A tree‐like hierarchical branching structure is present in many biological systems, such as the kidney, lung, mammary gland, and blood vessels. Most of these organs form through branching morphogenesis, where outward growth results in smaller and smaller branches. However, the blood vasculature is unique in that it exists as two trees (arterial and venous) connected at their tips. Obtaining this organization might therefore require unique developmental mechanisms. As reviewed here, recent data indicate that arterial trees often form in (...) reverse order. Accordingly, initial arterial endothelial cell differentiation occurs outside of arterial vessels. These pre‐artery cells then build trees by following a migratory path from smaller into larger arteries, a process guided by the forces imparted by blood flow. Thus, in comparison to other branched organs, arteries can obtain their structure through inward growth and coalescence. Here, new information on the underlying mechanisms is discussed, and how defects can lead to pathologies, such as hypoplastic arteries and arteriovenous malformations. -/- . (shrink)

It is increasingly suggested that shortages in the supply chain for human blood could be met by the development of techniques to manufacture human blood ex vivo. These techniques fall broadly under the umbrella of synthetic biology. We examine the biopolitical context surrounding the ex vivo culture of red blood cells through the linked concepts of alienation, immunity, bio-value and biosecuritization. We engage with diverse meanings of synthetic blood, and questions about how the discourses of (...) biosecurity and privatization of risk are linked to claims that the technology will address unmet needs and promote social justice. Through our discussion we contrast communitarian ideas that culturing red blood cells ‘extends the gift’ of adult blood donation with understandings of the immunitary logics that underpin the cord-blood economy. (shrink)

Sickle cell anemia is a disease characterized by abnormal hemoglobin structure. There is a mutation in the beta-globin gene that changes the sixth amino acid from glutamic acid to valine causing the mutated hemoglobin to polymerize reversibly when deoxygenated to form a gelatinous network of fibrous polymers that stiffen and distort the red blood cell membrane. This leads to episodes of microvascular vasoocclusion and premature RBC destruction leading to hemolytic anemia. For reasons that are unclear, some children develop a (...) large artery vasculopathy involving the intracranial arteries supplying the brain.The risk of stroke for a child with SCD is many times greater than that of a healthy child without SCD or heart disease. There is a technique that allows the identification of the children with SCD who have high risk even within this relatively high-risk group. And there is a highly effective preventive treatment. (shrink)

Reorganization of cell organelle‐deprived host red blood cells by the apicomplexan malaria parasite Plasmodium falciparum enables their cytoadherence to endothelial cells that line the microvasculature. This increases the time red blood cells infected with mature developmental stages remain within selected organs such as the brain to avoid the spleen passage, which can lead to severe complications and cumulate in patient death. The Maurer's clefts are a novel secretory organelle of parasite origin established by the parasite (...) in the cytoplasm of the host red blood cell in order to facilitate the establishment of cytoadherence by conducting the trafficking of immunovariant adhesins to the host cell surface. Another important function of the organelle is the sorting of other proteins the parasite traffics into its host cell. Although the organelle is of high importance for the pathology of malaria, additional putative functions, structure, and genesis remain shrouded in mystery more than a century after its discovery. In this review, we highlight our current knowledge about the Maurer's clefts and other novel secretory organelles established within the host cell cytoplasm by human‐pathogenic malaria parasites and other parasites that reside within human red blood cells. (shrink)

In response to emergencies, it is critical to investigate how to deliver emergency supplies efficiently and securely to disaster-affected areas and people. There is no doubt that blood is deemed one of the vital relief supplies, and ensuring smooth blood delivery may substantially alleviate subsequent impacts caused by the disaster. Taking red blood cell products as the research object, this work proposes a four-echelon blood supply chain model. Specifically, it includes blood donors, blood donation (...) houses, blood centres, and hospitals. Furthermore, numerical analysis is provided to test the feasibility of blood collection and distribution schemes and conduct sensitivity analysis to test the impacts of the relevant parameters, distance between blood donors and blood facilities, and times of blood donation) on the scheme. This research provides some scientific and reasonable support for decision makers and managerial implications for emergency departments and contributes to the study of emergent blood supply chain. (shrink)

It has long been known that the red blood cell contains a membrane skeleton that stabilizes the plasma membrane, determines its shape, and regulates the lateral distribution of the membrane glyco‐proteins to which it is attached. The way in which these functions are regulated in other cells has not been understood. It has now been shown that platelets also contain a membrane skeleton. In contrast to the membrane skeleton of the red blood cell, the platelet membrane skeleton (...) has actin‐binding protein, not spectrin, as a major component. The platelet membrane skeleton regulates the same cellular functions as the red blood cell membrane skeleton. Other cells may contain a membrane skeleton that is critical to their viability and normal functioning. (shrink)

The Indiana Court of Appeals, in JKB, Sr. v. Armour Pharmaceutical Co. ), held that the state's Blood Shield Act does not protect pharmaceutical companies that produce blood-derived products from product liability suits based on injuries attributable to tainted blood supplies. Blood shield statutes help to guarantee adequate blood supplies by limiting the liability of blood banks. This holding limits the defenses available to pharmaceutical companies sued under product liability theory.The defendant, Armour Pharmaceutical, produces (...) and sells clotting factor agents, which are derived through plasmapheresis. Plasmapheresis is a costly and complex donation process through which the plasma and red blood cells of a donor's blood are separated. After separation, the process returns the red blood cells to the donor but retains the plasma. (shrink)

Extracellular ATP released from necrotic cells in inflamed tissues activates the P2X7 receptor, stimulates the exposure of phosphatidylserine, and causes cell lysis. Recent findings indicated that XK, a paralogue of XKR8 lipid scramblase, forms a complex with VPS13A at the plasma membrane of T cells. Upon engagement by ATP, an unidentified signal(s) from the P2X7 receptor activates the XK‐VPS13A complex to scramble phospholipids, followed by necrotic cell death. P2X7 is expressed highly in CD25+CD4+ T cells but weakly (...) in CD8+ T cells, suggesting a role of this system in the activation of the immune system to prevent infection. On the other hand, a loss‐of‐function mutation in XK or VPS13A causes neuroacanthocytosis, indicating the crucial involvement of XK‐VPS13A‐mediated phospholipid scrambling at plasma membranes in the maintenance of homeostasis in the nervous and red blood cell systems. (shrink)

Clinical red blood cell transfusion guidelines have been widely adopted in clinical practice, resulting in standardized transfusion practices in hospitalized patients with anemia. Standardization of transfusion practice has been welcomed by clinicians and health systems as a mechanism for reducing unnecessary, harmful, and costly practice variation that results in healthcare disparities. However, overzealously applied guidelines can have deleterious consequences for individual patients, ultimately resulting in and/or exacerbating healthcare disparities, rather than resolving them. This article provides empirical examples of the (...) adverse consequences from the well-meaning attempt to standardize transfusion practice based on clinical practice guidelines and discusses the ethical implications of standardized transfusion practice. (shrink)

Mammalian neural cells contain at least two forms of brain spectrin: brain spectrin (240/235) which is located primarily in the axons and presynaptic terminals of neurons, and brain spectrin (240/235E) which is found in the cell bodies, dendrites and postsynaptic terminals of neurones. Brain spectrin (240/235E) is also found in certain glial cell types. Antibodies against red blood cell spectrin detect only brain spectrin (240/235E), while antibodies against brain spectrin isolated from axonal and synaptic membranes detect brain spectrin (...) (240/235). Previous apparent discrepancies in the literature concerning brain spectrin localization at the light microscope level were undoubtedly due to different laboratories detecting distinct brain spectrin subtypes, based on the particular antibody being utilized for immunohistochemistry. In this review we (1) discuss the data supporting the presence of at least two distinct subtypes of mammalian brain spectrin, (2) explain how these results reconcile previous discrepancies concerning the localization of spectrin within neural cells, and (3) suggest the future implications of these findings. (shrink)

A high percent of oxidative energy metabolism is needed to support brain growth during infancy. Unhealthy diets and limited nutrition, as well as other environmental insults, can compromise these essential developmental processes. In particular, iron deficiency anemia has been found to undermine both normal brain growth and neurobehavioral development. Even moderate ID may affect neural maturation because when iron is limited, it is prioritized first to red blood cells over the brain. A primate model was used to investigate (...) the neural effects of a transient ID and if deficits would persist after iron treatment. The large size and postnatal growth of the monkey brain makes the findings relevant to the metabolic and iron needs of human infants, and initiating treatment upon diagnosis of anemia reflects clinical practice. Specifically, this analysis determined whether brain maturation would still be compromised at 1 year of age if an anemic infant was treated promptly once diagnosed. The hematology and iron status of 41 infant rhesus monkeys was screened at 2-month intervals. Fifteen became ID; 12 met clinical criteria for anemia and were administered iron dextran and B vitamins for 1–2 months. MRI scans were acquired at 1 year. The volumetric and diffusion tensor imaging measures from the ID infants were compared with monkeys who remained continuously iron sufficient. A prior history of ID was associated with smaller total brain volumes, driven primarily by significantly less total gray matter and smaller GM volumes in several cortical regions. At the macrostructual level, the effect on white matter volumes was not as overt. However, DTI analyses of WM microstructure indicated two later-maturating anterior tracts were negatively affected. The findings reaffirm the importance of iron for normal brain development. Given that brain differences were still evident even after iron treatment and following recovery of iron-dependent hematological indices, the results highlight the importance of early detection and preemptive supplementation to limit the neural consequences of ID. (shrink)

Many elite athletes try to imitate the effects of high altitude training by using hypoxic air machines. These training devices are thought to boost the oxygen carrying capacity of the blood and the production of red blood cells which are believed to yield an important competitive advantage in endurance sports. Hypoxic air machines do not contravene current antidoping regulations. However, many sports practitioners and some officials have expressed a feeling of uneasiness towards this new training technique, comparing (...) it with traditional doping. And, indeed, the introduction of hypoxic air machines paves the way for allowing doping in a near future.All sports related arguments that have been advanced in defence of these machines also support traditional doping. For instance, some objectors argue that hypoxic air machines render “a chemical advantage” and should therefore be forbidden. A standard defence against this criticism is that “even if it becomes more effective, training is still necessary for users of hypoxic air machines”. The same answer, however, could be given by supporters of lifting the prohibition on doping. In a sense, every training technique yields a chemical process in the body.Consider now fairness in competition …. (shrink)

A hybrid model of cell dynamics is presented. It is illustrated by model examples and applied to study erythropoiesis (red blood cell production). In this approach, cells are considered as discrete objects while intra-cellular proteins and extra-cellular biochemical substances are described with continuous models. Spatial organization of erythropoiesis occurring in specific structures of the bone marrow, called erythroblastic island, is investigated.

In a companion review1 we discussed the data supporting the conclusion that at least two subtypes of spectrin exist in mammalian brain. One form is found in the cell bodies, dendrites, and post‐synaptic terminals of neurons (brain spectrin(240/235E)) and the other subtype is located in the axons and presynaptic terminals (brain spectrin(240/235)). Our recent understanding of brain spectrin subtype localization suggests a possible explanation for a conundrum concerning brain 4.1 localization. Amelin, an immunoreactive analogue of red blood cell (rbc) (...) cytoskeletal protein 4.1, is localized in neuronal cell bodies and dendrites when brain sections are stained with antibody against rbc protein 4.1. However, it has recently been suggested that synapsin I, a neuron‐specific phosphoprotein associated with the cytoplasmic surface of small synaptic vesicles, is related to erythrocyte 4.1. In this review we hypothesize that there are at least two forms of brain 4.1: a cell body/dendritic form (amelin) which is detected with rbc protein 4.1 antibody, and a unique form found exclusively in the presynaptic terminal (synapsin I). The binding of synapsin I to brain spectrin(240/235), and its ability to stimulate the spectrin/F‐actin interaction in a phosphorylation‐dependent manner suggests a model for the regulation of synaptic transmission mediated by the neuronal cytoskeleton. (shrink)

Included in the acute response of lowlanders exposed to reduced oxygen availability is an elevated red blood cell count due to increased erythropoietin (Epo) synthesis. According to current thinking, hypoxia is “sensed” by hydroxylases that permit Hypoxia Inducible Factor 1α (HIF‐1α) to complex with HIF‐1β to form a transcriptional activator (HIF‐1) that drives expression of hypoxia‐sensitive genes (such as EPO) under hypoxic conditions. In altitude‐adapted Andean natives, the Epo hypoxic response may be blunted; however, our data indicate that the (...) DNA sequences of the genes encoding Epo (including the 3′ regulatory region) and HIF‐1α appear to be conserved. Hence, adaptive changes in the Andean hypoxic response are not a consequence of changes in the primary sequence of these proteins or of known transcriptional regulatory domains of EPO. These results suggest that the altered erthropoietic response in Andean natives reflects adaptations in hypoxia sensing, rather than hypoxia response, mechanisms. BioEssays 25:515–519, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Imagine your body is populated by billions of respirocytes capable of delivering 236 times more oxygen than your natural red blood cells. These mechanical, micron sized spheres are appropriately programmed by your physician to meet your personal requirements, be it the treatment of anemia or the enhancement of your physical abilities. Robert Freitas’ vision of such artificial blood cells comprised of nanometer-scale components was published in 1998 in a peer-reviewed medical journal, and was the first medical (...) nanorobot design paper to be published.The fact that this proposal for a future blood substitute was accepted as worthy of publication in a scientific journal, despite the inventor's explicit statement that such a device could not be built at the time, clouds the criteria upon which an informed opinion about the feasibility of such devices could be formed. In that respect, the idea of respirocytes formidably testifies to the current “blurring of fact and fiction” occurring in the field of nanotechnology. (shrink)

Thanks to the extensive use of recombinant DNA technology and immunological methods, much insight into cellular functions of the human malaria parasite Plasmodium falciparum has been gained since it was learnt ten years ago how to grow this organism in culture. The amino acid sequence of over a dozen surface proteins of the parasite and of several proteins the parasite excretes into its most important host cell, the erythrocyte, have been determined. Interestingly many of these proteins show blocks of repeated (...) amino acids. Several proteins have been shown to be involved in specific aspects of the complex hostparasite interaction, such as penetration of host cells or increased stickiness of infected red blood cells in the blood vessels. Some of the proteins described here may be protective antigens and may become important in vaccine development. (shrink)

Consider four elite female runners who trained hard for a 1500‐meter race. Runner 1 took extra‐strength aspirin before the race. Runner 2 has a genetic condition that results in greater levels of testosterone in her body than the typical range for a woman. Runner 3 has been on a carefully scheduled regimen of the hormone erythropoietin (EPO), which has increased her red blood cell count. Runner 4 has a team of diet, sleep, and exercise experts who ensured that she (...) coordinated the exactly right balance of carbs and protein with her rest and workouts. Which of them cheated? Thomas Murray's Good Sport: Why Our Games Matter—and How Doping Undermines Them does not answer this question, but it provides tools to figure it out, and it argues that trying to answer is important. (shrink)

Erythropoietin (EPO), long appreciated as the chief endocrine regulator of red blood cell formation, is now recognized to exert many additional functions outside the bone marrow. Thus, the quest is on to define the full range of EPO functions in the physiology and pathology of non‐hematopoietic tissues. Two recent studies in man and mice have highlighted the importance of the mammalian skin as one peripheral tissue with a previously unsuspected role in EPO biology; both, as a target and as (...) a source of EPO. In addition, the skin has been proposed to function as an oxygen sensor. The present hypothesis essay critically reviews the currently available evidence for this and provides a unifying theoretical scenario for intracutaneous EPO functions and for a potential role of the skin in the control of EPO production. Mainly, we propose that the skin itself directly contributes to the up‐regulation of EPO plasma levels in response to hypoxia. (shrink)

Many biosystems are complex mixtures of disparate biofluids. To study contact and transport phenomena in these mixtures, one has to apply much information on the biofluids which are components of the mixtures. A lot of the corresponding data can be extracted by means of experiments. However, it is not always easy to obtain experimental results on rather deep physical characteristics of biofluids, especially if the bioparticles are complicated systems and the fluid coexists in the mixture with a large number of (...) other fluids. In these cases, the necessary data can, in principle, be extracted from those results which are easier to obtain experimentally. The present work proposes a method to evaluate the biofluid equilibrium pressure and electrochemical potential from common experimental values of the fluid concentration and absolute temperature as well as the fluid-particle mass, volume and spin. In so doing, the nonzero values of the particle volume are accounted for. The procedure is illustrated with a numerical example on the fluid of red blood cells (or erythrocytes) in human blood. The pressure values obtained are 49.1 and 38.8 micropascals for men and women respectively whereas the electrochemical-potential values are –2.124 and –2.130 electronvolts for men and women respectively. (shrink)

Plasmodium falciparum is the most deadly human malarial parasite, responsible for an estimated 207 million cases of disease and 627,000 deaths in 2012. Recent studies reveal that the parasite actively regulates a large fraction of its genes throughout its replicative cycle inside human red blood cells and that epigenetics plays an important role in this precise gene regulation. Here, we discuss recent advances in our understanding of three aspects of epigenetic regulation in P. falciparum: changes in histone modifications, (...) nucleosome occupancy and the three‐dimensional genome structure. We compare these three aspects of the P. falciparum epigenome to those of other eukaryotes, and show that large‐scale compartmentalization is particularly important in determining histone decomposition and gene regulation in P. falciparum. We conclude by presenting a gene regulation model for P. falciparum that combines the described epigenetic factors, and by discussing the implications of this model for the future of malaria research. (shrink)

Robust ex vivo expansion of umbilical cord blood (UCB) derived hematopoietic stem and progenitor cells (HSPCs) should enable the widespread use of UCB as a source of cells to treat hematologic and immune diseases. Novel approaches for HSPC expansion have recently been developed, setting the stage for the production of blood stem cell derived products that fulfill our current best known criteria of clinical relevance. Translating these technologies into clinical use requires bioengineering strategies to overcome challenges (...) of scale‐up, reproducibility, and product quality assurance. Clinical‐scale implementation should also define criteria and targets for cost‐effective cell manufacturing. As production strategies become more effective, new opportunities in the therapeutic use of ex vivo expanded hematopoietic cell products will emerge. Herein we examine key technological milestones that need to be met in order to move ex vivo expanded HSPC therapies from the bench‐top to the bedside in a robust and reliable manner. (shrink)

Robust ex vivo expansion of umbilical cord blood (UCB) derived hematopoietic stem and progenitor cells (HSPCs) should enable the widespread use of UCB as a source of cells to treat hematologic and immune diseases. Novel approaches for HSPC expansion have recently been developed, setting the stage for the production of blood stem cell derived products that fulfill our current best known criteria of clinical relevance. Translating these technologies into clinical use requires bioengineering strategies to overcome challenges (...) of scale‐up, reproducibility, and product quality assurance. Clinical‐scale implementation should also define criteria and targets for cost‐effective cell manufacturing. As production strategies become more effective, new opportunities in the therapeutic use of ex vivo expanded hematopoietic cell products will emerge. Herein we examine key technological milestones that need to be met in order to move ex vivo expanded HSPC therapies from the bench‐top to the bedside in a robust and reliable manner. (shrink)

Examining stem cell biology from a philosophy of science perspective, this book clarifies the field's central concept, the stem cell, as well as its aims, methods, models, explanations and evidential challenges. The first chapters discuss what stem cells are, how experiments identify them, and why these two issues cannot be completely separated. The basic concepts, methods and structure of the field are set out, as well as key limitations and challenges. The second part of the book shows how rigorous (...) explanations emerge from stem cell experiments, and compares these to other kinds of scientific explanation. Model organisms, the role of genes, and the significance of collaboration are also discussed. The last part of the book considers relations to systems biology and clinical medicine, arguing that both the mathematical models of the former, and ethical principles of the latter, are necessary for stem cell biology to deliver on its promises. (shrink)

Clinical success with human hematopoietic stem cell (HSC) transplantation establishes a paradigm for regenerative therapies with other types of stem cells. However, it remains generally challenging to therapeutically treat tissues after engineering of stem cells in vitro. Recent studies suggest that stem and progenitor cells sense physical features of their niches. Here, we review biophysical contributions to lineage decisions, maturation, and trafficking of blood and immune cells. Polarized cellular contractility and nuclear rheology are separately shown (...) to be functional markers of a hematopoietic hierarchy that predict the ability of a lineage to traffic in and out of the bone marrow niche. These biophysical determinants are regulated by a set of structural molecules, including cytoplasmic myosin‐II and nuclear lamins, which themselves are modulated by a diverse range of transcriptional and post‐translational mechanisms. Small molecules that target these mechanobiological circuits, along with novel bioengineering methods, could prove broadly useful in programming blood and immune cells for therapies ranging from blood transfusions to immune attack of tumors. (shrink)

The unsettling language of blood has been invoked throughout the history of Christianity. But until now there has been no truly sustained treatment of how Christians use blood to think with. Eugene F. Rogers Jr. discusses in his much-anticipated new book the sheer, surprising strangeness of Christian blood-talk, exploring the many and varied ways in which it offers a language where Christians cooperate, sacrifice, grow and disagree. He asks too how it is that blood-talk dominates when (...) other explanations would do, and how blood seeps into places where it seems hardly to belong. Reaching beyond academic disputes, to consider how religious debates fuel civil ones, he shows that it is not only theologians or clergy who engage in blood-talk, but also lawmakers, judges, generals, doctors and voters at large. Religious arguments have significant societal consequences, Rogers contends; and for that reason secular citizens must do their best to understand them. (shrink)

The establishment of distinct cellular identities was pivotal during the evolution of Metazoa, enabling the emergence of an array of specialized tissues with different functions. In most animals including vertebrates, cell specialization occurs in response to a combination of intrinsic (e.g., cellular ontogeny) and extrinsic (e.g., local environment) factors that drive the acquisition of unique characteristics at the single‐cell level. The first functional organ system to form in vertebrates is the cardiovascular system, which is lined by a network of endothelial (...) cells whose organ‐specific characteristics have long been recognized. Recent genetic analyses at the single‐cell level have revealed that heterogeneity exists not only at the organ level but also between neighboring endothelial cells. Thus, how endothelial heterogeneity is established has become a key question in vascular biology. Drawing upon evidence from multiple organ systems, here we will discuss the role that lineage history may play in establishing endothelial heterogeneity. (shrink)

The Red Market: On the Trail of the World’s Organ Brokers, Bone Thieves, Blood Farmers, and Child Traffickers Content Type Journal Article Category Book Review Pages 1-3 DOI 10.1007/s11673-012-9361-3 Authors Dominique E. Martin, 39 Eltham Street, Flemington, 3031 Australia Journal Journal of Bioethical Inquiry Online ISSN 1872-4353 Print ISSN 1176-7529.

The sophisticated function of the central nervous system (CNS) is largely supported by proper interactions between neural cells and blood vessels. Accumulating evidence has demonstrated that neurons and glial cells support the formation of blood vessels, which in turn, act as migratory scaffolds for these cell types. Neural progenitors are also involved in the regulation of blood vessel formation. This mutual interaction between neural cells and blood vessels is elegantly controlled by several chemokines, (...) growth factors, extracellular matrix, and adhesion molecules such as integrins. Recent research has revealed that newly migrating cell types along blood vessels repel other preexisting migrating cell types, causing them to detach from the blood vessels. In this review, we discuss vascular formation and cell migration, particularly during development. Moreover, we discuss how the crosstalk between blood vessels and neurons and glial cells could be related to neurodevelopmental disorders. (shrink)

Historical accounts of sickle cell disease tend to emphasize either its theoretical role in catalyzing the field of medical genetics or its clinical and social significance in representing the health-care disparities experienced by African Americans. This essay bridges these narratives by focusing on the discovery of sickle cells in marginalized Arabic-speaking communities of Yemen and Turkey in the 1950s. As in North America, sickle cell research in the Middle East unfolded along the social fractures of race. The essay analyzes (...) how British, Turkish, and Arab geneticists attempted to create evolutionary hypotheses that reconciled historical and sociological boundaries between white and African, Arab and Turk. As the parameters of Turkish and Arab nationalism shifted in the Cold War–era Middle East, so did the favored explanatory narratives for the presence of sickle cells in different communities, which assigned different degrees of importance to African ancestry, socially enforced endogamy, and evolutionary adaptations to malaria. (shrink)

Irigaray turns to Merleau-Ponty's intuitions about the perception of color to develop her own insights into the creative emergence of sexuate identity. As a quality of the flesh, color cannot be reduced to formal codes. The privileging of word and text inherent to Western culture suppresses the coming into being of the embodied subject in his or her own situated context. Color, tied as it is to a corporeal creativity could provide an important link since it facilitates reflection, and a (...) re-enfleshing through color of a differentiated sexuate identity tied to the imagination as well as to genetic identity. (shrink)

This essay examines the role of social interactions in the search for blood stem cells, in a recent episode of biomedical research. Linked to mid-20th century cell biology, genetics and radiation research, the search for blood stem cells coalesced in the 1960s and took a developmental turn in the late 1980s, with significant ramifications for immunology, stem cell and cancer biology. Like much contemporary biomedical research, this line of inquiry exhibits a complex social structure and includes (...) several prominent scientific successes, recognized as such by participating researchers. I use personal interviews and the published record to trace the social interactions crucial for scientific success in this episode. All recognized successes in this episode have two aspects: improved models of blood cell development, and new interfaces with other lines of research. The narrative of the search for blood stem cells thus yields a robust account of scientific success in practice, which generalizes to other scientific episodes and lends itself to expansion to include wider social contexts. (shrink)

This academic paper on Ethical issues of using umbilical cord blood stem cell therapy of John Stuart Mill perspective aim to investigate the new approaches in the treatment of diseases by using umbilical cord blood stem cells. And also to study ethical issues from the use of umbilical cord blood stem cells in the treatment of diseases considered by Mill’s utilitarianism. 21st century, the medical industry was interested in organ transplantation from stem cells especially (...) stem cells from the umbilical cord to treat chronic and degenerative organ diseases, blood cancer and organ transplantation which successful and widespread throughout the world. Thailand has about 900 new children with Leukemia every year. About 50 percent are leukemia which needs to be treated correctly and urgently. In general Standardized chemotherapy but if the cancer patient has a bad prognosis Or have recurrent cancer Patients need to be treated with bone marrow transplants or stem cells to have a chance to heal. According to Mill’s Utilitarianism, the ethical concepts that determine what is the basic criterion used to determine whether it should or should not concern with the popular benefit that the criterion used is the amount of happiness that results from actions. Treating the disease using stem cells will make the patient recover from the disease, healthier and happier in life. As Mill said "The correctness of an action depends on the tendency that the action will lead to happiness. (shrink)

Endosteal stem cells are a subclass of bone marrow skeletal stem cell populations that are particularly important for rapid bone formation occurring in growth and regeneration. These stem cells are strategically located near the bone surface in a specialized microenvironment of the endosteal niche. These stem cells are abundant in young stages but eventually depleted and replaced by other stem cell types residing in a non‐endosteal perisinusoidal niche. Single‐cell molecular profiling and in vivo cell lineage analyses play (...) key roles in discovering endosteal stem cells. Importantly, endosteal stem cells can transform into bone tumor‐making cells when deleterious mutations occur in tumor suppressor genes. The emerging hypothesis is that osteoblast‐chondrocyte transitional identities confer a special subset of endosteal stromal cells with stem cell‐like properties, which may make them susceptible for tumorigenic transformation. Endosteal stem cells are likely to represent an important therapeutic target of bone diseases caused by aberrant bone formation. (shrink)

Aircraft with increasingly high performance were important to the war effort in World War II. Changes in technology allowed aircraft to reach faster speeds and to complete missions at higher altitudes. With these changes came new obstacles for pilots who had to tolerate these stresses. Of primary concern to the U.S. War Department was the loss of consciousness that often occurred with high-speed maneuvers and especially during pull-up after dive-bombing missions. In some cases, pilots would experience up to 9G of (...) force during rapid ascent, much more than the 6G threshold that typically leads to loss of consciousness. In 1941, a research team in Red Wing, MN, proposed experiments to elucidate the mechanism .. (shrink)

There are no national recommendations for routine screening for sickle cell trait, nor is there guidance on whether or how to notify donors that they might be tested or identified as having sickle cell trait. As a result, the organizations that collect blood have implemented variable policies about whether and how to inform prospective donors of the possible screening and discovery of this noncommunicable condition. The question of what they should do is related to the broader question of how (...) to handle incidental and secondary findings. In a recent report, the Presidential Commission for the Study of Bioethical Issues outline a framework for handling such findings in the clinical, research, and direct‐to‐consumer contexts. While the commission's report did not directly address incidental and secondary findings in the public health context of blood donation, it made several overarching recommendations that apply in all contexts where such findings might arise. This essay outlines the special issues raised by discovering sickle cell trait in blood donation and considers the implications of the commission's framework for that problem. (shrink)

This paper investigates continuities and changes in the definition of sickle cell disease in 1950s Brazil, taking into account that diseases have a history and are recognized as such according to the knowledge and perceptions available in a certain historical period and specific location. In the post-war era, new diagnostic tools, inheritance theories and, in particular, discussions on the concepts of race and racial relations, both nationally and internationally, were changing previous racialist and racist views. Nonetheless, the Brazilian medical interpretations (...) of sickle cell disease continued to racialize it and even use deep-rooted racist formulations to explain its symptoms or the existence of the disease. It is argued that the celebration of racial mixture and racial democracy might have concealed racist presumptions biasing the study of sickle cell disease. Although race as a biological concept gradually gave way to other genetic expressions, in Brazilian medical papers on sickle cell disease, race continued to influence the interpretation of the disease, along with the persistence of concepts of heredity through blood mixture. (shrink)

This paper investigates continuities and changes in the definition of sickle cell disease in 1950s Brazil, taking into account that diseases have a history and are recognized as such according to the knowledge and perceptions available in a certain historical period and specific location. In the post-war era, new diagnostic tools, inheritance theories and, in particular, discussions on the concepts of race and racial relations, both nationally and internationally, were changing previous racialist and racist views. Nonetheless, the Brazilian medical interpretations (...) of sickle cell disease continued to racialize it and even use deep-rooted racist formulations to explain its symptoms or the existence of the disease. It is argued that the celebration of racial mixture and racial democracy might have concealed racist presumptions biasing the study of sickle cell disease. Although race as a biological concept gradually gave way to other genetic expressions, in Brazilian medical papers on sickle cell disease, race continued to influence the interpretation of the disease, along with the persistence of concepts of heredity through blood mixture. (shrink)

Melinda Fagan’s book on the philosophy of stem cell biology is a superb discussion of this exciting field of contemporary science, and the first book-length philosophical treatment of the subject. It contains a detailed and insightful examination of stem cell science, its structure, methods, and challenges.The book does not require any previous knowledge of stem cell biology—all the relevant scientific details and concepts, the central experimental procedures and results, as well as the historical development of the field, are presented in (...) as clear and accessible a way as possible. The presentation of the science starts in Chapter 1, with a general characterisation of stem cell biology, and continues throughout the book, with every chapter deepening and complicating the initial picture. Fagan’s lucid style makes even the more technical and detailed discussions of the research on human embryonic stem cells and on blood stem cells easy to follow.After the first in .. (shrink)

Ischemic stroke involves numerous and complex pathophysiological mechanisms including blood flow reduction, ionic exchanges, spreading depressions and cell death through necrosis or apoptosis. We used a mathematical model based on these phenomena to study the influences of intensity and duration of ischemia on the final size of the infarcted area. This model relies on a set of ordinary and partial differential equations. After a sensibility study, the model was used to carry out in silico experiments in various ischemic conditions. (...) The simulation results show that the proportion of apoptotic cells increases when the intensity of ischemia decreases, which contributes to the model validation. The simulation results also show that the influence of ischemia duration on the infarct size is more complicated. They suggest that reperfusion is beneficial when performed in the early stroke but may be either inefficacious or even deleterious when performed later after the stroke onset. This aggravation could be explained by the depolarisation waves which might continue to spread ischemic damage and by the speeding up of the apoptotic process leading to cell death. The effect of reperfusion on cell death through these two phenomena needs to be further studied in order to develop new therapeutic strategies for stroke patients. (shrink)

This paper explores the perspectives of women who have agreed that their umbilical cord blood may be collected for a public ‘cord blood bank’, for use in transplant medicine or research. Drawing on interview data from 27 mothers who agreed to the collection and use of their umbilical cord blood, these choices and the informed consent process are explored. It is shown that the needs of sick children requiring transplants are prominent in narrative accounts of cord (...) class='Hi'>blood banking, together with high expectations for future applications of stem cells. Given this dynamic, a concern arises that the complex and multiple uses of tissues and related data might be oversimplified in the consent process. In conclusion, the positive finding of a commitment to mutuality in cord blood banking among these women is underlined, and its implications for the wider debate on cord blood banking are discussed. (shrink)

Umbilical cord blood has become the focus of intense efforts to collect, screen and bank haematopoietic stem cells in hundreds of repositories around the world. UCB banking has developed through a broad spectrum of overlapping banking practices, sectors and institutional forms. Superficially at least, these sectors have been widely distinguished in bioethical and policy literature between notions of the ‘public’ and the ‘private’, the commons and the market respectively. Our purpose in this paper is to reflect more critically (...) on these distinctions and to articulate the complex practical and hybrid nature of cord blood as a ‘bio-object’ that straddles binary conceptions of the blood economies. The paper draws upon Roberto Esposito’s reflections on biopolitics and his attempt to transcend the dualistic polarisations of immunity and community, or the private and the public. We suggest that his thoughts on immunitary hospitality resonate with many of the actual features and realpolitik of a necessarily internationalised and globally distributed UCB ‘immunitary regime’. (shrink)

Para responder a la pregunta: ¿Qué es la literatura?, Sartre propone el concepto de unidad como su característica exclusiva que la relaciona con la sociedad por la vía del compromiso. Se analiza tal exclusividad, así como las objeciones de Adorno a la noción de compromiso, para encontrar, en medio de sus grandes diferencias, algunas afinidades que permitan establecer las relaciones entre la literatura y la sociedad. In response to the question "What is literature?", Sartre proposes the concept of unity as (...) the exclusive characteristic that relates it to society by means of commitment. This exclusivity is analyzed, along with Adorno's objections to the notion of commitment. In the midst of great differences, some affinities are found that permit the establishment of the relationship between literature and society. (shrink)

The blood‐brain barrier (BBB) is a complex structure formed by vascular endothelial cells, which serve to stabilize the homeostasic processes that are essential for neural functioning. The barrier relies on tight junctions between neighboring endothelial cells and a highly restricted passage of blood‐borne components through the endothelial lining. Selective transport mechanisms guarantee the essential import and export of metabolites through the BBB into and out of the neural microenvironment. The dual functions of barrier and carrier depend (...) on distinct proteins, some of which have been characterized in detail. (shrink)