Muromonab-CD3
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Muromonab-CD3
Muromonab-CD3 (brand name Orthoclone OKT3, marketed by Janssen-Cilag) is an immunosuppressant medication given to reduce acute rejection in people with organ transplants. It is a monoclonal antibody targeted at the CD3 receptor, a membrane protein on the surface of T cells. It is the first monoclonal antibody to be approved for clinical use in humans. Medical uses Muromonab-CD3 is approved for the therapy of acute, glucocorticoid-resistant rejection of allogeneic kidney, heart, and liver transplants. Unlike the monoclonal antibodies basiliximab and daclizumab, it is not approved for prophylaxis of transplant rejection, although a 1996 review has found it to be safe for that purpose. Contraindications Except under special circumstances, the drug is contraindicated for patients with an allergy against mouse proteins, as well as patients with uncompensated heart failure, uncontrolled arterial hypertension or epilepsy. It should not be used during pregnancy or lactation. Adver ...
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Immunosuppressant
Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system. Classification Immunosuppressive drugs can be classified into five groups: * glucocorticoids * cytostatics * antibodies * drugs acting on immunophilins * other drugs Glucocorticoids In pharmacologic (supraphysiologic) doses, glucocorticoids, such as prednisone, dexamethasone, and hydrocortisone are used to suppress various allergic, inflammatory, and autoimmune disorders. They are also administered as posttransplantory immunosuppressants to prevent the acute transplant rejection and graft-versus-host disease. Nevertheless, they do not prevent an infection and also inhibit later reparative processes. Immunosuppressive mechanism Glucocorticoids suppress cell-mediated immunity. They act by inhibiting gene expression of cytokines including Interleukin 1 (IL-1), IL-2, IL-3, IL-4, IL-5, ...
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CD3 (immunology)
CD3 ( cluster of differentiation 3) is a protein complex and T cell co-receptor that is involved in activating both the cytotoxic T cell (CD8+ naive T cells) and T helper cells (CD4+ naive T cells). It is composed of four distinct chains. In mammals, the complex contains a CD3γ chain, a CD3δ chain, and two CD3ε chains. These chains associate with the T-cell receptor (TCR) and the CD3-zeta (ζ-chain) to generate an activation signal in T lymphocytes. The TCR, CD3-zeta, and the other CD3 molecules together constitute the TCR complex. Structure The CD3γ, CD3δ, and CD3ε chains are highly related cell-surface proteins of the immunoglobulin superfamily containing a single extracellular immunoglobulin domain. A structure of the extracellular and transmembrane regions of the CD3γε/CD3δε/CD3ζζ/TCRαβ complex was solved with CryoEM, showing for the first time how the CD3 transmembrane regions enclose the TCR transmembrane regions in an open barrel. Containing ...
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Prophylaxis
Preventive healthcare, or prophylaxis, is the application of healthcare measures to prevent diseases.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental health and efficiency. Leavell, H. R., & Clark, E. G. (1979). Preventive Medicine for the Doctor in his Community (3rd ed.). Huntington, NY: Robert E. Krieger Publishing Company. Disease and disability are affected by environmental factors, genetic predisposition, disease agents, and lifestyle choices, and are dynamic processes that begin before individuals realize they are affected. Disease prevention relies on anticipatory actions that can be categorized as primal, primary, secondary, and tertiary prevention. Each year, millions of people die of preventable causes. A 2004 study showed that about half of all deaths in the United States in 2000 were due to preventable behaviors and exposures. Leading causes included cardiovascular disease, chron ...
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Myalgia
Myalgia or muscle pain is a painful sensation evolving from muscle tissue. It is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likely cause is viral infection, especially when there has been no injury. Long-lasting myalgia can be caused by metabolic myopathy, some nutritional deficiencies, ME/CFS, fibromyalgia, and amplified musculoskeletal pain syndrome. Causes The most common causes of myalgia are overuse, injury, and strain. Myalgia might also be caused by allergies, diseases, medications, or as a response to a vaccination. Dehydration at times results in muscle pain as well, especially for people involved in extensive physical activities such as workout. Muscle pain is also a common symptom in a variety of diseases, including infectious diseases, such as influenza, muscle abscesses, Lyme disease, malaria, trichinosis or poliomyelitis; autoimmune diseases, such as celiac disease, systemic ...
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Chills
Chills is a feeling of coldness occurring during a high fever, but sometimes is also a common symptom which occurs alone in specific people. It occurs during fever due to the release of cytokines and prostaglandins as part of the inflammatory response, which increases the set point for body temperature in the hypothalamus. The increased set point causes the body temperature to rise ( pyrexia), but also makes the patient feel cold or chills until the new set point is reached. Shivering also occurs along with chills because the patient's body produces heat during muscle contraction in a physiological attempt to increase body temperature to the new set point. When it does not accompany a high fever, it is normally a light chill. Sometimes a chill of medium power and short duration may occur during a scare, especially in scares of fear, commonly interpreted like or confused by trembling. Severe chills with violent shivering are called rigors. Pathophysiology Chills occur w ...
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Fever
Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, set point in the hypothalamus. There is no single agreed-upon upper limit for normal temperature: sources use values ranging between in humans. The increase in set point triggers increased muscle tone, muscle contractions and causes a feeling of cold or chills. This results in greater heat production and efforts to conserve heat. When the set point temperature returns to normal, a person feels hot, becomes Flushing (physiology), flushed, and may begin to Perspiration, sweat. Rarely a fever may trigger a febrile seizure, with this being more common in young children. Fevers do not typically go higher than . A fever can be caused by many medical conditions ranging from non-serious to life-threatening. This includes viral infection, viral, b ...
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Fatigue (medical)
Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated with medical conditions including autoimmune disease, organ failure, chronic pain conditions, mood disorders, heart disease, infectious diseases, and post-infectious-disease states. However, fatigue is complex and in up to a third of primary care cases no medical or psychiatric diagnosis is found. Fatigue (in the general usage sense of normal tiredness) often follows prolonged physical or mental activity. Physical fatigue results from muscle fatigue brought about by intense physical activity. Mental fatigue results from prolonged periods of cognitive activity which impairs cognitive ability, can manifest as sleepiness, lethargy, or directed attention fatigue, and can also impair physical performance. Definition Fatigue in a medical context is used to ...
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Cytokine Release Syndrome
In immunology, cytokine release syndrome (CRS) is a form of systemic inflammatory response syndrome (SIRS) that can be triggered by a variety of factors such as infections and certain drugs. It refers to cytokine storm syndromes (CSS) and occurs when large numbers of white blood cells are activated and release inflammatory cytokines, which in turn activate yet more white blood cells. CRS is also an adverse effect of some monoclonal antibody medications, as well as adoptive T-cell therapies. When occurring as a result of a medication, it is also known as an infusion reaction. The term cytokine storm is often used interchangeably with CRS but, despite the fact that they have similar clinical phenotype, their characteristics are different. When occurring as a result of a therapy, CRS symptoms may be delayed until days or weeks after treatment. Immediate-onset CRS is a cytokine storm, although severe cases of CRS have also been called cytokine storms. Signs and symptoms Symptoms ...
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Interferon Gamma
Interferon gamma (IFNG or IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock as a product of human leukocytes stimulated with phytohemagglutinin, and by others as a product of antigen-stimulated lymphocytes. It was also shown to be produced in human lymphocytes. or tuberculin-sensitized mouse peritoneal lymphocytes challenged with Mantoux test (PPD); the resulting supernatants were shown to inhibit growth of vesicular stomatitis virus. Those reports also contained the basic observation underlying the now widely employed interferon gamma release assay used to test for tuberculosis. In humans, the IFNG protein is encoded by the ''IFNG'' gene. Through cell signaling, interferon gamma plays a role in regulating the immune response of its target cell. A key signaling pathway that is activated by ...
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Tumor Necrosis Factor
Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors on other cells. It is a member of the tumor necrosis factor superfamily, a family of transmembrane proteins that are cytokines, chemical messengers of the immune system. Excessive production of TNF plays a critical role in several inflammatory diseases, and TNF-blocking drugs are often employed to treat these diseases. TNF is produced primarily by macrophages but is also produced in several other cell types, such as T cells, B cells, dendritic cells, and mast cells. It is produced rapidly in response to pathogens, cytokines, and environmental stressors. TNF is initially produced as a type II transmembrane protein (tmTNF), which is then cleaved by TNF alpha converting enzyme (TACE) into a soluble form (sTNF) and secreted from the cell ...
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Cytokines
Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes and mast cells, as well as Endothelium, endothelial cells, fibroblasts, and various stromal cells; a given cytokine may be produced by more than one type of cell. Due to their size, cytokines cannot cross the lipid bilayer of cells to enter the cytoplasm and therefore typically exert their functions by interacting with specific cytokine receptor, cytokine receptors on the target cell surface. Cytokines are especially important in the immune system; cytokines modulate the balance between humoral immunity, humoral and cell-mediated immunity, cell-based immune responses, and they regulate the maturation, growth, and responsiveness of particular cell populations. Some cytokines enhance or inhibit the action of other cytokines in complex way ...
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Lactation
Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process naturally occurs with all sexually mature female mammals, although it may predate mammals. The process of feeding milk in all female creatures is called ''nursing'', and in humans it is also called ''breastfeeding''. Newborn infants often produce some milk from their own breast tissue, known colloquially as witch's milk. In most species, lactation is a sign that the female has been pregnant at some point in her life, although in humans and goats, it can happen without pregnancy. Nearly every species of mammal has teats; except for monotremes, egg-laying mammals, which instead release milk through ducts in the abdomen. In only a handful of species of mammals, certain bat species, is milk production a normal Male lactation, male function. ''Galactopoiesis'' is the maintenance of milk production. This stage requires prolactin. Oxytocin is cr ...
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