Hemoglobin or haemoglobin, abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates as well as the tissues of some invertebrates. Haemoglobin in the blood carries oxygen from the gills to the rest of the body. There it releases the oxygen to permit aerobic respiration to provide energy to power the functions of the organism in the process called metabolism. A healthy individual has 12 to 16 grams of haemoglobin in every 100 ml of blood. In mammals, the protein makes up about 96% of the red blood cells' dry content, around 35% of the total content. Haemoglobin has an oxygen-binding capacity of 1.34 mL O2 per gram, which increases the total blood oxygen capacity seventy-fold compared to dissolved oxygen in blood. The mammalian hemoglobin molecule can bind up to four oxygen molecules. Hemoglobin is involved in the transport of other gases: It carries some of the body's respiratory carbon dioxide as carbaminohemoglobin, in which CO2 is bound to the heme protein.
The molecule carries the important regulatory molecule nitric oxide bound to a globin protein thiol group, releasing it at the same time as oxygen. Haemoglobin is found outside red blood cells and their progenitor lines. Other cells that contain haemoglobin include the A9 dopaminergic neurons in the substantia nigra, alveolar cells, retinal pigment epithelium, mesangial cells in the kidney, endometrial cells, cervical cells and vaginal epithelial cells. In these tissues, haemoglobin has a non-oxygen-carrying function as an antioxidant and a regulator of iron metabolism. Haemoglobin and haemoglobin-like molecules are found in many invertebrates and plants. In these organisms, haemoglobins may carry oxygen, or they may act to transport and regulate other small molecules and ions such as carbon dioxide, nitric oxide, hydrogen sulfide and sulfide. A variant of the molecule, called leghaemoglobin, is used to scavenge oxygen away from anaerobic systems, such as the nitrogen-fixing nodules of leguminous plants, before the oxygen can poison the system.
In 1825 J. F. Engelhard discovered that the ratio of iron to protein is identical in the hemoglobins of several species. From the known atomic mass of iron he calculated the molecular mass of hemoglobin to n × 16000, the first determination of a protein's molecular mass; this "hasty conclusion" drew a lot of ridicule at the time from scientists who could not believe that any molecule could be that big. Gilbert Smithson Adair confirmed Engelhard's results in 1925 by measuring the osmotic pressure of hemoglobin solutions; the oxygen-carrying property of hemoglobin was discovered by Hünefeld in 1840. In 1851, German physiologist Otto Funke published a series of articles in which he described growing hemoglobin crystals by successively diluting red blood cells with a solvent such as pure water, alcohol or ether, followed by slow evaporation of the solvent from the resulting protein solution. Hemoglobin's reversible oxygenation was described a few years by Felix Hoppe-Seyler. In 1959, Max Perutz determined the molecular structure of hemoglobin by X-ray crystallography.
This work resulted in his sharing with John Kendrew the 1962 Nobel Prize in Chemistry for their studies of the structures of globular proteins. The role of hemoglobin in the blood was elucidated by French physiologist Claude Bernard; the name hemoglobin is derived from the words heme and globin, reflecting the fact that each subunit of hemoglobin is a globular protein with an embedded heme group. Each heme group contains one iron atom, that can bind one oxygen molecule through ion-induced dipole forces; the most common type of hemoglobin in mammals contains four such subunits. Hemoglobin consists of protein subunits, these proteins, in turn, are folded chains of a large number of different amino acids called polypeptides; the amino acid sequence of any polypeptide created by a cell is in turn determined by the stretches of DNA called genes. In all proteins, it is the amino acid sequence that determines the protein's chemical properties and function. There is more than one hemoglobin gene: in humans, hemoglobin A is coded for by the genes, HBA1, HBA2, HBB.
The amino acid sequences of the globin proteins in hemoglobins differ between species. These differences grow with evolutionary distance between species. For example, the most common hemoglobin sequences in humans and chimpanzees are nearly identical, differing by only one amino acid in both the alpha and the beta globin protein chains; these differences grow larger between less related species. Within a species, different variants of hemoglobin always exist, although one sequence is a "most common" one in each species. Mutations in the genes for the hemoglobin protein in a species result in hemoglobin variants. Many of these mutant forms of hemoglobin cause no disease; some of these mutant forms of hemoglobin, cause a group of hereditary diseases termed the hemoglobinopathies. The best known hemoglobinopathy is sickle-cell disease, the first human disease whose mechanism was understood at the molecular level. A separate set of diseases called thalassemias involves underproduction of normal and sometimes abnormal hemoglobins, through problems and mutations in globin gene regulation.
All these diseases produce anemia. Variations in hemoglobin amino acid sequences, as with other proteins, may be adaptive. For example, hemoglobin has been found to adapt in different ways to
A proerythroblast is the earliest of four stages in development of the normoblast. In histology, it is difficult to distinguish it from the other "-blast" cells; the cytoplasm is blue in an H&E stain, indicating. Proerythroblasts arise from the CFU-e cells, give rise to basophilic erythroblasts. In the mouse, proerythroblasts are large committed progenitors that express high levels of transferrin receptor, the erythropoietin receptor, some c-Kit, are Ter119 -positive, their proliferative capacity is more limited compared to the CFU-e. In vivo, starting with the proerythroblast stage, erythroid cells undergo several more cell divisions while at the same time upregulating survival genes such as Bcl-xL, acquiring and storing large amounts of iron, ramping up the synthesis of hemoglobin and other erythroid genes and decreasing in cell size removing their nuclei and being released into the bloodstream as a reticulocyte. There are several Nucleoli on the nucleus and it occupies most of the cell volume.
The chromatins are consist of a network of fine red pink strands. The distinguished feature of pro erythroblast to its corresponding myeloblast in granulocytic series is that it carries more basophilic peripheral cytoplasm; some sources consider the terms "pronormoblast" and "proerythroblast" to be synonyms. However, other sources consider "proerythroblast" to be a parent term, divided into the following two categories: "pronormoblast" - normal development "promegaloblast" - abnormal development Histology image: 01804loa – Histology Learning System at Boston University - "Bone Marrow and Hemopoiesis: bone marrow smear, erythroblast series with proerythroblast" Histology image: 75_11 at the University of Oklahoma Health Sciences Center Histology at KUMC blood-blood04 Image and description at purdue.edu Histology of "promegaloblast" at marist.edu Interactive image at usuarios.lycos.es Overview at temple.edu
Dyserythropoiesis refers to the defective development of red blood cells called erythrocytes. This problem acquired, or inherited; some red blood cells may be destroyed within the bone marrow during the maturation process, whereas others can enter the circulation with abnormalities. These abnormalities can be functional and/or morphological, which can lead to anemia since there may be increased turnover of red blood cells. There are a number of diseases. Congenital/inherited causes include congenital dyserythropoietic anemia, pyruvate kinase deficiency, hereditary pyropoikilocytosis, abetalipoproteinemia. Acquired causes include nutrient deficiency/malnutrition, myelodysplasia, HIV infection, certain medications. Erythropoiesis Erythrocyte Congenital dyserythropoietic anemia
Nucleated red blood cell
All vertebrate organisms have hemoglobin-containing cells in their blood, with the exception of mammals, all of these red blood cells contain a nucleus. Mammals represent ~5,500 named species out of ~66,000 vertebrate species, within this ~8% subgroup, red blood cells are known as erythrocytes or RBCs and have no cell nucleus in mature organisms. In contrast, a nucleated red blood cell known by several other names, is a mammalian RBC that contains a cell nucleus. NRBCs occur in normal development as progenitor cells in the erythropoietic lineage and in pathological states. Nucleated RBCs are found only in the circulation of fetuses and newborn infants. After infancy, RBCs only contain a nucleus during the early stages of the cell's life, the nucleus is ejected as a normal part of cellular differentiation before the cell is released into the bloodstream. Thus, if NRBCs are seen on an adult's peripheral blood smear, it suggests that there is a high demand for the bone marrow to produce RBCs, immature RBCs are being released into circulation.
Possible pathologic causes include anemia, thalassemia, miliary tuberculosis, cancers involving bone marrow, in chronic hypoxemia. Several names are used for nucleated RBCs—erythroblast and megaloblast—with one minor variation in word sense; the name normoblast always refers to normal, healthy cells that are the immediate precursors of normal, mature RBCs. The name megaloblast always refers to abnormally developed precursors; the name erythroblast is used synonymously with normoblast, but at other times it is considered a hypernym. In the latter sense, there are two types of erythroblasts: normoblasts as cells that develop as expected, megaloblasts as unusually large erythroblasts that are associated with illness. There are four stages in the normal development of a normoblast. A megaloblast is an unusually large erythroblast that can be associated with vitamin B12 deficiency, folic acid deficiency, or both; this kind of anemia leads to macrocytes and the condition called macrocytosis. The cause of this cellular gigantism is an impairment in DNA replication that delays nuclear maturation and cell division.
Because RNA and cytoplasmic elements are synthesized at a constant rate despite the cells' impaired DNA synthesis, the cells show nuclear-cytoplasmic asynchrony. Erythropoiesis Haematopoiesis Hematopoietic stem cell Pronormoblasts Presented by the University of Virginia Basophilic Normoblasts Presented by the University of Virginia Polychromatophilic Normoblasts Presented by the University of Virginia Orthochromatic Normoblasts Presented by the University of Virginia Histology image: 01804loa – Histology Learning System at Boston University - "Bone Marrow and Hemopoiesis bone marrow smear, erythroblast series with proerythroblast " Histology at uiowa.edu
The median is the value separating the higher half from the lower half of a data sample. For a data set, it may be thought of as the "middle" value. For example, in the data set, the median is 6, the fourth largest, the fifth smallest, number in the sample. For a continuous probability distribution, the median is the value such that a number is likely to fall above or below it; the median is a used measure of the properties of a data set in statistics and probability theory. The basic advantage of the median in describing data compared to the mean is that it is not skewed so much by large or small values, so it may give a better idea of a "typical" value. For example, in understanding statistics like household income or assets which vary a mean may be skewed by a small number of high or low values. Median income, for example, may be a better way to suggest; because of this, the median is of central importance in robust statistics, as it is the most resistant statistic, having a breakdown point of 50%: so long as no more than half the data are contaminated, the median will not give an arbitrarily large or small result.
The median of a finite list of numbers can be found by arranging all the numbers from smallest to greatest. If there is an odd number of numbers, the middle one is picked. For example, consider the list of numbers 1, 3, 3, 6, 7, 8, 9This list contains seven numbers; the median is the fourth of them, 6. If there is an number of observations there is no single middle value. For example, in the data set 1, 2, 3, 4, 5, 6, 8, 9the median is the mean of the middle two numbers: this is / 2, 4.5.. The formula used to find the index of the middle number of a data set of n numerically ordered numbers is / 2; this either gives the halfway point between the two middle values. For example, with 14 values, the formula will give an index of 7.5, the median will be taken by averaging the seventh and eighth values. So the median can be represented by the following formula: m e d i a n = a ⌈ # x ÷ 2 ⌉ + a ⌈ # x ÷ 2 + 1 ⌉ 2 One can find the median using the Stem-and-Leaf Plot. There is no accepted standard notation for the median, but some authors represent the median of a variable x either as x͂ or as μ1/2 sometimes M.
In any of these cases, the use of these or other symbols for the median needs to be explicitly defined when they are introduced. The median is used for skewed distributions, which it summarizes differently from the arithmetic mean. Consider the multiset; the median is 2 in this case, it might be seen as a better indication of central tendency than the arithmetic mean of 4. The median is a popular summary statistic used in descriptive statistics, since it is simple to understand and easy to calculate, while giving a measure, more robust in the presence of outlier values than is the mean; the cited empirical relationship between the relative locations of the mean and the median for skewed distributions is, not true. There are, various relationships for the absolute difference between them. With an number of observations no value need be at the value of the median. Nonetheless, the value of the median is uniquely determined with the usual definition. A related concept, in which the outcome is forced to correspond to a member of the sample, is the medoid.
In a population, at most half have values less than the median and at most half have values greater than it. If each group contains less than half the population some of the population is equal to the median. For example, if a < b < c the median of the list is b, and, if a < b < c < d the median of the list is the mean of b and c. Indeed, as it is based on the middle data in a group, it is not necessary to know the value of extreme results in order to calculate a median. For example, in a psychology test investigating the time needed to solve a problem, if a small number of people failed to solve the problem at all in the given time a median can still be calculated; the median can be used as a measure of location when a distribution is skewed, when end-values are not known, or when one requires reduced importance to be attached to outliers, e.g. because they may be measurement errors. A median is only defined on ordered one-dimensional data, is independent of any distance metric. A geometric median, on the other hand, is defined in any number of dimensions.
The median is one of a number of ways
Giovanni Di Guglielmo
Giovanni Di Guglielmo was a Brazilian-born Italian hematologist, best known for the discovery of acute erythroid leukemia. Di Guglielmo was born in the son of Italian immigrants from Andretta, his parents decided to move back to Italy. After completing his high school studies in Avellino, in 1911 he graduated in Medicine and Surgery at the University of Naples. After being assistant of the haematologist Adolfo Ferrata, in 1916 Di Guglielmo got the university teaching qualification in medical special pathology. During the First World War he served as medical lieutenant, during this time he started writing on erythroleukemia and other leukemic diseases. In 1927 he was appointed professor of special pathology at the University of Modena, he served as professor in the universities of Pavia, Catania and Rome, he founded and directed several medical institutions, including the Center for the Study of the brucellosis in Catania, two scientific journals, Progresso medico and Haematologica. Di Guglielmo's studies focused on hematology.
He got international recognition for the discovery of acute erythroid leukemia known as "Di Guglielmo syndrome" or "Di Guglielmo's disease". He was author of over 230 scientific publications. Media related to Giovanni Di Guglielmo at Wikimedia Commons