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Wiskott–Aldrich Syndrome Protein
The Wiskott–Aldrich Syndrome protein (WASp) is a 502-amino acid protein expressed in cells of the hematopoietic system that in humans is encoded by the ''WAS'' gene. In the inactive state, WASp exists in an autoinhibited conformation with sequences near its C-terminus binding to a region near its N-terminus. Its activation is dependent upon CDC42 and PIP2 acting to disrupt this interaction, causing the WASp protein to 'open'. This exposes a domain near the WASp C-terminus that binds to and activates the Arp2/3 complex. Activated Arp2/3 nucleates new F-actin. WASp is the founding member of a gene family which also includes the broadly expressed N-WASP (neuronal Wiskott–Aldrich Syndrome protein), SCAR/ WAVE1, WASH, WHAMM, and JMY. WAML (WASP and MIM like), WAWH (WASP without WH1 domain), and WHIMP (WAVE Homology in Membrane Protrusions) have more recently been discovered. Structure and function The Wiskott–Aldrich syndrome (WAS) family of proteins share similar dom ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Amino Acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha amino acids appear in the genetic code. Amino acids can be classified according to the locations of the core structural functional groups, as Alpha and beta carbon, alpha- , beta- , gamma- or delta- amino acids; other categories relate to Chemical polarity, polarity, ionization, and side chain group type (aliphatic, Open-chain compound, acyclic, aromatic, containing hydroxyl or sulfur, etc.). In the form of proteins, amino acid '' residues'' form the second-largest component (water being the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. It is thought that they played a key role in enabling life ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GTPase
GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a protein domain common to many GTPases. Functions GTPases function as molecular switches or timers in many fundamental cellular processes. Examples of these roles include: * Signal transduction in response to activation of cell surface receptors, including transmembrane receptors such as those mediating taste, smell and vision. * Protein biosynthesis (a.k.a. translation) at the ribosome. * Regulation of cell differentiation, proliferation, division and movement. * Translocation of proteins through membranes. * Transport of vesicles within the cell, and vesicle-mediated secretion and uptake, through GTPase control of vesicle coat assembly. GTPases are active when bound to GTP and inactive when bound to GDP. In the generalized recepto ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phases Of Clinical Research
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases start with testing for safety in a few human subjects, then expand to many study participants (potentially tens of thousands) to determine if the treatment is effective. Clinical research is conducted on drug candidates, vaccine candidates, new medical devices, and new diagnostic assays. Summary Clinical trials testing potential medical products are commonly classified into four phases. The drug development process will normally proceed through all four phases over many years. If the drug successfully passes through Phases I, II, and III, it will usually be approved by the national regulatory authority for use in the general population. Phase IV trials are 'post-marketing' or 'surveillance' studies conducted to monitor safety over sever ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lentiviral Vector In Gene Therapy
Lentiviral vectors in gene therapy is a method by which genes can be inserted, modified, or deleted in organisms using lentiviruses. Lentiviruses are a family of viruses that are responsible for diseases like AIDS, which infect by inserting DNA into their host cells' genome. Many such viruses have been the basis of research using viruses in gene therapy, but the lentivirus is unique in its ability to infect non-dividing cells, and therefore has a wider range of potential applications. 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. To be effective in gene therapy, there must be insertion, alteration and/or removal of host cell genes. To do this, scientists use the lentivirus' mechanisms of infection to achieve a desired outcome to gene therapy. To understand the capabilities of a lentiviral vector, one has to consider the biology of the infection process. The l ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CD34
CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species. CD34 derives its name from the cluster of differentiation protocol that identifies cell surface antigens. CD34 was first described on hematopoietic stem cells independently by Civin et al. and Tindle et al. as a cell surface glycoprotein and functions as a cell-cell adhesion factor. It may also mediate the attachment of hematopoietic stem cells to bone marrow extracellular matrix or directly to stromal cells. Clinically, it is associated with the selection and enrichment of hematopoietic stem cells for bone marrow transplants. Due to these historical and clinical associations, CD34 expression is almost ubiquitously related to hematopoietic cells; however, it is actually found on many other cell types as well. Function The CD34 protein is a member of a family of single-pass transmembrane sialomucin proteins that show expression on early haematopoietic and vascul ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Autologous Blood Therapy
Autologous blood therapy, also known as autologous blood injection or autohemotherapy, comprises certain types of hemotherapy using a person's own blood ('' auto-'' + '' hemo-'' + ''therapy''). There are several kinds, the original belonging only to traditional medicine, alternative medicine and some newer kinds under investigation. The original, unscientific form is "the immediate intramuscular or subcutaneous reinjection of freshly drawn autologous blood". . It was used in the early 20th century, when some physicians believed that it had efficacy and logical mechanism of action; it was abandoned later as advancing science made clear that it lacked those. A Systematic Review of Autohemotherapy as a Treatment for Ur ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
OTL-103
OTL-103 (GSK-2696275) is a gene therapy for Wiskott–Aldrich syndrome, a rare primary immunodeficiency caused by mutations in the gene that codes for Wiskott–Aldrich syndrome protein (WASp). It was developed by Orchard Therapeutics in conjunction with GlaxoSmithKline. It is currently undergoing Phase I/II of clinical trials that are expected to conclude in October 2025. Development history OTL-103 is based on the lentiviral vector technology licensed from GlaxoSmithKline by Orchard Therapeutics in 2020. In 2019, the Food and Drug Administration granted OTL-103 Regenerative Medicine Advanced Therapy status. In the same year, the first clinical trial using OTL-103 for severe cases of Wiskott–Aldrich syndrome began at the San Raffaele Hospital in Milan, Italy. Orchard Therapeutics expected to file a Biologics License Application with the Food and Drug Administration in 2021, however, due to the COVID-19 pandemic's impact on drug development, this was postponed to 2022. Mecha ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
X-linked Thrombocytopenia
X-linked thrombocytopenia, also referred to as XLT or thrombocytopenia 1, is an inherited clotting disorder that primarily affects males. It is a ''WAS''-related disorder, meaning it is caused by a mutation in the Wiskott–Aldrich syndrome Wiskott–Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by eczema, thrombocytopenia (low platelet count), immune deficiency, and bloody diarrhea (secondary to the thrombocytopenia). It is also sometimes called the eczem ... (''WAS'') gene, which is located on the short arm of the X chromosome. ''WAS''-related disorders include Wiskott–Aldrich syndrome, XLT, and X-linked congenital neutropenia (XLN). Of the ''WAS''-related disorders, X-linked thrombocytopenia is considered to be the milder phenotype. Between 1 and 10 per million males worldwide are affected with this disorder. Females may be affected with this disorder but this is very rare since females have two X chromosomes and are therefore typically carriers of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Platelet
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby initiating a blood clot. Platelets have no cell nucleus; they are fragments of cytoplasm that are derived from the megakaryocytes of the bone marrow or lung, which then enter the circulation. Platelets are found only in mammals, whereas in other vertebrates (e.g. birds, amphibians), thrombocytes circulate as intact mononuclear cells. One major function of platelets is to contribute to hemostasis: the process of stopping bleeding at the site of interrupted endothelium. They gather at the site and, unless the interruption is physically too large, they plug the hole. First, platelets attach to substances outside the interrupted endothelium: ''adhesion''. Second, they change shape, turn on receptors and secrete chemical messengers: ''activatio ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Infection
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable disease, is an illness resulting from an infection. Infections can be caused by a wide range of pathogens, most prominently bacteria and viruses. Hosts can fight infections using their immune system. Mammalian hosts react to infections with an innate response, often involving inflammation, followed by an adaptive response. Specific medications used to treat infections include antibiotics, antivirals, antifungals, antiprotozoals, and antihelminthics. Infectious diseases resulted in 9.2 million deaths in 2013 (about 17% of all deaths). The branch of medicine that focuses on infections is referred to as infectious disease. Types Infections are caused by infectious agents (pathogens) including: * Bacteria (e.g. ''Mycobacterium tuberculosis'', ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Eczema
Dermatitis is inflammation of the Human skin, skin, typically characterized by itchiness, erythema, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become lichenification, thickened. The area of skin involved can vary from small to covering the entire body. Dermatitis is often called eczema, and the #Terminology, difference between those terms is not standardized. The exact cause of the condition is often unclear. Cases may involve a combination of allergy and venous stasis, poor venous return. The type of dermatitis is generally determined by the person's history and the location of the rash. For example, irritant dermatitis often occurs on the hands of those who frequently get them wet. Allergic contact dermatitis occurs upon exposure to an allergen, causing a hypersensitivity reaction in the skin. Prevention of atopic dermatitis is typically with essential fatty acids, and may be treated with moisturizers a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Thrombocytopenia
Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients and a third of surgical patients. A normal human platelet count ranges from 150,000 to 450,000 platelets/microliter (μl) of blood. Values outside this range do not necessarily indicate disease. One common definition of thrombocytopenia requiring emergency treatment is a platelet count below 50,000/μl. Thrombocytopenia can be contrasted with the conditions associated with an abnormally ''high'' level of platelets in the blood - thrombocythemia (when the cause is unknown), and thrombocytosis (when the cause is known). Signs and symptoms Thrombocytopenia usually has no symptoms and is picked up on a routine complete blood count. Some individuals with thrombocytopenia may experience external bleeding, such as nosebleeds or bleeding gums. S ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
