Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0728731 (prematurity)
 7,134 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to maintain adequate circulating numbers of blood cells, the bone marrow must produce billions of cells each day and must be able to rapidly increase production by 10-20-fold in response to infection and hemorrhage. The existence of circulating factors that regulate this process has been suspected for over 100 years. Recently, the genes encoding these growth factors were cloned and their functions are now identified. Interleukin-3 (IL-3) acts on the most primitive hematopoietic stem cell, driving this self-renewing cell to produce progeny of all hematopoietic lineages. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates the granulocyte-macrophage progenitor cell, as well as cells committed to the erythroid lineage, to differentiate. G-CSF and M-CSF stimulate the most differentiated myeloid progenitors to produce granulocytes and monocytes/macrophages, respectively. Erythropoietin stimulates the differentiation of late erythroid progenitors. In the lymphoid progenitor lineage, IL-2 stimulates T cell differentiation; IL-4 and IL-6 stimulate differentiation of B cells. The colony-stimulating factors also enhance function and cause activation of the mature cells whose production they induce. In clinical trials, these hormones have successfully ameliorated anemia in renal failure, chronic disease, and in prematurity. They have improved pancytopenias in aplastic anemia, myelodysplastic syndromes, and congenital cytopenias, and they have hastened recovery from chemotherapy and bone marrow transplantation.
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PMID:Hematopoietic hormones: from cloning to clinic. 267 59

The aim of this study was to evaluate the impact of prematurity, sepsis and stress on the neutrophil respiratory burst activity (NRBA) of neonates. For this purpose 122 healthy neonates (89 term and 33 preterm), 33 preterm stressed neonates, 59 septic neonates (12 term and 47 preterm) and 26 healthy adults were studied. The NRBA was assessed after in vitro stimulation by PMA using a whole blood flow cytometric microassay with dihydrorhodamine 123 (DHR 123). It was found that the percentage of responding neutrophils in term neonates was comparable to that found in adults (medians 83.5 and 89.8%, respectively), whereas it was significantly lower in the healthy preterm neonates (median 70.6%, p < 0.05). The NRBA was further depressed in the stressed (median = 63%) and septic neonates, both term and preterm (medians 60.5 and 54.3%, respectively). No correlation with the levels of G-CSF, TNF-alpha and IL-1 beta, which were found to be higher in the stressed and septic neonates, was observed. These findings indicate that prematurity, sepsis and stress significantly depress the respiratory burst activity of neonatal neutrophils.
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PMID:Impact of prematurity, stress and sepsis on the neutrophil respiratory burst activity of neonates. 933 91

This review has two objects: a brief recapitulation of the biological background of erythropoietin (EPO), and a review of its clinical utilization in hematology. EPO, both in its naturally occurring and recombinant form (rH-EPO), is a single chain glycoprotein with an approximate molecular weight of 30.000 to 34.000 kD. Its heavy glycosilation is essential for its activity in vivo, since asialoEPO is readily cleared by the heptic asialoglycoprotein receptor. This impedes the recombinant molecule's synthesis in biologic cultures other than mammalian cells (Chinese hamster's ovary cells), and inevitably increases costs. If in vitro glycosilation of E. coli-derived rH-EPO could be achieved, the clinical utilization of the product would be considerably enhanced, most especially when very high doses are necessary, as discussed later. There is no antigenic diversity between natural and recombinant EPO, so that out of the enormous clinical experience only one single case of immunization has been recorded. Almost paradoxically there are however three published cases of pure red cell aplasia (PRCA) caused by immunization against autologous EPO. It is now established that in adults EPO is synthetized in renal peritubular interstitial cells, although some residual activity remains in the liver. Hypoxia results in a rapid induction of EPO expression, although the role of the oxygen sensor system is still debated. Cellular targets are notoriously erythroid progenitors and precursors (BFU-E, CFU-E, early and intermediate erythroblasts). The global erythropoietic activity resulted in various effects (proliferation, differentiation, survival), but most probably each single effect is integrated with and complementary of the others. The utilization of rH-EPO in hematologic diseases came much later than its dramatic success in renal anemia. A variety of tools useful for assessing the possible beneficial effects of rH-EPO in clinical hematology has been proposed, among which a low level of endogenous EPO is a good predictor for therapeutic success. 'Hemopathic' anemia can be subdivided into three categories: patients with normal erythropoiesis due to inadequate EPO production (anemia of prematurity), patients with depressed but nonclonal erythropoiesis (chemotherapy, lymphoid malignancies such as multiple myeloma-MM and chronic lymphatic leukemia-CCL) and patients with at least partially clonal anemia, such as paroxysmal nocturnal hemoglobinuria (PNH), hemoglobinopaties, myelodysplastic syndromes (MDS) and others. Results in the first category of patients are, as expected, prompt and satisfactory with physiologic doses. Although therapeutic strategy for MM is moving fast to curative intents, the utilization of rH-EPO is indicated for the control of anemia in conservatively-treated patients. In the third category the most important and controversial area is MDS. Significant erythropoietic results are generally obtained in about 20% of patients; however, the association with G-CSF has considerably enhanced the response rate. In the field of bone marrow transplantation there is an inadequate production of endogenous EPO in the allogeneic setting, and randomized studies have shown the benefits of rH-EPO in this situation. However, the most important results have been obtained in post-major-ABO incompatible PRCA, when the removal of the recipient's isohemagglutinins does not resolve the anemia. High and very high doses of rH-EPO (even over 500 UI/kg/day for 2-4 weeks) may resolve this occasionally quite refractory condition. Although extremely expensive, this treatment may be life-saving when an otherwise successful allogeneic transplant is at the risk of failure because of this relatively uncommon but severe immunohematologic complication.
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PMID:[Erythropoietin: biochemical characteristics, biologic effects, indications and results of use in hematology]. 948 78

To establish levels of mediators of inflammation in cord blood and postnatal serum from extremely low gestational age newborns (ELGANs, < or =28 weeks), we measured sixteen markers of inflammation by recycling immunoaffinity chromatography in 15 ELGANs who had serum sampled at days 2-5. Median levels of IL-1, IL-6, IL-8, IL-11, IL-13, TNF-alpha, G-CSF, M-CSF, GM-CSF, MIP-1alpha, and RANTES were considerably higher than published values of these inflammatory mediators from term newborns. In three of eight ELGANS who had serial measurements taken, levels of IL-1, IL-6, IL-8, IL-11, TNF-alpha, G-CSF, and MIP-1alpha declined from initially very high levels to reach an apparent baseline towards the end of the first postnatal week. In these same three infants, GM-CSF and TGF-beta1 levels increased continuously during the first week. In the other five ELGANs, no consistent changes were observed. We speculate, that in some ELGANs, a fetal systemic inflammatory response is characterized by an antenatal wave of pro-inflammatory cytokines, followed by a second, postnatal wave of anti-inflammatory cytokines. Large epidemiologic studies are needed to clarify relationships among inflammation markers and their expression in the fetal and neonatal circulation over time. Such studies would also add to our understanding of the possible role of inflammatory mediators in the pathophysiology of the major complications of extreme prematurity.
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PMID:Mediators of fetal inflammation in extremely low gestational age newborns. 1123 31