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https://www.readbyqxmd.com/read/28728274/-a-retrospective-study-of-10-cases-of-post-transplant-bronchiolitis-obliterans
#1
J J Chai, T Liu, B Q Cai, H D Zhu
Objective: To analyze the clinical features of bronchiolitis obliterans syndrome (BOS) in patients with allogeneic hematopoietic stem cell transplantation (HSCT). Methods: This retrospective study included patients who underwent allogeneic HSCT from January 1998 to December 2016. The clinical features, radiological manifestations and treatment of clinically proven BOS were reviewed. Results: Of 681 patients who experienced HSCT, 10(1.47%) met the diagnostic criteria. The duration of BOS onset after transplantation was 5-48 months, averaging (18±15) months...
July 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28723575/crispr-mediated-integration-of-large-gene-cassettes-using-aav-donor-vectors
#2
Rasmus O Bak, Matthew H Porteus
The CRISPR/Cas9 system has recently been shown to facilitate high levels of precise genome editing using adeno-associated viral (AAV) vectors to serve as donor template DNA during homologous recombination (HR). However, the maximum AAV packaging capacity of ∼4.5 kb limits the donor size. Here, we overcome this constraint by showing that two co-transduced AAV vectors can serve as donors during consecutive HR events for the integration of large transgenes. Importantly, the method involves a single-step procedure applicable to primary cells with relevance to therapeutic genome editing...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28717403/the-potential-role-of-adult-stem-cells-in-the-management-of-the-rheumatic-diseases
#3
REVIEW
Tiziana Franceschetti, Cosimo De Bari
Adult stem cells are considered as appealing therapeutic candidates for inflammatory and degenerative musculoskeletal diseases. A large body of preclinical research has contributed to describing their immune-modulating properties and regenerative potential. Additionally, increasing evidence suggests that stem cell differentiation and function are disrupted in the pathogenesis of rheumatic diseases. Clinical studies have been limited, for the most part, to the application of adult stem cell-based treatments on small numbers of patients or as a 'salvage' therapy in life-threatening disease cases...
July 2017: Therapeutic Advances in Musculoskeletal Disease
https://www.readbyqxmd.com/read/28716883/role-of-the-%C3%AE-common-%C3%AE-c-family-of-cytokines-in-health-and-disease
#4
Timothy R Hercus, Winnie L T Kan, Sophie E Broughton, Denis Tvorogov, Hayley S Ramshaw, Jarrod J Sandow, Tracy L Nero, Urmi Dhagat, Emma J Thompson, Karen S Cheung Tung Shing, Duncan R McKenzie, Nicholas J Wilson, Catherine M Owczarek, Gino Vairo, Andrew D Nash, Vinay Tergaonkar, Timothy Hughes, Paul G Ekert, Michael S Samuel, Claudine S Bonder, Michele A Grimbaldeston, Michael W Parker, Angel F Lopez
The β common ([βc]/CD131) family of cytokines comprises granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5, all of which use βc as their key signaling receptor subunit. This is a prototypic signaling subunit-sharing cytokine family that has unveiled many biological paradigms and structural principles applicable to the IL-2, IL-4, and IL-6 receptor families, all of which also share one or more signaling subunits. Originally identified for their functions in the hematopoietic system, the βc cytokines are now known to be truly pleiotropic, impacting on multiple cell types, organs, and biological systems, and thereby controlling the balance between health and disease...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28714470/essential-role-of-fbxl5-mediated-cellular-iron-homeostasis-in-maintenance-of-hematopoietic-stem-cells
#5
Yoshiharu Muto, Masaaki Nishiyama, Akihiro Nita, Toshiro Moroishi, Keiichi I Nakayama
Hematopoietic stem cells (HSCs) are maintained in a hypoxic niche to limit oxidative stress. Although iron elicits oxidative stress, the importance of iron homeostasis in HSCs has been unknown. Here we show that iron regulation by the F-box protein FBXL5 is required for HSC self-renewal. Conditional deletion of Fbxl5 in mouse HSCs results in cellular iron overload and a reduced cell number. Bone marrow transplantation reveals that FBXL5-deficient HSCs are unable to reconstitute the hematopoietic system of irradiated recipients as a result of stem cell exhaustion...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28712386/neuropeptide-y-improves-cisplatin-induced-bone-marrow-dysfunction-without-blocking-chemotherapeutic-efficacy-in-a-cancer-mouse-model
#6
Min Hee Park, In Kyung Jung, Woo-Kie Min, Jin Ho Choi, Gyu Man Kim, Hee Kyung Jin, Jae-Sung Bae
Cisplatin is the most effective and widely used chemotherapeutic agent for many types of cancer. Unfortunately, its clinical use is limited by its adverse effects, notably bone marrow suppression leading to abnormal hematopoiesis. We previously revealed that neuropeptide Y (NPY) is responsible for the maintenance of hematopoietic stem cell (HSC) function by protecting the sympathetic nervous system (SNS) fibers survival from chemotherapy-induced bone marrow impairment. Here, we show the NPY-mediated protective effect against bone marrow dysfunction due to cisplatin in an ovarian cancer mouse model...
July 17, 2017: BMB Reports
https://www.readbyqxmd.com/read/28709801/lymphatic-endothelial-cells-control-initiation-of-lymph-node-organogenesis
#7
Lucas Onder, Urs Mörbe, Natalia Pikor, Mario Novkovic, Hung-Wei Cheng, Thomas Hehlgans, Klaus Pfeffer, Burkhard Becher, Ari Waisman, Thomas Rülicke, Jennifer Gommerman, Christopher G Mueller, Shinichiro Sawa, Elke Scandella, Burkhard Ludewig
Lymph nodes (LNs) are strategically situated throughout the body at junctures of the blood vascular and lymphatic systems to direct immune responses against antigens draining from peripheral tissues. The current paradigm describes LN development as a programmed process that is governed through the interaction between mesenchymal lymphoid tissue organizer (LTo) cells and hematopoietic lymphoid tissue inducer (LTi) cells. Using cell-type-specific ablation of key molecules involved in lymphoid organogenesis, we found that initiation of LN development is dependent on LTi-cell-mediated activation of lymphatic endothelial cells (LECs) and that engagement of mesenchymal stromal cells is a succeeding event...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28708597/mri-based-evaluation-of-multiorgan-iron-overload-is-a-predictor-of-adverse-outcomes-in-pediatric-patients-undergoing-allogeneic-hematopoietic-stem-cell-transplantation
#8
Natalia Maximova, Massimo Gregori, Giulia Boz, Roberto Simeone, Davide Zanon, Giulia Schillani, Floriana Zennaro
The medical records of 44 pediatric patients who underwent allogeneic transplantation from 2011 to 2015 were retrospectively reviewed. Magnetic resonance imaging was used to measure iron concentrations in the liver, spleen, pancreas and bone. These patients were divided into two groups, 18 with non-elevated (< 100 μmol/g; Group 1) liver iron concentration before transplantation and 26 with elevated (> 100 μmol/g; Group 2) concentration . We compared transplant-related outcomes in the two groups. Iron overload was a negative prognostic risk factor for sinusoidal obstruction syndrome (OR = 17), osteoporosis (OR = 6...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28707002/epigenetic-regulation-of-cellular-and-cytomegalovirus-genes-during-myeloid-cell-development
#9
Xue-Feng Liu, Mary Hummel, Michael Abecassis
Myeloid cells are important cell types that carry human cytomegalovirus. Latent viral DNA is present in CD34+ progenitor cells and their derived monocytes. However, differentiation of latently infected monocytes to mature macrophages or dendritic cells causes reactivation of latent viruses. During hematopoietic development, pluripotent genes are repressed, and lineage specific genes are activated in a step-wise manner. This process is governed by cell-type specific chromatin states. Enhancers in the hematopoietic system are highly dynamic and established by pioneer (first tier) transcription factors (TFs), which set the stage for second and third tier TF binding...
March 2017: Internal Medicine Review (Washington, D.C.: Online)
https://www.readbyqxmd.com/read/28702683/blood-on-the-tracks-hematopoietic-stem-cell-endothelial-cell-interactions-in-homing-and-engraftment
#10
REVIEW
Julie R Perlin, Audrey Sporrij, Leonard I Zon
Cells of the hematopoietic system undergo rapid turnover. Each day, humans require the production of about one hundred billion new blood cells for proper function. Hematopoietic stem cells (HSCs) are rare cells that reside in specialized niches and are required throughout life to produce specific progenitor cells that will replenish all blood lineages. There is, however, an incomplete understanding of the molecular and physical properties that regulate HSC migration, homing, engraftment, and maintenance in the niche...
August 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28702160/bk-virus-associated-hemorrhagic-cystitis-in-patients-with-allogeneic-hematopoietic-cell-transplantation-report-of-three-cases
#11
Duygu Mert, Hikmetullah Batgi, Alparslan Merdin, Sabahat Çeken, Mehmet Sinan Dal, Emre Tekgündüz, Fevzi Altuntaş, Mustafa Ertek
BK viras is a human polyoma viras. It is acquired in early childhood and remains life-long latent in the genitourinary system. BK virus replication is more common in receiving immunosuppressive therapy receiving patients and transplant patients. BK virus could cause hemorrhagic cystitis in patients with allogeneic stem cell transplantation. Hemorrhagic cystitis is a serious complication of hematopoietic stem cell transplantation. Hemorrhagic cystitis could cause morbidity and long stay in the hospital. Diagnosis is more frequently determined by the presence of BK virus DNA detected with quantitative or real-time PCR testing in serum or plasma and less often in urine...
June 1, 2017: Hematology Reports
https://www.readbyqxmd.com/read/28702025/cellular-and-molecular-defects-underlying-invasive-fungal-infections-revelations-from-endemic-mycoses
#12
REVIEW
Pamela P Lee, Yu-Lung Lau
The global burden of fungal diseases has been increasing, as a result of the expanding number of susceptible individuals including people living with human immunodeficiency virus (HIV), hematopoietic stem cell or organ transplant recipients, patients with malignancies or immunological conditions receiving immunosuppressive treatment, premature neonates, and the elderly. Opportunistic fungal pathogens such as Aspergillus, Candida, Cryptococcus, Rhizopus, and Pneumocystis jiroveci are distributed worldwide and constitute the majority of invasive fungal infections (IFIs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28700586/systematic-identification-and-characterization-of-regulatory-elements-derived-from-human-endogenous-retroviruses
#13
Jumpei Ito, Ryota Sugimoto, Hirofumi Nakaoka, Shiro Yamada, Tetsuaki Kimura, Takahide Hayano, Ituro Inoue
Human endogenous retroviruses (HERVs) and other long terminal repeat (LTR)-type retrotransposons (HERV/LTRs) have regulatory elements that possibly influence the transcription of host genes. We systematically identified and characterized these regulatory elements based on publicly available datasets of ChIP-Seq of 97 transcription factors (TFs) provided by ENCODE and Roadmap Epigenomics projects. We determined transcription factor-binding sites (TFBSs) using the ChIP-Seq datasets and identified TFBSs observed on HERV/LTR sequences (HERV-TFBSs)...
July 12, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28697759/the-distinct-biological-implications-of-asxl1-mutation-and-its-roles-in-leukemogenesis-revealed-by-a-knock-in-mouse-model
#14
Yueh-Chwen Hsu, Yu-Chiao Chiu, Chien-Chin Lin, Yuan-Yeh Kuo, Hsin-An Hou, Yi-Shiuan Tzeng, Chein-Jun Kao, Po-Han Chuang, Mei-Hsuan Tseng, Tzu-Hung Hsiao, Wen-Chien Chou, Hwei-Fang Tien
BACKGROUND: Additional sex combs-like 1 (ASXL1) is frequently mutated in myeloid malignancies. Recent studies showed that hematopoietic-specific deletion of Asxl1 or overexpression of mutant ASXL1 resulted in myelodysplasia-like disease in mice. However, actual effects of a "physiological" dose of mutant ASXL1 remain unexplored. METHODS: We established a knock-in mouse model bearing the most frequent Asxl1 mutation and studied its pathophysiological effects on mouse hematopoietic system...
July 11, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28696319/combined-epigenetic-and-differentiation-based-treatment-inhibits-neuroblastoma-tumor-growth-and-links-hif2%C3%AE-to-tumor-suppression
#15
Isabelle Westerlund, Yao Shi, Konstantinos Toskas, Stuart M Fell, Shuijie Li, Olga Surova, Erik Södersten, Per Kogner, Ulrika Nyman, Susanne Schlisio, Johan Holmberg
Neuroblastoma is a pediatric cancer characterized by variable outcomes ranging from spontaneous regression to life-threatening progression. High-risk neuroblastoma patients receive myeloablative chemotherapy with hematopoietic stem-cell transplant followed by adjuvant retinoid differentiation treatment. However, the overall survival remains low; hence, there is an urgent need for alternative therapeutic approaches. One feature of high-risk neuroblastoma is the high level of DNA methylation of putative tumor suppressors...
July 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28696061/outcomes-and-healthcare-utilization-in-children-and-young-adults-with-aplastic-anemia-a-multiinstitutional-analysis
#16
Ashish Gupta, Pingfu Fu, Hasan Hashem, Anant Vatsayan, Steven Shein, Jignesh Dalal
BACKGROUND: Aplastic anemia is a bone marrow failure syndrome with high mortality affecting children and young adults. Although current treatment guidelines recommend hematopoietic stem cell transplant (HCT) for patients with matched sibling donors, outcomes with alternate donor options have been improving. PROCEDURE: We analyzed a validated multiinstitutional pediatric cohort using one of the largest pediatric and young adult database, the Pediatric Health Information System, for patients diagnosed with aplastic anemia (AA) from 2006 to 2015...
July 11, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28695521/the-use-of-parp-inhibitors-in-cancer-therapy-use-as-adjuvant-with-chemotherapy-or-radiotherapy-use-as-a-single-agent-in-susceptible-patients-and-techniques-used-to-identify-susceptible-patients
#17
Sydney Shall, Terry Gaymes, Farzin Farzaneh, Nicola J Curtin, Ghulam J Mufti
This chapter describes some of the techniques in use in our laboratories for the investigation of PARP inhibitors in clinical medicine. More specifically, we are involved in investigating the utility of PARP inhibitors in the treatment of hematopoietic malignancies. We are also actively investigating the properties of the PARP systems in cell biology. We begin the chapter with a very brief history of the invention and use of PARP inhibitors. We then explain the underlying logic of the use of PARP inhibitors either in combination with chemo- or radiotherapy or as single agents used alone...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28694518/pdk1-plays-a-vital-role-on-hematopoietic-stem-cell-function
#18
Tianyuan Hu, Cong Li, Le Wang, Yingchi Zhang, Luyun Peng, Hui Cheng, Yajing Chu, Weili Wang, Hideo Ema, Yingdai Gao, Zhenyu Ju, Zhongzhou Yang, Xiaomin Wang, Tao Cheng, Weiping Yuan
3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a pivotal regulator in the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway that have been shown to play key roles in the functional development of B and T cells via activation of AGC protein kinases during hematopoiesis. However, the role of PDK1 in HSCs has not been fully defined. Here we specifically deleted the PDK1 gene in the hematopoietic system and found that PDK1-deficient HSCs exhibited impaired function and defective lineage commitment abilities...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28690869/the-clinical-impact-of-copy-number-variants-in-inherited-bone-marrow-failure-syndromes
#19
Nicolas Waespe, Santhosh Dhanraj, Manju Wahala, Elena Tsangaris, Tom Enbar, Bozana Zlateska, Hongbing Li, Robert J Klaassen, Conrad V Fernandez, Geoff D E Cuvelier, John K Wu, Yves D Pastore, Mariana Silva, Jeffrey H Lipton, Joseé Brossard, Bruno Michon, Sharon Abish, MacGregor Steele, Roona Sinha, Mark J Belletrutti, Vicky R Breakey, Lawrence Jardine, Lisa Goodyear, Liat Kofler, Michaela Cada, Lillian Sung, Mary Shago, Stephen W Scherer, Yigal Dror
Inherited bone marrow failure syndromes (IBMFSs) comprise a genetically heterogeneous group of diseases with hematopoietic failure and a wide array of physical malformations. Copy number variants (CNVs) were reported in some IBMFSs. It is unclear what impact CNVs play in patients evaluated for a suspected diagnosis of IBMFS. Clinical and genetic data of 323 patients from the Canadian Inherited Marrow Failure Registry from 2001 to 2014, who had a documented genetic work-up, were analyzed. Cases with pathogenic CNVs (at least 1 kilobasepairs) were compared to cases with other mutations...
May 10, 2017: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/28688831/local-chemical-sympathectomy-of-rat-bone-marrow-and-its-effect-on-marrow-cell-composition
#20
P Dubový, I Klusáková, L Kučera, J Osičková, J Chovancová, T Loja, J Mayer, M Doubek, M Joukal
Existing experimental studies of the effect of sympathetic nerve fibers on bone marrow cells are based on the systemic administration of neurotoxic 6-hydroxydopamine. The method of global chemical sympathectomy has some serious disadvantages and could lead to questionable results. We describe a new method of local chemical sympathectomy of rat femoral bone marrow using guanethidine (Ismelin) delivery using an osmotic mini pump. Local guanethidine treatment for 14days led to complete elimination of sympathetic fibers in femoral bone marrow in contrast to bone marrow of contralateral or naïve femurs...
June 23, 2017: Autonomic Neuroscience: Basic & Clinical
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