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The discovery in the late 1940's that sickle cell anemia is a "molecular disease" of hemoglobin was the crucial advance that gave birth to the scientific discipline of human molecular genetics. In subsequent years, with the continued expansion of knowledge about the biology and genetics of the hemoglobins, and particularly as a result of the characterization of the very large numbers of globin gene mutations, the human hemoglobin system has remained as the premier model of gene expression at the molecular level in man. With the recent explosion of new information about the genetic properties of the hemoglobins, it appears inevitable that this gene system will continue to occupy a unique position in human molecular genetics for many years in the future. Hemoglobin genetics has also recently come of age as a diagnostic and clinical discipline. The heightening of public awareness in recent years about sickle cell disease, thalassemia, and other inherited disorders has brought increasing demands for carrier detection services as well as for genetic counseling and education. The more recent development of prac tical and reliable methods for the antenatal diagnosis of hemoglobin dis orders has further increased the scope of clinical hemoglobin genetics, and it can be anticipated that these potent diagnostic techniques will have increasing application in the years ahead.
Completely revised new edition of the definitive reference on disorders of hemoglobin.
This presentation describes various aspects of the regulation of tissue oxygenation, including the roles of the circulatory system, respiratory system, and blood, the carrier of oxygen within these components of the cardiorespiratory system. The respiratory system takes oxygen from the atmosphere and transports it by diffusion from the air in the alveoli to the blood flowing through the pulmonary capillaries. The cardiovascular system then moves the oxygenated blood from the heart to the microcirculation of the various organs by convection, where oxygen is released from hemoglobin in the red blood cells and moves to the parenchymal cells of each tissue by diffusion. Oxygen that has diffused into cells is then utilized in the mitochondria to produce adenosine triphosphate (ATP), the energy currency of all cells. The mitochondria are able to produce ATP until the oxygen tension or PO2 on the cell surface falls to a critical level of about 4–5 mm Hg. Thus, in order to meet the energetic needs of cells, it is important to maintain a continuous supply of oxygen to the mitochondria at or above the critical PO2 . In order to accomplish this desired outcome, the cardiorespiratory system, including the blood, must be capable of regulation to ensure survival of all tissues under a wide range of circumstances. The purpose of this presentation is to provide basic information about the operation and regulation of the cardiovascular and respiratory systems, as well as the properties of the blood and parenchymal cells, so that a fundamental understanding of the regulation of tissue oxygenation is achieved.
Since the dawn of the era of molecular biology, hemoglobin has been subjected to more scrutiny than any other protein, and Bunn, Forget, and Ranney can each lay claim to major contributions to the saga of hemoglobin. Their well-organized, comprehensive, and superbly illustrated work is an excellent review of the abnormal hemoglobin field. Early chapters deal with the structure and function of human hemoglobin and the way in which this is modified in various disease states. Later sections deal with the various structural hemoglobin variants and their associated clinical manifestations, the thalassaemias, and the acquired disorders of hemoglobin. The sections that deal with the modification of hemoglobin function in various disease states are particularly good. The book contains an extensive and up-to-date bibliography and is remarkably free from errors of fact or type--the best standard of reference on the subject as of the year 1977.
Research on abnormal human hemoglobins (protein in blood that carries oxygen), has taught us about the inheritance, biochemistry, and distribution of these traits. This knowledge, coupled with mathematical research using computer models of population genetics, has enabled researchers to marry biological fact and genetic theory. This volume places medical understanding in an evolutionary framework. Using published data on the frequencies of abnormal hemoglobins in the world's populations, Livingston analyzes and interprets these frequencies in the light of world distribution of different forms of diseases such as malaria. He further develops the genetic theory of the evolutionary homeostasis. Livingston discusses the relation of abnormal hemoglobins to endemic malaria and, shows how natural selection pressures explain the known distribution of these traits. Where non-coinciding distributions arise, the book presents other genetic, anthropological, evolutionary, and epidemiological evidence to explain these discrepancies. This classic work remains a useful sourcebook for professors and graduate students of anthropology, genetics, epidemiology, and hematology.
The bright colour of haemoglobin has, from the very beginning, played a significant role in both the investigation of this compound as well as in the study of blood oxygen transport. Numerous optical methods have been developed for measuring haemoglobin concentration, oxygen saturation, and the principal dyshaemoglobins in vitro as well as in vivo.
This book focuses on respiratory proteins, the broad hemoglobin family, as well as the molluscan and arachnid hemocyanins (and their multifunctional roles). Featuring 20 chapters addressing invertebrate and vertebrate respiratory proteins, lipoproteins and other body fluid proteins, and drawing on the editors’ extensive research in the field, it is a valuable addition to the Subcellular Biochemistry book series. The book covers a wide range of topics, including lipoprotein structure and lipid transport; diverse annelid, crustacean and insect defense proteins; and insect and vertebrate immune complexes. It also discusses a number of other proteins, such as the hemerythrins; serum albumin; serum amyloid A; von Willebrand factor and its interaction with factor VIII; and C-reactive protein. Given its scope, the book appeals to biologists, biomedical scientists and clinicians, as well as advanced undergraduates and postgraduates in these disciplines. Available as a printed book and also as an e-book and e-chapters, the fascinating material included is easily accessible.
Haemoglobin is one of the most important molecules in the animal kingdom. Its function is to carry oxygen to tissues. In lower invertebrates the blood pigment is present in the haemolymph and is not bound in cells. Later in the course of phylo genesis haemoglobin remains associated with cells which produce it and in this form it reaches the peripheral circulation. In higher organisms the haemoglobin production is thus determined by two main factors: haemoglobin synthesis in erythroid cells and the formation of these erythroid cells which depends on cell proliferation in haematopoietic organs. Human haemoglobin is made up of two chains which combine from four different polypeptide chains formed in varying ratios in different periods of the life cycle. During the life span of humans the following haemoglobins are formed: embryonic haemoglobins Gower 1 and 2, foetal haemoglobin F and two adult haemoglobins A and A . E-and IX-chains are part of the embryonic haemoglobins Gower 1 (E4) and 2 Gower 2 (1X2E2). These haemoglobins predominate in embryos during the second month of pregnancy and at the end of the first trimester they are completely re placed by foetal haemoglobin F (~Y2). Adult haemoglobin A consists of two IX and two ~-chains and is the main component of red cells in adults. A relatively small component of red cells accounting for less than 2 % of the total haemo globin, is haemoglobin A2 (1X0).