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ADAMTS13

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90-408: 11093 279028 ENSG00000160323 ENSG00000281244 ENSMUSG00000014852 Q76LX8 Q769J6 NM_139025 NM_139026 NM_139027 NM_139028 NM_001001322 NM_001290463 NM_001290464 NM_001290465 NP_620594 NP_620595 NP_620596 NP_001001322 NP_001277392 NP_001277393 NP_001277394 ADAMTS13 ( a d isintegrin a nd m etalloproteinase with

180-409: A condenser . Some alchemists called this zinc oxide lana philosophica , Latin for "philosopher's wool", because it collected in wooly tufts, whereas others thought it looked like white snow and named it nix album . The name of the metal was probably first documented by Paracelsus , a Swiss-born German alchemist, who referred to the metal as "zincum" or "zinken" in his book Liber Mineralium II , in

270-428: A gamma ray . Zn has three excited metastable states and Zn has two. The isotopes Zn , Zn , Zn and Zn each have only one excited metastable state. The most common decay mode of a radioisotope of zinc with a mass number lower than 66 is electron capture . The decay product resulting from electron capture is an isotope of copper. The most common decay mode of

360-429: A t hrombo s pondin type 1 motif, member 13 )—also known as von Willebrand factor-cleaving protease (VWFCP)—is a zinc -containing metalloprotease enzyme that cleaves von Willebrand factor (vWf), a large protein involved in blood clotting . It is secreted into the blood and degrades large vWf multimers, decreasing their activity, hence ADAMTS13 acts to reduce thrombus formation. The ADAMTS13 gene maps to

450-461: A T cell response, and limited evidence for T cell responses implicates nucleoprotein antigens. In Celiac disease there are autoantibodies to tissue transglutaminase but the T cell response is to the foreign protein gliadin. This disparity has led to the idea that human autoimmune disease is in most cases (with probable exceptions including type I diabetes) based on a loss of B cell tolerance which makes use of normal T cell responses to foreign antigens in

540-406: A biochemical rather than a clinical discipline. By the 1950s, the modern understanding of autoantibodies and autoimmune diseases started to spread. More recently, it has become accepted that autoimmune responses are an integral part of vertebrate immune systems (sometimes termed "natural autoimmunity"). Autoimmunity should not be confused with alloimmunity . While a high level of autoimmunity

630-514: A by-product of smelting sulfide ores. Zinc in such remnants in smelting ovens was usually discarded as it was thought to be worthless. The manufacture of brass was known to the Romans by about 30 BC. They made brass by heating powdered calamine (zinc silicate or carbonate), charcoal and copper together in a crucible. The resulting calamine brass was then either cast or hammered into shape for use in weaponry. Some coins struck by Romans in

720-547: A deficit of zinc can compromise the vitality of primary algal communities, potentially destabilizing the intricate marine trophic structures and consequently impacting biodiversity. Brass , an alloy of copper and zinc in various proportions, was used as early as the third millennium BC in the Aegean area and the region which currently includes Iraq , the United Arab Emirates , Kalmykia , Turkmenistan and Georgia . In

810-400: A half-life of 243.66 days, is the least active radioisotope, followed by Zn with a half-life of 46.5 hours. Zinc has 10 nuclear isomers , of which Zn has the longest half-life, 13.76 h. The superscript m indicates a metastable isotope. The nucleus of a metastable isotope is in an excited state and will return to the ground state by emitting a photon in the form of

900-400: A majority of non-familial cases. Genomically, ADAMTS13 shares many properties with the 19 member ADAMTS family , all of which are characterised by a protease domain (the part that performs the protein hydrolysis), an adjacent disintegrin domain and one or more thrombospondin domains. ADAMTS13 in fact has eight thrombospondin domains. It has no hydrophobic transmembrane domain, and hence it

990-506: A metal which, when oxidized, produces pushpanjan , thought to be zinc oxide. Zinc mines at Zawar, near Udaipur in India, have been active since the Mauryan period ( c.  322 and 187 BCE). The smelting of metallic zinc here, however, appears to have begun around the 12th century AD. One estimate is that this location produced an estimated million tonnes of metallic zinc and zinc oxide from

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1080-417: A metal–carbon sigma bond . Cobalticyanide paper (Rinnmann's test for Zn) can be used as a chemical indicator for zinc. 4 g of K 3 Co(CN) 6 and 1 g of KClO 3 is dissolved on 100 ml of water. Paper is dipped in the solution and dried at 100 °C. One drop of the sample is dropped onto the dry paper and heated. A green disc indicates the presence of zinc. Various isolated examples of

1170-956: A persistent increased risk for autoimmune disease. It has been suggested that the slight, direct exchange of cells between mothers and their children during pregnancy may induce autoimmunity. This would tip the gender balance in the direction of the female. Another theory suggests the female high tendency to get autoimmunity is due to an imbalanced X-chromosome inactivation . The X-inactivation skew theory, proposed by Princeton University's Jeff Stewart, has recently been confirmed experimentally in scleroderma and autoimmune thyroiditis . Other complex X-linked genetic susceptibility mechanisms are proposed and under investigation. An interesting inverse relationship exists between infectious diseases and autoimmune diseases. In areas where multiple infectious diseases are endemic, autoimmune diseases are quite rarely seen. The reverse, to some extent, seems to hold true. The hygiene hypothesis attributes these correlations to

1260-457: A plasma metalloprotease enzyme when it was exposed to high levels of shear stress. In 1996, two research groups independently further characterized this enzyme. In the next two years, the same two groups showed that the congenital deficiency of a vWF-cleaving protease was associated with formation of platelet microthrombi in the small blood vessels. In addition, they reported that IgG antibodies directed against this same enzyme caused TTP in

1350-505: A process in 1758 for calcining zinc sulfide into an oxide usable in the retort process. Prior to this, only calamine could be used to produce zinc. In 1798, Johann Christian Ruberg improved on the smelting process by building the first horizontal retort smelter. Jean-Jacques Daniel Dony built a different kind of horizontal zinc smelter in Belgium that processed even more zinc. Italian doctor Luigi Galvani discovered in 1780 that connecting

1440-582: A quantity of what he called "calay" (from the Malay or Hindi word for tin) originating from Malabar off a cargo ship captured from the Portuguese in the year 1596. Libavius described the properties of the sample, which may have been zinc. Zinc was regularly imported to Europe from the Orient in the 17th and early 18th centuries, but was at times very expensive. Metallic zinc was isolated in India by 1300 AD. Before it

1530-401: A radioisotope of zinc with mass number higher than 66 is beta decay (β ), which produces an isotope of gallium . Zinc has an electron configuration of [Ar]3d 4s and is a member of the group 12 of the periodic table . It is a moderately reactive metal and strong reducing agent . The surface of the pure metal tarnishes quickly, eventually forming a protective passivating layer of

1620-619: A variety of aberrant ways. There are a large number of immunodeficiency syndromes that present clinical and laboratory characteristics of autoimmunity. The decreased ability of the immune system to clear infections in these patients may be responsible for causing autoimmunity through perpetual immune system activation. One example is common variable immunodeficiency , in which multiple autoimmune diseases are seen, e.g., inflammatory bowel disease, autoimmune thrombocytopenia and autoimmune thyroid disease. Familial hemophagocytic lymphohistiocytosis , an autosomal recessive primary immunodeficiency,

1710-403: Is a chalcophile , meaning the element is more likely to be found in minerals together with sulfur and other heavy chalcogens , rather than with the light chalcogen oxygen or with non-chalcogen electronegative elements such as the halogens . Sulfides formed as the crust solidified under the reducing conditions of the early Earth's atmosphere. Sphalerite , which is a form of zinc sulfide,

1800-466: Is also sometimes associated with the development of autoimmune and atopic phenomena. Certain individuals are genetically susceptible to developing autoimmune diseases. This susceptibility is associated with multiple genes plus other risk factors. Genetically predisposed individuals do not always develop autoimmune diseases. Three main sets of genes are suspected in many autoimmune diseases. These genes are related to: The first two, which are involved in

1890-444: Is an essential trace element for humans, animals, plants and for microorganisms and is necessary for prenatal and postnatal development. It is the second most abundant trace metal in humans after iron and it is the only metal which appears in all enzyme classes . Zinc is also an essential nutrient element for coral growth as it is an important cofactor for many enzymes. Zinc deficiency affects about two billion people in

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1980-594: Is another example. Pancytopenia , rashes, swollen lymph nodes and enlargement of the liver and spleen are commonly seen in such individuals. Presence of multiple uncleared viral infections due to lack of perforin are thought to be responsible. In addition to chronic and/or recurrent infections many autoimmune diseases including arthritis, autoimmune hemolytic anemia, scleroderma and type 1 diabetes mellitus are also seen in X-linked agammaglobulinemia (XLA). Recurrent bacterial and fungal infections and chronic inflammation of

2070-534: Is being smelted. In Britain, John Lane is said to have carried out experiments to smelt zinc, probably at Landore , prior to his bankruptcy in 1726. In 1738 in Great Britain, William Champion patented a process to extract zinc from calamine in a vertical retort -style smelter. His technique resembled that used at Zawar zinc mines in Rajasthan , but no evidence suggests he visited the Orient. Champion's process

2160-475: Is characterised by a form of von Willebrand disease (type 2a). Zinc Zinc is a chemical element with the symbol Zn and atomic number 30. It is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodic table . In some respects, zinc is chemically similar to magnesium : both elements exhibit only one normal oxidation state (+2), and

2250-527: Is hard and brittle at most temperatures but becomes malleable between 100 and 150 °C. Above 210 °C, the metal becomes brittle again and can be pulverized by beating. Zinc is a fair conductor of electricity . For a metal, zinc has relatively low melting (419.5 °C) and boiling point (907 °C). The melting point is the lowest of all the d-block metals aside from mercury and cadmium ; for this reason among others, zinc, cadmium, and mercury are often not considered to be transition metals like

2340-464: Is implicated by the formation of a yellow diamagnetic glass by dissolving metallic zinc in molten ZnCl 2 . The [Zn 2 ] core would be analogous to the [Hg 2 ] cation present in mercury (I) compounds. The diamagnetic nature of the ion confirms its dimeric structure. The first zinc(I) compound containing the Zn–Zn bond, (η -C 5 Me 5 ) 2 Zn 2 . Binary compounds of zinc are known for most of

2430-914: Is involved in regulating the activity of immune cells, and so variations in this gene can lead to dysregulation of the immune response, making individuals more susceptible to autoimmune diseases. Most autoimmune diseases are sex-related ; a s a whole, women are much more likely to develop autoimmune disease than men. Being female is the single greatest risk factor for developing autoimmune disease than any other genetic or environmental risk factor yet discovered. Autoimmune conditions overrepresented in women include: lupus , primary biliary cholangitis , Graves' disease , Hashimoto's thyroiditis , and multiple sclerosis , among many others. A few autoimmune diseases that men are just as or more likely to develop as women include: ankylosing spondylitis , type 1 diabetes mellitus , granulomatosis with polyangiitis , primary sclerosing cholangitis , and psoriasis . The reasons for

2520-410: Is known as Special High Grade, often abbreviated SHG , and is 99.995% pure. Worldwide, 95% of new zinc is mined from sulfidic ore deposits, in which sphalerite (ZnS) is nearly always mixed with the sulfides of copper, lead and iron. Zinc mines are scattered throughout the world, with the main areas being China, Australia, and Peru. China produced 38% of the global zinc output in 2014. Zinc metal

2610-511: Is necessary for the leaching process. If deposits of zinc carbonate , zinc silicate , or zinc-spinel (like the Skorpion Deposit in Namibia ) are used for zinc production, the roasting can be omitted. For further processing two basic methods are used: pyrometallurgy or electrowinning . Pyrometallurgy reduces zinc oxide with carbon or carbon monoxide at 950 °C (1,740 °F) into

2700-517: Is not anchored in the cell membrane. Deficiency of ADAMTS13 was originally discovered in Upshaw Schulman Syndrome , the recurring familial form of thrombotic thrombocytopenic purpura . By that time it was already suspected that TTP occurred in the autoimmune form as well, owing to its response to plasmapheresis and characterisation of IgG inhibitors. Since the discovery of ADAMTS13, specific epitopes on its surface have been shown to be

2790-508: Is present in all individuals, even in normal health state. It causes autoimmune diseases if self-reactivity can lead to tissue damage. In the later 19th century, it was believed that the immune system was unable to react against the body's own tissues. Paul Ehrlich , at the turn of the 20th century, proposed the concept of horror autotoxicus . Ehrlich later adjusted his theory to recognize the possibility of autoimmune tissue attacks, but believed certain innate protection mechanisms would prevent

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2880-437: Is produced using extractive metallurgy . The ore is finely ground, then put through froth flotation to separate minerals from gangue (on the property of hydrophobicity ), to get a zinc sulfide ore concentrate consisting of about 50% zinc, 32% sulfur, 13% iron, and 5% SiO 2 . Roasting converts the zinc sulfide concentrate to zinc oxide: The sulfur dioxide is used for the production of sulfuric acid, which

2970-610: Is termed an " autoimmune disease ". Prominent examples include celiac disease , diabetes mellitus type 1 , Henoch–Schönlein purpura , systemic lupus erythematosus , Sjögren syndrome , eosinophilic granulomatosis with polyangiitis , Hashimoto's thyroiditis , Graves' disease , idiopathic thrombocytopenic purpura , Addison's disease , rheumatoid arthritis , ankylosing spondylitis , polymyositis , dermatomyositis , and multiple sclerosis . Autoimmune diseases are very often treated with steroids . Autoimmunity means presence of antibodies or T cells that react with self-protein and

3060-594: Is the ability of an individual to ignore "self", while reacting to "non-self". This breakage leads to the immune system mounting an effective and specific immune response against self antigens. The exact genesis of immunological tolerance is still elusive, but several theories have been proposed since the mid-twentieth century to explain its origin. Three hypotheses have gained widespread attention among immunologists: In addition, two other theories are under intense investigation: Tolerance can also be differentiated into "central" and "peripheral" tolerance, on whether or not

3150-584: Is the most heavily mined zinc-containing ore because its concentrate contains 60–62% zinc. Other source minerals for zinc include smithsonite (zinc carbonate ), hemimorphite (zinc silicate ), wurtzite (another zinc sulfide), and sometimes hydrozincite (basic zinc carbonate ). With the exception of wurtzite, all these other minerals were formed by weathering of the primordial zinc sulfides. Identified world zinc resources total about 1.9–2.8 billion tonnes . Large deposits are in Australia, Canada and

3240-450: Is unhealthy, a low level of autoimmunity may actually be beneficial. Taking the experience of a beneficial factor in autoimmunity further, one might hypothesize with intent to prove that autoimmunity is always a self-defense mechanism of the mammal system to survive. The system does not randomly lose the ability to distinguish between self and non-self; the attack on cells may be the consequence of cycling metabolic processes necessary to keep

3330-731: The antigen pigeon cytochrome c peptide, as determined by ZAP70 phosphorylation , proliferation, and interleukin 2 production. Thus Stefanova et al. (2002) demonstrated that self-MHC recognition (which, if too strong may contribute to autoimmune disease) maintains the responsiveness of CD4+ T cells when foreign antigens are absent. Pioneering work by Noel Rose and Ernst Witebsky in New York, and Roitt and Doniach at University College London provided clear evidence that, at least in terms of antibody-producing B cells (B lymphocytes), diseases such as rheumatoid arthritis and thyrotoxicosis are associated with loss of immunological tolerance , which

3420-469: The metalloids and all the nonmetals except the noble gases . The oxide ZnO is a white powder that is nearly insoluble in neutral aqueous solutions, but is amphoteric , dissolving in both strong basic and acidic solutions. The other chalcogenides ( ZnS , ZnSe , and ZnTe ) have varied applications in electronics and optics. Pnictogenides ( Zn 3 N 2 , Zn 3 P 2 , Zn 3 As 2 and Zn 3 Sb 2 ),

3510-518: The spinal cord of a freshly dissected frog to an iron rail attached by a brass hook caused the frog's leg to twitch. He incorrectly thought he had discovered an ability of nerves and muscles to create electricity and called the effect " animal electricity ". The galvanic cell and the process of galvanization were both named for Luigi Galvani, and his discoveries paved the way for electrical batteries , galvanization, and cathodic protection . Galvani's friend, Alessandro Volta , continued researching

3600-403: The 12th to 16th centuries. Another estimate gives a total production of 60,000 tonnes of metallic zinc over this period. The Rasaratna Samuccaya , written in approximately the 13th century AD, mentions two types of zinc-containing ores: one used for metal extraction and another used for medicinal purposes. Zinc was distinctly recognized as a metal under the designation of Yasada or Jasada in

3690-610: The 16th century. The word is probably derived from the German zinke , and supposedly meant "tooth-like, pointed or jagged" (metallic zinc crystals have a needle-like appearance). Zink could also imply "tin-like" because of its relation to German zinn meaning tin. Yet another possibility is that the word is derived from the Persian word سنگ seng meaning stone. The metal was also called Indian tin , tutanego , calamine , and spinter . German metallurgist Andreas Libavius received

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3780-422: The 24th most abundant element. It also makes up 312 ppm of the solar system, where it is the 22nd most abundant element. Typical background concentrations of zinc do not exceed 1 μg/m in the atmosphere; 300 mg/kg in soil; 100 mg/kg in vegetation; 20 μg/L in freshwater and 5 μg/L in seawater. The element is normally found in association with other base metals such as copper and lead in ores . Zinc

3870-443: The 9th century AD when a distillation process was employed to make pure zinc. Alchemists burned zinc in air to form what they called " philosopher's wool " or "white snow". The element was probably named by the alchemist Paracelsus after the German word Zinke (prong, tooth). German chemist Andreas Sigismund Marggraf is credited with discovering pure metallic zinc in 1746. Work by Luigi Galvani and Alessandro Volta uncovered

3960-561: The Christian era are made of what is probably calamine brass. The oldest known pills were made of the zinc carbonates hydrozincite and smithsonite. The pills were used for sore eyes and were found aboard the Roman ship Relitto del Pozzino , wrecked in 140 BC. The Berne zinc tablet is a votive plaque dating to Roman Gaul made of an alloy that is mostly zinc. The Charaka Samhita , thought to have been written between 300 and 500 AD, mentions

4050-700: The MHC complex remain the subject of research, in animal models of disease (Linda Wicker's extensive genetic studies of diabetes in the NOD mouse) , and in patients (Brian Kotzin's linkage analysis of susceptibility to lupus erythematosus ). In recent studies, the gene PTPN22 has emerged as a significant factor linked to various autoimmune diseases, such as Type I diabetes, rheumatoid arthritis, systemic lupus erythematosus, Hashimoto's thyroiditis, Graves' disease, Addison's disease, Myasthenia Gravis, vitiligo, systemic sclerosis, juvenile idiopathic arthritis, and psoriatic arthritis. PTPN22

4140-530: The United States, with the largest reserves in Iran . The most recent estimate of reserve base for zinc (meets specified minimum physical criteria related to current mining and production practices) was made in 2009 and calculated to be roughly 480 Mt. Zinc reserves, on the other hand, are geologically identified ore bodies whose suitability for recovery is economically based (location, grade, quality, and quantity) at

4230-518: The Zn and Mg ions are of similar size. Zinc is the 24th most abundant element in Earth's crust and has five stable isotopes . The most common zinc ore is sphalerite (zinc blende), a zinc sulfide mineral. The largest workable lodes are in Australia, Asia, and the United States. Zinc is refined by froth flotation of the ore, roasting , and final extraction using electricity ( electrowinning ). Zinc

4320-436: The above-stated checking mechanisms operate in the central lymphoid organs (thymus and bone marrow) or the peripheral lymphoid organs (lymph node, spleen, etc., where self-reactive B-cells may be destroyed). It must be emphasised that these theories are not mutually exclusive, and evidence has been mounting suggesting that all of these mechanisms may actively contribute to vertebrate immunological tolerance. A puzzling feature of

4410-433: The autoimmune response from becoming pathological. In 1904, this theory was challenged by the discovery of a substance in the serum of patients with paroxysmal cold hemoglobinuria that reacted with red blood cells. During the following decades, a number of conditions could be linked to autoimmune responses. However, the authoritative status of Ehrlich's postulate hampered the understanding of these findings. Immunology became

4500-419: The basic zinc carbonate , Zn 5 (OH) 6 (CO 3 ) 2 , by reaction with atmospheric carbon dioxide . Zinc burns in air with a bright bluish-green flame, giving off fumes of zinc oxide . Zinc reacts readily with acids , alkalis and other non-metals. Extremely pure zinc reacts only slowly at room temperature with acids. Strong acids, such as hydrochloric or sulfuric acid , can remove

4590-642: The blood chemistry in homeostasis. Second, autoimmunity may have a role in allowing a rapid immune response in the early stages of an infection when the availability of foreign antigens limits the response (i.e., when there are few pathogens present). In their study, Stefanova et al. (2002) injected an anti- MHC class II antibody into mice expressing a single type of MHC Class II molecule (H-2 ) to temporarily prevent CD4+ T cell-MHC interaction. Naive CD4+ T cells (those that have not encountered non-self antigens before) recovered from these mice 36 hours post-anti-MHC administration showed decreased responsiveness to

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4680-420: The chromate ZnCrO 4 (one of the few colored zinc compounds) are a few examples of other common inorganic compounds of zinc. Organozinc compounds are those that contain zinc– carbon covalent bonds. Diethylzinc ( (C 2 H 5 ) 2 Zn ) is a reagent in synthetic chemistry. It was first reported in 1848 from the reaction of zinc and ethyl iodide , and was the first compound known to contain

4770-440: The developing world and is associated with many diseases. In children, deficiency causes growth retardation, delayed sexual maturation, infection susceptibility, and diarrhea . Enzymes with a zinc atom in the reactive center are widespread in biochemistry, such as alcohol dehydrogenase in humans. Consumption of excess zinc may cause ataxia , lethargy , and copper deficiency . In marine biomes, notably within polar regions,

4860-545: The documented loss of tolerance seen in spontaneous human autoimmunity is that it is almost entirely restricted to the autoantibody responses produced by B lymphocytes. Loss of tolerance by T cells has been extremely hard to demonstrate, and where there is evidence for an abnormal T cell response it is usually not to the antigen recognised by autoantibodies. Thus, in rheumatoid arthritis there are autoantibodies to IgG Fc but apparently no corresponding T cell response. In systemic lupus there are autoantibodies to DNA, which cannot evoke

4950-555: The effect and invented the Voltaic pile in 1800. Volta's pile consisted of a stack of simplified galvanic cells , each being one plate of copper and one of zinc connected by an electrolyte . By stacking these units in series, the Voltaic pile (or "battery") as a whole had a higher voltage, which could be used more easily than single cells. Electricity is produced because the Volta potential between

5040-538: The effects of smoking correlate with the presence of antibodies to citrullinated peptides . Several mechanisms are thought to be operative in the pathogenesis of autoimmune diseases, against a backdrop of genetic predisposition and environmental modulation. It is beyond the scope of this article to discuss each of these mechanisms exhaustively, but a summary of some of the important mechanisms have been described: The roles of specialized immunoregulatory cell types, such as regulatory T cells , NKT cells , γδ T-cells in

5130-533: The electrochemical properties of zinc by 1800. Corrosion -resistant zinc plating of iron ( hot-dip galvanizing ) is the major application for zinc. Other applications are in electrical batteries , small non-structural castings, and alloys such as brass. A variety of zinc compounds are commonly used, such as zinc carbonate and zinc gluconate (as dietary supplements), zinc chloride (in deodorants), zinc pyrithione (anti- dandruff shampoos), zinc sulfide (in luminescent paints), and dimethylzinc or diethylzinc in

5220-439: The formation of Zn 2 Cl 2 , a zinc compound with a +1 oxidation state. No compounds of zinc in positive oxidation states other than +1 or +2 are known. Calculations indicate that a zinc compound with the oxidation state of +4 is unlikely to exist. Zn(III) is predicted to exist in the presence of strongly electronegative trianions; however, there exists some doubt around this possibility. But in 2021 another compound

5310-416: The genesis of autoimmune conditions, or conditions that simulate autoimmune diseases. The most striking of these is the drug-induced lupus erythematosus . Usually, withdrawal of the offending drug cures the symptoms in a patient. Cigarette smoking is now established as a major risk factor for both incidence and severity of rheumatoid arthritis . This may relate to abnormal citrullination of proteins, since

5400-808: The gut and lungs are seen in chronic granulomatous disease (CGD) as well. CGD is a caused by decreased production of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase by neutrophils. Hypomorphic RAG mutations are seen in patients with midline granulomatous disease; an autoimmune disorder that is commonly seen in patients with granulomatosis with polyangiitis and NK/T cell lymphomas. Wiskott–Aldrich syndrome (WAS) patients also present with eczema, autoimmune manifestations, recurrent bacterial infections and lymphoma. In autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy also autoimmunity and infections coexist: organ-specific autoimmune manifestations (e.g., hypoparathyroidism and adrenocortical failure) and chronic mucocutaneous candidiasis. Finally, IgA deficiency

5490-653: The host immune signaling. A paradoxical observation has been the strong association of certain microbial organisms with autoimmune diseases. For example, Klebsiella pneumoniae and coxsackievirus B have been strongly correlated with ankylosing spondylitis and diabetes mellitus type 1 , respectively. This has been explained by the tendency of the infecting organism to produce super-antigens that are capable of polyclonal activation of B-lymphocytes , and production of large amounts of antibodies of varying specificities, some of which may be self-reactive (see below). Certain chemical agents and drugs can also be associated with

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5580-461: The hydroxide Zn(OH) 2 forms as a white precipitate . In stronger alkaline solutions, this hydroxide is dissolved to form zincates ( [Zn(OH) 4 ] ). The nitrate Zn(NO 3 ) 2 , chlorate Zn(ClO 3 ) 2 , sulfate ZnSO 4 , phosphate Zn 3 (PO 4 ) 2 , molybdate ZnMoO 4 , cyanide Zn(CN) 2 , arsenite Zn(AsO 2 ) 2 , arsenate Zn(AsO 4 ) 2 ·8H 2 O and

5670-570: The immune-manipulating strategies of pathogens. While such an observation has been variously termed as spurious and ineffective, according to some studies, parasite infection is associated with reduced activity of autoimmune disease. The putative mechanism is that the parasite attenuates the host immune response in order to protect itself. This may provide a serendipitous benefit to a host that also has autoimmune disease. The details of parasite immune modulation are not yet known, but may include secretion of anti-inflammatory agents or interference with

5760-469: The innate immune system at the other extreme. Within this scheme, the full spectrum of autoimmunity can be included. Many common human autoimmune diseases can be seen to have a substantial innate immune mediated immunopathology using this new scheme. This new classification scheme has implications for understanding disease mechanisms and for therapy development. Diagnosis of autoimmune disorders largely rests on accurate history and physical examination of

5850-455: The medical Lexicon ascribed to the Hindu king Madanapala (of Taka dynasty) and written about the year 1374. Smelting and extraction of impure zinc by reducing calamine with wool and other organic substances was accomplished in the 13th century in India. The Chinese did not learn of the technique until the 17th century. Alchemists burned zinc metal in air and collected the resulting zinc oxide on

5940-572: The metal, which is distilled as zinc vapor to separate it from other metals, which are not volatile at those temperatures. The zinc vapor is collected in a condenser. The equations below describe this process: In electrowinning , zinc is leached from the ore concentrate by sulfuric acid and impurities are precipitated: Autoimmune In immunology , autoimmunity is the system of immune responses of an organism against its own healthy cells , tissues and other normal body constituents. Any disease resulting from this type of immune response

6030-404: The ninth chromosome (9q34). Since 1982 it had been known that thrombotic thrombocytopenic purpura (TTP), one of the microangiopathic hemolytic anemias (see below), was characterized in its familial form by the presence in plasma of unusually large von Willebrand factor multimers (ULVWF). In 1994, vWF was shown to be cleaved between a tyrosine at position 1605 and a methionine at 1606 by

6120-420: The organic laboratory. Zinc is a bluish-white, lustrous, diamagnetic metal, though most common commercial grades of the metal have a dull finish. It is somewhat less dense than iron and has a hexagonal crystal structure , with a distorted form of hexagonal close packing , in which each atom has six nearest neighbors (at 265.9 pm) in its own plane and six others at a greater distance of 290.6 pm. The metal

6210-525: The passivating layer and the subsequent reaction with the acid releases hydrogen gas. The chemistry of zinc is dominated by the +2 oxidation state. When compounds in this oxidation state are formed, the outer shell s electrons are lost, yielding a bare zinc ion with the electronic configuration [Ar]3d . In aqueous solution an octahedral complex, [Zn(H 2 O) 6 ] is the predominant species. The volatilization of zinc in combination with zinc chloride at temperatures above 285 °C indicates

6300-473: The pathogenesis of autoimmune disease are under investigation. Autoimmune diseases can be broadly divided into systemic and organ-specific or localised autoimmune disorders, depending on the principal clinico-pathologic features of each disease. Using the traditional "organ specific" and "non-organ specific" classification scheme, many diseases have been lumped together under the autoimmune disease umbrella. However, many chronic inflammatory human disorders lack

6390-477: The patient, and high index of suspicion against a backdrop of certain abnormalities in routine laboratory tests (example, elevated C-reactive protein ). In several systemic disorders, serological assays which can detect specific autoantibodies can be employed. Localised disorders are best diagnosed by immunofluorescence of biopsy specimens. Autoantibodies are used to diagnose many autoimmune diseases. The levels of autoantibodies are measured to determine

6480-406: The peroxide ( ZnO 2 ), the hydride ( ZnH 2 ), and the carbide ( ZnC 2 ) are also known. Of the four halides , ZnF 2 has the most ionic character, while the others ( ZnCl 2 , ZnBr 2 , and ZnI 2 ) have relatively low melting points and are considered to have more covalent character. In weak basic solutions containing Zn ions,

6570-486: The progress of the disease. Treatments for autoimmune disease have traditionally been immunosuppressive , anti-inflammatory , or palliative . Managing inflammation is critical in autoimmune diseases. Non-immunological therapies, such as hormone replacement in Hashimoto's thyroiditis or Type 1 diabetes mellitus treat outcomes of the autoaggressive response, thus these are palliative treatments. Dietary manipulation limits

6660-587: The recognition of antigens, are inherently variable and susceptible to recombination. These variations enable the immune system to respond to a very wide variety of invaders, but may also give rise to lymphocytes capable of self-reactivity. Fewer correlations exist with MHC class I molecules. The most notable and consistent is the association between HLA B27 and spondyloarthropathies like ankylosing spondylitis and reactive arthritis . Correlations may exist between polymorphisms within class II MHC promoters and autoimmune disease. The contributions of genes outside

6750-399: The remainder, have been found that are 2,500 years old. A possibly prehistoric statuette containing 87.5% zinc was found in a Dacian archaeological site. Strabo writing in the 1st century BC (but quoting a now lost work of the 4th century BC historian Theopompus ) mentions "drops of false silver" which when mixed with copper make brass. This may refer to small quantities of zinc that is

6840-541: The reserve lifetime for zinc has remained unchanged. About 346 million tonnes have been extracted throughout history to 2002, and scholars have estimated that about 109–305 million tonnes are in use. Five stable isotopes of zinc occur in nature, with Zn being the most abundant isotope (49.17% natural abundance ). The other isotopes found in nature are Zn (27.73%), Zn (4.04%), Zn (18.45%), and Zn (0.61%). Several dozen radioisotopes have been characterized. Zn , which has

6930-497: The rest of the d-block metals. Many alloys contain zinc, including brass. Other metals long known to form binary alloys with zinc are aluminium , antimony , bismuth , gold , iron, lead , mercury, silver , tin , magnesium , cobalt , nickel , tellurium , and sodium . Although neither zinc nor zirconium is ferromagnetic , their alloy, ZrZn 2 , exhibits ferromagnetism below 35  K . Zinc makes up about 75  ppm  (0.0075%) of Earth's crust , making it

7020-529: The same crystal structure , and in other circumstances where ionic radius is a determining factor, the chemistry of zinc has much in common with that of magnesium. In other respects, there is little similarity with the late first-row transition metals. Zinc tends to form bonds with a greater degree of covalency and much more stable complexes with N - and S - donors. Complexes of zinc are mostly 4- or 6- coordinate , although 5-coordinate complexes are known. Zinc(I) compounds are very rare. The [Zn 2 ] ion

7110-581: The second known zinc-containing enzyme in 1955. Zinc is the fourth most common metal in use, trailing only iron , aluminium , and copper with an annual production of about 13 million tonnes. The world's largest zinc producer is Nyrstar , a merger of the Australian OZ Minerals and the Belgian Umicore . About 70% of the world's zinc originates from mining, while the remaining 30% comes from recycling secondary zinc. Commercially pure zinc

7200-511: The second millennium BC it was used in the regions currently including West India , Uzbekistan , Iran , Syria , Iraq, and Israel . Zinc metal was not produced on a large scale until the 12th century in India, though it was known to the ancient Romans and Greeks. The mines of Rajasthan have given definite evidence of zinc production going back to the 6th century BC. The oldest evidence of pure zinc comes from Zawar, in Rajasthan, as early as

7290-592: The severity of celiac disease. Steroidal or NSAID treatment limits inflammatory symptoms of many diseases. IVIG is used for CIDP and GBS . Specific immunomodulatory therapies, such as the TNFα antagonists (e.g. etanercept ), the B cell depleting agent rituximab , the anti-IL-6 receptor tocilizumab and the costimulation blocker abatacept have been shown to be useful in treating RA. Some of these immunotherapies may be associated with increased risk of adverse effects, such as susceptibility to infection. Helminthic therapy

7380-448: The sex role in autoimmunity vary. Women appear to generally mount larger inflammatory responses than men when their immune systems are triggered, increasing the risk of autoimmunity. Involvement of sex steroids is indicated by that many autoimmune diseases tend to fluctuate in accordance with hormonal changes, for example: during pregnancy, in the menstrual cycle, or when using oral contraception. A history of pregnancy also appears to leave

7470-509: The target of inhibitory antibodies. Low levels of ADAMTS13 are also associated with an increased risk of arterial thrombosis, including myocardial infarction and cerebrovascular disease. Finally, since the link between aortic valve stenosis and angiodysplasia was proven to be due to high shear stress ( Heyde's syndrome ), it has been accepted that increased exposure of vWf to ADAMTS13 due to various reasons would predispose to bleeding by causing increased degradation of vWf. This phenomenon

7560-429: The telltale associations of B and T cell driven immunopathology. In the last decade it has been firmly established that tissue "inflammation against self " does not necessarily rely on abnormal T and B cell responses. This has led to the recent proposal that the spectrum of autoimmunity should be viewed along an "immunological disease continuum", with classical autoimmune diseases at one extreme and diseases driven by

7650-520: The time of determination. Since exploration and mine development is an ongoing process, the amount of zinc reserves is not a fixed number and sustainability of zinc ore supplies cannot be judged by simply extrapolating the combined mine life of today's zinc mines. This concept is well supported by data from the United States Geological Survey (USGS), which illustrates that although refined zinc production increased 80% between 1990 and 2010,

7740-423: The two metal plates makes electrons flow from the zinc to the copper and corrode the zinc. The non-magnetic character of zinc and its lack of color in solution delayed discovery of its importance to biochemistry and nutrition. This changed in 1940 when carbonic anhydrase , an enzyme that scrubs carbon dioxide from blood, was shown to have zinc in its active site . The digestive enzyme carboxypeptidase became

7830-498: The use of impure zinc in ancient times have been discovered. Zinc ores were used to make the zinc–copper alloy brass thousands of years prior to the discovery of zinc as a separate element. Judean brass from the 14th to 10th centuries BC contains 23% zinc. Knowledge of how to produce brass spread to Ancient Greece by the 7th century BC, but few varieties were made. Ornaments made of alloys containing 80–90% zinc, with lead, iron, antimony , and other metals making up

7920-589: Was isolated in Europe, it was imported from India in about 1600 CE. Postlewayt 's Universal Dictionary , a contemporary source giving technological information in Europe, did not mention zinc before 1751 but the element was studied before then. Flemish metallurgist and alchemist P. M. de Respour reported that he had extracted metallic zinc from zinc oxide in 1668. By the start of the 18th century, Étienne François Geoffroy described how zinc oxide condenses as yellow crystals on bars of iron placed above zinc ore that

8010-421: Was reported with more evidence that had the oxidation state of +3 with the formula ZnBeB 11 (CN) 12 . Zinc chemistry is similar to the chemistry of the late first-row transition metals, nickel and copper, though it has a filled d-shell and compounds are diamagnetic and mostly colorless. The ionic radii of zinc and magnesium happen to be nearly identical. Because of this some of the equivalent salts have

8100-503: Was used through 1851. German chemist Andreas Marggraf normally gets credit for isolating pure metallic zinc in the West, even though Swedish chemist Anton von Swab had distilled zinc from calamine four years previously. In his 1746 experiment, Marggraf heated a mixture of calamine and charcoal in a closed vessel without copper to obtain a metal. This procedure became commercially practical by 1752. William Champion's brother, John, patented

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