Complement component 4
Complement component 4, in humans, is a protein involved in the intricate complement system, originating from the human leukocyte antigen system. It serves a number of critical functions in immunity and autoimmunity with the other numerous components. Furthermore, it is a crucial factor in connecting the recognition pathways of the overall system instigated by antibody-antigen complexes to the other effector proteins of the innate immune response. For example, the severity of a dysfunctional complement system can lead to fatal diseases and infections. Complex variations of it can lead to schizophrenia. Yet, the C4 protein derives from a simple two-locus allelic model, the C4A-C4B genes, that allows for an abundant variation in the levels of their respective proteins within a population. Defined in the context of the Chido/Rodgers blood group system, the C4A-C4B genetic model is under investigation for its possible role in schizophrenia risk and development. One of the earlier genetic studies on the C4 protein identified two different groups, found within a human serum, called the Chido/Rogers blood groups.
O’Neill et al. have demonstrated that two different C4 loci express the different Ch/Rg antigens on the membranes of erythrocytes. More the two proteins, Ch and Rg, function together as a medium for interaction between the Ab-Ag complex and other complement components. Moreover, the two loci are linked to the HLA, or the human analog of the major histocompatibility complex on the short arm of chromosome 6, whereas they were believed to have been expressed by two codominant alleles at a single locus. In gel electrophoresis studies, O’Neill et al. have identified two genetic variants: F, signifying the presence or absence of four fast moving bands, S, signifying the presence or absence of four slow moving bands. The homogeneity or heterogeneity of the two loci, with the addition of these null genes, allow for duplication/non-duplication of the C4 loci. Therefore, having separate loci for C4, C4F and C4S account for producing multiple allelic forms, leading to the great size and copy number variation.
Two important contributors and Porter, in their study of cloning the human C4 gene, which consists of 3 subparts, showed that all six of their clones contained the same C4 gene. Regarding the subunits, the α-, β-, γ-chains were before found to have molecular weights of ~95,000, 78,000, 31,000 all joined by interchain disulfide bridges. In a study by Roos et al. the α-chains between the C4A and C4B were found to be different, proving that there is a structural difference between the two variants. Moreover, they implicated that a lack of C4 activity could be attributed to the structural differences between the α-chains. Carroll and Porter demonstrated that there is a 1,500-bp region that acts as an intron in the genomic sequence, which they believed to be the known C4d region, a byproduct of C4 activity. Carroll et al. published work that characterized the structure and organization of the C4 genes, which are situated in the HLA class III region and linked with C2 and factor B on the chromosome.
Through experiments involving restriction mapping, nucleotide sequence analysis, hybridization with C4A and C4B, they found that the genes are fairly similar though they have their differences. For example, single nucleotide polymorphisms were detected, which allowed them to be class differences between C4A and C4B. Furthermore and allelic differences would affect the performance of the C4 proteins with the immune complex. By overlapping cDNA cloned fragments, they were able to determine that the C4 loci, an estimated 16 kilobase long, are spaced by 10 kb and aligned 30 kb from the factor B locus. In the same year, studies relatedly identified a 98 kb region of the chromosome the four class III genes are linked, which does not allow for cross-overs to occur. Using protein variants visualized by electrophoresis, the four structural genes were located between HLA-B and HLA-D. More they verified the proposed molecular map in which the gene order went from factor B, C4B, C4A, C2 with C2 nearest to HLA-B.
In another study, Law et al. continued to delve deeper, this time comparing the properties of both the C4A and C4B, both of which are substantial players in the human immunity system. Through methods that include incubation, different pH levels, treatment with methylamine, they had biochemically illustrated the different reactivities of the C4 genes. More the C4B has shown to react much more efficiently and despite the 7 kb difference between C4A and C4B. In whole serum, C4B alleles performed at a rate several fold greater during hemolytic activity, in direct comparison with C4A alleles. Biochemically, they found that C4A reacted more with an antibody’s amino acid side chains and antigens that are amino groups, while C4B reacted better with carbohydrate hydroxyl groups. Thus, upon analysis of the varying reactivities, they proposed that the exceptional polymorphism of C4 genes may bring about some biological advantages. Though at this point in time, the genomic and derived amino acid sequence of either C4A or C4B had yet to be determined.
The early studies vastly expanded the knowledge of the C4 complex, laying down the foundations that paved the way to discovering the gene and protein structures. C. Yu determined the complete seq
The blood vessels are a part of the circulatory system, microcirculation, that transports blood throughout the human body. These vessels are designed to transport nutrients and oxygen to the tissues of the body, they take waste and carbon dioxide and carry them away from the tissues and back to the heart. Blood vessels are needed to sustain life. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the word vascular, meaning relating to the blood vessels, is derived from the Latin vas, meaning vessel. Some structures -- such as cartilage, the epithelium, the lens and cornea of the eye -- do not contain blood vessels and are labeled avascular; the arteries and veins have three layers. The middle layer is thicker in the arteries than it is in the veins: The inner layer, tunica intima, is the thinnest layer, it is a single layer of flat cells glued by a polysaccharide intercellular matrix, surrounded by a thin layer of subendothelial connective tissue interlaced with a number of circularly arranged elastic bands called the internal elastic lamina.
A thin membrane of elastic fibers in the tunica intima run parallel to the vessel. The middle layer tunica media is the thickest layer in arteries, it consists of circularly arranged elastic fiber, connective tissue, polysaccharide substances, the second and third layer are separated by another thick elastic band called external elastic lamina. The tunica media may be rich in vascular smooth muscle. Veins don't have the external elastic lamina, but only an internal one; the tunica media is thicker in the arteries rather than the veins. The outer layer is the thickest layer in veins, it is made of connective tissue. It contains nerves that supply the vessel as well as nutrient capillaries in the larger blood vessels. Capillaries consist of little more than a layer of endothelium and occasional connective tissue; when blood vessels connect to form a region of diffuse vascular supply it is called an anastomosis. Anastomoses provide critical alternative routes for blood to flow in case of blockages. There is a layer of muscle surrounding the arteries and the veins which help contract and expand the vessels.
This creates enough pressure for blood to be pumped around the body. Blood vessels are part of the circulatory system, together with the blood; the biggest difference in the structure of arteries and veins is the presence of valves. Backflow of blood is prevented in arteries by the heart; however in veins, one-direction valves are used to prevent backflow as a result of a decrease in blood pressure as the blood passes through the circulatory system. There are various kinds of blood vessels: Arteries Elastic arteries Distributing arteries Arterioles Capillaries Venules Veins Large collecting vessels, such as the subclavian vein, the jugular vein, the renal vein and the iliac vein. Venae cavae. Sinusoids Extremely small vessels located within bone marrow, the spleen, the liver, they are grouped as "arterial" and "venous", determined by whether the blood in it is flowing away from or toward the heart. The term "arterial blood" is used to indicate blood high in oxygen, although the pulmonary artery carries "venous blood" and blood flowing in the pulmonary vein is rich in oxygen.
This is because they are carrying the blood to and from the lungs to be oxygenated. Blood vessels function to transport blood. In general and arterioles transport oxygenated blood from the lungs to the body and its organs, veins and venules transport deoxygenated blood from the body to the lungs. Blood vessels circulate blood throughout the circulatory system Oxygen is the most critical nutrient carried by the blood. In all arteries apart from the pulmonary artery, hemoglobin is saturated with oxygen. In all veins apart from the pulmonary vein, the saturation of hemoglobin is about 75%. In addition to carrying oxygen, blood carries hormones, waste products and nutrients for cells of the body. Blood vessels do not engage in the transport of blood. Blood is propelled through arterioles through pressure generated by the heartbeat. Blood vessels transport red blood cells which contain the oxygen necessary for daily activities; the amount of red blood cells present in your vessels has an effect on your health.
Hematocrit tests can be performed to calculate the proportion of red blood cells in your blood. Higher proportions result in conditions such as dehydration or heart disease while lower proportions could lead to anemia and long-term blood loss. Blood vessels transport red blood cells which contain the oxygen necessary for daily activities; the amount of red blood cells present in your vessels has an effect on your health. Hematocrit tests can be performed to calculate the proportion of red blood cells in your blood. Higher proportions result in conditions such as dehydration or heart disease while lower proportions could lead to anemia and long-term blood loss. Permeability of the endothelium is pivotal in the release of nutrients to the tissue, it is increased in inflammation in response to histamine and interleukins, which leads to most of the
A microscope is an instrument used to see objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small structures using such an instrument. Microscopic means invisible to the eye. There are many types of microscopes, they may be grouped in different ways. One way is to describe the way the instruments interact with a sample to create images, either by sending a beam of light or electrons to a sample in its optical path, or by scanning across, a short distance from the surface of a sample using a probe; the most common microscope is the optical microscope, which uses light to pass through a sample to produce an image. Other major types of microscopes are the fluorescence microscope, the electron microscope and the various types of scanning probe microscopes. Although objects resembling lenses date back 4000 years and there are Greek accounts of the optical properties of water-filled spheres followed by many centuries of writings on optics, the earliest known use of simple microscopes dates back to the widespread use of lenses in eyeglasses in the 13th century.
The earliest known examples of compound microscopes, which combine an objective lens near the specimen with an eyepiece to view a real image, appeared in Europe around 1620. The inventor is unknown. Several revolve around the spectacle-making centers in the Netherlands including claims it was invented in 1590 by Zacharias Janssen and/or Zacharias' father, Hans Martens, claims it was invented by their neighbor and rival spectacle maker, Hans Lippershey, claims it was invented by expatriate Cornelis Drebbel, noted to have a version in London in 1619. Galileo Galilei seems to have found after 1610 that he could close focus his telescope to view small objects and, after seeing a compound microscope built by Drebbel exhibited in Rome in 1624, built his own improved version. Giovanni Faber coined the name microscope for the compound microscope Galileo submitted to the Accademia dei Lincei in 1625; the first detailed account of the microscopic anatomy of organic tissue based on the use of a microscope did not appear until 1644, in Giambattista Odierna's L'occhio della mosca, or The Fly's Eye.
The microscope was still a novelty until the 1660s and 1670s when naturalists in Italy, the Netherlands and England began using them to study biology. Italian scientist Marcello Malpighi, called the father of histology by some historians of biology, began his analysis of biological structures with the lungs. Robert Hooke's Micrographia had a huge impact because of its impressive illustrations. A significant contribution came from Antonie van Leeuwenhoek who achieved up to 300 times magnification using a simple single lens microscope, he sandwiched a small glass ball lens between the holes in two metal plates riveted together, with an adjustable-by-screws needle attached to mount the specimen. Van Leeuwenhoek re-discovered red blood cells and spermatozoa, helped popularise the use of microscopes to view biological ultrastructure. On 9 October 1676, van Leeuwenhoek reported the discovery of micro-organisms; the performance of a light microscope depends on the quality and correct use of the condensor lens system to focus light on the specimen and the objective lens to capture the light from the specimen and form an image.
Early instruments were limited until this principle was appreciated and developed from the late 19th to early 20th century, until electric lamps were available as light sources. In 1893 August Köhler developed a key principle of sample illumination, Köhler illumination, central to achieving the theoretical limits of resolution for the light microscope; this method of sample illumination produces lighting and overcomes the limited contrast and resolution imposed by early techniques of sample illumination. Further developments in sample illumination came from the discovery of phase contrast by Frits Zernike in 1953, differential interference contrast illumination by Georges Nomarski in 1955. In the early 20th century a significant alternative to the light microscope was developed, an instrument that uses a beam of electrons rather than light to generate an image; the German physicist, Ernst Ruska, working with electrical engineer Max Knoll, developed the first prototype electron microscope in 1931, a transmission electron microscope.
The transmission electron microscope works on similar principles to an optical microscope but uses electrons in the place of light and electromagnets in the place of glass lenses. Use of electrons, instead of light, allows for much higher resolution. Development of the transmission electron microscope was followed in 1935 by the development of the scanning electron microscope by Max Knoll. Although TEMs were being used for research before WWII, became popular afterwards, the SEM was not commercially available until 1965. Transmission electron microscopes became popular following the Second World War. Ernst Ruska, working at Siemens, developed the first commercial transmission electron microscope and, in the 1950s, major scientific conferences on electron microscopy started being held. In 1965, the first commercial scanning electron microscope was developed by Profess
Blood is a body fluid in humans and other animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells. In vertebrates, it is composed of blood cells suspended in blood plasma. Plasma, which constitutes 55% of blood fluid, is water, contains proteins, mineral ions, carbon dioxide, blood cells themselves. Albumin is the main protein in plasma, it functions to regulate the colloidal osmotic pressure of blood; the blood cells are red blood cells, white blood cells and platelets. The most abundant cells in vertebrate blood are red blood cells; these contain hemoglobin, an iron-containing protein, which facilitates oxygen transport by reversibly binding to this respiratory gas and increasing its solubility in blood. In contrast, carbon dioxide is transported extracellularly as bicarbonate ion transported in plasma. Vertebrate blood is bright red when its hemoglobin is oxygenated and dark red when it is deoxygenated.
Some animals, such as crustaceans and mollusks, use hemocyanin to carry oxygen, instead of hemoglobin. Insects and some mollusks use a fluid called hemolymph instead of blood, the difference being that hemolymph is not contained in a closed circulatory system. In most insects, this "blood" does not contain oxygen-carrying molecules such as hemoglobin because their bodies are small enough for their tracheal system to suffice for supplying oxygen. Jawed vertebrates have an adaptive immune system, based on white blood cells. White blood cells help to resist parasites. Platelets are important in the clotting of blood. Arthropods, using hemolymph, have hemocytes as part of their immune system. Blood is circulated around the body through blood vessels by the pumping action of the heart. In animals with lungs, arterial blood carries oxygen from inhaled air to the tissues of the body, venous blood carries carbon dioxide, a waste product of metabolism produced by cells, from the tissues to the lungs to be exhaled.
Medical terms related to blood begin with hemo- or hemato- from the Greek word αἷμα for "blood". In terms of anatomy and histology, blood is considered a specialized form of connective tissue, given its origin in the bones and the presence of potential molecular fibers in the form of fibrinogen. Blood performs many important functions within the body, including: Supply of oxygen to tissues Supply of nutrients such as glucose, amino acids, fatty acids Removal of waste such as carbon dioxide and lactic acid Immunological functions, including circulation of white blood cells, detection of foreign material by antibodies Coagulation, the response to a broken blood vessel, the conversion of blood from a liquid to a semisolid gel to stop bleeding Messenger functions, including the transport of hormones and the signaling of tissue damage Regulation of core body temperature Hydraulic functions Blood accounts for 7% of the human body weight, with an average density around 1060 kg/m3 close to pure water's density of 1000 kg/m3.
The average adult has a blood volume of 5 litres, composed of plasma and several kinds of cells. These blood cells consist of erythrocytes and thrombocytes. By volume, the red blood cells constitute about 45% of whole blood, the plasma about 54.3%, white cells about 0.7%. Whole blood exhibits non-Newtonian fluid dynamics. If all human hemoglobin were free in the plasma rather than being contained in RBCs, the circulatory fluid would be too viscous for the cardiovascular system to function effectively. One microliter of blood contains: 4.7 to 6.1 million, 4.2 to 5.4 million erythrocytes: Red blood cells contain the blood's hemoglobin and distribute oxygen. Mature red blood cells lack a nucleus and organelles in mammals; the red blood cells are marked by glycoproteins that define the different blood types. The proportion of blood occupied by red blood cells is referred to as the hematocrit, is about 45%; the combined surface area of all red blood cells of the human body would be 2,000 times as great as the body's exterior surface.
4,000–11,000 leukocytes: White blood cells are part of the body's immune system. The cancer of leukocytes is called leukemia. 200,000 -- 500,000 thrombocytes: Also called platelets. Fibrin from the coagulation cascade creates a mesh over the platelet plug. About 55% of blood is blood plasma, a fluid, the blood's liquid medium, which by itself is straw-yellow in color; the blood plasma volume totals of 2.7–3.0 liters in an average human. It is an aqueous solution containing 92% water, 8% blood plasma proteins, trace amounts of other materials. Plasma circulates dissolved nutrients, such as glucose, amino acids, fatty acids, removes waste products, such as carbon dioxide and lactic acid. Other important components include: Serum albumin Blood-clotting factors Immunoglobulins lipoprotein particles Various
A blood bank is a center where blood gathered as a result of blood donation is stored and preserved for use in blood transfusion. The term "blood bank" refers to a division of a hospital where the storage of blood product occurs and where proper testing is performed. However, it sometimes refers to a collection center, indeed some hospitals perform collection. For blood donation agencies in various countries, see List of blood donation agencies and List of blood donation agencies in the United States. Whole blood or blood with RBC, is transfused to patients with anaemia/iron deficiency, it helps to improve the oxygen saturation in blood. It can be stored at 1.0 °C-6.0 °C for 35–45 days. Platelet transfusion, is transfused to those; this can be stored at room temperature for 5–7 days. The donation of Plasma is called. Plasma transfusion is indicated to patients with severe infections or serious burns. Fresh frozen plasma can be stored at a low temperature of -25 °C for up to 12 months. While the first blood transfusions were made directly from donor to receiver before coagulation, it was discovered that by adding anticoagulant and refrigerating the blood it was possible to store it for some days, thus opening the way for the development of blood banks.
John Braxton Hicks was the first to experiment with chemical methods to prevent the coagulation of blood at St Mary's Hospital, London in the late 19th century. His attempts, using phosphate of soda, were unsuccessful; the first non-direct transfusion was performed on March 27, 1914 by the Belgian doctor Albert Hustin, though this was a diluted solution of blood. The Argentine doctor Luis Agote used a much less diluted solution in November of the same year. Both used sodium citrate as an anticoagulant; the First World War acted as a catalyst for the rapid development of blood banks and transfusion techniques. Canadian Lieutenant Lawrence Bruce Robertson was instrumental in persuading the Royal Army Medical Corps to adopt the use of blood transfusion at the Casualty Clearing Stations for the wounded. In October 1915, Robertson performed his first wartime transfusion with a syringe to a patient suffering from multiple shrapnel wounds, he followed this up with four subsequent transfusions in the following months, his success was reported to Sir Walter Morley Fletcher, director of the Medical Research Committee.
Robertson published his findings in the British Medical Journal in 1916, and—with the help of a few like minded individuals —was able to persuade the British authorities of the merits of blood transfusion. Robertson went on to establish the first blood transfusion apparatus at a Casualty Clearing Station on the Western Front in the spring of 1917. Oswald Hope Robertson, a medical researcher and U. S. Army officer was attached to the RAMC in 1917, where he was instrumental in establishing the first blood banks, in preparation for the anticipated Third Battle of Ypres, he used sodium citrate as the anticoagulant, the blood was extracted from punctures in the vein, was stored in bottles at British and American Casualty Clearing Stations along the Front. He experimented with preserving separated red blood cells in iced bottles. Geoffrey Keynes, a British surgeon, developed a portable machine that could store blood to enable transfusions to be carried out more easily; the world's first blood donor service was established in 1921 by the secretary of the British Red Cross, Percy Oliver.
Volunteers were subjected to a series of physical tests to establish their blood group. The London Blood Transfusion Service expanded rapidly. By 1925, it was providing services for 500 patients and it was incorporated into the structure of the British Red Cross in 1926. Similar systems were established in other cities including Sheffield and Norwich, the service's work began to attract international attention. Similar services were established in France, Austria, Belgium and Japan. Vladimir Shamov and Sergei Yudin in the Soviet Union pioneered the transfusion of cadaveric blood from deceased donors. Yudin performed such a transfusion for the first time on March 23, 1930 and reported his first seven clinical transfusions with cadaveric blood at the Fourth Congress of Ukrainian Surgeons at Kharkiv in September. In 1930, Yudin organized the world's first blood bank at the Nikolay Sklifosovsky Institute, which set an example for the establishment of further blood banks in different regions of the Soviet and in other countries.
By the mid-1930s Soviet had set up a system of at least 65 large blood centers and more than 500 subsidiary ones, all storing "canned" blood and shipping it to all corners of the country. One of the earliest blood banks was established by Frederic Durán-Jordà during the Spanish Civil War in 1936. Duran joined the Transfusion Service at the Barcelona Hospital at the start of the conflict, but the hospital was soon overwhelmed by the demand for blood and the paucity of available donors. With support from the Department of Health of the Spanish Republican Army, Duran established a blood bank for the use of wounded soldiers and civilians; the 300–400 ml of extracted blood was mixed with 10% citrate solution in a modified Duran Erlenmeyer flask. The blood was stored in a sterile glass enclosed under pressure at 2 °C. During 30 months of work, the Transfusion Service of Barcelona registered 30,000 donors, processed 9,000 liters of blood. In 1937 Bernard Fantus, director of therapeutics at the Cook County Hospital in Chicago, established the one of the fir
American and British English spelling differences
Many of the differences between American and British English date back to a time when spelling standards had not yet developed. For instance, some spellings seen as "American" today were once used in Britain and some spellings seen as "British" were once used in the United States. A "British standard" began to emerge following the 1755 publication of Samuel Johnson's A Dictionary of the English Language, an "American standard" started following the work of Noah Webster and in particular his An American Dictionary of the English Language, first published in 1828. Webster's efforts at spelling reform were somewhat effective in his native country, resulting in certain well-known patterns of spelling differences between the American and British varieties of English. However, English-language spelling reform has been adopted otherwise, so modern English orthography varies somewhat between countries and is far from phonemic in any country. In the early 18th century, English spelling was inconsistent.
These differences became noticeable after the publishing of influential dictionaries. Today's British English spellings follow Johnson's A Dictionary of the English Language, while many American English spellings follow Webster's An American Dictionary of the English Language. Webster was a proponent of English spelling reform for reasons both nationalistic. In A Companion to the American Revolution, John Algeo notes: "it is assumed that characteristically American spellings were invented by Noah Webster, he was influential in popularizing certain spellings in America, but he did not originate them. Rather he chose existing options such as center and check for the simplicity, analogy or etymology". William Shakespeare's first folios, for example, used spellings like center and color as much as centre and colour. Webster did attempt to introduce some reformed spellings, as did the Simplified Spelling Board in the early 20th century, but most were not adopted. In Britain, the influence of those who preferred the Norman spellings of words proved to be decisive.
Spelling adjustments in the United Kingdom had little effect on today's American spellings and vice versa. For the most part, the spelling systems of most Commonwealth countries and Ireland resemble the British system. In Canada, the spelling system can be said to follow both British and American forms, Canadians are somewhat more tolerant of foreign spellings when compared with other English-speaking nationalities. Australian spelling has strayed from British spelling, with some American spellings incorporated as standard. New Zealand spelling is identical to British spelling, except in the word fiord. There is an increasing use of macrons in words that originated in Māori and an unambiguous preference for -ise endings. Most words ending in an unstressed -our in British English end in -or in American English. Wherever the vowel is unreduced in pronunciation, e.g. contour, velour and troubadour the spelling is consistent everywhere. Most words of this kind came from Latin, they were first adopted into English from early Old French, the ending was spelled -or or -ur.
After the Norman conquest of England, the ending became -our to match the Old French spelling. The -our ending was not only used in new English borrowings, but was applied to the earlier borrowings that had used -or. However, -or was still sometimes found, the first three folios of Shakespeare's plays used both spellings before they were standardised to -our in the Fourth Folio of 1685. After the Renaissance, new borrowings from Latin were taken up with their original -or ending and many words once ending in -our went back to -or. Many words of the -our/or group do not have a Latin counterpart; some 16th- and early 17th-century British scholars indeed insisted that -or be used for words from Latin and -our for French loans. Webster's 1828 dictionary had only -or and is given much of the credit for the adoption of this form in the United States. By contrast, Johnson's 1755 dictionary used -our for all words still so spelled in Britain, but for words where the u has since been dropped: ambassadour, governour, inferiour, superiour.
Johnson, unlike Webster, was not an advocate of spelling reform, but chose the spelling best derived, as he saw it, from among the variations in his sources. He preferred French over Latin spellings because, as he put it, "the French supplied us". English speakers who moved to America took these preferences with them, H. L. Mencken notes that "honor appears in the 1776 Declaration of Independence, but it seems to have got there rather by accident than by design. In Jefferson's original draft it is spelled "honour". In Britain, examples of color, behavior and neighbor appear in Old Bailey court records from the 17th and 18th centuries, whereas there are thousands of examples of their -our counterparts. One notable exception is honor. Honor and honour were frequent in Br