Organ Specificity
Kidney
Liver
Sensitivity and Specificity
Substrate Specificity
A comparison of affinity constants for muscarine-sensitive acetylcholine receptors in guinea-pig atrial pacemaker cells at 29 degrees C and in ileum at 29 degrees C and 37 degrees C. (1/12667)
1 The affinity of 17 compounds for muscarine-sensitive acetylcholine receptors in atrial pacemaker cells and ileum of the guinea-pig has been measured at 29 degrees C in Ringer-Locke solution. Measurements were also made at 37 degrees C with 7 of them. 2 Some of the compounds had much higher affinity for the receptors in the ileum than for those in the atria. For the most selective compound, 4-diphenylacetoxy-N-methylpiperidine methiodide, the difference was approximately 20-fold. The receptors in the atria are therefore different the structure from those in the ileum. 3 The effect of temperature on affinity are not the same for all the compounds, tested indicating different enthalpies and entropies of adsorption and accounting for some of the difficulty experienced in predicting the affinity of new compounds. (+info)The mouse Aire gene: comparative genomic sequencing, gene organization, and expression. (2/12667)
Mutations in the human AIRE gene (hAIRE) result in the development of an autoimmune disease named APECED (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy; OMIM 240300). Previously, we have cloned hAIRE and shown that it codes for a putative transcription-associated factor. Here we report the cloning and characterization of Aire, the murine ortholog of hAIRE. Comparative genomic sequencing revealed that the structure of the AIRE gene is highly conserved between human and mouse. The conceptual proteins share 73% homology and feature the same typical functional domains in both species. RT-PCR analysis detected three splice variant isoforms in various mouse tissues, and interestingly one isoform was conserved in human, suggesting potential biological relevance of this product. In situ hybridization on mouse and human histological sections showed that AIRE expression pattern was mainly restricted to a few cells in the thymus, calling for a tissue-specific function of the gene product. (+info)RFLAT-1: a new zinc finger transcription factor that activates RANTES gene expression in T lymphocytes. (3/12667)
RANTES (Regulated upon Activation, Normal T cell Expressed and Secreted) is a chemoattractant cytokine (chemokine) important in the generation of inflammatory infiltrate and human immunodeficiency virus entry into immune cells. RANTES is expressed late (3-5 days) after activation in T lymphocytes. Using expression cloning, we identified the first "late" T lymphocyte associated transcription factor and named it "RANTES Factor of Late Activated T Lymphocytes-1" (RFLAT-1). RFLAT-1 is a novel, phosphorylated, zinc finger transcription factor that is expressed in T cells 3 days after activation, coincident with RANTES expression. While Rel proteins play the dominant role in RANTES gene expression in fibroblasts, RFLAT-1 is a strong transactivator for RANTES in T cells. (+info)A concise promoter region of the heart fatty acid-binding protein gene dictates tissue-appropriate expression. (4/12667)
The heart fatty acid-binding protein (HFABP) is a member of a family of binding proteins with distinct tissue distributions and diverse roles in fatty acid metabolism, trafficking, and signaling. Other members of this family have been shown to possess concise promoter regions that direct appropriate tissue-specific expression. The basis for the specific expression of the HFABP has not been previously evaluated, and the mechanisms governing expression of metabolic genes in the heart are not completely understood. We used transient and permanent transfections in ventricular myocytes, skeletal myocytes, and nonmyocytic cells to map regulatory elements in the HFABP promoter, and audited results in transgenic mice. Appropriate tissue-specific expression in cell culture and in transgenic mice was dictated by 1.2 kb of the 5'-flanking sequence of FABP3, the HFABP gene. Comparison of orthologous murine and human genomic sequences demonstrated multiple regions of near-identity within this promoter region, including a CArG-like element close to the TATA box. Binding and transactivation studies demonstrated that this element can function as an atypical myocyte enhancer-binding factor 2 site. Interactions with adjacent sites are likely to be necessary for fully appropriate, tissue-specific, developmental and metabolic regulation. (+info)Integrin subunit gene expression is regionally differentiated in adult brain. (5/12667)
Integrins are a diverse family of heterodimeric (alphabeta) adhesion receptors recently shown to be concentrated within synapses and involved in the consolidation of long-term potentiation. Whether neuronal types or anatomical systems in the adult rat brain are coded by integrin type was studied in the present experiments by mapping the relative densities of mRNAs for nine alpha and four beta subunits. Expression patterns were markedly different and in some regions complementary. General results and areas of notable labeling were as follows: alpha1-limited neuronal expression, neocortical layer V, hippocampal CA3; alpha3 and alpha5-diffuse neuronal and glial labeling, Purkinje cells, hippocampal stratum pyramidale, locus coeruleus (alpha3); alpha4- discrete limbic regions, olfactory cortical layer II, hippocampal CA2; alpha6-most prominently neuronal, neocortical subplate, endopiriform, subiculum; alpha7-discrete, all neocortical layers, hippocampal granule cells and CA3, cerebellar granule and Purkinje cells, all efferent cranial nerve nuclei; alpha8-discrete neuronal, deep cortex, hippocampal CA1, basolateral amygdala, striatum; alphaV-all cortical layers, striatum, Purkinje cells; beta4-dentate gyrus granule cells; beta5-broadly distributed, neocortex, medial amygdala, cerebellar granule and Purkinje cells, efferent cranial nerve nuclei; alpha2, beta2, and beta3-mRNAs not detected. These results establish that brain subfields express different balances of integrin subunits and thus different integrin receptors. Such variations will determine which matrix proteins are recognized by neurons and the types of intraneuronal signaling generated by matrix binding. They also could generate important differences in synaptic plasticity across brain systems. (+info)Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes. (6/12667)
Dysfunction of the pancreatic beta cell is an important defect in the pathogenesis of type 2 diabetes, although its exact relationship to the insulin resistance is unclear. To determine whether insulin signaling has a functional role in the beta cell we have used the Cre-loxP system to specifically inactivate the insulin receptor gene in the beta cells. The resultant mice exhibit a selective loss of insulin secretion in response to glucose and a progressive impairment of glucose tolerance. These data indicate an important functional role for the insulin receptor in glucose sensing by the pancreatic beta cell and suggest that defects in insulin signaling at the level of the beta cell may contribute to the observed alterations in insulin secretion in type 2 diabetes. (+info)UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells. (7/12667)
Uncoupling proteins (UCPs) are a family of mitochondrial transporter proteins that have been implicated in thermoregulatory heat production and maintenance of the basal metabolic rate. We have identified and partially characterized a novel member of the human uncoupling protein family, termed uncoupling protein-4 (UCP4). Protein sequence analyses showed that UCP4 is most related to UCP3 and possesses features characteristic of mitochondrial transporter proteins. Unlike other known UCPs, UCP4 transcripts are exclusively expressed in both fetal and adult brain tissues. UCP4 maps to human chromosome 6p11.2-q12. Consistent with its potential role as an uncoupling protein, UCP4 is localized to the mitochondria and its ectopic expression in mammalian cells reduces mitochondrial membrane potential. These findings suggest that UCP4 may be involved in thermoregulatory heat production and metabolism in the brain. (+info)The latrophilin family: multiply spliced G protein-coupled receptors with differential tissue distribution. (8/12667)
Latrophilin is a brain-specific Ca2+-independent receptor of alpha-latrotoxin, a potent presynaptic neurotoxin. We now report the finding of two novel latrophilin homologues. All three latrophilins are unusual G protein-coupled receptors. They exhibit strong similarities within their lectin, olfactomedin and transmembrane domains but possess variable C-termini. Latrophilins have up to seven sites of alternative splicing; some splice variants contain an altered third cytoplasmic loop or a truncated cytoplasmic tail. Only latrophilin-1 binds alpha-latrotoxin; it is abundant in brain and is present in endocrine cells. Latrophilin-3 is also brain-specific, whereas latrophilin-2 is ubiquitous. Together, latrophilins form a novel family of heterogeneous G protein-coupled receptors with distinct tissue distribution and functions. (+info)Organ specificity, in the context of immunology and toxicology, refers to the phenomenon where a substance (such as a drug or toxin) or an immune response primarily affects certain organs or tissues in the body. This can occur due to various reasons such as:
1. The presence of specific targets (like antigens in the case of an immune response or receptors in the case of drugs) that are more abundant in these organs.
2. The unique properties of certain cells or tissues that make them more susceptible to damage.
3. The way a substance is metabolized or cleared from the body, which can concentrate it in specific organs.
For example, in autoimmune diseases, organ specificity describes immune responses that are directed against antigens found only in certain organs, such as the thyroid gland in Hashimoto's disease. Similarly, some toxins or drugs may have a particular affinity for liver cells, leading to liver damage or specific drug interactions.
A kidney, in medical terms, is one of two bean-shaped organs located in the lower back region of the body. They are essential for maintaining homeostasis within the body by performing several crucial functions such as:
1. Regulation of water and electrolyte balance: Kidneys help regulate the amount of water and various electrolytes like sodium, potassium, and calcium in the bloodstream to maintain a stable internal environment.
2. Excretion of waste products: They filter waste products from the blood, including urea (a byproduct of protein metabolism), creatinine (a breakdown product of muscle tissue), and other harmful substances that result from normal cellular functions or external sources like medications and toxins.
3. Endocrine function: Kidneys produce several hormones with important roles in the body, such as erythropoietin (stimulates red blood cell production), renin (regulates blood pressure), and calcitriol (activated form of vitamin D that helps regulate calcium homeostasis).
4. pH balance regulation: Kidneys maintain the proper acid-base balance in the body by excreting either hydrogen ions or bicarbonate ions, depending on whether the blood is too acidic or too alkaline.
5. Blood pressure control: The kidneys play a significant role in regulating blood pressure through the renin-angiotensin-aldosterone system (RAAS), which constricts blood vessels and promotes sodium and water retention to increase blood volume and, consequently, blood pressure.
Anatomically, each kidney is approximately 10-12 cm long, 5-7 cm wide, and 3 cm thick, with a weight of about 120-170 grams. They are surrounded by a protective layer of fat and connected to the urinary system through the renal pelvis, ureters, bladder, and urethra.
The liver is a large, solid organ located in the upper right portion of the abdomen, beneath the diaphragm and above the stomach. It plays a vital role in several bodily functions, including:
1. Metabolism: The liver helps to metabolize carbohydrates, fats, and proteins from the food we eat into energy and nutrients that our bodies can use.
2. Detoxification: The liver detoxifies harmful substances in the body by breaking them down into less toxic forms or excreting them through bile.
3. Synthesis: The liver synthesizes important proteins, such as albumin and clotting factors, that are necessary for proper bodily function.
4. Storage: The liver stores glucose, vitamins, and minerals that can be released when the body needs them.
5. Bile production: The liver produces bile, a digestive juice that helps to break down fats in the small intestine.
6. Immune function: The liver plays a role in the immune system by filtering out bacteria and other harmful substances from the blood.
Overall, the liver is an essential organ that plays a critical role in maintaining overall health and well-being.
Sensitivity and specificity are statistical measures used to describe the performance of a diagnostic test or screening tool in identifying true positive and true negative results.
* Sensitivity refers to the proportion of people who have a particular condition (true positives) who are correctly identified by the test. It is also known as the "true positive rate" or "recall." A highly sensitive test will identify most or all of the people with the condition, but may also produce more false positives.
* Specificity refers to the proportion of people who do not have a particular condition (true negatives) who are correctly identified by the test. It is also known as the "true negative rate." A highly specific test will identify most or all of the people without the condition, but may also produce more false negatives.
In medical testing, both sensitivity and specificity are important considerations when evaluating a diagnostic test. High sensitivity is desirable for screening tests that aim to identify as many cases of a condition as possible, while high specificity is desirable for confirmatory tests that aim to rule out the condition in people who do not have it.
It's worth noting that sensitivity and specificity are often influenced by factors such as the prevalence of the condition in the population being tested, the threshold used to define a positive result, and the reliability and validity of the test itself. Therefore, it's important to consider these factors when interpreting the results of a diagnostic test.
Substrate specificity in the context of medical biochemistry and enzymology refers to the ability of an enzyme to selectively bind and catalyze a chemical reaction with a particular substrate (or a group of similar substrates) while discriminating against other molecules that are not substrates. This specificity arises from the three-dimensional structure of the enzyme, which has evolved to match the shape, charge distribution, and functional groups of its physiological substrate(s).
Substrate specificity is a fundamental property of enzymes that enables them to carry out highly selective chemical transformations in the complex cellular environment. The active site of an enzyme, where the catalysis takes place, has a unique conformation that complements the shape and charge distribution of its substrate(s). This ensures efficient recognition, binding, and conversion of the substrate into the desired product while minimizing unwanted side reactions with other molecules.
Substrate specificity can be categorized as:
1. Absolute specificity: An enzyme that can only act on a single substrate or a very narrow group of structurally related substrates, showing no activity towards any other molecule.
2. Group specificity: An enzyme that prefers to act on a particular functional group or class of compounds but can still accommodate minor structural variations within the substrate.
3. Broad or promiscuous specificity: An enzyme that can act on a wide range of structurally diverse substrates, albeit with varying catalytic efficiencies.
Understanding substrate specificity is crucial for elucidating enzymatic mechanisms, designing drugs that target specific enzymes or pathways, and developing biotechnological applications that rely on the controlled manipulation of enzyme activities.
Antibody specificity refers to the ability of an antibody to bind to a specific epitope or antigenic determinant on an antigen. Each antibody has a unique structure that allows it to recognize and bind to a specific region of an antigen, typically a small portion of the antigen's surface made up of amino acids or sugar residues. This highly specific binding is mediated by the variable regions of the antibody's heavy and light chains, which form a pocket that recognizes and binds to the epitope.
The specificity of an antibody is determined by its unique complementarity-determining regions (CDRs), which are loops of amino acids located in the variable domains of both the heavy and light chains. The CDRs form a binding site that recognizes and interacts with the epitope on the antigen. The precise fit between the antibody's binding site and the epitope is critical for specificity, as even small changes in the structure of either can prevent binding.
Antibody specificity is important in immune responses because it allows the immune system to distinguish between self and non-self antigens. This helps to prevent autoimmune reactions where the immune system attacks the body's own cells and tissues. Antibody specificity also plays a crucial role in diagnostic tests, such as ELISA assays, where antibodies are used to detect the presence of specific antigens in biological samples.
Ruth Clayton
