Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant human erythropoietin (r-HuEPO) is of interest to pediatric hematologists and neonatologists because it may prove to be an effective alternative to blood transfusions in preventing and treating anemia in premature infants. The anemia of prematurity is the most promising setting for initial clinical trials. However, it is conceivable that recombinant erythropoietin will be given at birth to low-birth-weight infants in an effort to stimulate endogenous erythropoiesis and thereby prevent some of the erythrocyte transfusions required to replace blood sampled for laboratory tests. Beyond its appeal as a therapeutic alternative to red blood cell transfusions, recombinant human erythropoietin is likely to be the first member of an entirely new class of drugs to be used widely in neonatal medicine. These are drugs produced by cloning normal human genes and expressing them in the laboratory. Because many of the problems of premature birth are caused by developmental immaturity, transiently replacing crucial proteins with exact copies produced by the techniques of recombinant DNA technology is an approach that may have a major impact on morbidity and mortality of neonates. Carefully designed, controlled clinical trials will be essential to determine the role of new agents like r-HuEPO in the treatment of medical problems of premature infants.
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PMID:Anemia of prematurity: progress and prospects. 217 57

To investigate immaturity of hematopoietic progenitor cells in umbilical cord blood mononuclear cells (CB-MNC), the formation of macroscopic colonies and mixed-cell colonies was assayed by methylcellulose culture with various combinations of cytokines (stem cell factor [SCF], interleukin [IL]-3, IL-6, granulocyte-colony stimulating factor [G-CSF], erythropoietin [EPO]) and compared with bone marrow (BM)-MNC. Moreover, distribution of the subpopulations divided by CD34, CD38, HLA-DR and CD33 was compared by flow-cytometry. Colonies derived from CB-MNC were so large that they could be observed with the naked eye and consisted of a variety of types of hematopoietic cells. Mixed-cell colonies were formed to a much greater extent in CB-MNC than in BM-MNC. Addition of EPO, IL-3, and SCF had rapid effects on the growth of mixed-cell colonies. The subpopulations of immature hematopoietic progenitor cells (CD34+, CD38-, HLA-DR-), which are supposed to be able to differentiate into hematopoietic precursors and stromal cells, were significantly higher in CB-MNC (8.7 +/- 6.6%) than in BM-MNC (0.0 +/- 0.1%; P < 0.001). These results suggest that CB is a rich source of immature hematopoietic progenitor cells compared to BM.
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PMID:Umbilical cord blood as a rich source of immature hematopoietic stem cells. 787 75

The problems of immunologic adaptation during the transitional period from intra- to extrauterine life are responsible for the physiologic immaturity of the immune function in newborn infants. In preterm neonates the immunodeficiency is more severe and prolonged and is associated with a higher incidence of infections and sepsis. Furthermore, due to immaturity of the hematologic system, anemia, thrombocytopenia, and neutropenia are frequently observed in very low birth weight infants. The dysregulation of cytokine and hematopoietic growth factor synthesis is an important contributory factor to the complex deficiency of immunologic and hematologic function in the neonate and may explain the reduced incidence of acute graft-versus-host disease observed after cord blood transplantation in children. Human milk is a rich source of most of the cytokines that are reduced in the neonate. Granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and erythropoietin are currently under evaluation in newborn infants with septic neutropenia or anemia of prematurity.
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PMID:Hematopoietic growth factor levels in term and preterm infants. 1022 41

Endoglin (CD105) is a component of the transforming growth factor-beta (TGF-beta) receptor (TGF-betaR) complex. Together with betaglycan, CD105 is considered as a TGF-betaR accessory molecule (also called TGF-betaRIII), but its functions in the receptor-ligand interactions are still poorly understood. A small subset of human CD34+ hematopoietic stem/progenitor cells that has phenotypic and functional features suggestive of very primitive hematopoietic cells expresses the CD105 antigen. CD34+/CD105+ cells recirculate in the peripheral blood of mobilized subjects and can be purified by immunomagnetic isolation strategies. The hematopoietic potential of these CD34+/CD105+ cells appears to be sustained by a combination of hematopoietic and non-hematopoietic cytokines, which comprises Flt3 ligand, erythropoietin, interleukin-15 and vascular endothelial growth factor. Endogenous TGF-beta1 is a crucial factor for the maintenance of CD34+/CD105+ immaturity acting through positive modulation of both CD105 and CD34 molecules in the absence of relevant effects on the cell cycle profile. CD105 is absent on very primitive CD34-/lineage-/CD45+ (CD34-Lin-) human hematopoietic cells isolated from cord blood. However, in vitro exposure of CD34-Lin- cells to exogenous TGF-beta1 causes the appearance of a discrete population of CD34+/CD105+ cells. Collectively, available data on CD105 expression and function in primitive hematopoiesis indicate that this molecule could cooperate with the dissociation of TGF-beta1 cell cycle effects from its other effects on cell survival and differentiation.
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PMID:CD105 (endoglin) expression on hematopoietic stem/progenitor cells. 1191

Premature infants are among the most frequently transfused groups of patients, usually receiving red cells. The immaturity of the immune system, its lesser ability to cope with a metabolic load and the presence of maternal antibodies, all complicate the picture. Conservation of blood to minimize losses and the need for replacement transfusion is an important strategy that has already been successful in reducing the need for transfusion on neonatal units. The advent of erythropoietin provides another strategy for reducing the need for transfusion. It is unfortunate that the sickest patients who require the most transfusion poorly respond to erythropoietin. Main concern is the long-term consequences of transfusion. Presently the aim is to minimize transfusion risks and give transfusions only when they are indicated.
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PMID:Blood transfusion in newborn. 1470 32

The history of retinopathy of prematurity (ROP) gives a prime example of how dangerous the uncontrolled introduction of a new medical treatment--particularly in the field of neonatology--may be. The most important risk factors for the development of ROP are the immaturity of premature infants as well as uncontrolled and/or inadequate treatment with oxygen. In comparison to the fetus, the premature infant is exposed to a nonphysiologically high oxygen concentration. This hyperoxia leads to formation of aggressive oxygen radicals on the one hand and, on the other hand, to temporarily reduced production of growth factors such as vascular endothelial growth factor and erythropoietin, which both play an important role in the pathogenesis of ROP. The most important measure to prevent ROP is restrictive and carefully monitored oxygen treatment. Medical treatment to prevent ROP includes injection of D-penicillamine and retinol, but the available data are still limited, particularly with regard to the long-term effects of this treatment. A higher oxygenation in prethreshold ROP does not lead to recovery of ocular findings, but it increases the incidence of pulmonary complications. A reduction of light intensity in neonatal intensive care units proved not to be efficient for preventing ROP. To avoid blindness, standardized screening of the risk group is needed.
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PMID:[Risk factors and prevention of retinopathy of prematurity]. 1906 7

The impermeant nature of the intestinal barrier is maintained by tight junctions (TJs) formed between adjacent intestinal epithelial cells. Disruption of TJs and loss of barrier function are associated with a number of gastrointestinal diseases, including neonatal necrotizing enterocolitis (NEC), the leading cause of death from gastrointestinal diseases in preterm infants. Human milk is protective against NEC, and the human milk factor erythropoietin (Epo) has been shown to protect endothelial cell-cell and blood-brain barriers. We hypothesized that Epo may also protect intestinal epithelial barriers, thereby lowering the incidence of NEC. Our data demonstrate that Epo protects enterocyte barrier function by supporting expression of the TJ protein ZO-1. As immaturity is a key factor in NEC, Epo regulation of ZO-1 in the human fetal immature H4 intestinal epithelial cell line was examined and demonstrated Epo-stimulated ZO-1 expression in a dose-dependent manner through the PI3K/Akt pathway. In a rat NEC model, oral administration of Epo lowered the incidence of NEC from 45 to 23% with statistical significance. In addition, Epo treatment protected intestinal barrier function and prevented loss of ZO-1 at the TJs in vivo. These effects were associated with elevated Akt phosphorylation in the intestine. This study reveals a novel role of Epo in the regulation of intestinal epithelial TJs and barrier function and suggests the possible use of enteral Epo as a therapeutic agent for gut diseases.
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PMID:Erythropoietin protects intestinal epithelial barrier function and lowers the incidence of experimental neonatal necrotizing enterocolitis. 2126 73

The stimulation of central chemoreceptors by CO2 is considered essential for breathing. The supporting evidence include the fact that central apnea in neonates correlates with immaturity of the CO2-sensing mechanism, and that congenital central hypoventilation syndrome (CCHS) is characterized by the absence of a ventilatory response to elevated PCO2. We reported previously that cerebral erythropoietin (Epo) is a potent respiratory stimulant upon normoxia and hypoxia. The injection of soluble Epo receptor (sEpoR; the natural EpoR competitor to bind Epo) via the cisterna magna (ICI: intra-cisternal injection) decreases basal ventilation in adult and newborn mice. Moreover, sEpoR induces respiratory depression in adult and newborn mice exposed to hypoxia. In this study we tested the hypothesis that endogenous brain Epo also modulates the respiratory stimulation induced by the activation of central CO2 chemoreceptors. Adult and newborn male and female mice received an injection of sEpoR or vehicle via the cisterna magna. Twenty-four hours later basal minute ventilation and the ventilatory response to hypercapnia (5% CO2) were evaluated by plethysmography. Our results did not show a difference in the hypercapnic response between sEpoR and vehicle-injected male or female mice at postnatal or adult ages. We concluded that endogenous brain Epo does not contribute to modulating the PCO2-mediated central activation of breathing.
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PMID:The central chemosensitivity is not altered by cerebral erythropoietin. 2647 8

Mechanical ventilation is a risk factor for cerebral inflammation and brain injury in preterm neonates. The risk increases proportionally with the intensity of treatment. Recent studies have shown that cerebral inflammation and injury can be initiated in the delivery room. At present, initiation of intermittent positive pressure ventilation (IPPV) in the delivery room is one of the least controlled interventions a preterm infant will likely face. Varying pressures and volumes administered shortly after birth are sufficient to trigger pathways of ventilation-induced lung and brain injury. The pathways involved in ventilation-induced brain injury include a complex inflammatory cascade and haemodynamic instability, both of which have an impact on the brain. However, regardless of the strategy employed to deliver IPPV, any ventilation has the potential to have an impact on the immature brain. This is particularly important given that preterm infants are already at a high risk for brain injury simply due to immaturity. This highlights the importance of improving the initial respiratory support in the delivery room. We review the mechanisms of ventilation-induced brain injury and discuss the need for, and the most likely, current therapeutic agents to protect the preterm brain. These include therapies already employed clinically, such as maternal glucocorticoid therapy and allopurinol, as well as other agents, such as erythropoietin, human amnion epithelial cells and melatonin, already showing promise in preclinical studies. Their mechanisms of action are discussed, highlighting their potential for use immediately after birth.
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PMID:Ventilation-Induced Brain Injury in Preterm Neonates: A Review of Potential Therapies. 2710 30

We sought to briefly describe current models of endogenous erythropoietin (EPO) pleiotropic properties to make four points clear. First, endogenous EPO regulates erythroid cell apoptosis so that red blood cell production is balanced against the number of cells destroyed in order to maintain optimal tissue oxygen levels (i.e., consistent with provision of homeostatic functional signaling information). Second, preclinical and clinical studies alike provide additional evidence of other (i.e., extraerythropoietic) immune-related and growth/trophic properties. Third, EPO might also be increased as an antiinflammatory response to other proinflammatory cytokines, and not because it is an inflammatory protein, in which case, it would make the association between EPO and these other proteins an epiphenomenon. Fourth, on the other hand, EPO might also act as a tissue protector or it could reflect immaturity/vulnerability of the brain or of the systems responsible for protecting it. Each of these scenarios is plausible, and all are probably true in certain circumstances.
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PMID:Endogenous Erythropoietin. 2862 24


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