Glycoprotein hormone, secreted chiefly by the KIDNEY in the adult and the LIVER in the FETUS, that acts on erythroid stem cells of the BONE MARROW to stimulate proliferation and differentiation.
Cell surface proteins that bind erythropoietin with high affinity and trigger intracellular changes influencing the behavior of cells.
The production of red blood cells (ERYTHROCYTES). In humans, erythrocytes are produced by the YOLK SAC in the first trimester; by the liver in the second trimester; by the BONE MARROW in the third trimester and after birth. In normal individuals, the erythrocyte count in the peripheral blood remains relatively constant implying a balance between the rate of erythrocyte production and rate of destruction.
A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.
An increase in the total red cell mass of the blood. (Dorland, 27th ed)
Proteins prepared by recombinant DNA technology.
The cells in the erythroid series derived from MYELOID PROGENITOR CELLS or from the bi-potential MEGAKARYOCYTE-ERYTHROID PROGENITOR CELLS which eventually give rise to mature RED BLOOD CELLS. The erythroid progenitor cells develop in two phases: erythroid burst-forming units (BFU-E) followed by erythroid colony-forming units (CFU-E); BFU-E differentiate into CFU-E on stimulation by ERYTHROPOIETIN, and then further differentiate into ERYTHROBLASTS when stimulated by other factors.
The volume of packed RED BLOOD CELLS in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, ANEMIA shows a low value; POLYCYTHEMIA, a high value.
The oxygen-carrying proteins of ERYTHROCYTES. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements.
Immature, nucleated ERYTHROCYTES occupying the stage of ERYTHROPOIESIS that follows formation of ERYTHROID PRECURSOR CELLS and precedes formation of RETICULOCYTES. The normal series is called normoblasts. Cells called MEGALOBLASTS are a pathologic series of erythroblasts.
The number of RETICULOCYTES per unit volume of BLOOD. The values are expressed as a percentage of the ERYTHROCYTE COUNT or in the form of an index ("corrected reticulocyte index"), which attempts to account for the number of circulating erythrocytes.
Agents which improve the quality of the blood, increasing the hemoglobin level and the number of erythrocytes. They are used in the treatment of anemias.
The number of RED BLOOD CELLS per unit volume in a sample of venous BLOOD.
A myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood.
A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.
Strains of MURINE LEUKEMIA VIRUS that are replication-defective and rapidly transforming. The envelope gene plays an essential role in initiating erythroleukemia (LEUKEMIA, ERYTHROBLASTIC, ACUTE), manifested by splenic foci, SPLENOMEGALY, and POLYCYTHEMIA. Spleen focus-forming viruses are generated by recombination with endogenous retroviral sequences.
The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.
The mildest form of erythroblastosis fetalis in which anemia is the chief manifestation.
A multilineage cell growth factor secreted by LYMPHOCYTES; EPITHELIAL CELLS; and ASTROCYTES which stimulates clonal proliferation and differentiation of various types of blood and tissue cells.
Therapy for the insufficient cleansing of the BLOOD by the kidneys based on dialysis and including hemodialysis, PERITONEAL DIALYSIS, and HEMODIAFILTRATION.
Progenitor cells from which all blood cells derive.
A cytologic technique for measuring the functional capacity of stem cells by assaying their activity.
A signal transducer and activator of transcription that mediates cellular responses to a variety of CYTOKINES. Stat5 activation is associated with transcription of CELL CYCLE regulators such as CYCLIN KINASE INHIBITOR P21 and anti-apoptotic genes such as BCL-2 GENES. Stat5 is constitutively activated in many patients with acute MYELOID LEUKEMIA.
Relatively complete absence of oxygen in one or more tissues.
Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin.
A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN.
A myeloproliferative disorder of unknown etiology, characterized by abnormal proliferation of all hematopoietic bone marrow elements and an absolute increase in red cell mass and total blood volume, associated frequently with splenomegaly, leukocytosis, and thrombocythemia. Hematopoiesis is also reactive in extramedullary sites (liver and spleen). In time myelofibrosis occurs.
The introduction of whole blood or blood component directly into the blood stream. (Dorland, 27th ed)
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
Illegitimate use of substances for a desired effect in competitive sports. It includes humans and animals.
The major protein constituents of milk are CASEINS and whey proteins such as LACTALBUMIN and LACTOGLOBULINS. IMMUNOGLOBULINS occur in high concentrations in COLOSTRUM and in relatively lower concentrations in milk. (Singleton and Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed, p554)
A basic helix-loop-helix transcription factor that plays a role in APOPTOSIS. It is composed of two subunits: ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR and HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Established cell cultures that have the potential to propagate indefinitely.
Diazo derivatives of aniline, used as a reagent for sugars, ketones, and aldehydes. (Dorland, 28th ed)
The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) producing leukemia of the reticulum-cell type with massive infiltration of liver, spleen, and bone marrow. It infects DBA/2 and Swiss mice.
Immature ERYTHROCYTES. In humans, these are ERYTHROID CELLS that have just undergone extrusion of their CELL NUCLEUS. They still contain some organelles that gradually decrease in number as the cells mature. RIBOSOMES are last to disappear. Certain staining techniques cause components of the ribosomes to precipitate into characteristic "reticulum" (not the same as the ENDOPLASMIC RETICULUM), hence the name reticulocytes.
A hematopoietic growth factor and the ligand of the cell surface c-kit protein (PROTO-ONCOGENE PROTEINS C-KIT). It is expressed during embryogenesis and is a growth factor for a number of cell types including the MAST CELLS and the MELANOCYTES in addition to the HEMATOPOIETIC STEM CELLS.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
The development and formation of various types of BLOOD CELLS. Hematopoiesis can take place in the BONE MARROW (medullary) or outside the bone marrow (HEMATOPOIESIS, EXTRAMEDULLARY).
The techniques used to draw blood from a vein for diagnostic purposes or for treatment of certain blood disorders such as erythrocytosis, hemochromatosis, polycythemia vera, and porphyria cutanea tarda.
Volume of circulating ERYTHROCYTES . It is usually measured by RADIOISOTOPE DILUTION TECHNIQUE.
Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Anemia characterized by a decrease in the ratio of the weight of hemoglobin to the volume of the erythrocyte, i.e., the mean corpuscular hemoglobin concentration is less than normal. The individual cells contain less hemoglobin than they could have under optimal conditions. Hypochromic anemia may be caused by iron deficiency from a low iron intake, diminished iron absorption, or excessive iron loss. It can also be caused by infections or other diseases, therapeutic drugs, lead poisoning, and other conditions. (Stedman, 25th ed; from Miale, Laboratory Medicine: Hematology, 6th ed, p393)
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The series of cells in the red blood cell lineage at various stages of differentiation.
A condition of decreased oxygen content at the cellular level.
Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.
Iron-containing proteins that are widely distributed in animals, plants, and microorganisms. Their major function is to store IRON in a nontoxic bioavailable form. Each ferritin molecule consists of ferric iron in a hollow protein shell (APOFERRITINS) made of 24 subunits of various sequences depending on the species and tissue types.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Puncture of a vein to draw blood for therapeutic purposes. Bloodletting therapy has been used in Talmudic and Indian medicine since the medieval time, and was still practiced widely in the 18th and 19th centuries. Its modern counterpart is PHLEBOTOMY.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Elements of limited time intervals, contributing to particular results or situations.
A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis.
A GATA transcription factor that is specifically expressed in hematopoietic lineages and plays an important role in the CELL DIFFERENTIATION of ERYTHROID CELLS and MEGAKARYOCYTES.
The transfer of erythrocytes from a donor to a recipient or reinfusion to the donor.
Dioxygenase enzymes that specifically hydroxylate a PROLINE residue on the HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT. They are OXYGEN-dependent enzymes that play an important role in mediating cellular adaptive responses to HYPOXIA.
Unstable isotopes of iron that decay or disintegrate emitting radiation. Fe atoms with atomic weights 52, 53, 55, and 59-61 are radioactive iron isotopes.
These growth factors comprise a family of hematopoietic regulators with biological specificities defined by their ability to support proliferation and differentiation of blood cells of different lineages. ERYTHROPOIETIN and the COLONY-STIMULATING FACTORS belong to this family. Some of these factors have been studied and used in the treatment of chemotherapy-induced neutropenia, myelodysplastic syndromes, and bone marrow failure syndromes.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Membrane glycoproteins found in high concentrations on iron-utilizing cells. They specifically bind iron-bearing transferrin, are endocytosed with its ligand and then returned to the cell surface where transferrin without its iron is released.

Oligomerization and scaffolding functions of the erythropoietin receptor cytoplasmic tail. (1/819)

Signal transduction by the erythropoietin receptor (EPOR) is activated by ligand-mediated receptor homodimerization. However, the relationship between extracellular and intracellular domain oligomerization remains poorly understood. To assess the requirements for dimerization of receptor cytoplasmic sequences for signaling, we overexpressed mutant EPORs in combination with wild-type (WT) EPOR to drive formation of heterodimeric (i.e. WT-mutant) receptor complexes. Dimerization of the membrane-proximal portion of the EPOR cytoplasmic region was found to be critical for the initiation of mitogenic signaling. However, dimerization of the entire EPOR cytoplasmic region was not required. To examine this process more closely, we generated chimeras between the intracellular and transmembrane portions of the EPOR and the extracellular domains of the interleukin-2 receptor beta and gammac chains. These chimeras allowed us to assess more precisely the signaling role of each receptor chain because only heterodimers of WT and mutant receptor chimeras form in the presence of interleukin-2. Coexpression studies demonstrated that a functional receptor complex requires the membrane-proximal region of each receptor subunit in the oligomer to permit activation of JAK2 but only one membrane-distal tail to activate STAT5 and to support cell proliferation. Thus, this study defines key relationships involved in the assembly and activation of the EPOR signal transduction complex which may be applicable to other homodimeric cytokine receptors.  (+info)

Human, rat, and mouse kidney cells express functional erythropoietin receptors. (2/819)

BACKGROUND: Erythropoietin (EPO), secreted by fibroblast-like cells in the renal interstitium, controls erythropoiesis by regulating the survival, proliferation, and differentiation of erythroid progenitor cells. We examined whether renal cells that are exposed to EPO express EPO receptors (EPO-R) through which analogous cytokine responses might be elicited. METHODS: Normal human and rat kidney tissue and defined cell lines of human, rat, and mouse kidney were screened, using reverse transcription-polymerase chain reaction, nucleotide sequencing, ligand binding, and Western blotting, for the expression of EPO-R. EPO's effects on DNA synthesis and cell proliferation were also examined. RESULTS: EPO-R transcripts were readily detected in cortex, medulla, and papilla of human and rat kidney, in mesangial (human, rat), proximal tubular (human, mouse), and medullary collecting duct cells (human). Nucleotide sequences of EPO-R cDNAs from renal cells were identical to those of erythroid precursor cells. Specific 125I-EPO binding revealed a single class of high- to intermediate-affinity EPO-Rs in each tested cell line (kD 96 pm to 1. 4 nm; Bmax 0.3 to 7.0 fmol/mg protein). Western blots of murine proximal tubular cell membranes revealed an EPO-R protein of approximately 68 kDa. EPO stimulated DNA synthesis and cell proliferation dose dependently. CONCLUSION: This is the first direct demonstration, to our knowledge, that renal cells possess EPO-Rs through which EPO stimulates mitogenesis. This suggests currently unrecognized cytokine functions for EPO in the kidney, which may prove beneficial in the repair of an injured kidney while being potentially detrimental in renal malignancies.  (+info)

Role of cytokine signaling molecules in erythroid differentiation of mouse fetal liver hematopoietic cells: functional analysis of signaling molecules by retrovirus-mediated expression. (3/819)

Erythropoietin (EPO) and its cell surface receptor (EPOR) play a central role in proliferation, differentiation, and survival of erythroid progenitors. Signals induced by EPO have been studied extensively by using erythroid as well as nonerythroid cell lines, and various controversial results have been reported as to the role of signaling molecules in erythroid differentiation. Here we describe a novel approach to analyze the EPO signaling by using primary mouse fetal liver hematopoietic cells to avoid possible artifacts due to established cell lines. Our strategy is based on high-titer retrovirus vectors with a bicistronic expression system consisting of an internal ribosome entry site (IRES) and green fluorescent protein (GFP). By placing the cDNA for a signaling molecule in front of IRES-GFP, virus-infected cells can be viably sorted by fluorescence-activated cell sorter, and the effect of expression of the signaling molecule can be assessed. By using this system, expression of cell-survival genes such as Bcl-2 and Bcl-XL was found to enhance erythroid colony formation from colony-forming unit-erythroid (CFU-E) in response to EPO. However, their expression was not sufficient for erythroid colony formation from CFU-E alone, indicating that EPO induces signals for erythroid differentiation. To examine the role of EPOR tyrosine residues in erythroid differentiation, we introduced a chimeric EGFR-EPOR receptor, which has the extracellular domain of the EGF receptor and the intracellular domain of the EPOR, as well as a mutant EGFR-EPOR in which all the cytoplasmic tyrosine residues are replaced with phenylalanine, and found that tyrosine residues of EPOR are essential for erythroid colony formation from CFU-E. We further analyzed the function of the downstream signaling molecules by expressing modified signaling molecules and found that both JAK2/STAT5 and Ras, two major signaling pathways activated by EPOR, are involved in full erythroid differentiation.  (+info)

Localization and characterization of curved DNA in the human erythropoietin receptor gene by experimental and theoretical approaches. (4/819)

We report here the locations of curved DNA in the human erythropoietin receptor gene. A total of 13 DNA bend sites were mapped by circular permutation assays, appearing at an average interval of 651.2+/-214.6 (S.D.) in the 8-kb region. The bend centers in these 13 bend sites were confirmed by oligonucleotide-based assays where most of these centers had bend angles higher than that shown by (AAACCGGGCC) x (A)20 and lower than that shown by (AAACCGGGCC)2 x (A)10. DNA curvature mapping by TRIF software, which is based on the distribution of dinucleotides, primarily AA and TT, provided a highly accurate prediction for the locations of the bend sites. They showed approximately 20 degrees to 40 degrees of bend angles demonstrated by the oligonucleotide assays and by computer analysis.  (+info)

Expression of the erythropoietin receptor by trophoblast cellsin the human placenta. (5/819)

Nonclassical sites of erythropoietin (EPO) and erythropoietin receptor (EPO-R) expression have been described that suggest new physiological roles for this hormone unrelated to erythropoiesis. The recent finding of EPO expression by trophoblast cells in the human placenta prompted us to consider whether these cells also express EPO-R. With use of immunocytochemistry, EPO-R was identified in villous and extravillous cytotrophoblast cells, as well as in the syncytiotrophoblast at all gestational ages. EPO-R was also expressed by cells within the villous core, including endothelial cells of fetoplacental blood vessels. Placental tissues and isolated and immunopurified trophoblast cells, as well as trophoblast-derived choriocarcinoma Jar cells, expressed immunoreactive EPO-R on Western blot. EPO-R mRNA was also detected in the same placental tissues and trophoblast cells by nested-primer reverse transcription-polymerase chain reaction. Finally, EPO-R was functional insofar as the receptor was phosphorylated on tyrosine residues in response to exogenous EPO treatment of cultured trophoblast or Jar cells. Thus, the present findings support the hypothesis that trophoblast cells of the human placenta express EPO-R. In view of these results, taken together with previous work demonstrating EPO expression by the same cells, an autocrine role for this hormone in the survival, proliferation, or differentiation of placental trophoblast cells is proposed.  (+info)

FLI-1 inhibits differentiation and induces proliferation of primary erythroblasts. (6/819)

Friend virus-induced erythroleukemia involves two members of the ETS family of transcriptional regulators, both activated via proviral insertion in the corresponding loci. Spi-1/PU.1 is expressed in the disease induced by the original Friend virus SFFV(F-MuLV) complex in adult mice. In contrast, FLI-1 is overexpressed in about 75% of the erythroleukemias induced by the F-MuLV helper virus in newborn mice. To analyse the consequences of the enforced expression of FLI-1 on erythroblast differentiation and proliferation and to compare its activity to that of PU.1/Spi-1, we used a heterologous system of avian primary erythroblasts previously described to study the cooperation between Spi-1/PU.1 and the other molecular alterations observed in SFFV-induced disease. FLI-1 was found: (i) to inhibit the apoptotic cell death program normally activated in erythroblasts following Epo deprivation; (ii) to inhibit the terminal differentiation program induced in these cells in response to Epo and; (iii) to induce their proliferation. However, in contrast to Spi-1/PU.1, the effects of FLI-1 on erythroblast, differentiation and proliferation did not require its cooperation with an abnormally activated form of the EpoR. Enhanced survival of FLI-1 expressing erythroblasts correlated with the upregulation of bcl2 expression. FLI-1 also prevented the rapid downregulation of cyclin D2 and D3 expression normally observed during Epo-induced differentiation and delayed the downregulation of several other genes involved in cell cycle or cell proliferation control. Our results show that overexpression of FLI-1 profoundly deregulates the normal balance between differentiation and proliferation in primary erythroblasts. Thus, the activation of FLI-1 expression observed at the onset of F-MuLV-induced erythroleukemia may provide a proliferative advantage to virus infected cells that would otherwise undergo terminal differentiation or cell death.  (+info)

Human recombinant erythropoietin inhibits interleukin-1beta-stimulated nitric oxide and cyclic guanosine monophosphate production in cultured rat vascular smooth-muscle cells. (7/819)

BACKGROUND: Recently rat vascular smooth-muscle cells (VSMC) have been shown to possess Epo receptor, and respond to various cytokines for producing nitric oxide (NO). In the present study we examined the effect of pharmacological dose of human recombinant erythropoietin (rHuEpo) on the IL-1beta-induced NO and cGMP production as well as inducible nitric oxide synthase (iNOS) in cultured rat VSMC. METHODS: Nitrite, a stable metabolite of NO, and intracellular cGMP contents were assayed by Griess method and enzyme immunoassay. iNOS mRNA expression was analysed by Northern blotting. RESULTS: RHuEpo inhibited IL-1beta-induced nitrite production in a dose- and time-dependent manner with concomitant changes of intracellular cGMP contents. On the other hand, rHuEpo did not inhibit atrial natriuretic peptide- (ANP) or sodium nitroprusside (SNP)-induced nitrite and cGMP production at all. While rHuEpo inhibited IL-1beta-induced iNOS mRNA expression, rHuEpo vehicle did not affect IL-1beta-induced iNOS mRNA expression. CONCLUSIONS: It is suggested that a pharmacological dose of rHuEpo inhibits IL-1beta-induced NO and cGMP production as well as iNOS mRNA expression, presumably via the Epo receptor.  (+info)

HGF activates signal transduction from EPO receptor on human cord blood CD34+/CD45+ cells. (8/819)

Hepatocyte growth factor (HGF) is a multifunctional cytokine with early hematopoiesis-stimulatory activity. Here, we focus on its erythropoiesis-stimulatory effect on highly purified human hematopoietic progenitor cells (CD34+/CD45+ cells) derived from the cord blood. In immunoblot analyses, c-met protein (a receptor of HGF) was detected in the CD34+/CD45+ cells, although the expression levels were different among samples. The c-met expression was facilitated by incubation of the cells with stem cell factor (SCF) or interleukin 3 (IL-3), even if the expression level had been low. IL-6, G-CSF, or erythropoietin (EPO) did not show such a stimulatory effect on the c-met expression of the cells. When HGF was added to the CD34+/CD45+ cells in the presence of SCF, the numbers of CD36+/CD11b- cells (very early erythroid lineage cells) and BFU-E increased. EPO-dependent tyrosine phosphorylation of Stat 5 also increased, but the EPO receptor (EPO-R) expression remained unchanged in the CD34+/CD45+ cells treated with SCF + HGF. Our present study suggests that stimulation of the HGF/c-met signal is concomitant with induction of c-met protein by SCF. The subsequent enhancement of signal transduction via the activation of Stat 5 from the EPO-R plays a crucial role in the commitment of hematopoietic stem cells into erythroid lineage cells.  (+info)

Erythropoietin (EPO) is a hormone that is primarily produced by the kidneys and plays a crucial role in the production of red blood cells in the body. It works by stimulating the bone marrow to produce more red blood cells, which are essential for carrying oxygen to various tissues and organs.

EPO is a glycoprotein that is released into the bloodstream in response to low oxygen levels in the body. When the kidneys detect low oxygen levels, they release EPO, which then travels to the bone marrow and binds to specific receptors on immature red blood cells called erythroblasts. This binding triggers a series of events that promote the maturation and proliferation of erythroblasts, leading to an increase in the production of red blood cells.

In addition to its role in regulating red blood cell production, EPO has also been shown to have neuroprotective effects and may play a role in modulating the immune system. Abnormal levels of EPO have been associated with various medical conditions, including anemia, kidney disease, and certain types of cancer.

EPO is also used as a therapeutic agent for the treatment of anemia caused by chronic kidney disease, chemotherapy, or other conditions that affect red blood cell production. Recombinant human EPO (rhEPO) is a synthetic form of the hormone that is produced using genetic engineering techniques and is commonly used in clinical practice to treat anemia. However, misuse of rhEPO for performance enhancement in sports has been a subject of concern due to its potential to enhance oxygen-carrying capacity and improve endurance.

Erythropoietin receptors are cell surface proteins found on immature red blood cell precursors in the bone marrow. They bind to the hormone erythropoietin (EPO), which is produced by the kidneys in response to low oxygen levels in the blood. When EPO binds to its receptor, it activates a signaling pathway that promotes the survival, proliferation, and differentiation of red blood cell precursors, leading to increased production of red blood cells. This process is critical for maintaining adequate oxygen delivery to tissues in the body. Mutations in the erythropoietin receptor gene can lead to various blood disorders, including anemia and polycythemia.

Erythropoiesis is the process of forming and developing red blood cells (erythrocytes) in the body. It occurs in the bone marrow and is regulated by the hormone erythropoietin (EPO), which is produced by the kidneys. Erythropoiesis involves the differentiation and maturation of immature red blood cell precursors called erythroblasts into mature red blood cells, which are responsible for carrying oxygen to the body's tissues. Disorders that affect erythropoiesis can lead to anemia or other blood-related conditions.

Anemia is a medical condition characterized by a lower than normal number of red blood cells or lower than normal levels of hemoglobin in the blood. Hemoglobin is an important protein in red blood cells that carries oxygen from the lungs to the rest of the body. Anemia can cause fatigue, weakness, shortness of breath, and a pale complexion because the body's tissues are not getting enough oxygen.

Anemia can be caused by various factors, including nutritional deficiencies (such as iron, vitamin B12, or folate deficiency), blood loss, chronic diseases (such as kidney disease or rheumatoid arthritis), inherited genetic disorders (such as sickle cell anemia or thalassemia), and certain medications.

There are different types of anemia, classified based on the underlying cause, size and shape of red blood cells, and the level of hemoglobin in the blood. Treatment for anemia depends on the underlying cause and may include dietary changes, supplements, medication, or blood transfusions.

Polycythemia is a medical condition characterized by an abnormal increase in the total red blood cell (RBC) mass or hematocrit (the percentage of RBCs in the blood). This results in a higher-than-normal viscosity of the blood, which can lead to various complications such as impaired circulation, increased risk of blood clots, and reduced oxygen supply to the tissues.

There are two main types of polycythemia: primary and secondary. Primary polycythemia, also known as polycythemia vera, is a rare myeloproliferative neoplasm caused by genetic mutations that lead to excessive production of RBCs in the bone marrow. Secondary polycythemia, on the other hand, is a reactive condition triggered by various factors such as chronic hypoxia (low oxygen levels), high altitude, smoking, or certain medical conditions like sleep apnea, heart disease, or kidney tumors.

Symptoms of polycythemia may include fatigue, headaches, dizziness, shortness of breath, itching, and a bluish or reddish tint to the skin (cyanosis). Treatment depends on the underlying cause and severity of the condition and may involve phlebotomy, medications to reduce RBC production, and management of associated complications.

Recombinant proteins are artificially created proteins produced through the use of recombinant DNA technology. This process involves combining DNA molecules from different sources to create a new set of genes that encode for a specific protein. The resulting recombinant protein can then be expressed, purified, and used for various applications in research, medicine, and industry.

Recombinant proteins are widely used in biomedical research to study protein function, structure, and interactions. They are also used in the development of diagnostic tests, vaccines, and therapeutic drugs. For example, recombinant insulin is a common treatment for diabetes, while recombinant human growth hormone is used to treat growth disorders.

The production of recombinant proteins typically involves the use of host cells, such as bacteria, yeast, or mammalian cells, which are engineered to express the desired protein. The host cells are transformed with a plasmid vector containing the gene of interest, along with regulatory elements that control its expression. Once the host cells are cultured and the protein is expressed, it can be purified using various chromatography techniques.

Overall, recombinant proteins have revolutionized many areas of biology and medicine, enabling researchers to study and manipulate proteins in ways that were previously impossible.

Erythroid precursor cells, also known as erythroblasts or normoblasts, are early stage cells in the process of producing mature red blood cells (erythrocytes) in the bone marrow. These cells are derived from hematopoietic stem cells and undergo a series of maturation stages, including proerythroblast, basophilic erythroblast, polychromatophilic erythroblast, and orthochromatic erythroblast, before becoming reticulocytes and then mature red blood cells. During this maturation process, the cells lose their nuclei and become enucleated, taking on the biconcave shape and flexible membrane that allows them to move through small blood vessels and deliver oxygen to tissues throughout the body.

Hematocrit is a medical term that refers to the percentage of total blood volume that is made up of red blood cells. It is typically measured as part of a complete blood count (CBC) test. A high hematocrit may indicate conditions such as dehydration, polycythemia, or living at high altitudes, while a low hematocrit may be a sign of anemia, bleeding, or overhydration. It is important to note that hematocrit values can vary depending on factors such as age, gender, and pregnancy status.

Hemoglobin (Hb or Hgb) is the main oxygen-carrying protein in the red blood cells, which are responsible for delivering oxygen throughout the body. It is a complex molecule made up of four globin proteins and four heme groups. Each heme group contains an iron atom that binds to one molecule of oxygen. Hemoglobin plays a crucial role in the transport of oxygen from the lungs to the body's tissues, and also helps to carry carbon dioxide back to the lungs for exhalation.

There are several types of hemoglobin present in the human body, including:

* Hemoglobin A (HbA): This is the most common type of hemoglobin, making up about 95-98% of total hemoglobin in adults. It consists of two alpha and two beta globin chains.
* Hemoglobin A2 (HbA2): This makes up about 1.5-3.5% of total hemoglobin in adults. It consists of two alpha and two delta globin chains.
* Hemoglobin F (HbF): This is the main type of hemoglobin present in fetal life, but it persists at low levels in adults. It consists of two alpha and two gamma globin chains.
* Hemoglobin S (HbS): This is an abnormal form of hemoglobin that can cause sickle cell disease when it occurs in the homozygous state (i.e., both copies of the gene are affected). It results from a single amino acid substitution in the beta globin chain.
* Hemoglobin C (HbC): This is another abnormal form of hemoglobin that can cause mild to moderate hemolytic anemia when it occurs in the homozygous state. It results from a different single amino acid substitution in the beta globin chain than HbS.

Abnormal forms of hemoglobin, such as HbS and HbC, can lead to various clinical disorders, including sickle cell disease, thalassemia, and other hemoglobinopathies.

Erythroblasts are immature red blood cells that are produced in the bone marrow. They are also known as normoblasts and are a stage in the development of red blood cells, or erythrocytes. Erythroblasts are larger than mature red blood cells and have a nucleus, which is lost during the maturation process. These cells are responsible for producing hemoglobin, the protein that carries oxygen in the blood. Abnormal increases or decreases in the number of erythroblasts can be indicative of certain medical conditions, such as anemia or leukemia.

A reticulocyte count is a laboratory test that measures the percentage of reticulocytes in the peripheral blood. Reticulocytes are immature red blood cells produced in the bone marrow and released into the bloodstream. They contain residual ribosomal RNA, which gives them a reticular or net-like appearance under a microscope when stained with certain dyes.

The reticulocyte count is often used as an indicator of the rate of red blood cell production in the bone marrow. A higher than normal reticulocyte count may indicate an increased production of red blood cells, which can be seen in conditions such as hemolysis, blood loss, or response to treatment of anemia. A lower than normal reticulocyte count may suggest a decreased production of red blood cells, which can be seen in conditions such as bone marrow suppression, aplastic anemia, or vitamin deficiencies.

The reticulocyte count is usually expressed as a percentage of the total number of red blood cells, but it can also be reported as an absolute reticulocyte count (the actual number of reticulocytes per microliter of blood). The normal range for the reticulocyte count varies depending on the laboratory and the population studied.

Hematinics are a class of medications and dietary supplements that are used to enhance the production of red blood cells or hemoglobin in the body. They typically contain iron, vitamin B12, folic acid, or other nutrients that are essential for the synthesis of hemoglobin and the formation of red blood cells.

Iron is a critical component of hematinics because it plays a central role in the production of hemoglobin, which is the protein in red blood cells that carries oxygen throughout the body. Vitamin B12 and folic acid are also important nutrients for red blood cell production, as they help to regulate the growth and division of red blood cells in the bone marrow.

Hematinics are often prescribed to treat anemia, which is a condition characterized by a low red blood cell count or abnormally low levels of hemoglobin in the blood. Anemia can be caused by a variety of factors, including nutritional deficiencies, chronic diseases, and inherited genetic disorders.

Examples of hematinics include ferrous sulfate (an iron supplement), cyanocobalamin (vitamin B12), and folic acid. These medications are available in various forms, such as tablets, capsules, and liquids, and can be taken orally or by injection. It is important to follow the dosage instructions carefully and to inform your healthcare provider of any other medications you are taking, as hematinics can interact with certain drugs and may cause side effects.

Erythrocyte count, also known as red blood cell (RBC) count, is a laboratory test that measures the number of red blood cells in a sample of blood. Red blood cells are important because they carry oxygen from the lungs to the rest of the body. A low erythrocyte count may indicate anemia, while a high count may be a sign of certain medical conditions such as polycythemia. The normal range for erythrocyte count varies depending on a person's age, sex, and other factors.

Erythroblastic Leukemia, Acute (also known as Acute Erythroid Leukemia or AEL) is a subtype of acute myeloid leukemia (AML), which is a type of cancer affecting the blood and bone marrow. In this condition, there is an overproduction of erythroblasts (immature red blood cells) in the bone marrow, leading to their accumulation and interference with normal blood cell production. This results in a decrease in the number of functional red blood cells, white blood cells, and platelets in the body. Symptoms may include fatigue, weakness, frequent infections, and easy bruising or bleeding. AEL is typically treated with chemotherapy and sometimes requires stem cell transplantation.

Janus Kinase 2 (JAK2) is a tyrosine kinase enzyme that plays a crucial role in intracellular signal transduction. It is named after the Roman god Janus, who is depicted with two faces, as JAK2 has two similar phosphate-transferring domains. JAK2 is involved in various cytokine receptor-mediated signaling pathways and contributes to hematopoiesis, immune function, and cell growth.

Mutations in the JAK2 gene have been associated with several myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. The most common mutation is JAK2 V617F, which results in a constitutively active enzyme that promotes uncontrolled cell proliferation and survival, contributing to the development of these MPNs.

"Spleen Focus-Forming Virus" (SFFV) is not a widely used medical term, but it is a term from the field of virology. SFFV is a type of retrovirus that primarily infects mice and causes erythroleukemia, a cancer of the blood-forming organs. The virus is called "Spleen Focus-Forming" because when it infects mice, it initially replicates in the spleen and forms distinct foci or clusters of infected cells.

The virus contains an oncogene called v-abl, which is a cancer-causing gene that contributes to the development of leukemia in infected animals. SFFV is closely related to another retrovirus called Friend Virus (FV), and together they are referred to as the FV complex. These viruses have been extensively studied as models for retroviral-induced leukemogenesis and have provided valuable insights into the mechanisms of cancer development.

Chronic kidney failure, also known as chronic kidney disease (CKD) stage 5 or end-stage renal disease (ESRD), is a permanent loss of kidney function that occurs gradually over a period of months to years. It is defined as a glomerular filtration rate (GFR) of less than 15 ml/min, which means the kidneys are filtering waste and excess fluids at less than 15% of their normal capacity.

CKD can be caused by various underlying conditions such as diabetes, hypertension, glomerulonephritis, polycystic kidney disease, and recurrent kidney infections. Over time, the damage to the kidneys can lead to a buildup of waste products and fluids in the body, which can cause a range of symptoms including fatigue, weakness, shortness of breath, nausea, vomiting, and confusion.

Treatment for chronic kidney failure typically involves managing the underlying condition, making lifestyle changes such as following a healthy diet, and receiving supportive care such as dialysis or a kidney transplant to replace lost kidney function.

Neonatal anemia is a condition characterized by a lower-than-normal number of red blood cells or lower-than-normal levels of hemoglobin in the blood of a newborn infant. Hemoglobin is the protein in red blood cells that carries oxygen to the body's tissues.

There are several types and causes of neonatal anemia, including:

1. Anemia of prematurity: This is the most common type of anemia in newborns, especially those born before 34 weeks of gestation. It occurs due to a decrease in red blood cell production and a shorter lifespan of red blood cells in premature infants.
2. Hemolytic anemia: This type of anemia is caused by the destruction of red blood cells at a faster rate than they can be produced. It can result from various factors, such as incompatibility between the mother's and baby's blood types, genetic disorders like G6PD deficiency, or infections.
3. Fetomaternal hemorrhage: This condition occurs when there is a significant transfer of fetal blood into the maternal circulation during pregnancy or childbirth, leading to anemia in the newborn.
4. Iron-deficiency anemia: Although rare in newborns, iron-deficiency anemia can occur if the mother has low iron levels during pregnancy, and the infant does not receive adequate iron supplementation after birth.
5. Anemia due to nutritional deficiencies: Rarely, neonatal anemia may result from a lack of essential vitamins or minerals like folate, vitamin B12, or copper in the newborn's diet.

Symptoms of neonatal anemia can vary but may include pallor, lethargy, poor feeding, rapid heartbeat, and difficulty breathing. Diagnosis typically involves a complete blood count (CBC) to measure red blood cell count, hemoglobin levels, and other parameters. Treatment depends on the underlying cause of anemia and may include iron supplementation, transfusions, or management of any underlying conditions.

Interleukin-3 (IL-3) is a type of cytokine, which is a small signaling protein that modulates the immune response, cell growth, and differentiation. IL-3 is primarily produced by activated T cells and mast cells. It plays an essential role in the survival, proliferation, and differentiation of hematopoietic stem cells, which give rise to all blood cell types. Specifically, IL-3 supports the development of myeloid lineage cells, including basophils, eosinophils, mast cells, megakaryocytes, and erythroid progenitors.

IL-3 binds to its receptor, the interleukin-3 receptor (IL-3R), which consists of two subunits: CD123 (the alpha chain) and CD131 (the beta chain). The binding of IL-3 to its receptor triggers a signaling cascade within the cell that ultimately leads to changes in gene expression, promoting cell growth and differentiation. Dysregulation of IL-3 production or signaling has been implicated in several hematological disorders, such as leukemia and myelodysplastic syndromes.

Renal dialysis is a medical procedure that is used to artificially remove waste products, toxins, and excess fluids from the blood when the kidneys are no longer able to perform these functions effectively. This process is also known as hemodialysis.

During renal dialysis, the patient's blood is circulated through a special machine called a dialyzer or an artificial kidney, which contains a semi-permeable membrane that filters out waste products and excess fluids from the blood. The cleaned blood is then returned to the patient's body.

Renal dialysis is typically recommended for patients with advanced kidney disease or kidney failure, such as those with end-stage renal disease (ESRD). It is a life-sustaining treatment that helps to maintain the balance of fluids and electrolytes in the body, prevent the buildup of waste products and toxins, and control blood pressure.

There are two main types of renal dialysis: hemodialysis and peritoneal dialysis. Hemodialysis is the most common type and involves using a dialyzer to filter the blood outside the body. Peritoneal dialysis, on the other hand, involves placing a catheter in the abdomen and using the lining of the abdomen (peritoneum) as a natural filter to remove waste products and excess fluids from the body.

Overall, renal dialysis is an essential treatment option for patients with kidney failure, helping them to maintain their quality of life and prolong their survival.

Hematopoietic stem cells (HSCs) are immature, self-renewing cells that give rise to all the mature blood and immune cells in the body. They are capable of both producing more hematopoietic stem cells (self-renewal) and differentiating into early progenitor cells that eventually develop into red blood cells, white blood cells, and platelets. HSCs are found in the bone marrow, umbilical cord blood, and peripheral blood. They have the ability to repair damaged tissues and offer significant therapeutic potential for treating various diseases, including hematological disorders, genetic diseases, and cancer.

A Colony-Forming Units (CFU) assay is a type of laboratory test used to measure the number of viable, or living, cells in a sample. It is commonly used to enumerate bacteria, yeast, and other microorganisms. The test involves placing a known volume of the sample onto a nutrient-agar plate, which provides a solid growth surface for the cells. The plate is then incubated under conditions that allow the cells to grow and form colonies. Each colony that forms on the plate represents a single viable cell from the original sample. By counting the number of colonies and multiplying by the known volume of the sample, the total number of viable cells in the sample can be calculated. This information is useful in a variety of applications, including monitoring microbial populations, assessing the effectiveness of disinfection procedures, and studying microbial growth and survival.

Stat5 (Signal Transducer and Activator of Transcription 5) is a transcription factor that plays a crucial role in various cellular processes, including growth, survival, and differentiation. It exists in two closely related isoforms, Stat5a and Stat5b, which are encoded by separate genes but share significant sequence homology and functional similarity.

When activated through phosphorylation by receptor or non-receptor tyrosine kinases, Stat5 forms homodimers or heterodimers that translocate to the nucleus. Once in the nucleus, these dimers bind to specific DNA sequences called Stat-binding elements (SBEs) in the promoter regions of target genes, leading to their transcriptional activation or repression.

Stat5 is involved in various physiological and pathological conditions, such as hematopoiesis, lactation, immune response, and cancer progression. Dysregulation of Stat5 signaling has been implicated in several malignancies, including leukemias, lymphomas, and breast cancer, making it an attractive therapeutic target for these diseases.

Anoxia is a medical condition that refers to the absence or complete lack of oxygen supply in the body or a specific organ, tissue, or cell. This can lead to serious health consequences, including damage or death of cells and tissues, due to the vital role that oxygen plays in supporting cellular metabolism and energy production.

Anoxia can occur due to various reasons, such as respiratory failure, cardiac arrest, severe blood loss, carbon monoxide poisoning, or high altitude exposure. Prolonged anoxia can result in hypoxic-ischemic encephalopathy, a serious condition that can cause brain damage and long-term neurological impairments.

Medical professionals use various diagnostic tests, such as blood gas analysis, pulse oximetry, and electroencephalography (EEG), to assess oxygen levels in the body and diagnose anoxia. Treatment for anoxia typically involves addressing the underlying cause, providing supplemental oxygen, and supporting vital functions, such as breathing and circulation, to prevent further damage.

Subcutaneous injection is a route of administration where a medication or vaccine is delivered into the subcutaneous tissue, which lies between the skin and the muscle. This layer contains small blood vessels, nerves, and connective tissues that help to absorb the medication slowly and steadily over a period of time. Subcutaneous injections are typically administered using a short needle, at an angle of 45-90 degrees, and the dose is injected slowly to minimize discomfort and ensure proper absorption. Common sites for subcutaneous injections include the abdomen, thigh, or upper arm. Examples of medications that may be given via subcutaneous injection include insulin, heparin, and some vaccines.

In the context of medicine, iron is an essential micromineral and key component of various proteins and enzymes. It plays a crucial role in oxygen transport, DNA synthesis, and energy production within the body. Iron exists in two main forms: heme and non-heme. Heme iron is derived from hemoglobin and myoglobin in animal products, while non-heme iron comes from plant sources and supplements.

The recommended daily allowance (RDA) for iron varies depending on age, sex, and life stage:

* For men aged 19-50 years, the RDA is 8 mg/day
* For women aged 19-50 years, the RDA is 18 mg/day
* During pregnancy, the RDA increases to 27 mg/day
* During lactation, the RDA for breastfeeding mothers is 9 mg/day

Iron deficiency can lead to anemia, characterized by fatigue, weakness, and shortness of breath. Excessive iron intake may result in iron overload, causing damage to organs such as the liver and heart. Balanced iron levels are essential for maintaining optimal health.

Polycythemia Vera is a type of myeloproliferative neoplasm, a group of rare blood cancers. In Polycythemia Vera, the body produces too many red blood cells, leading to an increased risk of blood clots and thickening of the blood, which can cause various symptoms such as fatigue, headache, dizziness, and itching. It can also lead to enlargement of the spleen. The exact cause of Polycythemia Vera is not known, but it is associated with genetic mutations in the JAK2 gene in most cases. It is a progressive disease that can lead to complications such as bleeding, thrombosis, and transformation into acute leukemia if left untreated.

A blood transfusion is a medical procedure in which blood or its components are transferred from one individual (donor) to another (recipient) through a vein. The donated blood can be fresh whole blood, packed red blood cells, platelets, plasma, or cryoprecipitate, depending on the recipient's needs. Blood transfusions are performed to replace lost blood due to severe bleeding, treat anemia, support patients undergoing major surgeries, or manage various medical conditions such as hemophilia, thalassemia, and leukemia. The donated blood must be carefully cross-matched with the recipient's blood type to minimize the risk of transfusion reactions.

Erythrocytes, also known as red blood cells (RBCs), are the most common type of blood cell in circulating blood in mammals. They are responsible for transporting oxygen from the lungs to the body's tissues and carbon dioxide from the tissues to the lungs.

Erythrocytes are formed in the bone marrow and have a biconcave shape, which allows them to fold and bend easily as they pass through narrow blood vessels. They do not have a nucleus or mitochondria, which makes them more flexible but also limits their ability to reproduce or repair themselves.

In humans, erythrocytes are typically disc-shaped and measure about 7 micrometers in diameter. They contain the protein hemoglobin, which binds to oxygen and gives blood its red color. The lifespan of an erythrocyte is approximately 120 days, after which it is broken down in the liver and spleen.

Abnormalities in erythrocyte count or function can lead to various medical conditions, such as anemia, polycythemia, and sickle cell disease.

Doping in sports is the use of prohibited substances or methods to improve athletic performance. The World Anti-Doping Agency (WADA) defines doping as "the occurrence of one or more of the following anti-doping rule violations":

1. Presence of a prohibited substance in an athlete's sample
2. Use or attempted use of a prohibited substance or method
3. Evading, refusing, or failing to submit to sample collection
4. Whereabouts failures (three missed tests or filing failures within a 12-month period)
5. Tampering or attempted tampering with any part of the doping control process
6. Possession, trafficking, or administration of a prohibited substance or method
7. Complicity in an anti-doping rule violation
8. Prohibited association with a person who has been serving a period of ineligibility for an anti-doping rule violation

Doping is considered unethical and harmful to the integrity of sports, as it provides an unfair advantage to those who engage in it. It can also have serious health consequences for athletes. Various international and national organizations, including WADA and the United States Anti-Doping Agency (USADA), work to prevent doping in sports through education, testing, and enforcement of anti-doping rules.

Milk proteins are a complex mixture of proteins that are naturally present in milk, consisting of casein and whey proteins. Casein makes up about 80% of the total milk protein and is divided into several types including alpha-, beta-, gamma- and kappa-casein. Whey proteins account for the remaining 20% and include beta-lactoglobulin, alpha-lactalbumin, bovine serum albumin, and immunoglobulins. These proteins are important sources of essential amino acids and play a crucial role in the nutrition of infants and young children. Additionally, milk proteins have various functional properties that are widely used in the food industry for their gelling, emulsifying, and foaming abilities.

Hypoxia-Inducible Factor 1 (HIF-1) is a transcription factor that plays a crucial role in the cellular response to low oxygen levels, also known as hypoxia. It is a heterodimeric protein composed of two subunits: HIF-1α and HIF-1β.

Under normoxic conditions (adequate oxygen supply), HIF-1α is constantly produced but rapidly degraded by proteasomes due to the action of prolyl hydroxylases, which mark it for destruction in the presence of oxygen. However, under hypoxic conditions, the activity of prolyl hydroxylases is inhibited, leading to the stabilization and accumulation of HIF-1α.

Once stabilized, HIF-1α translocates to the nucleus and forms a complex with HIF-1β. This complex then binds to hypoxia-responsive elements (HREs) in the promoter regions of various genes involved in angiogenesis, glucose metabolism, erythropoiesis, cell survival, and other processes that help cells adapt to low oxygen levels.

By activating these target genes, HIF-1 plays a critical role in regulating the body's response to hypoxia, including promoting the formation of new blood vessels (angiogenesis), enhancing anaerobic metabolism, and inhibiting cell proliferation and apoptosis under low oxygen conditions. Dysregulation of HIF-1 has been implicated in several diseases, such as cancer, cardiovascular disease, and ischemic disorders.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

Phenylhydrazines are organic compounds that contain a phenyl group (a benzene ring with a hydrogen atom substituted by a hydroxy group) and a hydrazine group (-NH-NH2). They are aromatic amines that have been used in various chemical reactions, including the formation of azos and hydrazones. In medicine, phenylhydrazines were once used as vasodilators to treat angina pectoris, but their use has largely been discontinued due to their toxicity and potential carcinogenicity.

Bone marrow is the spongy tissue found inside certain bones in the body, such as the hips, thighs, and vertebrae. It is responsible for producing blood-forming cells, including red blood cells, white blood cells, and platelets. There are two types of bone marrow: red marrow, which is involved in blood cell production, and yellow marrow, which contains fatty tissue.

Red bone marrow contains hematopoietic stem cells, which can differentiate into various types of blood cells. These stem cells continuously divide and mature to produce new blood cells that are released into the circulation. Red blood cells carry oxygen throughout the body, white blood cells help fight infections, and platelets play a crucial role in blood clotting.

Bone marrow also serves as a site for immune cell development and maturation. It contains various types of immune cells, such as lymphocytes, macrophages, and dendritic cells, which help protect the body against infections and diseases.

Abnormalities in bone marrow function can lead to several medical conditions, including anemia, leukopenia, thrombocytopenia, and various types of cancer, such as leukemia and multiple myeloma. Bone marrow aspiration and biopsy are common diagnostic procedures used to evaluate bone marrow health and function.

Bone marrow cells are the types of cells found within the bone marrow, which is the spongy tissue inside certain bones in the body. The main function of bone marrow is to produce blood cells. There are two types of bone marrow: red and yellow. Red bone marrow is where most blood cell production takes place, while yellow bone marrow serves as a fat storage site.

The three main types of bone marrow cells are:

1. Hematopoietic stem cells (HSCs): These are immature cells that can differentiate into any type of blood cell, including red blood cells, white blood cells, and platelets. They have the ability to self-renew, meaning they can divide and create more hematopoietic stem cells.
2. Red blood cell progenitors: These are immature cells that will develop into mature red blood cells, also known as erythrocytes. Red blood cells carry oxygen from the lungs to the body's tissues and carbon dioxide back to the lungs.
3. Myeloid and lymphoid white blood cell progenitors: These are immature cells that will develop into various types of white blood cells, which play a crucial role in the body's immune system by fighting infections and diseases. Myeloid progenitors give rise to granulocytes (neutrophils, eosinophils, and basophils), monocytes, and megakaryocytes (which eventually become platelets). Lymphoid progenitors differentiate into B cells, T cells, and natural killer (NK) cells.

Bone marrow cells are essential for maintaining a healthy blood cell count and immune system function. Abnormalities in bone marrow cells can lead to various medical conditions, such as anemia, leukopenia, leukocytosis, thrombocytopenia, or thrombocytosis, depending on the specific type of blood cell affected. Additionally, bone marrow cells are often used in transplantation procedures to treat patients with certain types of cancer, such as leukemia and lymphoma, or other hematologic disorders.

Friend murine leukemia virus (F-MuLV) is a type of retrovirus that specifically infects mice. It was first discovered by Charlotte Friend in the 1950s and has since been widely used as a model system to study retroviral pathogenesis, oncogenesis, and immune responses.

F-MuLV is a complex retrovirus that contains several accessory genes, including gag, pol, env, and others. The virus can cause leukemia and other malignancies in susceptible mice, particularly when it is transmitted from mother to offspring through the milk.

The virus is also known to induce immunosuppression, which makes infected mice more susceptible to other infections and diseases. F-MuLV has been used extensively in laboratory research to investigate various aspects of retroviral biology, including viral entry, replication, gene expression, and host immune responses.

It is important to note that Friend murine leukemia virus only infects mice and is not known to cause any disease in humans or other animals.

Reticulocytes are immature red blood cells that still contain remnants of organelles, such as ribosomes and mitochondria, which are typically found in developing cells. These organelles are involved in the process of protein synthesis and energy production, respectively. Reticulocytes are released from the bone marrow into the bloodstream, where they continue to mature into fully developed red blood cells called erythrocytes.

Reticulocytes can be identified under a microscope by their staining characteristics, which reveal a network of fine filaments or granules known as the reticular apparatus. This apparatus is composed of residual ribosomal RNA and other proteins that have not yet been completely eliminated during the maturation process.

The percentage of reticulocytes in the blood can be used as a measure of bone marrow function and erythropoiesis, or red blood cell production. An increased reticulocyte count may indicate an appropriate response to blood loss, hemolysis, or other conditions that cause anemia, while a decreased count may suggest impaired bone marrow function or a deficiency in erythropoietin, the hormone responsible for stimulating red blood cell production.

Stem Cell Factor (SCF), also known as Kit Ligand or Steel Factor, is a growth factor that plays a crucial role in the regulation of hematopoiesis, which is the process of producing various blood cells. It is a glycoprotein that binds to the c-Kit receptor found on hematopoietic stem cells and progenitor cells, promoting their survival, proliferation, and differentiation into mature blood cells.

SCF is involved in the development and function of several types of blood cells, including red blood cells, white blood cells, and platelets. It also plays a role in the maintenance and self-renewal of hematopoietic stem cells, which are essential for the continuous production of new blood cells throughout an individual's lifetime.

In addition to its role in hematopoiesis, SCF has been implicated in various other biological processes, such as melanogenesis, gametogenesis, and tissue repair and regeneration. Dysregulation of SCF signaling has been associated with several diseases, including certain types of cancer, bone marrow failure disorders, and autoimmune diseases.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Hematopoiesis is the process of forming and developing blood cells. It occurs in the bone marrow and includes the production of red blood cells (erythropoiesis), white blood cells (leukopoiesis), and platelets (thrombopoiesis). This process is regulated by various growth factors, hormones, and cytokines. Hematopoiesis begins early in fetal development and continues throughout a person's life. Disorders of hematopoiesis can result in conditions such as anemia, leukopenia, leukocytosis, thrombocytopenia, or thrombocytosis.

Phlebotomy is a medical term that refers to the process of making an incision in a vein, usually in the arm, in order to draw blood. It is also commonly known as venipuncture. This procedure is performed by healthcare professionals for various purposes such as diagnostic testing, blood donation, or therapeutic treatments like phlebotomy for patients with hemochromatosis (a condition where the body absorbs too much iron from food).

The person who performs this procedure is called a phlebotomist. They must be trained in the proper techniques to ensure that the process is safe and relatively pain-free for the patient, and that the blood sample is suitable for laboratory testing.

Erythrocyte volume, also known as red cell volume or hematocrit, is the proportion of whole blood that is made up of erythrocytes or red blood cells. It is typically expressed as a percentage and can be measured using a centrifuge to separate the components of a blood sample by density.

The erythrocyte volume is an important clinical parameter because it can provide information about a person's health status, such as their hydration level, altitude acclimatization, and the presence of certain medical conditions like anemia or polycythemia. Changes in erythrocyte volume can also have significant effects on the body's oxygen-carrying capacity and overall cardiovascular function.

Hypoxia-Inducible Factor 1 (HIF-1) is a transcription factor that plays a crucial role in the body's response to low oxygen levels, also known as hypoxia. HIF-1 is a heterodimeric protein composed of two subunits: an alpha subunit (HIF-1α) and a beta subunit (HIF-1β).

The alpha subunit, HIF-1α, is the regulatory subunit that is subject to oxygen-dependent degradation. Under normal oxygen conditions (normoxia), HIF-1α is constantly produced in the cell but is rapidly degraded by proteasomes due to hydroxylation of specific proline residues by prolyl hydroxylase domain-containing proteins (PHDs). This hydroxylation reaction requires oxygen as a substrate, and under hypoxic conditions, the activity of PHDs is inhibited, leading to the stabilization and accumulation of HIF-1α.

Once stabilized, HIF-1α translocates to the nucleus, where it heterodimerizes with HIF-1β and binds to hypoxia-responsive elements (HREs) in the promoter regions of target genes. This binding results in the activation of gene transcription programs that promote cellular adaptation to low oxygen levels. These adaptive responses include increased erythropoiesis, angiogenesis, glucose metabolism, and pH regulation, among others.

Therefore, HIF-1α is a critical regulator of the body's response to hypoxia, and its dysregulation has been implicated in various pathological conditions, including cancer, cardiovascular disease, and neurodegenerative disorders.

Cell division is the process by which a single eukaryotic cell (a cell with a true nucleus) divides into two identical daughter cells. This complex process involves several stages, including replication of DNA, separation of chromosomes, and division of the cytoplasm. There are two main types of cell division: mitosis and meiosis.

Mitosis is the type of cell division that results in two genetically identical daughter cells. It is a fundamental process for growth, development, and tissue repair in multicellular organisms. The stages of mitosis include prophase, prometaphase, metaphase, anaphase, and telophase, followed by cytokinesis, which divides the cytoplasm.

Meiosis, on the other hand, is a type of cell division that occurs in the gonads (ovaries and testes) during the production of gametes (sex cells). Meiosis results in four genetically unique daughter cells, each with half the number of chromosomes as the parent cell. This process is essential for sexual reproduction and genetic diversity. The stages of meiosis include meiosis I and meiosis II, which are further divided into prophase, prometaphase, metaphase, anaphase, and telophase.

In summary, cell division is the process by which a single cell divides into two daughter cells, either through mitosis or meiosis. This process is critical for growth, development, tissue repair, and sexual reproduction in multicellular organisms.

Hypochromic anemia is a type of anemia characterized by the presence of red blood cells that have lower than normal levels of hemoglobin and appear paler in color than normal. Hemoglobin is a protein in red blood cells that carries oxygen from the lungs to the rest of the body. In hypochromic anemia, there may be a decrease in the production or increased destruction of red blood cells, leading to a reduced number of red blood cells and insufficient oxygen supply to the tissues.

Hypochromic anemia can result from various underlying medical conditions, including iron deficiency, thalassemia, chronic inflammation, lead poisoning, and certain infections or chronic diseases. Treatment for hypochromic anemia depends on the underlying cause and may include iron supplements, dietary changes, medications, or blood transfusions.

Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.

Erythroid cells are a type of blood cell that develops in the bone marrow and mature into red blood cells (RBCs), also known as erythrocytes. These cells play a crucial role in the body's oxygen-carrying capacity by transporting oxygen from the lungs to the body's tissues and carbon dioxide from the tissues to the lungs.

The development of erythroid cells begins with hematopoietic stem cells, which can differentiate into various types of blood cells. Through a series of maturation stages, including proerythroblasts, basophilic erythroblasts, polychromatophilic erythroblasts, and orthochromatic erythroblasts, these cells gradually lose their nuclei and organelles to become reticulocytes. Reticulocytes are immature RBCs that still contain some residual ribosomes and are released into the bloodstream. Over time, they mature into fully functional RBCs, which have a biconcave shape and a flexible membrane that allows them to navigate through small blood vessels.

Erythroid cells are essential for maintaining adequate oxygenation of body tissues, and their production is tightly regulated by various hormones and growth factors, such as erythropoietin (EPO), which stimulates the proliferation and differentiation of erythroid progenitor cells. Abnormalities in erythroid cell development or function can lead to various blood disorders, including anemia, polycythemia, and myelodysplastic syndromes.

Cell hypoxia, also known as cellular hypoxia or tissue hypoxia, refers to a condition in which the cells or tissues in the body do not receive an adequate supply of oxygen. Oxygen is essential for the production of energy in the form of ATP (adenosine triphosphate) through a process called oxidative phosphorylation. When the cells are deprived of oxygen, they switch to anaerobic metabolism, which produces lactic acid as a byproduct and can lead to acidosis.

Cell hypoxia can result from various conditions, including:

1. Low oxygen levels in the blood (hypoxemia) due to lung diseases such as chronic obstructive pulmonary disease (COPD), pneumonia, or high altitude.
2. Reduced blood flow to tissues due to cardiovascular diseases such as heart failure, peripheral artery disease, or shock.
3. Anemia, which reduces the oxygen-carrying capacity of the blood.
4. Carbon monoxide poisoning, which binds to hemoglobin and prevents it from carrying oxygen.
5. Inadequate ventilation due to trauma, drug overdose, or other causes that can lead to respiratory failure.

Cell hypoxia can cause cell damage, tissue injury, and organ dysfunction, leading to various clinical manifestations depending on the severity and duration of hypoxia. Treatment aims to correct the underlying cause and improve oxygen delivery to the tissues.

Neuroprotective agents are substances that protect neurons or nerve cells from damage, degeneration, or death caused by various factors such as trauma, inflammation, oxidative stress, or excitotoxicity. These agents work through different mechanisms, including reducing the production of free radicals, inhibiting the release of glutamate (a neurotransmitter that can cause cell damage in high concentrations), promoting the growth and survival of neurons, and preventing apoptosis (programmed cell death). Neuroprotective agents have been studied for their potential to treat various neurological disorders, including stroke, traumatic brain injury, Parkinson's disease, Alzheimer's disease, and multiple sclerosis. However, more research is needed to fully understand their mechanisms of action and to develop effective therapies.

Ferritin is a protein in iron-metabolizing cells that stores iron in a water-soluble form. It is found inside the cells (intracellular) and is released into the bloodstream when the cells break down or die. Measuring the level of ferritin in the blood can help determine the amount of iron stored in the body. High levels of ferritin may indicate hemochromatosis, inflammation, liver disease, or other conditions. Low levels of ferritin may indicate anemia, iron deficiency, or other conditions.

Cell differentiation is the process by which a less specialized cell, or stem cell, becomes a more specialized cell type with specific functions and structures. This process involves changes in gene expression, which are regulated by various intracellular signaling pathways and transcription factors. Differentiation results in the development of distinct cell types that make up tissues and organs in multicellular organisms. It is a crucial aspect of embryonic development, tissue repair, and maintenance of homeostasis in the body.

Bloodletting is a medical procedure that was commonly used in the past to balance the four humors of the body, which were believed to be blood, phlegm, black bile, and yellow bile. The procedure involved withdrawing blood from a patient through various methods such as venesection (making an incision in a vein), leeches, or cupping.

The theory behind bloodletting was that if one humor became overabundant, it could cause disease or illness. By removing some of the excess humor, practitioners believed they could restore balance and promote healing. Bloodletting was used to treat a wide variety of conditions, including fever, inflammation, and pain.

While bloodletting is no longer practiced in modern medicine, it was once a common treatment for many different ailments. The practice dates back to ancient times and was used by various cultures throughout history, including the Greeks, Romans, Egyptians, and Chinese. However, its effectiveness as a medical treatment has been called into question, and it is now considered an outdated and potentially harmful procedure.

A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.

The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.

The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.

In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.

In the field of medicine, "time factors" refer to the duration of symptoms or time elapsed since the onset of a medical condition, which can have significant implications for diagnosis and treatment. Understanding time factors is crucial in determining the progression of a disease, evaluating the effectiveness of treatments, and making critical decisions regarding patient care.

For example, in stroke management, "time is brain," meaning that rapid intervention within a specific time frame (usually within 4.5 hours) is essential to administering tissue plasminogen activator (tPA), a clot-busting drug that can minimize brain damage and improve patient outcomes. Similarly, in trauma care, the "golden hour" concept emphasizes the importance of providing definitive care within the first 60 minutes after injury to increase survival rates and reduce morbidity.

Time factors also play a role in monitoring the progression of chronic conditions like diabetes or heart disease, where regular follow-ups and assessments help determine appropriate treatment adjustments and prevent complications. In infectious diseases, time factors are crucial for initiating antibiotic therapy and identifying potential outbreaks to control their spread.

Overall, "time factors" encompass the significance of recognizing and acting promptly in various medical scenarios to optimize patient outcomes and provide effective care.

Cobalt is a chemical element with the symbol Co and atomic number 27. It is a hard, silver-white, lustrous, and brittle metal that is found naturally only in chemically combined form, except for small amounts found in meteorites. Cobalt is used primarily in the production of magnetic, wear-resistant, and high-strength alloys, as well as in the manufacture of batteries, magnets, and pigments.

In a medical context, cobalt is sometimes used in the form of cobalt-60, a radioactive isotope, for cancer treatment through radiation therapy. Cobalt-60 emits gamma rays that can be directed at tumors to destroy cancer cells. Additionally, small amounts of cobalt are present in some vitamin B12 supplements and fortified foods, as cobalt is an essential component of vitamin B12. However, exposure to high levels of cobalt can be harmful and may cause health effects such as allergic reactions, lung damage, heart problems, and neurological issues.

GATA1 (Global Architecture of Tissue/stage-specific Transcription Factors 1) is a transcription factor that belongs to the GATA family, which recognizes and binds to the (A/T)GATA(A/G) motif in the DNA. It plays a crucial role in the development and differentiation of hematopoietic cells, particularly erythroid, megakaryocytic, eosinophilic, and mast cell lineages.

GATA1 regulates gene expression by binding to specific DNA sequences and recruiting other co-factors that modulate chromatin structure and transcriptional activity. Mutations in the GATA1 gene can lead to various blood disorders such as congenital dyserythropoietic anemia type II, Diamond-Blackfan anemia, acute megakaryoblastic leukemia (AMKL), and myelodysplastic syndrome.

In summary, GATA1 Transcription Factor is a protein that binds to specific DNA sequences in the genome and regulates gene expression, playing a critical role in hematopoietic cell development and differentiation.

An erythrocyte transfusion, also known as a red blood cell (RBC) transfusion, is the process of transferring compatible red blood cells from a donor to a recipient. This procedure is typically performed to increase the recipient's oxygen-carrying capacity, usually in situations where there is significant blood loss, anemia, or impaired red blood cell production.

During the transfusion, the donor's red blood cells are collected, typed, and tested for compatibility with the recipient's blood to minimize the risk of a transfusion reaction. Once compatible units are identified, they are infused into the recipient's circulation through a sterile intravenous (IV) line. The recipient's body will eventually eliminate the donated red blood cells within 100-120 days as part of its normal turnover process.

Erythrocyte transfusions can be lifesaving in various clinical scenarios, such as trauma, surgery, severe anemia due to chronic diseases, and hematologic disorders. However, they should only be used when necessary, as there are potential risks associated with the procedure, including allergic reactions, transmission of infectious diseases, transfusion-related acute lung injury (TRALI), and iron overload in cases of multiple transfusions.

Hypoxia-Inducible Factor (HIF) is a transcription factor that plays a crucial role in the body's response to low oxygen levels (hypoxia). HIF is composed of two subunits: an alpha subunit and a beta subunit. Under normal oxygen conditions, the alpha subunit is constantly being broken down by prolyl hydroxylase domain-containing proteins, which are a type of enzyme known as HIF-Proline Dioxygenases (HIF-PDOs).

HIF-PDOs post-translationally modify the HIF alpha subunit by adding a hydroxyl group to specific proline residues. This modification marks the HIF alpha subunit for degradation by the proteasome, a complex that breaks down unneeded or damaged proteins in the cell. However, under hypoxic conditions, the activity of HIF-PDOs is inhibited, leading to the stabilization and accumulation of HIF alpha subunits.

Once stabilized, HIF alpha subunits dimerize with HIF beta subunits and translocate to the nucleus where they bind to hypoxia response elements (HREs) in the DNA. This binding induces the expression of genes involved in various cellular responses to hypoxia, such as angiogenesis, metabolic reprogramming, and erythropoiesis. Therefore, HIF-PDOs play a critical role in regulating the body's response to low oxygen levels by controlling the stability and activity of HIF.

"Iron radioisotopes" refer to specific forms of the element iron that have unstable nuclei and emit radiation. These isotopes are often used in medical imaging and treatment procedures due to their ability to be detected by specialized equipment. Common iron radioisotopes include Iron-52, Iron-55, Iron-59, and Iron-60. They can be used as tracers to study the distribution, metabolism, or excretion of iron in the body, or for targeted radiation therapy in conditions such as cancer.

Hematopoietic cell growth factors are a group of glycoproteins that stimulate the proliferation, differentiation, and survival of hematopoietic cells, which are the precursor cells that give rise to all blood cells. These growth factors include colony-stimulating factors (CSFs) such as granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and macrophage colony-stimulating factor (M-CSF), as well as erythropoietin (EPO) and thrombopoietin (TPO).

G-CSF primarily stimulates the production of neutrophils, a type of white blood cell that plays a crucial role in the immune response to bacterial infections. GM-CSF stimulates the production of both granulocytes and monocytes/macrophages, while M-CSF specifically stimulates the production of monocytes/macrophages. EPO stimulates the production of red blood cells, while TPO stimulates the production of platelets.

Hematopoietic cell growth factors are used clinically to treat a variety of conditions associated with impaired hematopoiesis, such as chemotherapy-induced neutropenia, aplastic anemia, and congenital disorders of hematopoiesis. They can also be used to mobilize hematopoietic stem cells from the bone marrow into the peripheral blood for collection and transplantation.

A kidney, in medical terms, is one of two bean-shaped organs located in the lower back region of the body. They are essential for maintaining homeostasis within the body by performing several crucial functions such as:

1. Regulation of water and electrolyte balance: Kidneys help regulate the amount of water and various electrolytes like sodium, potassium, and calcium in the bloodstream to maintain a stable internal environment.

2. Excretion of waste products: They filter waste products from the blood, including urea (a byproduct of protein metabolism), creatinine (a breakdown product of muscle tissue), and other harmful substances that result from normal cellular functions or external sources like medications and toxins.

3. Endocrine function: Kidneys produce several hormones with important roles in the body, such as erythropoietin (stimulates red blood cell production), renin (regulates blood pressure), and calcitriol (activated form of vitamin D that helps regulate calcium homeostasis).

4. pH balance regulation: Kidneys maintain the proper acid-base balance in the body by excreting either hydrogen ions or bicarbonate ions, depending on whether the blood is too acidic or too alkaline.

5. Blood pressure control: The kidneys play a significant role in regulating blood pressure through the renin-angiotensin-aldosterone system (RAAS), which constricts blood vessels and promotes sodium and water retention to increase blood volume and, consequently, blood pressure.

Anatomically, each kidney is approximately 10-12 cm long, 5-7 cm wide, and 3 cm thick, with a weight of about 120-170 grams. They are surrounded by a protective layer of fat and connected to the urinary system through the renal pelvis, ureters, bladder, and urethra.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Transferrin receptors are membrane-bound proteins found on the surface of many cell types, including red and white blood cells, as well as various tissues such as the liver, brain, and placenta. These receptors play a crucial role in iron homeostasis by regulating the uptake of transferrin, an iron-binding protein, into the cells.

Transferrin binds to two ferric ions (Fe3+) in the bloodstream, forming a complex known as holo-transferrin. This complex then interacts with the transferrin receptors on the cell surface, leading to endocytosis of the transferrin-receptor complex into the cell. Once inside the cell, the acidic environment within the endosome causes the release of iron ions from the transferrin molecule, which can then be transported into the cytoplasm for use in various metabolic processes.

After releasing the iron, the apo-transferrin (iron-free transferrin) is recycled back to the cell surface and released back into the bloodstream, where it can bind to more ferric ions and repeat the cycle. This process helps maintain appropriate iron levels within the body and ensures that cells have access to the iron they need for essential functions such as DNA synthesis, energy production, and oxygen transport.

In summary, transferrin receptors are membrane-bound proteins responsible for recognizing and facilitating the uptake of transferrin-bound iron into cells, playing a critical role in maintaining iron homeostasis within the body.

Erythropoietin receptor has been shown to interact with: CRKL, Erythropoietin, Grb2, Janus kinase 2, LYN, PIK3R1, PTPN6, SOCS2 ... Zhu Y, DAndrea AD (Mar 1994). "The molecular physiology of erythropoietin and the erythropoietin receptor". Current Opinion in ... Socolovsky M, Dusanter-Fourt I, Lodish HF (May 1997). "The prolactin receptor and severely truncated erythropoietin receptors ... "CrkL is recruited through its SH2 domain to the erythropoietin receptor and plays a role in Lyn-mediated receptor signaling". ...
N2 - Objective: The erythropoietin receptor (EpoR) stimulates erythro- cyte proliferation after erythropoietin binding. EpoR ... AB - Objective: The erythropoietin receptor (EpoR) stimulates erythro- cyte proliferation after erythropoietin binding. EpoR ... Objective: The erythropoietin receptor (EpoR) stimulates erythro- cyte proliferation after erythropoietin binding. EpoR belongs ... abstract = "Objective: The erythropoietin receptor (EpoR) stimulates erythro- cyte proliferation after erythropoietin binding. ...
Involvement of SH2-containing phosphotyrosine phosphatase Syp in erythropoietin receptor signal transduction pathways. ... Involvement of SH2-containing phosphotyrosine phosphatase Syp in erythropoietin receptor signal transduction pathways. ... Involvement of SH2-containing phosphotyrosine phosphatase Syp in erythropoietin receptor signal transduction pathways. ... Erythropoietin (Epo) regulates the proliferation and differentiation of erythroid precursors. The phosphorylation of proteins ...
The erythropoietin receptor: Dimerization, activation, and tumorigenesis. / Lodish, H. F.; Hilton, D.; Longmore, G. その他. In: ... The erythropoietin receptor: Dimerization, activation, and tumorigenesis. H. F. Lodish, D. Hilton, G. Longmore, S. S. Watowich ... The erythropoietin receptor: Dimerization, activation, and tumorigenesis. Cold Spring Harbor Symposia on Quantitative Biology. ... The erythropoietin receptor : Dimerization, activation, and tumorigenesis. In: Cold Spring Harbor Symposia on Quantitative ...
EPOR: erythropoietin receptor. *EPX: eosinophil peroxidase. *ERAP1: endoplasmic reticulum aminopeptidase 1. *ERCC2: ERCC ...
Erythropoietin-induced recruitment of Shc via a receptor phosphotyrosine-independent, Jak2-associated pathway. J Biol Chem. ... Erythropoietin-induced recruitment of Shc via a receptor phosphotyrosine-independent, Jak2-associated pathway. ... Erythropoietin-induced recruitment of Shc via a receptor phosphotyrosine-independent, Jak2-associated pathway. ...
involved_in erythropoietin-mediated signaling pathway ISS Inferred from Sequence or Structural Similarity. more info ... KIT KIT proto-oncogene, receptor tyrosine kinase [Homo sapiens] KIT KIT proto-oncogene, receptor tyrosine kinase [Homo sapiens] ... KIT proto-oncogene, receptor tyrosine kinaseprovided by HGNC. Primary source. HGNC:HGNC:6342 See related. Ensembl: ... mast/stem cell growth factor receptor Kit. Names. c-Kit protooncogene. p145 c-kit. piebald trait protein. proto-oncogene c-Kit ...
GHR is a member of the cytokine receptor superfamily that includes prolactin receptor, erythropoietin receptor, leptin receptor ... GHR is a member of the cytokine receptor superfamily that includes prolactin receptor, erythropoietin receptor, leptin receptor ... GHR is usually a member of the cytokine receptor superfamily that includes prolactin receptor, erythropoietin receptor, leptin ... method of inhibit surface area receptor signaling has been antireceptor antibodies that stop either ligand binding or receptor ...
Differential effects of haloperidol and olanzapine on the expression of erythropoietin and its receptor in rat hippocampus and ... Differential effects of haloperidol and olanzapine on the expression of erythropoietin and its receptor in rat hippocampus and ... Differential effects of haloperidol and olanzapine on the expression of erythropoietin and its receptor in rat hippocampus and ... T1 - Differential effects of haloperidol and olanzapine on the expression of erythropoietin and its receptor in rat hippocampus ...
Transduction of recombinant human erythropoietin receptor cDNA into daughter progenitors derived from single CD343+ cord blood ... Dive into the research topics of Transduction of recombinant human erythropoietin receptor cDNA into daughter progenitors ...
Once-Monthly Continuous Erythropoietin Receptor Activator (C.E.R.A.) in Patients with Hemodialysis-Dependent Chronic Kidney ... Once-Monthly Continuous Erythropoietin Receptor Activator (C.E.R.A.) in Patients with Hemodialysis-Dependent Chronic Kidney ... Anemia, chronic kidney diseaseContinuous erythropoiesisHemodialysisReceptor activatorEfficacyPatient subgroupsPooled analysis ...
Shared and unique determinants of the erythropoietin (EPO) receptor are important for binding EPO and EPO mimetic peptide. ... Dive into the research topics of Shared and unique determinants of the erythropoietin (EPO) receptor are important for binding ...
keywords = "Erythrocyte, Erythropoieisis, Erythropoietin receptor, Soluble receptor, Xenopus",. author = "Youichi Aizawa and ... Aizawa, Y, Nogawa, N, Kosaka, N, Maeda, Y, Watanabe, T, Miyazaki, H & Kato, T 2005, Expression of erythropoietin receptor-like ... title = "Expression of erythropoietin receptor-like molecule in Xenopus laevis and erythrocytopenia upon administration of its ... T1 - Expression of erythropoietin receptor-like molecule in Xenopus laevis and erythrocytopenia upon administration of its ...
J:8454 McDonald JD, et al., Cloning, sequencing, and evolutionary analysis of the mouse erythropoietin gene. Mol Cell Biol. ...
Finch CA: Erythropoiesis, erythropoietin, and iron. Blood 1982;60:1241-1246.. 24.. Greenman J, Jacobs A: The effect of iron ... Soluble Transferrin Receptor-1 Levels in Mice Do Not Affect Iron Absorption Subject Area: Hematology , Oncology ... Serum transferrin receptor is a truncated form of tissue receptor. J Biol Chem 1990;265:19077-19081. ... Soluble transferrin receptor-1 (sTfR1) concentrations are increased in the plasma under two conditions that are associated with ...
Erythropoietin attenuates cardiac dysfunction in experimental sepsis in mice via activation of the beta-common receptor. Dis ... Toll-Like Receptors. Toll-like receptors are transmembrane glycoproteins, which recognize many PAMPs with extracellular domains ... Peroxisome proliferator-activated receptor (PPAR), a nuclear receptor, regulates cardiac fatty acid oxidation. Drosatos et al. ... Toll-like receptor 2 plays a critical role in cardiac dysfunction during polymicrobial sepsis. Crit Care Med (2010) 38(5):1335- ...
... recombinant human erythropoietin; RIA, radioimmunoassay; EPOR, EPO receptor. ... Pharmacokinetic/Pharmacodynamic Analysis of Paradoxal Regulation of Erythropoietin Production in Acute Anemia. N. H. Al-Huniti ... Pharmacokinetic/Pharmacodynamic Analysis of Paradoxal Regulation of Erythropoietin Production in Acute Anemia. N. H. Al-Huniti ... Pharmacokinetic/Pharmacodynamic Analysis of Paradoxal Regulation of Erythropoietin Production in Acute Anemia. N. H. Al-Huniti ...
Erythropoietin (EPO). *Erythropoietin-Fc. *Methoxy polyethylene glycol-epoetin beta (CERA/Mircera). *Peginesatide ... Receptor/signaling modulators. Signaling peptide/protein receptor modulators. Growth factor receptor modulators. ... Cytokine receptor modulators,state=autocollapse}}. *shows the template collapsed to the title bar if there is a {{navbar}}. , a ... Cytokine receptor modulators,state=collapsed}}. to show the template collapsed, i.e., hidden apart from its title bar ...
Erythropoietin (EPO). *Erythropoietin-Fc. *Methoxy polyethylene glycol-epoetin beta (CERA/Mircera). *Peginesatide ... Receptor/signaling modulators. Signaling peptide/protein receptor modulators. Growth factor receptor modulators. ... Death receptor 6 (DR6), also known as tumor necrosis factor receptor superfamily member 21 (TNFRSF21), is a cell surface ... The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor has been shown to activate NF-κB ...
Erythropoietin (EPO). *Erythropoietin-Fc. *Methoxy polyethylene glycol-epoetin beta (CERA/Mircera). *Peginesatide ... Receptor/signaling modulators. Signaling peptide/protein receptor modulators. Growth factor receptor modulators. ... Interferon-gamma receptor. References. *↑ 1.0 1.1 "Entrez Gene: IFNGR1 interferon gamma receptor 1".. .mw-parser-output cite. ... Interferon gamma receptor 1 (IFNGR1) also known as CD119 (Cluster of Differentiation 119), is a protein that in humans is ...
View Human Erythropoietin R (NP_000112) VersaClone cDNA in cDNA Clones. ... The biological effects of Epo are mediated by the Erythropoietin receptor (Epo R). At the protein sequence level, the human Epo ... Background: Erythropoietin R. Erythropoietin (Epo) is a 30-kDa, heavily glycosylated protein produced primarily by the kidney. ... Reviews for Human Erythropoietin R (NP_000112) VersaClone cDNA. There are currently no reviews for this product. Be the first ...
Are erythropoietin receptors (EpoR) present on tumors? • Are the downstream effects of these receptors also present in tumors? ... Erythropoietin and its receptor are likely candidates, as they are known to stimulate proliferation and inhibit apoptosis in ... 4. Farrell F, Lee A: The erythropoietin receptor and its expression in tumor cells and other tissues. Oncologist 9(suppl 5):18- ... 7. Lai SY, Grandis JR: Understanding the presence and function of erythropoietin receptors on cancer cells. J Clin Oncol 24: ...
Table 2-5: Role of erythropoietin in the nervous system. Table 2-6: Ionotropic glutamate receptors. Table 2-7: Classification ... Figure 2-1: Mechanism of neuroprotective effect of sigma-1 receptor agonists. Figure 2-2: NMDA receptor ion channel complex. ... Adenosine A2A receptor antagonists for neuroprotection in stress. *Role of neurotrophic factors in stress-induced psychiatric ... of metabotropic glutamate receptors (mGluRs). Table 2-8: Methods for neuroprotection based on nonpharmacological ...
1.1 ERYTHROPOIETIN-RECEPTOR AGONISTS, E.G.. *Darbepoetins (dEPO). *Erythropoietins (EPO). *EPO-based constructs [e.g. EPO-Fc, ... Activin receptor IIB competitors such as: *Decoy activin receptors (e.g. ACE-031) ... Anti-activin receptor IIB antibodies (e.g. bimagrumab). *Myostatin inhibitors such as: *Agents reducing or ablating myostatin ... Selective androgen receptor modulators [SARMs, e.g. andarine, enobosarm (ostarine), LGD-4033 (ligandrol), RAD140, S-23 and YK- ...
34, 35] Impaired erythropoietin (EPO) production and activity and EPO receptor responsiveness have also been observed. ... Serum erythropoietin and aging: a longitudinal analysis. J Am Geriatr Soc. 2005 Aug. 53(8):1360-5. [QxMD MEDLINE Link]. ... Renal function, erythropoietin, and anemia of older persons: the InCHIANTI study. Arch Intern Med. 2005 Oct 24. 165(19):2222-7 ... Erythropoietin deficiency causes anemia in nephrotic children with normal kidney function. Am J Kidney Dis. 2001 Apr. 37(4):736 ...
Truncated erythropoietin receptor causes dominantly inherited benign human erythrocytosis. Proc Natl Acad Sci U S A 1993;90: ... confers extreme phenotype as in the example of a gain-of-function mutation erythropoietin receptor in the Olympic cross-country ... Blood transcriptional signature of recombinant human erythropoietin administration and implications for antidoping strategies. ... Validation of whole-blood transcriptome signature during microdose recombinant human erythropoietin (rHuEpo) administration. ...
What set Mäntyranta apart from his competitors is a mutation in his erythropoietin receptor (EPOR) gene. ...
... aryl hydrocarbon receptor nuclear translocator; BCRP, breast cancer resistance protein; Epo, erythropoietin; HCONT, hepatocytes ... Geisterfer M, Richards C, Baumann M, Fey G, Gywnne D, and Gauldie J (1993) Regulation of IL-6 and the hepatic IL-6 receptor in ... Burk O, Arnold KA, Geick A, Tegude H, and Eichelbaum M (2005) A role for constitutive androstane receptor in the regulation of ... Ellery JM and Nicholls PJ (2002) Alternate signalling pathways from the interleukin-2 receptor. Cytokine Growth Factor Rev 13: ...
2016) Erythropoietin (EPO)-receptor signaling induces cell death of primary myeloma cells in vitro. Journal of Hematology & ... 2016) Erythropoietin (EPO)-receptor signaling induces cell death of primary myeloma cells in vitro. Journal of Hematology & ... 2019) Ectonucleotidase CD39 and Checkpoint Signalling Receptor Programmed Death 1 are Highly Elevated in Intratumoral Immune ... 2019) Ectonucleotidase CD39 and Checkpoint Signalling Receptor Programmed Death 1 are Highly Elevated in Intratumoral Immune ...

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