52-479: PLAB or Plab may refer to: Science and technology [ edit ] GDF15 (Growth/differentiation factor 15), a protein Photronics Inc (NASDAQ: PLAB), an American semiconductor photomask manufacturer Phospholipase A Professional and Linguistic Assessments Board , a UK medical test Other uses [ edit ] Pimsleur Language Aptitude Battery ,
104-399: A chemotactic gradient created by the local cells to reach the site of injury. The loss of function ( functio laesa ) is probably the result of a neurological reflex in response to pain. In addition to cell-derived mediators, several acellular biochemical cascade systems—consisting of preformed plasma proteins—act in parallel to initiate and propagate the inflammatory response. These include
156-452: A gene on human chromosome 19 is a stub . You can help Misplaced Pages by expanding it . Inflammation Inflammation (from Latin : inflammatio ) is part of the biological response of body tissues to harmful stimuli, such as pathogens , damaged cells, or irritants . The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin calor , dolor , rubor , tumor , and functio laesa ). Inflammation
208-401: A lipid storage disorder, is now understood as a chronic inflammatory condition involving the arterial walls. Research has established a fundamental role for inflammation in mediating all stages of atherosclerosis from initiation through progression and, ultimately, the thrombotic complications from it. These new findings reveal links between traditional risk factors like cholesterol levels and
260-454: A construction site – for the purpose of aiding phagocytic debridement and wound repair later on. Some of the exuded tissue fluid is also funneled by lymphatics to the regional lymph nodes, flushing bacteria along to start the recognition and attack phase of the adaptive immune system . Acute inflammation is characterized by marked vascular changes, including vasodilation , increased permeability and increased blood flow, which are induced by
312-410: A few days. Cytokines and chemokines promote the migration of neutrophils and macrophages to the site of inflammation. Pathogens, allergens, toxins, burns, and frostbite are some of the typical causes of acute inflammation. Toll-like receptors (TLRs) recognize microbial pathogens. Acute inflammation can be a defensive mechanism to protect tissues against injury. Inflammation lasting 2–6 weeks
364-633: A foreign language test Paya Lebar Air Base , a military airbase in Singapore Darrin Plab (born 1970), retired American high jumper Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title PLAB . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=PLAB&oldid=869569455 " Category : Disambiguation pages Hidden categories: Short description
416-464: A high-fat diet with recombinant growth differentiating factor 15 (GDF15) reduces obesity and improves glycemic control through glial-cell-derived neurotrophic factor family receptor α-like (GFRAL)-dependent suppression of food intake. Fibroblast-specific loss of GDF15 expression in a model of 3D reconstructed human skin induced epidermal thinning, a hallmark of skin aging . GDF15 plays a so far undisclosed role in mitochondrial homeostasis to delay both
468-464: A progressive shift in the type of cells present at the site of inflammation, such as mononuclear cells , and involves simultaneous destruction and healing of the tissue. Inflammation has also been classified as Type 1 and Type 2 based on the type of cytokines and helper T cells (Th1 and Th2) involved. The earliest known reference for the term inflammation is around the early 15th century. The word root comes from Old French inflammation around
520-568: A role in regulating inflammatory pathways and to be involved in regulating apoptosis , angiogenesis , cell repair and cell growth , which are biological processes observed in cardiovascular and neoplastic disorders. GDF15 has shown to be a strong prognostic protein in patients with different diseases such as heart diseases and cancer. In cardiovascular tissues it is shown that GDF15 concentrations increase in response to atherosclerosis , ischemia/reperfusion injury and heart failure . In patients with coronary artery disease (CAD), GDF15
572-406: A specific cell type. Such an approach may limit side effects that are unrelated to the tumor of interest, and may help preserve vital homeostatic functions and developmental processes in the organism. There is some evidence from 2009 to suggest that cancer-related inflammation (CRI) may lead to accumulation of random genetic alterations in cancer cells. In 1863, Rudolf Virchow hypothesized that
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#1732852435446624-403: A systemic response known as anaphylaxis . Inflammatory myopathies are caused by the immune system inappropriately attacking components of muscle, leading to signs of muscle inflammation. They may occur in conjunction with other immune disorders, such as systemic sclerosis , and include dermatomyositis , polymyositis , and inclusion body myositis . Due to the central role of leukocytes in
676-474: A urethral infection because urethral microbial invasion is the most common cause of urethritis. However, the inflammation–infection distinction is crucial in situations in pathology and medical diagnosis that involve inflammation that is not driven by microbial invasion, such as cases of atherosclerosis , trauma , ischemia , and autoimmune diseases (including type III hypersensitivity ). Biological: Chemical: Psychological: Acute inflammation
728-605: A vascular phase that occurs first, followed by a cellular phase involving immune cells (more specifically myeloid granulocytes in the acute setting). The vascular component of acute inflammation involves the movement of plasma fluid , containing important proteins such as fibrin and immunoglobulins ( antibodies ), into inflamed tissue. Upon contact with PAMPs, tissue macrophages and mastocytes release vasoactive amines such as histamine and serotonin , as well as eicosanoids such as prostaglandin E2 and leukotriene B4 to remodel
780-471: A vast variety of human diseases. The immune system is often involved with inflammatory disorders, as demonstrated in both allergic reactions and some myopathies , with many immune system disorders resulting in abnormal inflammation. Non-immune diseases with causal origins in inflammatory processes include cancer, atherosclerosis , and ischemic heart disease . Examples of disorders associated with inflammation include: Atherosclerosis, formerly considered
832-803: A worse sense of smell during a cold, or having difficulty breathing when bronchitis is present. Loss of function has multiple causes. The process of acute inflammation is initiated by resident immune cells already present in the involved tissue, mainly resident macrophages , dendritic cells , histiocytes , Kupffer cells and mast cells . These cells possess surface receptors known as pattern recognition receptors (PRRs), which recognize (i.e., bind) two subclasses of molecules: pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). PAMPs are compounds that are associated with various pathogens , but which are distinguishable from host molecules. DAMPs are compounds that are associated with host-related injury and cell damage. At
884-467: Is a generic response, and therefore is considered a mechanism of innate immunity , whereas adaptive immunity is specific to each pathogen. Inflammation is a protective response involving immune cells , blood vessels , and molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out damaged cells and tissues, and initiate tissue repair. Too little inflammation could lead to progressive tissue destruction by
936-469: Is a short-term process, usually appearing within a few minutes or hours and begins to cease upon the removal of the injurious stimulus. It involves a coordinated and systemic mobilization response locally of various immune, endocrine and neurological mediators of acute inflammation. In a normal healthy response, it becomes activated, clears the pathogen and begins a repair process and then ceases. Acute inflammation occurs immediately upon injury, lasting only
988-775: Is associated with a 30% increased risk of developing major depressive disorder, supporting the link between inflammation and mental health. An allergic reaction, formally known as type 1 hypersensitivity , is the result of an inappropriate immune response triggering inflammation, vasodilation, and nerve irritation. A common example is hay fever , which is caused by a hypersensitive response by mast cells to allergens . Pre-sensitised mast cells respond by degranulating , releasing vasoactive chemicals such as histamine. These chemicals propagate an excessive inflammatory response characterised by blood vessel dilation, production of pro-inflammatory molecules, cytokine release, and recruitment of leukocytes. Severe inflammatory response may mature into
1040-445: Is designated subacute inflammation. Inflammation is characterized by five cardinal signs , (the traditional names of which come from Latin): The first four (classical signs) were described by Celsus ( c. 30 BC –38 AD). Pain is due to the release of chemicals such as bradykinin and histamine that stimulate nerve endings. Acute inflammation of the lung (usually in response to pneumonia ) does not cause pain unless
1092-399: Is different from Wikidata All article disambiguation pages All disambiguation pages GDF15 5VT2 , 5VZ3 , 5VZ4 , 6Q2J 9518 23886 ENSG00000130513 ENSMUSG00000038508 Q99988 Q9Z0J7 NM_004864 NM_011819 NM_001330687 NP_004855 NP_001317616 NP_035949 Growth/differentiation factor 15 is a protein that in humans
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#17328524354461144-476: Is encoded by the GDF15 gene . GDF15 was first identified as Macrophage inhibitory cytokine-1 or MIC-1. It is a protein belonging to the transforming growth factor beta superfamily . Under normal conditions, GDF15 is expressed in low concentrations in most organs and upregulated because of injury of organs such as liver , kidney , heart and lung . The function of GDF15 is not fully clear but it seems to have
1196-416: Is mediated by mononuclear cells such as monocytes and lymphocytes . Various leukocytes , particularly neutrophils, are critically involved in the initiation and maintenance of inflammation. These cells must be able to move to the site of injury from their usual location in the blood, therefore mechanisms exist to recruit and direct leukocytes to the appropriate place. The process of leukocyte movement from
1248-442: Is shown to be associated with adverse outcome such as mortality, myocardial infarction , stroke and with bleeding. However, elevated GDF15 levels in diseases such as cancer and heart disease may be the result of inflammation caused by these diseases. Note that GDF15 is necessary for surviving both bacterial and viral infections , as well as sepsis . The protective effects of GDF15 were largely independent of pathogen control or
1300-572: The bone marrow may result in abnormal or few leukocytes. Certain drugs or exogenous chemical compounds are known to affect inflammation. Vitamin A deficiency, for example, causes an increase in inflammatory responses, and anti-inflammatory drugs work specifically by inhibiting the enzymes that produce inflammatory eicosanoids . Additionally, certain illicit drugs such as cocaine and ecstasy may exert some of their detrimental effects by activating transcription factors intimately involved with inflammation (e.g. NF-κB ). Inflammation orchestrates
1352-424: The complement system activated by bacteria and the coagulation and fibrinolysis systems activated by necrosis (e.g., burn, trauma). Acute inflammation may be regarded as the first line of defense against injury. Acute inflammatory response requires constant stimulation to be sustained. Inflammatory mediators are short-lived and are quickly degraded in the tissue. Hence, acute inflammation begins to cease once
1404-521: The microenvironment around tumours, contributing to proliferation, survival and migration. Cancer cells use selectins , chemokines and their receptors for invasion, migration and metastasis. On the other hand, many cells of the immune system contribute to cancer immunology , suppressing cancer. Molecular intersection between receptors of steroid hormones, which have important effects on cellular development, and transcription factors that play key roles in inflammation, such as NF-κB , may mediate some of
1456-452: The 14th century, which then comes from Latin inflammatio or inflammationem . Literally, the term relates to the word "flame", as the property of being "set on fire" or "to burn". The term inflammation is not a synonym for infection . Infection describes the interaction between the action of microbial invasion and the reaction of the body's inflammatory response—the two components are considered together in discussion of infection, and
1508-407: The actions of various inflammatory mediators. Vasodilation occurs first at the arteriole level, progressing to the capillary level, and brings about a net increase in the amount of blood present, causing the redness and heat of inflammation. Increased permeability of the vessels results in the movement of plasma into the tissues, with resultant stasis due to the increase in the concentration of
1560-909: The blood to the tissues through the blood vessels is known as extravasation and can be broadly divided up into a number of steps: Extravasated neutrophils in the cellular phase come into contact with microbes at the inflamed tissue. Phagocytes express cell-surface endocytic pattern recognition receptors (PRRs) that have affinity and efficacy against non-specific microbe-associated molecular patterns (PAMPs). Most PAMPs that bind to endocytic PRRs and initiate phagocytosis are cell wall components, including complex carbohydrates such as mannans and β- glucans , lipopolysaccharides (LPS), peptidoglycans , and surface proteins. Endocytic PRRs on phagocytes reflect these molecular patterns, with C-type lectin receptors binding to mannans and β-glucans, and scavenger receptors binding to LPS. Upon endocytic PRR binding, actin - myosin cytoskeletal rearrangement adjacent to
1612-419: The body to harmful stimuli, and is achieved by the increased movement of plasma and leukocytes (in particular granulocytes ) from the blood into the injured tissues. A series of biochemical events propagates and matures the inflammatory response, involving the local vascular system , the immune system , and various cells in the injured tissue. Prolonged inflammation, known as chronic inflammation , leads to
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1664-498: The cells within blood – a condition characterized by enlarged vessels packed with cells. Stasis allows leukocytes to marginate (move) along the endothelium , a process critical to their recruitment into the tissues. Normal flowing blood prevents this, as the shearing force along the periphery of the vessels moves cells in the blood into the middle of the vessel. * non-exhaustive list The cellular component involves leukocytes , which normally reside in blood and must move into
1716-438: The development and propagation of inflammation, defects in leukocyte functionality often result in a decreased capacity for inflammatory defense with subsequent vulnerability to infection. Dysfunctional leukocytes may be unable to correctly bind to blood vessels due to surface receptor mutations, digest bacteria ( Chédiak–Higashi syndrome ), or produce microbicides ( chronic granulomatous disease ). In addition, diseases affecting
1768-417: The efficacy of the phagocytic process, enhancing the lysosomal elimination of the infective agent. * non-exhaustive list Specific patterns of acute and chronic inflammation are seen during particular situations that arise in the body, such as when inflammation occurs on an epithelial surface, or pyogenic bacteria are involved. Inflammatory abnormalities are a large group of disorders that underlie
1820-430: The factors that promote chronic inflammation. A 2014 study reported that 60% of Americans had at least one chronic inflammatory condition, and 42% had more than one. Common signs and symptoms that develop during chronic inflammation are: As defined, acute inflammation is an immunovascular response to inflammatory stimuli, which can include infection or trauma. This means acute inflammation can be broadly divided into
1872-421: The harmful stimulus (e.g. bacteria) and compromise the survival of the organism. However inflammation can also have negative effects. Too much inflammation, in the form of chronic inflammation, is associated with various diseases, such as hay fever , periodontal disease , atherosclerosis , and osteoarthritis . Inflammation can be classified as acute or chronic . Acute inflammation is the initial response of
1924-400: The inflamed tissue via extravasation to aid in inflammation. Some act as phagocytes , ingesting bacteria, viruses, and cellular debris. Others release enzymatic granules that damage pathogenic invaders. Leukocytes also release inflammatory mediators that develop and maintain the inflammatory response. In general, acute inflammation is mediated by granulocytes , whereas chronic inflammation
1976-483: The inflammation involves the parietal pleura , which does have pain-sensitive nerve endings . Heat and redness are due to increased blood flow at body core temperature to the inflamed site. Swelling is caused by accumulation of fluid. The fifth sign, loss of function , is believed to have been added later by Galen , Thomas Sydenham or Rudolf Virchow . Examples of loss of function include pain that inhibits mobility, severe swelling that prevents movement, having
2028-513: The local vasculature. Macrophages and endothelial cells release nitric oxide . These mediators vasodilate and permeabilize the blood vessels , which results in the net distribution of blood plasma from the vessel into the tissue space. The increased collection of fluid into the tissue causes it to swell ( edema ). This exuded tissue fluid contains various antimicrobial mediators from the plasma such as complement , lysozyme , antibodies , which can immediately deal damage to microbes, and opsonise
2080-548: The magnitude of inflammatory response, suggesting a role in disease tolerance. Metformin was shown to cause increased levels of GDF15. This increase mediates the effect of body weight loss by metformin. Further study has shown weight loss is promoted by maintaining energy expenditure in addition to appetite suppression. Elevations in GDF15 reduce food intake and body mass in animal models through binding to glial cell-derived neurotrophic factor family receptor alpha-like ( GFRAL ) and
2132-505: The microbes in preparation for the cellular phase. If the inflammatory stimulus is a lacerating wound, exuded platelets , coagulants , plasmin and kinins can clot the wounded area using vitamin K-dependent mechanisms and provide haemostasis in the first instance. These clotting mediators also provide a structural staging framework at the inflammatory tissue site in the form of a fibrin lattice – as would construction scaffolding at
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2184-406: The most critical effects of inflammatory stimuli on cancer cells. This capacity of a mediator of inflammation to influence the effects of steroid hormones in cells is very likely to affect carcinogenesis. On the other hand, due to the modular nature of many steroid hormone receptors, this interaction may offer ways to interfere with cancer progression, through targeting of a specific protein domain in
2236-555: The onset of cellular senescence and the appearance of age-related changes in a 3D human skin model. It has been also associated as a causal factor in hyperemesis gravidarum , a severe form of morning sickness . GDF15 is being evaluated as a therapeutic target for treatment of cancer cachexia. In September 2024, Pfizer disclosed that the anti-GDF15 monoclonal antibody ponsegromab led to significant increases in body weight in patients with non-small cell lung cancer, pancreatic cancer, and colorectal cancer. This article on
2288-484: The onset of an infection, burn, or other injuries, these cells undergo activation (one of the PRRs recognize a PAMP or DAMP) and release inflammatory mediators responsible for the clinical signs of inflammation. Vasodilation and its resulting increased blood flow causes the redness ( rubor ) and increased heat ( calor ). Increased permeability of the blood vessels results in an exudation (leakage) of plasma proteins and fluid into
2340-501: The phagolysosomes then kill microbes inside the phagocyte. Phagocytic efficacy can be enhanced by opsonization . Plasma derived complement C3b and antibodies that exude into the inflamed tissue during the vascular phase bind to and coat the microbial antigens. As well as endocytic PRRs, phagocytes also express opsonin receptors Fc receptor and complement receptor 1 (CR1), which bind to antibodies and C3b, respectively. The co-stimulation of endocytic PRR and opsonin receptor increases
2392-487: The plasma membrane occurs in a way that endocytoses the plasma membrane containing the PRR-PAMP complex, and the microbe. Phosphatidylinositol and Vps34 - Vps15 - Beclin1 signalling pathways have been implicated to traffic the endocytosed phagosome to intracellular lysosomes , where fusion of the phagosome and the lysosome produces a phagolysosome. The reactive oxygen species , superoxides and hypochlorite bleach within
2444-589: The recruitment of the receptor tyrosine kinase RET in the hindbrain . In both mice and humans have shown that metformin and exercise increase circulating levels of GDF15. GDF15 might also exert anti-inflammatory effects through mechanisms that are not fully understood. These unique and distinct mechanisms for suppressing food intake and inflammation makes GDF15 an appealing candidate to treat many metabolic diseases, including obesity , type 2 diabetes mellitus , non-alcoholic fatty liver disease , cardiovascular disease and cancer cachexia . Treatment of rodents fed
2496-482: The stimulus has been removed. Chronic inflammation is inflammation that lasts for months or years. Macrophages, lymphocytes , and plasma cells predominate in chronic inflammation, in contrast to the neutrophils that predominate in acute inflammation. Diabetes , cardiovascular disease , allergies , and chronic obstructive pulmonary disease (COPD) are examples of diseases mediated by chronic inflammation. Obesity , smoking, stress and insufficient diet are some of
2548-410: The tissue ( edema ), which manifests itself as swelling ( tumor ). Some of the released mediators such as bradykinin increase the sensitivity to pain ( hyperalgesia , dolor ). The mediator molecules also alter the blood vessels to permit the migration of leukocytes, mainly neutrophils and macrophages , to flow out of the blood vessels (extravasation) and into the tissue. The neutrophils migrate along
2600-771: The treatment of atherosclerosis have focused on addressing inflammation directly. New anti-inflammatory drugs, such as monoclonal antibodies targeting IL-1β, have been studied in large clinical trials, showing promising results in reducing cardiovascular events. These drugs offer a potential new avenue for treatment, particularly for patients who do not respond adequately to statins. However, concerns about long-term safety and cost remain significant barriers to widespread adoption. Inflammatory processes can be triggered by negative cognition or their consequences, such as stress, violence, or deprivation. Negative cognition may therefore contribute to inflammation, which in turn can lead to depression. A 2019 meta-analysis found that chronic inflammation
2652-1042: The underlying mechanisms of atherogenesis . Clinical studies have shown that this emerging biology of inflammation in atherosclerosis applies directly to people. For instance, elevation in markers of inflammation predicts outcomes of people with acute coronary syndromes , independently of myocardial damage. In addition, low-grade chronic inflammation, as indicated by levels of the inflammatory marker C-reactive protein , prospectively defines risk of atherosclerotic complications, thus adding to prognostic information provided by traditional risk factors, such as LDL levels. Moreover, certain treatments that reduce coronary risk also limit inflammation. Notably, lipid-lowering medications such as statins have shown anti-inflammatory effects, which may contribute to their efficacy beyond just lowering LDL levels. This emerging understanding of inflammation’s role in atherosclerosis has had significant clinical implications, influencing both risk stratification and therapeutic strategies. Recent developments in
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#17328524354462704-519: The word is used to imply a microbial invasive cause for the observed inflammatory reaction. Inflammation , on the other hand, describes just the body's immunovascular response, regardless of cause. But, because the two are often correlated , words ending in the suffix -itis (which means inflammation) are sometimes informally described as referring to infection: for example, the word urethritis strictly means only "urethral inflammation", but clinical health care providers usually discuss urethritis as
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