Nucleophosmin (NPM), also known as nucleolar phosphoprotein B23 or numatrin, is a protein that in humans is encoded by the NPM1gene.[4][5]
NPM1 is associated with nucleolarribonucleoprotein structures and binds single-stranded and double-stranded nucleic acids, but it binds preferentially G-quadruplex forming nucleic acids. It is involved in the biogenesis of ribosomes and may assist small basic proteins in their transport to the nucleolus. Its regulation through SUMOylation (by SENP3 and SENP5) is another facet of the protein's regulation and cellular functions.
It is located in the nucleolus, but it can be translocated to the nucleoplasm in case of serum starvation or treatment with anticancer drugs. The protein is phosphorylated.
NPM1 gene is up-regulated, mutated and chromosomally translocated in many tumor types. Chromosomal aberrations involving NPM1 were found in patients with non-Hodgkin lymphoma, acute promyelocytic leukemia, myelodysplastic syndrome, and acute myelogenous leukemia.[7] Heterozygous mice for NPM1 are vulnerable to tumor development. In solid tumors NPM1 is frequently found overexpressed, and it is thought that NPM1 could promote tumor growth by inactivation of the tumor suppressor p53/ARF pathway; on the contrary, when expressed at low levels, NPM1 could suppress tumor growth by the inhibition of centrosome duplication.
Of high importance is NPM involvement in acute myelogenous leukemia,[8] where a mutated protein lacking a folded C-terminal domain (NPM1c+) has been found in the cytoplasm in patients. This aberrant localization has been linked to the development of the disease, and is associated with improved clinical outcomes. Strategies against this subtype of acute myelogenous leukemia include the refolding of the C-terminal domain using pharmalogical chaperones and the displacement of the protein from nucleolus to nucleoplasm, which has been linked to apoptotic mechanisms. It has also been shown that in the context of clonal hematopoiesis of undetermined significance harboring a DNMT3A mutation, subsequent NPM1 mutations drive progression into overt myeloproliferative neoplasm.[9]
The 2;5 chromosomal translocation is associated with approximately 60% of anaplastic large-cell lymphomas(ALCLs), type ALK-positive anaplastic large cell lymphoma and very rare cases of ALCL type primary cutaneous anaplastic large cell lymphoma. The translocation creates a fusion gene consisting of the ALK (anaplastic lymphoma kinase) gene and the nucleophosmin (NPM) gene: the 3' half of ALK, derived from chromosome 2 and coding for the catalytic domain, is fused to the 5' portion of NPM from chromosome 5. The product of the NPM-ALK fusion gene is oncogenic. In a smaller fraction of ALCL patients, the 3' half of ALK is fused to the 5' sequence of TPM3 gene, encoding for tropomyosin 3. In rare cases, ALK is fused to other 5' fusion partners, such as TFG, ATIC, CLTC1, TPM4, MSN, ALO17, MYH9.[58] Adenocarcinoma of the lung[edit]
The EML4-ALK fusion gene is responsible for approximately 3-5% of non-small-cell lung cancer (NSCLC). The vast majority of cases are adenocarcinomas. The standard test used to detect this gene in tumor samples is fluorescence in situ hybridization (FISH) by a US FDA approved kit. Recently Roche Ventana obtained approval in China and European Union countries to test this mutation by immunohistochemistry.[59] Other techniques like reverse-transcriptase PCR (RT-PCR) can also be used to detect lung cancers with an ALK gene fusion but not recommended.[citation needed] ALK lung cancers are found in patients of all ages, although on average these patients tend to be younger. ALK lung cancers are more common in light cigarette smokers or nonsmokers, but a significant number of patients with this disease are current or former cigarette smokers. EML4-ALK-rearrangement in NSCLC is exclusive and not found in EGFR- or KRAS-mutated tumors.[60] Gene rearrangements and overexpression in other tumours[edit] Familial cases of neuroblastoma[61] Inflammatory myofibroblastic tumor[62][63] Adult[64][65] and pediatric[66][67]renal cell carcinomas Esophageal squamous cell carcinoma[68][69] Breast cancer,[70] notably the inflammatory subtype[71] Colonic adenocarcinoma[70] Glioblastoma multiforme[72][73] Anaplastic thyroid cancer[74]
A dimer (/ˈdaɪmər/) (di-, "two" + -mer, "parts") is an oligomer consisting of two monomers joined by bonds that can be either strong or weak, covalent or intermolecular. The term homodimer is used when the two molecules are identical (e.g. A–A) and heterodimer when they are not (e.g. A–B). The reverse of dimerisation is often called dissociation. When two oppositely charged ions associate into dimers, they are referred to as Bjerrum pairs,[1] after Niels Bjerrum.
https://en.wikipedia.org/wiki/Dimer_(chemistry)
Nucleophosmin (NPM), also known as nucleolar phosphoprotein B23 or numatrin, is a protein that in humans is encoded by the NPM1gene.[4][5]
NPM1 is associated with nucleolarribonucleoprotein structures and binds single-stranded and double-stranded nucleic acids, but it binds preferentially G-quadruplex forming nucleic acids. It is involved in the biogenesis of ribosomes and may assist small basic proteins in their transport to the nucleolus. Its regulation through SUMOylation (by SENP3 and SENP5) is another facet of the protein's regulation and cellular functions.
It is located in the nucleolus, but it can be translocated to the nucleoplasm in case of serum starvation or treatment with anticancer drugs. The protein is phosphorylated.
Methotrexate was first made in 1947 and initially was used to treat cancer, as it was less toxic than the then current treatments.[7] In 1956 it provided the first cures of a metastatic cancer.[8] It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.[9] Methotrexate is available as a generic medication.[4] In 2018, it was the 123rd most commonly prescribed medication in the United States, with more than 5million prescriptions.[10][11]
https://en.wikipedia.org/wiki/Methotrexate
Bacillus thuringiensis (or Bt) is a Gram-positive, soil-dwelling bacterium, the most commonly used biological pesticideworldwide. B. thuringiensis also occurs naturally in the gut of caterpillars of various types of moths and butterflies, as well on leaf surfaces, aquatic environments, animal feces, insect-rich environments, and flour mills and grain-storage facilities.[1][2] It has also been observed to parasitize other moths such as Cadra calidella—in laboratory experiments working with C. calidella, many of the moths were diseased due to this parasite.[3]
As a toxic mechanism, cry proteins bind to specific receptors on the membranes of mid-gut (epithelial) cells of the targeted pests, resulting in their rupture. Other organisms (including humans, other animals and non-targeted insects) that lack the appropriate receptors in their gut cannot be affected by the cry protein, and therefore are not affected by Bt.[8][9]
Ancylostomiasis is a hookworm disease caused by infection with Ancylostomahookworms. The name is derived from Greek ancylos αγκύλος "crooked, bent" and stoma στόμα "mouth".
Ancylostomiasis is also known as miner's anaemia, tunnel disease, brickmaker's anaemia and Egyptian chlorosis. Helminthiasis may also refer to ancylostomiasis, but this term also refers to all other parasitic wormdiseases as well. In the United Kingdom, if acquired in the context of working in a mine, the condition is eligible for Industrial Injuries Disability Benefit. It is a prescribed disease (B4) under the relevant legislation.§[1]
Ancylostomiasis is caused when hookworms, present in large numbers, produce aniron deficiency anemiaby sucking blood from the host's intestinal walls.
The Strongyloides stercoralis nematode can parasitize humans. The adult parasitic stage lives in tunnels in the mucosa of the small intestine. The genus Strongyloides contains 53 species,[2][3] and S. stercoralis is the type species. S. stercoralishas been reported in other mammals, including cats and dogs. However, it seems that the species in dogs is typically not S. stercoralis, but the related species S. canis. Non-human primates are more commonly infected with S. fuelleborni and S. cebus, although S. stercoralis has been reported in captive primates. Other species of Strongyloides that are naturally parasitic in humans, but with restricted distributions, are S. fuelleborni in central Africa and S. kellyi in Papua New Guinea.
Hypochromic anemiais a generic term for any type ofanemiain which thered blood cellsare paler than normal. (Hypo- refers toless, andchromicmeanscolour.) A normal red blood cell has a biconcave disk shape and will have an area of pallor in its center when viewed microscopically. In hypochromic cells, this area of central pallor is increased. This decrease in redness is due to a disproportionate reduction of red cellhemoglobin(the pigment that imparts the red color) in proportion to the volume of the cell. Clinically the color can be evaluated by themean corpuscular hemoglobin(MCH) ormean corpuscular hemoglobin concentration(MCHC). The MCHC is considered the better parameter of the two as it adjusts for effect the size of the cell has on its amount of hemoglobin.[1]Hypochromia is clinically defined as below the normal MCH reference range of 27–33 picograms/cell in adults or below the normal MCHC reference range of 33–36 g/dL in adults.[2]
Red blood cells will also be small (microcytic), leading to substantial overlap with the category of microcytic anemia. The most common causes of this kind of anemia are iron deficiency and thalassemia.
Hypochromic anemia was historically known as chlorosis or green sickness for the distinct skin tinge sometimes present in patients, in addition to more general symptoms such as a lack of energy, shortness of breath, dyspepsia, headaches, a capricious or scanty appetiteand amenorrhea.
Mass deworming, also calledpreventive chemotherapy,[1][2]is the process of treating large numbers of people, particularly children, forhelminthiasis(for example soil-transmitted helminths (STH)) andschistosomiasisin areas with a high prevalence of these conditions.[3][4]It involves treating everyone – often all children who attend schools, using existing infrastructure to save money – rather than testing first and then only treating selectively. Serious side effects have not been reported when administering the medication to those without worms,[1][2]and testing for the infection is many times more expensive than treating it. So for the same amount of money, mass deworming can treat more people more cost-effectively than selective deworming.[5]Mass deworming is one example ofmass drug administration.[3]
Mass deworming of children can be carried out by administering mebendazole and albendazole which are two types of anthelmintic drug.[5] The cost of providing one tablet every six to twelve months per child (typical doses) is relatively low.[6]
Allergic rhinitis, also known ashay fever, is a type ofinflammation in the nosethat occurs when theimmune systemoverreacts toallergensin the air.[6]Signs and symptoms include a runny or stuffy nose,sneezing, red, itchy, and watery eyes, and swelling around the eyes.[1]The fluid from the nose is usually clear.[2]Symptom onset is often within minutes following allergen exposure, and can affect sleep and the ability to work or study.[2][8]Some people may develop symptoms only during specific times of the year, often as a result ofpollenexposure.[3]Many people with allergic rhinitis also haveasthma,allergic conjunctivitis, oratopic dermatitis.[2]
Allergic rhinitis is typically triggered by environmental allergens such as pollen, pet hair, dust, or mold.[3] Inherited genetics and environmental exposures contribute to the development of allergies.[3] Growing up on a farm and having multiple siblings decreases this risk.[2] The underlying mechanism involves IgE antibodies that attach to an allergen, and subsequently result in the release of inflammatory chemicals such as histamine from mast cells.[2]Diagnosis is typically based on a combination of symptoms and a skin prick test or blood tests for allergen-specific IgE antibodies.[4] These tests, however, can be falsely positive.[4] The symptoms of allergies resemble those of the common cold; however, they often last for more than two weeks and typically do not include a fever.[3]
Exposure to animals early in life might reduce the risk of developing these specific allergies.[3] Several different types of medications reduce allergic symptoms, including nasal steroids, antihistamines, such as diphenhydramine, cromolyn sodium, and leukotriene receptor antagonists such as montelukast.[5] Oftentimes, medications do not completely control symptoms, and they may also have side effects.[2] Exposing people to larger and larger amounts of allergen, known as allergen immunotherapy (AIT), is often effective.[6] The allergen can be given as an injection under the skin or as a tablet under the tongue.[6] Treatment typically lasts three to five years, after which benefits may be prolonged.[6]
Allergic rhinitis is the type of allergy that affects the greatest number of people.[9] In Western countries, between 10 and 30% of people are affected in a given year.[2][7] It is most common between the ages of twenty and forty.[2] The first accurate description is from the 10th-century physician Rhazes.[10] In 1859, Charles Blackley identified pollen as the cause.[11] In 1906, the mechanism was determined by Clemens von Pirquet.[9] The link with hay came about due to an early (and incorrect) theory that the symptoms were brought about by the smell of new hay.[12][13]
Ovine pulmonary adenocarcinoma (OPA), also known as ovine pulmonary adenomatosis, or jaagsiekte, is a chronic and contagious disease of the lungs of sheep and goats. OPA is caused by a retrovirus called jaagsiekte sheep retrovirus (JSRV).
Lentivirus is a genus of retroviruses that cause chronic and deadly diseases characterized by long incubation periods, in the human and other mammalian species.[1] The best known lentivirus is the human immunodeficiency virus (HIV), which causes AIDS. Lentiviruses are also hosted in apes, cows, goats, horses, cats, and sheep.[1] Recently, lentiviruses have been found in monkeys, lemurs, Malayan flying lemur (neither a true lemur nor a primate), rabbits, and ferrets. Lentiviruses and their hosts have worldwide distribution. Lentiviruses can integrate a significant amount of viralcDNA into the DNA of the host cell and can efficiently infect nondividing cells, so they are one of the most efficient methods of gene delivery.[2] Lentiviruses can become endogenous(ERV), integrating their genome into the host germline genome, so that the virus is henceforth inherited by the host's descendants.
https://en.wikipedia.org/wiki/Lentivirus
The enzootic nasal tumor virus of the betaretrovirus genus is a carcinogenic retrovirus that causes enzootic nasal adenocarcinoma in sheep and goats.[1] Strain ENTV-1 is found in sheep and strain ENTV-2 is found in goats.[2][3] The virus causes tumor growth in the upper nasal cavity and is closely related to JSRV which also causes respiratory tumors in ovine.[4]The disease, enzootic nasal adenocarcinoma is common in North America and is found in sheep and goats on every continent except New Zealand and Australia.[5] There are more than 27 betaretroviruses similar to ENVT and JSRV in the ovine genome.[6][7] In the future, research on ENTV may become important in studying viruses that cause human lung cancer.[8]