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Foralumab
Foralumab (TZLS-401), being researched by Tiziana Life Sciences) is a fully human monoclonal antibody that binds to CD3 epsilon of the T cell receptor- CD3 complex. It is currently being studied in a randomized, double-blind placebo-controlled, multicenter dose-ranging study in a nasal formulation in patients with non-active secondary progressive multiple sclerosis (SPMS). Clinical research Nasal administration Phase 1 Nasal foralumab was studied at the Brigham and Women's Hospital, at the Ann Romney Center. Twenty-seven (9 per group) healthy volunteers received either nasal foralumab (10ug, 50ug, or 250ug daily for 5 days) or they received nasal placebo. Nasal foralumab induced CD8+ Regulatory T cells and reduced CD4+ Suppressor T Cells. Foralumab induced LAP, TIGIT, and KLRG1 immune checkpoint molecules. The treatment was well tolerated by all subjects. The researchers concluded that the Immune effects of nasal foralumab were optimal at the 50ug dose. Phase 2 - ...
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CD3 Epsilon
CD3e molecule, epsilon also known as CD3E is a polypeptide which in humans is encoded by the ''CD3E'' gene which resides on chromosome 11. Function The protein encoded by this gene is the CD3-epsilon polypeptide, which together with CD3-gamma, -delta and -zeta, and the T-cell receptor alpha/beta and gamma/delta heterodimers, forms the T cell receptor- CD3 complex. This complex plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. The genes encoding the epsilon, gamma and delta polypeptides are located in the same cluster on chromosome 11. The epsilon polypeptide plays an essential role in T-cell development. Clinical significance Defects in this gene cause severe immunodeficiency. This gene has also been linked to a susceptibility to type I diabetes in women. Interactions T-cell surface glycoprotein CD3 epsilon chain has been shown to interact with TOP2B, CD3EAP and NCK2. See also * CD3 (immunology) * Cluster ...
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Regulatory T Cell
The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain immune tolerance, tolerance to self-antigens, and prevent autoimmune disease. Treg cells are immunosuppression, immunosuppressive and generally suppress or downregulation and upregulation, downregulate induction and proliferation of effector T cells. Treg cells express the biomarkers CD4, FOXP3, and CD25 and are thought to be derived from the same cell lineage, lineage as naïve T helper cell, CD4+ cells. Because effector T cells also express CD4 and CD25, Treg cells are very difficult to effectively discern from effector CD4+, making them difficult to study. Research has found that the cytokine Transforming growth factor beta, transforming growth factor beta (TGF-β) is essential for Treg cells to differentiate from naïve CD4+ cells and is important in maintaining Treg cell homeostas ...
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Dexamethasone
Dexamethasone is a fluorinated glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive pulmonary disease (COPD), croup, brain swelling, eye pain following eye surgery, superior vena cava syndrome (a complication of some forms of cancer), and along with antibiotics in tuberculosis. In adrenocortical insufficiency, it may be used in combination with a mineralocorticoid medication such as fludrocortisone. In preterm labor, it may be used to improve outcomes in the baby. It may be given by mouth, as an injection into a muscle, as an injection into a vein, as a topical cream or ointment for the skin or as a topical ophthalmic solution to the eye. The effects of dexamethasone are frequently seen within a day and last for about three days. The long-term use of dexamethasone may result in thrush, bone loss, cataracts, easy bruising, or muscle weakness. It is in pregnancy category C in the United S ...
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Placebo
A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials to test the efficacy of medical treatments. In a placebo-controlled trial, any change in the control group is known as the ''placebo response'', and the difference between this and the result of no treatment is the ''placebo effect''. Placebos in clinical trials should ideally be indistinguishable from so-called verum treatments under investigation, except for the latter's particular hypothesized medicinal effect. This is to shield test participants (with their consent) from knowing who is getting the placebo and who is getting the treatment under test, as patients' and clinicians' expectations of efficacy can influence results. The idea of a placebo effect was discussed in 18th century psychology, but became more prominent in the 20th ...
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COVID-19
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. In January 2020, the disease spread worldwide, resulting in the COVID-19 pandemic. The symptoms of COVID‑19 can vary but often include fever, fatigue, cough, breathing difficulties, anosmia, loss of smell, and ageusia, loss of taste. Symptoms may begin one to fourteen days incubation period, after exposure to the virus. At least a third of people who are infected asymptomatic, do not develop noticeable symptoms. Of those who develop symptoms noticeable enough to be classified as patients, most (81%) develop mild to moderate symptoms (up to mild pneumonia), while 14% develop severe symptoms (dyspnea, hypoxia (medical), hypoxia, or more than 50% lung involvement on imaging), and 5% develop critical symptoms (respiratory failure, shock (circulatory), shock, or organ dysfunction, multiorgan dysfunction). Older people have a higher risk of developing severe symptoms. Some complicati ...
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Howard L
Howard is a masculine given name derived from the English surname Howard. ''The Oxford Dictionary of English Christian Names'' notes that "the use of this surname as a christian name is quite recent and there seems to be no particular reason for it except that it is the name of several noble families". The surname has a number of possible origins; in the case of the noble family, the likely source is the Norse given name Hávarðr, composed of the elements ''há'' ("high") and ''varðr'' ("guardian"). Diminutives include Howie and Ward. Howard reached peak popularity in the United States in the 1920s, when it ranked as the 26th most popular boys' name. As of 2018, it had fallen to 968th place. People with the given name * Howard Allen (1949–2020), American serial killer * Howard Duane Allman (1946–1971), American guitar virtuoso * Howard Anderson (other), name of several people * Howard Andrew (1934–2021), American poker player * Howard Ashman (1950–1991), Ame ...
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Microglia
Microglia are a type of glia, glial cell located throughout the brain and spinal cord of the central nervous system (CNS). Microglia account for about around 5–10% of cells found within the brain. As the resident macrophage cells, they act as the first and main form of active immune defense in the CNS. Microglia originate in the yolk sac under tightly regulated molecular conditions. These cells (and other neuroglia including astrocytes) are distributed in large non-overlapping regions throughout the CNS. Microglia are key cells in overall brain maintenancethey are constantly scavenging the CNS for senile plaques, plaques, damaged or unnecessary neurons and synapses, and infectious agents. Since these processes must be efficient to prevent potentially fatal damage, microglia are extremely sensitive to even small pathological changes in the CNS. This sensitivity is achieved in part by the presence of unique potassium channels that respond to even small changes in extracellular pota ...
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Positron Emission Tomography
Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, regional chemical composition, and absorption. Different tracers are used for various imaging purposes, depending on the target process within the body, such as: * Fluorodeoxyglucose ( 18F">sup>18FDG or FDG) is commonly used to detect cancer; * 18Fodium fluoride">sup>18Fodium fluoride (Na18F) is widely used for detecting bone formation; * Oxygen-15 (15O) is sometimes used to measure blood flow. PET is a common imaging technique, a medical scintillography technique used in nuclear medicine. A radiopharmaceutical—a radioisotope attached to a drug—is injected into the body as a tracer. When the radiopharmaceutical undergoes beta plus decay, a positron is emitted, and when the positron interacts with an ordinary electron, the tw ...
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Radioactive Tracer
A radioactive tracer, radiotracer, or radioactive label is a synthetic derivative of a natural compound in which one or more atoms have been replaced by a radionuclide (a radioactive atom). By virtue of its radioactive decay, it can be used to explore the mechanism of chemical reactions by tracing the path that the radioisotope follows from reactants to products. Radiolabeling or radiotracing is thus the radioactive form of isotopic labeling. In biological contexts, experiments that use radioisotope tracers are sometimes called radioisotope feeding experiments. Radioisotopes of hydrogen, carbon, phosphorus, sulfur, and iodine have been used extensively to trace the path of biochemical reactions. A radioactive tracer can also be used to track the distribution of a substance within a natural system such as a cell or tissue, or as a flow tracer to track fluid flow. Radioactive tracers are also used to determine the location of fractures created by hydraulic fracturing in nat ...
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Outcome Measure
An outcome measure, endpoint, effect measure or measure of effect is a measure within medical practice or research, (primarily clinical trials) which is used to assess the effect, both positive and negative, of an intervention or treatment. Measures can often be quantified using effect sizes. Outcomes measures can be patient-reported, or gathered through laboratory tests such as blood work, urine samples etc. or through medical examination. Outcomes measures should be relevant to the target of the intervention (be it a single person or a target population). Depending on the design of a trial, outcome measures can be either primary outcomes, in which case the trial is designed around finding an adequate study size (through proper randomization and power calculation). Secondary or tertiary outcomes are outcome measures which are added after the design of the study is finalized, for example when data has already been collected. A study can have multiple primary outcome measures. Ou ...
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Immune Checkpoint
Immune checkpoints are regulators of the immune system. These pathways are crucial for self-tolerance, which prevents the immune system from attacking cells indiscriminately. However, some cancers can protect themselves from attack by stimulating immune checkpoint targets. Inhibitory checkpoint molecules are targets for cancer immunotherapy due to their potential for use in multiple types of cancers. Currently approved checkpoint inhibitors block CTLA4, PD-1 and PD-L1. For the related basic science discoveries, James P. Allison and Tasuku Honjo won the Tang Prize, Tang Prize in Biopharmaceutical Science and the Nobel Prize in Physiology or Medicine in 2018. Stimulatory checkpoint molecules Four stimulatory checkpoint molecules are members of the TNF receptor superfamily, tumor necrosis factor (TNF) receptor superfamily—CD27, CD40, OX40, GITR and CD137. Another two stimulatory checkpoint molecules belong to the B7-CD28 superfamily—CD28 itself and ICOS. * CD27: This molec ...
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KLRG1
Killer cell lectin-like receptor subfamily G member 1 is a protein that in humans is encoded by the ''KLRG1'' gene. Function Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells without previous activation. They can also regulate specific humoral and cell-mediated immunity. The protein encoded by this gene belongs to the killer cell lectin-like receptor (KLR) family, which is a group of transmembrane proteins preferentially expressed in NK cells. Studies in mice suggested that the expression of this gene may be regulated by MHC class I molecules. KLRG1 is a lymphocyte co-inhibitory, or immune checkpoint, receptor expressed predominantly on late-differentiated effector and effector memory CD8+ T and NK cells. Its ligands are E-cadherin and N-cadherin Cadherin-2 also known as Neural cadherin (N-cadherin), is a protein that in humans is encoded by the ''CDH2'' gene. CDH2 has also been designated as CD325 (cluster of d ...
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