradicated-melanoma-in-mice-by-eliciting-cd4-t-cell-mediated-antitumor-memory-immune-response
#2
Kun He, Ping Liu, Lisa X Xu
Tumor metastasis is a major concern in tumor therapy. In our previous studies, a novel tumor therapeutic modality of the cryo-thermal therapy has been presented, highlighting its effect on the suppression of distal metastasis and leading to long-term survival in 4T1 murine mammary carcinoma model. To demonstrate the therapeutic efficacy in other aggressive tumor models and further investigate the mechanism of long-term survival induced, in this study, spontaneous metastatic murine B16F10 melanoma model was used...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28329703/successful-and-maladaptive-t-cell-aging
#3
REVIEW
Jörg J Goronzy, Cornelia M Weyand
Throughout life, the T cell system adapts to shifting resources and demands, resulting in a fundamentally restructured immune system in older individuals. Here we review the cellular and molecular features of an aged immune system and discuss the trade-offs inherent to these adaptive mechanisms. Processes include homeostatic proliferation that maintains compartment size at the expense of partial loss in stemness and incomplete differentiation and the activation of negative regulatory programs, which constrain effector T cell expansion and prevent increasing oligoclonality but also interfere with memory cell generation...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28321178/post-training-inactivation-of-the-anterior-thalamic-nuclei-impairs-spatial-performance-on-the-radial-arm-maze
#4
Ryan E Harvey, Shannon M Thompson, Lilliana M Sanchez, Ryan M Yoder, Benjamin J Clark
The limbic thalamus, specifically the anterior thalamic nuclei (ATN), contains brain signals including that of head direction cells, which fire as a function of an animal's directional orientation in an environment. Recent work has suggested that this directional orientation information stemming from the ATN contributes to the generation of hippocampal and parahippocampal spatial representations, and may contribute to the establishment of unique spatial representations in radially oriented tasks such as the radial arm maze...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28314976/enzyme-replacement-therapy-and-beyond-in-memoriam-roscoe-o-brady-m-d-1923-2016
#5
REVIEW
Markus Ries
Lysosomal storage disorders are strong candidates for the development of specific innovative therapies. The discovery of enzyme deficiencies is an important milestone in understanding the underlying cause of disease. Being able to replace the first missing enzyme in a lysosomal storage required three decades of dedicated research. Successful drug development for lysosomal storage disorders was fostered by the U.S. Orphan Drug Act. Various optimization strategies have the potential to overcome the current limitations of enzyme replacement therapies...
March 17, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28293817/cd4-memory-t-cells-retain-surface-expression-of-cd31-independently-of-thymic-function-in-patients-with-lymphoproliferative-disorders-following-autologous-hematopoietic-stem-cell-transplantation
#6
Egor V Batorov, Marina A Tikhonova, Irina V Kryuchkova, Vera V Sergeevicheva, Svetlana A Sizikova, Galina Y Ushakova, Dariya S Batorova, Andrey V Gilevich, Alexander A Ostanin, Ekaterina Y Shevela, Elena R Chernykh
High-dose chemotherapy with autologous hematopoietic stem-cell transplantation (AHSCT) causes severe and long-lasting immunodeficiency in patients with lymphoproliferative disorders. The thymus begins to restore the T-cell repertoire approximately from the sixth month post-transplant. We assessed the dynamics of post-transplant recovery of CD4(+)CD45RA(+)CD31(+) T cells, "recent thymic emigrants" (RTEs), and a poorly described subtype of CD4(+)CD45RA(-)CD31(+) T cells in 90 patients with lymphoproliferative disorders following high-dose chemotherapy with AHSCT...
March 14, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28293550/dock-8-deficiency-ebv-lymphomatoid-granulomatosis-and-intrafamilial-variation-in-presentation
#7
Victoria R Dimitriades, Vincent Devlin, Stefania Pittaluga, Helen C Su, Steven M Holland, Wyndham Wilson, Kieron Dunleavy, Nirali N Shah, Alexandra F Freeman
Dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive, combined immunodeficiency within the spectrum of hyper-IgE syndromes. Epstein-Barr virus-positive lymphomatoid granulomatosis (LYG) (EBV + LYG) is a rare diagnosis and a previously unreported presentation of DOCK8 deficiency. A 10-year-old girl was initially evaluated for mild eczema and recurrent sinopulmonary infections. She had normal immunoglobulins with elevated IgE, poor polysaccharide response with low switched memory B cells, low CD4 count, and normal mitogen and antigen responses...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28284008/effective-and-persistent-antitumor-activity-of-her2-directed-car-t-cells-against-gastric-cancer-cells-in-vitro-and-xenotransplanted-tumors-in-vivo
#8
Yanjing Song, Chuan Tong, Yao Wang, Yunhe Gao, Hanren Dai, Yelei Guo, Xudong Zhao, Yi Wang, Zizheng Wang, Weidong Han, Lin Chen
Human epidermal growth factor receptor 2 (HER2) proteins are overexpressed in a high proportion of gastric cancer (GC) cases and affect the maintenance of cancer stem cell (CSC) subpopulations, which are used as targets for the clinical treatment of patients with HER2-positive GC. Despite improvements in survival, numerous HER2-positive patients fail treatment with trastuzumab, highlighting the need for more effective therapies. In this study, we generated a novel type of genetically modified human T cells, expressing a chimeric antigen receptor (CAR), and targeting the GC cell antigen HER2, which harbors the CD137 and CD3ζ moieties...
March 10, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28281429/single-centre-experience-of-allogeneic-haemopoietic-stem-cell-transplant-in-paediatric-patients-in-cape-town-south-africa
#9
A Van Eyssen, N Novitsky, P De Wit, T Schlaphoff, V Thomas, D Pillay, M Hendricks, A Davidson
BACKGROUND: Allogeneic haemopoietic stem cell transplant (Allo-HSCT) is a specialised and costly intervention, associated with significant morbidity and mortality. It is used to treat a broad range of paediatric conditions. South Africa (SA) is an upper middle-income country with limitations on healthcare spending. The role of paediatric Allo-HSCT in this setting is reviewed. OBJECTIVES: To review paediatric patients who underwent Allo-HSCT at the Groote Schuur Hospital/University of Cape Town Private Academic Hospital transplant unit in Cape Town, South Africa, and received post-transplant care at Red Cross War Memorial Children's Hospital, over the period January 2006 - December 2014 in respect of indications for the transplant, donor sources, conditioning regimens, treatment-related morbidity and overall survival (OS)...
February 27, 2017: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/28280003/epigenetic-memory-in-response-to-environmental-stressors
#10
Paolo Vineis, Aristotelis Chatziioannou, Vincent T Cunliffe, James M Flanagan, Mark Hanson, Micheline Kirsch-Volders, Soterios Kyrtopoulos
Exposure to environmental stressors, toxicants, and nutrient deficiencies can affect DNA in several ways. Some exposures cause damage and alter the structure of DNA, but there is increasing evidence that the same or other environmental exposures, including those that occur during fetal development in utero, can cause epigenetic effects that modulate DNA function and gene expression. Some epigenetic changes to DNA that affect gene transcription are at least partially reversible (i.e., they can be enzymatically reversed after cessation of exposure to environmental agents), but some epigenetic modifications seem to persist, even for decades...
March 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28279965/lower-levels-of-vitamin-a-are-associated-with-increased-gastrointestinal-graft-versus-host-disease-in-children
#11
Dana T Lounder, Pooja Khandelwal, Christopher Dandoy, Sonata Jodele, Michael Grimley, Gregory Wallace, Adam Lane, Cynthia Taggart, Ashley Teusink-Cross, Kelly Lake, Stella M Davies
Vitamin A promotes development of mucosal tolerance and enhances differentiation of regulatory T cells. Vitamin A deficiency impairs epithelial integrity, increasing intestinal permeability. We hypothesized that higher vitamin A levels would reduce risk of graft versus host disease through reduced intestinal permeability, reduced mucosal injury, and reduced lymphocyte homing to the gut. We tested this hypothesis in a cohort study of 114 consecutive patients undergoing allogeneic stem cell transplant. Free vitamin A levels were measured in plasma at day 30 post-transplant...
March 9, 2017: Blood
https://www.readbyqxmd.com/read/28279665/multiple-sevoflurane-anesthesia-in-pregnant-mice-inhibits-neurogenesis-of-fetal-hippocampus-via-repressing-transcription-factor-pax6
#12
Fang Fang, Ruixue Song, Xiaomim Ling, Mengyuan Peng, Zhanggang Xue, Jing Cang
Sevoflurane is widely used in non-obstetric surgeries of pregnant women, but its influences on fetal brain are still not fully known. We set out to assess the effects of multiple maternal sevoflurane exposure on neurogenesis and cognitive dysfunction in fetus and offspring. Pregnant mice (gestational day 15.5) and cultured mouse neural stem cells (NSCs) received daily sevoflurane exposure (2.5%×2h and 4.1%×2h respectively) for three consecutive days. Cognitive function of the offspring was determined with the Morris water maze...
March 6, 2017: Life Sciences
https://www.readbyqxmd.com/read/28275376/immunological-balance-is-associated-with-clinical-outcome-after-autologous-hematopoietic-stem-cell-transplantation-in-type-1-diabetes
#13
Kelen C R Malmegrim, Júlia T C de Azevedo, Lucas C M Arruda, Joana R F Abreu, Carlos E B Couri, Gislane L V de Oliveira, Patricia V B Palma, Gabriela T Scortegagna, Ana B P L Stracieri, Daniela A Moraes, Juliana B E Dias, Fabiano Pieroni, Renato Cunha, Luiza Guilherme, Nathália M Santos, Milton C Foss, Dimas T Covas, Richard K Burt, Belinda P Simões, Júlio C Voltarelli, Bart O Roep, Maria C Oliveira
Autologous hematopoietic stem cell transplantation (AHSCT) increases C-peptide levels and induces insulin independence in patients with type 1 diabetes. This study aimed to investigate how clinical outcomes may associate with the immunological status, especially concerning the balance between immunoregulation and autoreactivity. Twenty-one type 1 diabetes patients were monitored after AHSCT and assessed every 6 months for duration of insulin independence, C-peptide levels, frequencies of islet-specific autoreactive CD8(+) T cells (CTL), regulatory lymphocyte subsets, thymic function, and T-cell repertoire diversity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28261874/samp8-mice-as-a-neuropathological-model-of-accelerated-brain-aging-and-dementia-toshio-takeda-s-legacy-and-future-directions
#14
REVIEW
Ichiro Akiguchi, Mercè Pallàs, Herbert Budka, Haruhiko Akiyama, Masaki Ueno, Jingxian Han, Hideo Yagi, Tomohumi Nishikawa, Yoichi Chiba, Hiroshi Sugiyama, Ryoya Takahashi, Keiko Unno, Keiichi Higuchi, Masanori Hosokawa
Senescence accelerated mice P8 (SAMP8) show significant age-related deteriorations in memory and learning ability in accordance with early onset and rapid advancement of senescence. Brains of SAMP8 mice reveal an age-associated increase of PAS-positive granular structures in the hippocampal formation and astrogliosis in the brain stem and hippocampus. A spongy degeneration in the brain stem appears at 1 month of age and reaches a maximum at 4-8 months. In addition, clusters of activated microglia also appear around the vacuoles in the brain stem...
March 6, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28261198/a-fas-hi-lymphoproliferative-phenotype-reveals-non-apoptotic-fas-signaling-in-htlv-1-associated-neuroinflammation
#15
Soraya Maria Menezes, Fabio E Leal, Tim Dierckx, Ricardo Khouri, Daniele Decanine, Gilvaneia Silva-Santos, Saul V Schnitman, Ramon Kruschewsky, Giovanni López, Carolina Alvarez, Michael Talledo, Eduardo Gotuzzo, Douglas F Nixon, Jurgen Vercauteren, David Brassat, Roland Liblau, Anne Mieke Vandamme, Bernardo Galvão-Castro, Johan Van Weyenbergh
Human T-cell lymphotropic virus (HTLV)-1 was the first human retrovirus to be associated to cancer, namely adult T-cell leukemia (ATL), but its pathogenesis remains enigmatic, since only a minority of infected individuals develops either ATL or the neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A functional FAS -670 polymorphism in an interferon (IFN)-regulated STAT1-binding site has been associated to both ATL and HAM/TSP susceptibility. Fas(hi) T stem cell memory (Tscm) cells have been identified as the hierarchical apex of ATL, but have not been investigated in HAM/TSP...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28250775/preferential-lineage-specific-differentiation-of-osteoblast-derived-induced-pluripotent-stem-cells-into-osteoprogenitors
#16
Casey L Roberts, Silvia S Chen, Angela C Murchison, Rebecca A Ogle, Michael P Francis, Roy C Ogle, Patrick C Sachs
While induced pluripotent stem cells (iPSCs) hold great clinical promise, one hurdle that remains is the existence of a parental germ-layer memory in reprogrammed cells leading to preferential differentiation fates. While it is problematic for generating cells vastly different from the reprogrammed cells' origins, it could be advantageous for the reliable generation of germ-layer specific cell types for future therapeutic use. Here we use human osteoblast-derived iPSCs (hOB-iPSCs) to generate induced osteoprogenitors (iOPs)...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28244243/angiotensin-ii-causes-apoptosis-of-adult-hippocampal-neural-stem-cells-and-memory-impairment-through-the-action-on-ampk-pgc1%C3%AE-signaling-in-heart-failure
#17
Min-Seok Kim, Geun-Hee Lee, Yong-Min Kim, Byoung-Wook Lee, Hae Yun Nam, U-Cheol Sim, Suk-Jung Choo, Seong-Woon Yu, Jae-Joong Kim, Yunhee Kim Kwon, Seong Who Kim
Data are limited on the mechanisms underlying memory impairment in heart failure (HF). We hypothesized that angiotensin II (Ang II) may determine the fate of adult hippocampal neural stem cells (HCNs), a cause of memory impairment in HF. HCNs with neurogenesis potential were isolated and cultured from adult rat hippocampi. Ang II decreased HCN proliferation in dose- and time-dependent manners. Moreover, Ang II treatment (1 µM) for 48 hours induced apoptotic death, which was attenuated by pretreatment with Ang II receptor blockers (ARBs)...
February 28, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28243610/pet-imaging-of-neurogenic-activity-in-the-adult-brain-toward-in-vivo-imaging-of-human-neurogenesis
#18
Yasuhisa Tamura, Yosky Kataoka
Neural stem cells are present in 2 neurogenic regions, the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), and continue to generate new neurons throughout life. Adult hippocampal neurogenesis is linked to a variety of psychiatric disorders such as depression and anxiety, and to the therapeutic effects of antidepressants, as well as learning and memory. In vivo imaging for hippocampal neurogenic activity may be used to diagnose psychiatric disorders and evaluate the therapeutic efficacy of antidepressants...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28238547/hallmarks-of-alzheimer-s-disease-in-stem-cell-derived-human-neurons-transplanted-into-mouse-brain
#19
Ira Espuny-Camacho, Amaia M Arranz, Mark Fiers, An Snellinx, Kunie Ando, Sebastian Munck, Jerome Bonnefont, Laurie Lambot, Nikky Corthout, Lorna Omodho, Elke Vanden Eynden, Enrico Radaelli, Ina Tesseur, Selina Wray, Andreas Ebneth, John Hardy, Karelle Leroy, Jean-Pierre Brion, Pierre Vanderhaeghen, Bart De Strooper
Human pluripotent stem cells (PSCs) provide a unique entry to study species-specific aspects of human disorders such as Alzheimer's disease (AD). However, in vitro culture of neurons deprives them of their natural environment. Here we transplanted human PSC-derived cortical neuronal precursors into the brain of a murine AD model. Human neurons differentiate and integrate into the brain, express 3R/4R Tau splice forms, show abnormal phosphorylation and conformational Tau changes, and undergo neurodegeneration...
February 15, 2017: Neuron
https://www.readbyqxmd.com/read/28237546/seasonal-variation-in-telencephalon-cell-proliferation-in-adult-female-tsinling-dwarf-skinks-scincella-tsinlingensis
#20
Chun Yang, Limin Wang, Xiangyang Xing, Yanyan Gao, Li Guo
In adult mammals, neurogenesis is limited to specific niches in the brain, but considerable adult neurogenesis occurs in many brain regions in non-mammalian vertebrates. Non-mammalian vertebrates provide invaluablecomparativematerial for understanding the core mechanisms ofadultneural stem cell maintenance and fate, but phylogenetic differences in adult neurogenesis remain poorly understood. Here we examine cell proliferation seasonality in the telencephalon of adult female tsinling dwarf skinks (Scincella tsinlingensis) by injecting wild animals caught in summer, autumn and spring, and animals caught in autumn and raised under winter conditions, with 5-Bromo-2'-deoxyuridine (BrdU)...
February 22, 2017: Brain Research
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