bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Members of the Wnt Gene Family in Human Hematopoiesis
Authors: Van Den Berg David J. , Sharma Arun K. , Bruno Edward , Hoffman Ron 
Published: October 2019

The hematopoietic system is derived from ventral mesoderm. A number of genes that are important in mesoderm development have been identified including members of the transforming growth factor-β (TGF-β) superfamily, the fibroblast growth factor (FGF) family, and the Wnt gene family. Because TGF-β plays a pleiotropic role in hematopoiesis, we wished to determine if other genes that are important in mesoderm development, specifically members of theWnt gene family, may play a role in hematopoiesis. Three members of the Wnt gene family (Wnt-5A, Wnt-2B, and Wnt-10B) were identified and cloned from human fetal bone stromal cells. These genes are expressed to varying levels in hematopoietic cell lines derived from T cells, B cells, myeloid cells, and erythroid cells; however, only Wnt-5A was expressed in CD34+Lin− primitive progenitor cells. The in vitro biological activity of these Wnt genes on CD34+Lin− hematopoietic progenitors was determined in a feeder cell coculture system and assayed by quantitating progenitor cell numbers, CD34+ cell numbers, and numbers of differentiated cell types. The number of hematopoietic progenitor cells was markedly affected by exposure to stromal cell layers expressing Wnt genes with 10- to 20-fold higher numbers of mixed colony-forming units (CFU-MIX), 1.5- to 2.6-fold higher numbers of CFU-granulocyte macrophage (CFU-GM), and greater than 10-fold higher numbers of burst-forming units-erythroid (BFU-E) in the Wnt-expressing cocultures compared with the controls. Colony formation by cells expanded on theWnt-expressing cocultures was similar for each of the three genes, indicating similar action on primitive progenitor cells; however, Wnt-10B showed differential activity on erythroid progenitors (BFU-E) compared with Wnt-5A and Wnt-2B. Cocultures containing Wnt-10B alone or in combination with all three Wnt genes had threefold to fourfold lower BFU-E colony numbers than the Wnt-5A– or Wnt-2B–expressing cocultures. The frequency of CD34+ cells was higher inWnt-expressing cocultures and cellular morphology indicated that coculture in the presence of Wnt genes resulted in higher numbers of less differentiated hematopoietic cells and fewer mature cells than controls. These data indicate that the gene products of theWnt family function as hematopoietic growth factors, and that they may exhibit higher specificity for earlier progenitor cells.© 1998 by The American Society of Hematology.
Mcl-1 in Transgenic Mice Promotes Survival in a Spectrum of Hematopoietic Cell Types and Immortalization in the Myeloid Lineage
Authors: Zhou Ping , Qian Liping , Bieszczad Christine K. , Noelle Randolph , Binder Michael , Levy Norman B. , Craig Ruth W. 
Published: October 2019

Mcl-1 is a member of the Bcl-2 family that is expressed in early monocyte differentiation and that can promote viability on transfection into immature myeloid cells. However, the effects of Mcl-1 are generally short lived compared with those of Bcl-2 and are not obvious in some transfectants. To further explore the effects of this gene, mice were produced that expressed Mcl-1 as a transgene in hematolymphoid tissues. The Mcl-1 transgene was found to cause moderate viability enhancement in a wide range of hematopoietic cell types, including lymphoid (B and T) as well as myeloid cells at both immature and mature stages of differentiation. However, enhanced hematopoietic capacity in transgenic bone marrow and spleen was not reflected in any change in pool sizes in the peripheral blood. In addition, among transgenic cells, mature T cells remained long lived compared with B cells and macrophages could live longer than either of these. Interestingly, when hematopoietic cells were maintained in tissue culture in the presence of interleukin-3, Mcl-1 enhanced the probability of outgrowth of continuously proliferating myeloid cell lines. Thus, Mcl-1 transgenic cells remained subject to normal in vivo homeostatic mechanisms controlling viable cell number, but these constraints could be overridden under specific conditions in vitro. Within the organism, Bcl-2 family members may act at “viability gates” along the differentiation continuum, functioning as part of a system for controlled hematopoietic cell amplification. Enforced expression of even a moderate viability-promoting member of this family such as Mcl-1, within a conducive intra- and extracellular environment in isolation from normal homeostatic constraints, can substantially increase the probability of cell immortalization.© 1998 by The American Society of Hematology.
Detection of a Complex That Associates With the Bβ Fibrinogen G−455-A Polymorphism
Authors: Brown Erika T. , Fuller Gerald M. 
Published: October 2019

The promoter region of the Bβ fibrinogen gene containing the polymorphic site (G−455-A) shows an increase in fibrinogen levels for individuals containing an adenine rather than a guanine. Two methods were used to explore the possible functional role of this region. Electrophoretic mobility shift assays (EMSAs) were performed using specific DNA probes containing base sequences pertinent to the allelic site. Specific DNA binding proteins were detected and their binding characteristics were determined. Secondly, we placed DNA fragments containing different −455 nucleotide substitutions of the Bβ promoter upstream of a luciferase reporter gene and transfected them into HepG2 cells to determine their effect on transactivation. An adenine at position −455 resulted in greater luciferase activity than when a guanine was present. UV cross-linking bound protein to the DNA demonstrated a 47-kD protein binding preferentially to the site when a guanine rather than an adenine was present at −455. We hypothesize that a transactivation protein complex associates with the site, but its association is stronger when guanine is present, thereby slowing downstream Bβ gene transcription. These data provide the first molecular evidence that accounts for the increase in fibrinogen in individuals carrying this allele.© 1998 by The American Society of Hematology.
Hepatitis C Virus Infection Involves CD34+Hematopoietic Progenitor Cells in Hepatitis C Virus Chronic Carriers
Authors: Sansonno Domenico , Lotesoriere Claudio , Cornacchiulo Vito , Fanelli Massimo , Gatti Pietro , Iodice Giuseppe , Racanelli Vito , Dammacco Franco 
Published: October 2019

Although hepatitis C virus (HCV) mainly affects hepatocytes, infection is widespread and involves immunologically privileged sites. Whether lymphoid cells represent further targets of early HCV infection, or whether other cells in the hematopoietic microenvironment may serve as a potential virus reservoir, is still unclear. We studied whether pluripotent hematopoietic CD34+ cells support productive HCV infection and can be used to establish an in vitro infection system for HCV. Six patients were selected as part of a cohort of HCV chronic carriers who developed a neoplastic disease. Reverse transcriptase-polymerase chain reaction (RT-PCR) and branched DNA signal amplification assays were used to detect and quantitate HCV RNA in extracted nucleic acids from purified bone marrow and peripheral blood CD34+ cells. Direct in situ RT-PCR, flow cytometry analysis, and immunocytochemistry were applied to demonstrate specific viral genomic sequences and structural and nonstructural virus-related proteins in intact cells. Results indicated that both positive and negative HCV RNA strands and viral proteins were present in CD34+ cells from all HCV-positive patients and in none of the controls. Additional experiments showed that a complete viral cycle took place in CD34+ cells in vitro. Spontaneous increases in viral titers indicated that virions were produced by infected hematopoietic progenitor cells. To further define the cellular tropism, we attempted to infect CD34+ cells in vitro. We were unable to demonstrate viral uptake by cells. These findings suggest that HCV replication can occur in the early differentiation stages of hematopoietic progenitor cells, and that they may be an important source of virus production.© 1998 by The American Society of Hematology.
A Multicenter Prospective Study on the Risk of Acquiring Liver Disease in Anti–Hepatitis C Virus Negative Patients Affected From Homozygous β-Thalassemia
Authors: Prati Daniele , Zanella Alberto , Farma Elena , De Mattei Claudia , Bosoni Patrizia , Zappa Manuela , Picone Alessandra , Mozzi Fulvio , Rebulla Paolo , Cappellini Maria Domenica , Allain Jean-Pierre , Sirchia Girolamo 
Published: October 2019

Although the risk of transfusion-transmitted hepatitis has been recently reduced, transfusion-dependent β-thalassemia patients may still develop liver disease due to viral infection or iron overload. We assessed the frequency and causes of liver dysfunction in a cohort of anti–hepatitis C virus (HCV) negative thalassemics. Of 1,481 thalassemics enrolled in 31 centers, 219 (14.8%) tested anti-HCV− by second-generation assays; 181 completed a 3-year follow-up program consisting of alanine-aminotransferase (ALT) measurement at each transfusion and anti-HCV determination by third-generation enzyme-immunoassay (EIA-3) at the end of study. Serum ferritin levels were determined at baseline and at the end of follow-up. Ten patients were anti-HCV+ by EIA-3 at the end of follow-up. Of them, seven were already positive in 1992 to 1993 when the initial sera were retested by EIA-3, one tested indeterminate by confirmatory assay, and two had true seroconversion (incidence, 4.27/1,000 person years; risk of infection, 1/7,100 blood units, 95% confidence interval [CI], 1 in 2,000-1 in 71,000 units). At baseline, 67 of 174 thalassemics had abnormal ALT. Of those with normal ALT, seven subsequently developed at least one episode of moderate ALT increase (incidence, 24.6/1,000 person-years). All of the 20 patients with ferritin values ≥3,000 ng/mL had clinically relevant ALT abnormalities, as compared with 53 of 151 with <3,000 ng/mL (P< .005). Hepatic dysfunction is still frequent in thalassemics. Although it is mainly attributable to siderosis and primary HCV infection, the role of undiscovered transmissible agents cannot be excluded.
© 1998 by The American Society of Hematology.
Osteoclast-Mediated Bone Resorption Is Stimulated During Short-Term Administration of Granulocyte Colony-Stimulating Factor But Is Not Responsible for Hematopoietic Progenitor Cell Mobilization
Authors: Takamatsu Yasushi , Simmons Paul J. , Moore Robert J. , Morris Howard A. , To Luen B. , Lévesque Jean-Pierre 
Published: October 2019

The cellular and molecular mechanisms responsible for hematopoietic progenitor cell (HPC) mobilization from bone marrow (BM) into peripheral blood after administration of cytokines such as granulocyte colony-stimulating factor (G-CSF) are still unknown. In this study we show that high concentrations of soluble calcium induce the detachment of BM CD34+ HPC adherent on fibronectin, a major component of BM extracellular matrix. Because G-CSF has been shown to induce osteoporosis in patients with congenital neutropenia and in G-CSF–overexpressing transgenic mice, we hypothesized that short-term G-CSF administration may be sufficient to induce bone resorption, resulting in the release of soluble calcium in the endosteum leading in turn to the inhibition of attachment to fibronectin and the egress of HPC from the BM. We show herein that in humans, serum osteocalcin concentration, a specific marker of bone formation, is strongly reduced after 3 days of G-CSF administration. Furthermore, in patients mobilized with G-CSF either alone or in association with stem cell factor or interleukin-3, the reduction of serum osteocalcin is significantly correlated with the number of HPC mobilized in peripheral blood. Urine levels of deoxypyridinoline (DPyr), a specific marker of bone resorption, gradually elevated during the time course of G-CSF administration until day 7 after cessation of G-CSF, showing a simultaneous stimulation of bone degradation during G-CSF–induced HPC mobilization. In an in vivo murine model, we found that the number of osteoclasts was dramatically increased paralleling the elevation of DPyr after G-CSF administration. When pamidronate, an inhibitor of osteoclast-mediated bone resorption, was administered together with G-CSF in mice, the G-CSF–induced increase of DPyr levels was completely abolished whereas the numbers of colony-forming cells mobilized in peripheral blood were not decreased, but unexpectedly increased relative to the numbers elicited by G-CSF alone. Collectively, our data therefore show that short-term administration of G-CSF induces bone degradation by a simultaneous inhibition of bone formation and an enhanced osteoclast-mediated bone resorption. This increased bone resorption is inhibited by pamidronate without reducing G-CSF–induced HPC mobilization, suggesting that the activation of bone resorption after G-CSF administration is not the direct cause of HPC mobilization as initially hypothesized, but a parallel event.© 1998 by The American Society of Hematology.
Graphene Oxide in a Composite with Silver Nanoparticles Reduces the Fibroblast and Endothelial Cell Cytotoxicity of an Antibacterial Nanoplatform
Authors: Wierzbicki Mateusz , Jaworski Sławomir , Sawosz Ewa , Jung Anna , Gielerak Grzegorz , Jaremek Henryk , Łojkowski Witold , Woźniak Bartosz , Stobiński Leszek , Małolepszy Artur , Chwalibog André 
Published: October 2019

Abstract
Antibacterial surfaces coated with nanomaterials, including silver nanoparticles, are considered effective alternative antimicrobial agents that can be used instead of antibiotics and chemical agents. However, reports of the potential toxicity of these materials raise questions about the safety of their use in biomedical applications. The objective of this research was to reduce the human cell cytotoxicity of silver nanoparticle-coated polyurethane foils by complexing silver nanoparticles with graphene oxide. The antimicrobial activity of nanoplatforms coated with silver nanoparticles, graphene oxide and the composite of silver nanoparticles and graphene oxide was assessed with Salmonella enteritidis. Cytotoxicity was analysed by an analysis of the viability and morphology of human fibroblasts, human umbilical vein endothelial cells (HUVECs) and chicken embryo chorioallantoic membrane. Additionally, the synthesis level of inflammatory proteins was examined for fibroblasts cultured on different nanoplatforms. The nanoplatform coated with the silver nanoparticles and graphene oxide composite showed strongest antibacterial properties, although nanoplatforms coated with only silver nanoparticles or graphene oxide also resulted in decreased S. enteritidis growth. Furthermore, a nanoplatform coated with silver nanoparticles and graphene oxide composite showed limited immunological stimulation and significantly reduced cytotoxicity towards fibroblasts, HUVECs and chicken embryo chorioallantoic membrane in comparison to the nanoplatform coated only with silver nanoparticles, due to the higher stability of the nanomaterials in the nanocomposite.
Genetic diversity and structure of Chinese grass shrimp, Palaemonetes sinensis, inferred from transcriptome-derived microsatellite markers
Authors: Zhao Yingying , Zhu Xiaochen , Li Zhi , Xu Weibin , Dong Jing , Wei Hua , Li Yingdong , Li Xiaodong 
Published: October 2019

AbstractBackgroundThe Chinese grass shrimp,Palaemonetes sinensis, is an economically important freshwater shrimp in China, and the study of genetic diversity and structure can positively contribute to the exploration of germplasm resources and assist in the understanding ofP. sinensisaquaculture. Microsatellite markers are widely used in research of genetic backgrounds since it is considered an important molecular marker for the analyses of genetic diversity and structure. Hence, the aim of this study was to evaluate the genetic diversity and structure of wildP. sinensispopulations in China using the polymorphic microsatellite makers from the transcriptome.ResultsSixteen polymorphic microsatellite markers were developed forP. sinensisfrom transcriptome, and analyzed for differences in genetic diversity and structure in multiple wildP. sinensispopulations in China. Totally of 319 individual shrimps from seven different populations were genotyped to find that allelic polymorphisms varied in two to thirteen alleles seen in the entire loci. Compared to other populations analyzed, the two populations including LD and SJ showed lower genetic diversity. Both the genetic distance (D) and Wrights fixation index (FST) comparing any two populations also indicated that LD and SJ populations differed from the other five populations. An UPGMA tree analysis showed three main clusters containing SJ, LD and other populations which were also confirmed using STRUCTURE analysis.ConclusionThis is the first study where polymorphic microsatellite markers from the transcriptome were used to analyze genetic diversity and structures of different wildP. sinensispopulations. All the polymorphic microsatellite makers are believed useful for evaluating the extent of the genetic diversity and population structure ofP. sinensis. Compared to the other five populations, the LD and SJ populations exhibited lower genetic diversity, and the genetic structure was differed from the other five populations. Therefore, they needed to be protected against further declines in genetic diversity. The other five populations, LP, LA, LSL, LSY and LSH, are all belonging to Liaohe River Drainage with a relatively high genetic diversity, and hence can be considered as hot spots for in-situ conservation ofP. sinensisas well as sources of desirable alleles for breeding values.
Ipilimumab-induced renal granulomatous arteritis: a case report
Authors: Lemoine Mathilde , Dilly Baptiste , Curie Alexandre , Hébert Vivien , Laurent Charlotte , Hanoy Mélanie , Grangé Steven , Guerrot Dominique , François Arnaud , Bertrand Dominique 
Published: October 2019

Abstract

Background
Immune Checkpoint Inhibitors (ICPIs) are promising new drugs in treatment of advanced tumours targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein-1 (PD1) or its ligand (PDL-1). Ipilimumab is a monoclonal antibody targeting the CTLA-4 receptor used in treatment of metastatic melanoma. By increasing activity of the immune system, ICPIs lead to immune-related adverse events, such as dermatitis, colitis or hepatitis. ICPIs-related kidney adverse events are rare and acute tubulointerstitial nephritis with or without granuloma have mainly been reported.

Case presentation
We report a case of acute kidney injury in a patient with melanoma treated by ipilimumab. Kidney biopsy revealed acute interlobular and juxtaglomerular granulomatous arteritis, which has not yet been reported in patients treated by ICPIs. Kidney function partially recovered after ipilimumab discontinuation and oral prednisone. Unfortunately, the patient died a few months later from progression of his melanoma.

Conclusion
This case highlights a new mechanism of acute kidney injury related to ICPIs and supports the interest of kidney biopsy in case of ICPIs related acute renal failure.
Describing mortality trends for major cancer sites in 133 intermediate regions of Brazil and an ecological study of its causes
Authors: Bigoni Alessandro , Ferreira Antunes José Leopoldo , Weiderpass Elisabete , Kjærheim Kristina 
Published: October 2019

AbstractBackgroundIn Brazil, 211 thousand (16.14%) of all death certificates in 2016 identified cancer as the underlying cause of death, and it is expected that around 320 thousand will receive a cancer diagnosis in 2019. We aimed to describe trends of cancer mortality from 1996 to 2016, in 133 intermediate regions of Brazil, and to discuss macro-regional differences of trends by human development and healthcare provision.MethodsThis ecological study assessed georeferenced official data on population and mortality, health spending, and healthcare provision from Brazilian governmental agencies. The regional office of the United Nations Development Program provided data on the Human Development Index in Brazil. Deaths by misclassified or unspecified causes (garbage codes) were redistributed proportionally to known causes. Age-standardized mortality rates used the world population as reference. Prais-Winsten autoregression allowed calculating trends for each region, sex and cancer type.ResultsTrends were predominantly on the increase in the North and Northeast, whereas they were mainly decreasing or stationary in the South, Southeast, and Center-West. Also, the variation of trends within intermediate regions was more pronounced in the North and Northeast. Intermediate regions with higher human development, government health spending, and hospital beds had more favorable trends for all cancers and many specific cancer types.ConclusionsPatterns of cancer trends in the country reflect differences in human development and the provision of health resources across the regions. Increasing trends of cancer mortality in low-income Brazilian regions can overburden their already fragile health infrastructure. Improving the healthcare provision and reducing socioeconomic disparities can prevent increasing trends of mortality by all cancers and specific cancer types in Brazilian more impoverished regions.
Comparison of vascular parameters between normal cynomolgus macaques and healthy humans by optical coherence tomography angiography
Authors: Peng Jingyi , Zhong Liuxueying , Ma Li , Jin Jiayi , Zheng Yongxin , Jin Chenjin 
Published: October 2019

AbstractBackgroundThe metabolic activity of retina is higher than other human tissues and is crucial to the vision. Cynomolgus macaques is widely used in ophthalmic disease research. The evaluation and comparison of macular and optic disc vascular circulation parameters between normal adult cynomolgus macaques and healthy adult humans using OCT-A can promote better use of nonhuman primate models in studies of ophthalmic vascular disease.MethodsTwelve normal adult cynomolgus macaques with a mean age of 4.91 ± 0.43 years were studied for data collection. The macula of 28 adult healthy humans (14 males and 14 females), with a mean age of 25.11 ± 6.21 years and the optic discs of 9 adult healthy humans (4 males and 5 females) with a mean age of 28.56 ± 6.78 years were measured. The vessel density (VD) was measured using an RTVue XR with AngioVue. The scan sizes of the macular and optic discs were 3 × 3 mm and 4.5 × 4.5 mm, respectively.ResultsOCT-A can image the superficial and deep capillary plexuses and radial peripapillary capillary network. In RPC layer of the optic disc, the VD in the nasal quadrant was lower than the VD in the inferior temporal quadrant. Similarities and significant differences in VD between healthy humans and cynomolgus macaques were obtained using OCT-A.ConclusionsThis study provides normal vascular parameters for adult cynomolgus macaques using OCT-A to help establish an optical parameter database for cynomolgus macaques and compare VD between healthy humans and cynomolgus macaques to promote choroid-retinopathy research.Trial registrationCurrent Controlled TrialsNCT03692169, retrospectively registered on 26 sept 2018.