Buttock cells are cells having a notched appearance that are found in certain malignancies, such as non-Hodgkin's lymphoma, mycosis fungoides, Sézary syndrome. Clue cell Koilocyte Large cell
Monoclonal antibodies are antibodies that are made by identical immune cells that are all clones of a unique parent cell. Monoclonal antibodies can have monovalent affinity. In contrast, polyclonal antibodies bind to multiple epitopes and are made by several different plasma cell lineages. Bispecific monoclonal antibodies can be engineered, by increasing the therapeutic targets of one single monoclonal antibody to two epitopes. Given any substance, it is possible to produce monoclonal antibodies that bind to that substance; this has become an important tool in biochemistry, molecular biology, medicine. When used as medications, non-proprietary drug names end in -mab and many immunotherapy specialists use the word mab anacronymically; the idea of "magic bullets" was first proposed by Paul Ehrlich, who, at the beginning of the 20th century, postulated that, if a compound could be made that selectively targeted a disease-causing organism a toxin for that organism could be delivered along with the agent of selectivity.
He and Élie Metchnikoff received the 1908 Nobel Prize for Physiology or Medicine for this work, which led to an effective syphilis treatment by 1910. In the 1970s, the B-cell cancer multiple myeloma was known, it was understood. This was used to study the structure of antibodies, but it was not yet possible to produce identical antibodies specific to a given antigen. In 1975, Georges Köhler and César Milstein succeeded in making fusions of myeloma cell lines with B cells to create hybridomas that could produce antibodies, specific to known antigens and that were immortalized, they shared the Nobel Prize in Medicine in 1984 for the discovery. In 1988, Greg Winter and his team pioneered the techniques to humanize monoclonal antibodies, eliminating the reactions that many monoclonal antibodies caused in some patients. Much of the work behind production of monoclonal antibodies is rooted in the production of hybridomas, which involves identifying antigen-specific plasma/plasmablast cells that produce antibodies specific to an antigen of interest and fusing these cells with myeloma cells.
Rabbit B-cells can be used to form a rabbit hybridoma. Polyethylene glycol is used to fuse adjacent plasma membranes, but the success rate is low, so a selective medium in which only fused cells can grow is used; this is possible because myeloma cells have lost the ability to synthesize hypoxanthine-guanine-phosphoribosyl transferase, an enzyme necessary for the salvage synthesis of nucleic acids. The absence of HGPRT is not a problem for these cells unless the de novo purine synthesis pathway is disrupted. Exposing cells to aminopterin, makes them unable to use the de novo pathway and become auxotrophic for nucleic acids, thus requiring supplementation to survive; the selective culture medium is called HAT medium because it contains hypoxanthine and thymidine. This medium is selective for fused cells. Unfused myeloma cells cannot grow because they lack HGPRT and thus cannot replicate their DNA. Unfused spleen cells cannot grow indefinitely because of their limited life span. Only fused hybrid cells, referred to as hybridomas, are able to grow indefinitely in the medium because the spleen cell partner supplies HGPRT and the myeloma partner has traits that make it immortal.
This mixture of cells is diluted and clones are grown from single parent cells on microtitre wells. The antibodies secreted by the different clones are assayed for their ability to bind to the antigen or immuno-dot blot; the most productive and stable clone is selected for future use. The hybridomas can be grown indefinitely in a suitable cell culture medium, they can be injected into mice. There, they produce; the medium must be enriched during in vitro selection to further favour hybridoma growth. This can be achieved by the use of a layer of feeder fibrocyte cells or supplement medium such as briclone. Culture-media conditioned by macrophages can be used. Production in cell culture is preferred as the ascites technique is painful to the animal. Where alternate techniques exist, ascites is considered unethical. Several monoclonal antibody technologies had been developed such as phage display, single B cell culture, single cell amplification from various B cell populations and single plasma cell interrogation technologies.
Different from traditional hybridoma technology, the newer technologies use molecular biology techniques to amplify the heavy and light chains of the antibody genes by PCR and produce in either bacterial or mammalian systems with recombinant technology. One of the advantages of the new technologies is applicable to multiple animals, such as rabbit, llama and other common experimental animals in the laboratory. After obtaining either a media sample of cultured hybridomas or a sample of ascites fluid, the desired antibodies must be extracted. Cell culture sample contaminants consist of media components such as growth factors and transferrins. In contrast, the in vivo sample is to have host antibodies, nucleases, nucleic acids and viruses. In both cases, other secretions by the hybridomas such as cytokines may be present. There may be b
Integrins are transmembrane receptors that facilitate cell-extracellular matrix adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, organization of the intracellular cytoskeleton, movement of new receptors to the cell membrane; the presence of integrins allows flexible responses to events at the cell surface. Several types of integrins exist, one cell may have multiple different types on its surface. Integrins are found in all animals. Integrins work alongside other receptors such as cadherins, the immunoglobulin superfamily cell adhesion molecules and syndecans, to mediate cell–cell and cell–matrix interaction. Ligands for integrins include fibronectin, vitronectin and laminin. Integrins are obligate heterodimers, meaning that they have two subunits: α and β. Integrins in mammals have twenty-four α and nine β subunits, in Drosophila five α and two β subunits, in Caenorhabditis nematodes two α subunits and one β subunit.
The α and β subunits each possess several cytoplasmic domains. Variants of some subunits are formed by differential RNA splicing. Through different combinations of the α and β subunits, around 24 unique integrins are generated. Integrin subunits have short cytoplasmic domains of 40 -- 70 amino acids; the exception is the beta-4 subunit, which has a cytoplasmic domain of 1,088 amino acids, one of the largest of any membrane protein. Outside the cell membrane, the α and β chains lie close together along a length of about 23 nm, they have been compared to lobster claws, although they don't "pinch" their ligand, they chemically interact with it at the insides of the "tips" of their "pinchers". The molecular mass of the integrin subunits can vary from 90 kDa to 160 kDa. Beta subunits have four cysteine-rich repeated sequences. Both α and β subunits bind several divalent cations; the role of divalent cations in the α subunit is unknown, but may stabilize the folds of the protein. The cations in the β subunits are more interesting: they are directly involved in coordinating at least some of the ligands that integrins bind.
Integrins can be categorized in multiple ways. For example, some α chains have an additional structural element inserted toward the N-terminal, the alpha-A domain. Integrins carrying this domain either bind to collagens, or act as cell-cell adhesion molecules; this α-I domain is the binding site for ligands of such integrins. Those integrins that don't carry this inserted domain have an A-domain in their ligand binding site, but this A-domain is found on the β subunit. In both cases, the A-domains carry up to three divalent cation binding sites. One is permanently occupied in physiological concentrations of divalent cations, carries either a calcium or magnesium ion, the principal divalent cations in blood at median concentrations of 1.4 mM and 0.8 mM. The other two sites become occupied by cations when ligands bind—at least for those ligands involving an acidic amino acid in their interaction sites. An acidic amino acid features in the integrin-interaction site of many ECM proteins, for example as part of the amino acid sequence Arginine-Glycine-Aspartic acid.
Despite many years of effort, discovering the high-resolution structure of integrins proved to be challenging, as membrane proteins are classically difficult to purify, as integrins are large and linked to many sugar trees. Low-resolution images of detergent extracts of intact integrin GPIIbIIIa, obtained using electron microscopy, data from indirect techniques that investigate the solution properties of integrins using ultracentrifugation and light scattering, were combined with fragmentary high-resolution crystallographic or NMR data from single or paired domains of single integrin chains, molecular models postulated for the rest of the chains; the X-ray crystal structure obtained for the complete extracellular region of one integrin, αvβ3, shows the molecule to be folded into an inverted V-shape that brings the ligand-binding sites close to the cell membrane. More the crystal structure was obtained for the same integrin bound to a small ligand containing the RGD-sequence, the drug cilengitide.
As detailed above, this revealed why divalent cations are critical for RGD-ligand binding to integrins. The interaction of such sequences with integrins is believed to be a primary switch by which ECM exerts its effects on cell behaviour; the structure poses many questions regarding ligand binding and signal transduction. The ligand binding site is directed towards the C-terminal of the integrin, the region where the molecule emerges from the cell membrane. If it emerges orthogonally from the membrane, the ligand binding site would be obstructed as integrin ligands are massive and well cross-linked components of the ECM. In fact, little is known about the angle that membrane proteins subtend to the plane of the membrane; the default assumption is that they emerge rather like little lollipops, but the evidence for thi
B cells known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system by secreting antibodies. Additionally, B cells present secrete cytokines. In mammals, B cells mature in the bone marrow, at the core of most bones. In birds, B cells mature in the bursa of Fabricius, a lymphoid organ.. B cells, unlike the other two classes of lymphocytes, T cells and natural killer cells, express B cell receptors on their cell membrane. BCRs allow the B cell to bind to a specific antigen, against which it will initiate an antibody response. B cells develop from hematopoietic stem cells. HSCs first differentiate into multipotent progenitor cells common lymphoid progenitor cells. From here, their development into B cells occurs in several stages, each marked by various gene expression patterns and immunoglobulin H chain and L chain gene loci arrangements, the latter due to B cells undergoing VJ recombination as they develop.
B cells undergo two types of selection while developing in the bone marrow to ensure proper development. Positive selection occurs through antigen-independent signaling involving both the pre-BCR and the BCR. If these receptors do not bind to their ligand, B cells do not receive the proper signals and cease to develop. Negative selection occurs through the binding of self-antigen with the BCR; this negative selection process leads to a state of central tolerance, in which the mature B cells don't bind with self antigens present in the bone marrow. To complete development, immature B cells migrate from the bone marrow into the spleen as transitional B cells, passing through two transitional stages: T1 and T2. Throughout their migration to the spleen and after spleen entry, they are considered T1 B cells. Within the spleen, T1 B cells transition to T2 B cells. T2 B cells differentiate into either follicular B cells or marginal zone B cells depending on signals received through the BCR and other receptors.
Once differentiated, they are now considered naive B cells. B cell activation occurs in the secondary lymphoid organs, such as the lymph nodes. After B cells mature in the bone marrow, they migrate through the blood to SLOs, which receive a constant supply of antigen through circulating lymph. At the SLO, B cell activation begins when the B cell binds to an antigen via its BCR. Although the events taking place after activation have yet to be determined, it is believed that B cells are activated in accordance with the kinetic segregation model determined in T lymphocytes; this model denotes that before antigen stimulation, receptors diffuse through the membrane coming into contact with Lck and CD45 in equal frequency, rendering a net equilibrium of phosphorylation and non-phosphorylation. It is only when the cell comes in contact with an antigen presenting cell that the larger CD45 is displaced due to the close distance between the two membranes; this allows for net phosphorylation of the BCR and the initiation of the signal transduction pathway.
Of the three B cell subsets, FO B cells preferentially undergo T cell-dependent activation while MZ B cells and B1 B cells preferentially undergo T cell-independent activation. B cell activation is enhanced through the activity of CD21, a surface receptor in complex with surface proteins CD19 and CD81; when a BCR binds an antigen tagged with a fragment of the C3 complement protein, CD21 binds the C3 fragment, co-ligates with the bound BCR, signals are transduced through CD19 and CD81 to lower the activation threshold of the cell. It has been shown that CD20 is directly required for BCR signalling in B cells, therapeutically used anti-CD20 antibodies such rituximab eliminate the B cells that have a high potential for activation of the BCR signalling pathway, it has been described that BCR signalling and B cell activation is inhibited by p53 stabilization during DNA damage response. Antigens that activate B cells with the help of T-cell are known as T cell-dependent antigens and include foreign proteins.
They are named as such because they are unable to induce a humoral response in organisms that lack T cells. B cell response to these antigens takes multiple days, though antibodies generated have a higher affinity and are more functionally versatile than those generated from T cell-independent activation. Once a BCR binds a TD antigen, the antigen is taken up into the B cell through receptor-mediated endocytosis and presented to T cells as peptide pieces in complex with MHC-II molecules on the cell membrane. T helper cells follicular T helper cells, that were activated with the same antigen recognize and bind these MHC-II-peptide complexes through their T cell receptor. Following TCR-MHC-II-peptide binding, T cells express the surface protein CD40L as well as cytokines such as IL-4 and IL-21. CD40L serves as a necessary co-stimulatory factor for B cell activation by binding the B cell surface receptor CD40, which promotes B cell proliferation, immunoglobulin class switching, somatic hypermutation as well as sustains T cell growth and differentiation.
T cell-derived cytokines bound
A micrograph or photomicrograph is a photograph or digital image taken through a microscope or similar device to show a magnified image of an object. This is opposed to a macrograph or photomacrograph, an image, taken on a microscope but is only magnified less than 10 times. Micrography is the art of using microscopes to make photographs. A micrograph contains extensive details of microstructure. A wealth of information can be obtained from a simple micrograph like behavior of the material under different conditions, the phases found in the system, failure analysis, grain size estimation, elemental analysis and so on. Micrographs are used in all fields of microscopy. A light micrograph or photomicrograph is a micrograph prepared using an optical microscope, a process referred to as photomicroscopy. At a basic level, photomicroscopy may be performed by connecting a camera to a microscope, thereby enabling the user to take photographs at reasonably high magnification. Scientific use began in England in 1850 by Prof Richard Hill Norris FRSE for his studies of blood cells.
Roman Vishniac was a pioneer in the field of photomicroscopy, specializing in the photography of living creatures in full motion. He made major developments in light-interruption photography and color photomicroscopy. Photomicrographs may be obtained using a USB microscope attached directly to a home computer or laptop. An electron micrograph is a micrograph prepared using an electron microscope. Micrographs have micron bars, or magnification ratios, or both. Magnification is a ratio between the size of an object on its real size. Magnification can be a misleading parameter as it depends on the final size of a printed picture and therefore varies with picture size. A scale bar, or micron bar, is a line of known length displayed on a picture; the bar can be used for measurements on a picture. When the picture is resized the bar is resized making it possible to recalculate the magnification. Ideally, all pictures destined for publication/presentation should be supplied with a scale bar. All but one of the micrographs presented on this page do not have a micron bar.
The microscope has been used for scientific discovery. It has been linked to the arts since its invention in the 17th century. Early adopters of the microscope, such as Robert Hooke and Antonie van Leeuwenhoek, were excellent illustrators. After the invention of photography in the 1820s the microscope was combined with the camera to take pictures instead of relying on an artistic rendering. Since the early 1970s individuals have been using the microscope as an artistic instrument. Websites and traveling art exhibits such as the Nikon Small World and Olympus Bioscapes have featured a range of images for the sole purpose of artistic enjoyment; some collaborative groups, such as the Paper Project have incorporated microscopic imagery into tactile art pieces as well as 3D immersive rooms and dance performances. Close-up Digital microscope Macro photography Microphotograph Microscopy USB microscope Make a Micrograph – This presentation by the research department of Children's Hospital Boston shows how researchers create a three-color micrograph.
Shots with a Microscope – a basic, comprehensive guide to photomicrography Scientific photomicrographs – free scientific quality photomicrographs by Doc. RNDr. Josef Reischig, CSc. Micrographs of 18 natural fibres by the International Year of Natural Fibres 2009 Seeing Beyond the Human Eye Video produced by Off Book - Solomon C. Fuller bio Charles Krebs Microscopic Images Dennis Kunkel Microscopy Andrew Paul Leonard, APL Microscopic Cell Centered Database - Montage Nikon Small World Olympus Bioscapes Other examples
A medical guideline is a document with the aim of guiding decisions and criteria regarding diagnosis and treatment in specific areas of healthcare. Such documents have been in use for thousands of years during the entire history of medicine. However, in contrast to previous approaches, which were based on tradition or authority, modern medical guidelines are based on an examination of current evidence within the paradigm of evidence-based medicine, they include summarized consensus statements on best practice in healthcare. A healthcare provider is obliged to know the medical guidelines of his or her profession, has to decide whether to follow the recommendations of a guideline for an individual treatment. Modern clinical guidelines identify and evaluate the highest quality evidence and most current data about prevention, prognosis, therapy including dosage of medications, risk/benefit and cost-effectiveness, they define the most important questions related to clinical practice and identify all possible decision options and their outcomes.
Some guidelines contain computation algorithms to be followed. Thus, they integrate the identified decision points and respective courses of action with the clinical judgement and experience of practitioners. Many guidelines place the treatment alternatives into classes to help providers in deciding which treatment to use. Additional objectives of clinical guidelines are to standardize medical care, to raise quality of care, to reduce several kinds of risk and to achieve the best balance between cost and medical parameters such as effectiveness, sensitivity, etc, it has been demonstrated that the use of guidelines by healthcare providers such as hospitals is an effective way of achieving the objectives listed above, although they are not the only ones. Guidelines are produced at national or international levels by medical associations or governmental bodies, such as the United States Agency for Healthcare Research and Quality. Local healthcare providers may produce their own set of guidelines or adapt them from existing top-level guidelines.
Special computer software packages known as guideline execution engines have been developed to facilitate the use of medical guidelines in concert with an electronic medical record system. The Guideline Interchange Format is a computer representation format for clinical guidelines that can be used with such engines; the USA and other countries maintain medical guideline clearinghouses. In the USA, the National Guideline Clearinghouse maintains a catalog of high-quality guidelines published by various health and medical associations. In the United Kingdom, clinical practice guidelines are published by the National Institute for Health and Care Excellence. In The Netherlands, two bodies—the Institute for Healthcare Improvement and College of General Practitioners —have published specialist and primary care guidelines, respectively. In Germany, the German Agency for Quality in Medicine coordinates a national program for disease management guidelines. All these organisations are now members of the Guidelines International Network, an international network of organisations and individuals involved in clinical practice guidelines.
Checklists have been used in medical practice to attempt to ensure that clinical practice guidelines are followed. An example is the Surgical Safety Checklist developed for the World Health Organization by Dr. Atul Gawande. According to a meta-analysis after introduction of the checklist mortality dropped by 23% and all complications by 40%, but further high-quality studies are required to make the meta-analysis more robust. In the UK, a study on the implementation of a checklist for provision of medical care to elderly patients admitting to hospital found that the checklist highlighted limitations with frailty assessment in acute care and motivated teams to review routine practices, but that work is needed to understand whether and how checklists can be embedded in complex multidisciplinary care. Guidelines may lose their clinical relevance as they age and newer research emerges. 20% of strong recommendations when based on opinion rather than trials, from practice guidelines may be retracted.
The New York Times reported in 2004 that some simple clinical practice guidelines are not followed to the extent they might be. It has been found that providing a nurse or other medical assistant with a checklist of recommended procedures can result in the attending physician being reminded in a timely manner regarding procedures that might have been overlooked. Guidelines may have conflict of interest; as such, the quality of guidelines may vary especially for guidelines that are published on-line and have not had to follow methodological reporting standards required by reputable clearinghouses. Guidelines may make recommendations. In response to many of these problems with traditional guidelines, the BMJ created a new series of trustworthy guidelines focused on the most pressing medical issues called BMJ Rapid Recommendations; the American Heart Association Guidelines for the Prevention of Infective Endocarditis The BMJ Rapid Recommendation guideline on transcatheter aortic valve implantation versus surgical aortic valve replacement for aortic stenosis.
Clinical formulation Clinical prediction rule Clinical trial protocol Medical algorithm Treatment Guidelines from The Medical Letter British Columbia Medical Guidelines – In Canada, British Columbia's guidelines and protocol
In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. We can talk about balanced and unbalanced translocation, distinguish two main types: reciprocal-, Robertsonian translocation. Reciprocal translocation is a chromosome abnormality caused by exchange of parts between non-homologous chromosomes. Put, two broken off fragments of two different chromosomes are switched. Robertsonian translocation occurs when two non-homologous chromosomes get attached, meaning that given two healthy pairs of chromosomes, one of each pair "sticks" together. A gene fusion may be created, it is detected on a karyotype of affected cells. Translocations can be unbalanced. Reciprocal translocations are an exchange of material between non-homologous chromosomes. Estimates of incidence range from about 1 in 500 to 1 in 625 human newborns; such translocations are harmless and may be found through prenatal diagnosis. However, carriers of balanced reciprocal translocations have increased risks of creating gametes with unbalanced chromosome translocations, leading to miscarriages or children with abnormalities.
Genetic counseling and genetic testing are offered to families that may carry a translocation. Most balanced translocation carriers are healthy and do not have any symptoms, but about 6% of them have a range of symptoms that may include autism, intellectual disability, or congenital anomalies. A gene disrupted or disregulated at the breakpoint of the translocation carrier is the cause of these symptoms, it is important to distinguish between chromosomal translocations occurring in gametogenesis, due to errors in meiosis, translocations that occur in cellular division of somatic cells, due to errors in mitosis. The former results in a chromosomal abnormality featured in all cells of the offspring, as in translocation carriers. Somatic translocations, on the other hand, result in abnormalities featured only in the affected cell line, as in chronic myelogenous leukemia with the Philadelphia chromosome translocation. Nonreciprocal translocation involves the transfer of genes from one chromosome to another nonhomologous chromosome.
Robertsonian translocation is a type of translocation caused by breaks at or near the centromeres of two acrocentric chromosomes. The reciprocal exchange of parts gives rise to one large metacentric chromosome and one small chromosome that may be lost from the organism with little effect because it contains so few genes; the resulting karyotype in humans leaves only 45 chromosomes, since two chromosomes have fused together. This has no direct effect on the phenotype, since the only genes on the short arms of acrocentrics are common to all of them and are present in variable copy number. Robertsonian translocations have been seen involving all combinations of acrocentric chromosomes; the most common translocation in humans involves chromosomes 13 and 14 and is seen in about 0.97 / 1000 newborns. Carriers of Robertsonian translocations are not associated with any phenotypic abnormalities, but there is a risk of unbalanced gametes that lead to miscarriages or abnormal offspring. For example, carriers of Robertsonian translocations involving chromosome 21 have a higher risk of having a child with Down syndrome.
This is known as a'translocation Downs'. This is due to a mis-segregation during gametogenesis; the mother has a higher risk of transmission than the father. Robertsonian translocations involving chromosome 14 carry a slight risk of uniparental disomy 14 due to trisomy rescue; some human diseases caused by translocations are: Cancer: Several forms of cancer are caused by acquired translocations. Translocations have been described in solid malignancies such as Ewing's sarcoma. Infertility: One of the would-be parents carries a balanced translocation, where the parent is asymptomatic but conceived fetuses are not viable. Down syndrome is caused in a minority of cases by a Robertsonian translocation of the chromosome 21 long arm onto the long arm of chromosome 14. Chromosomal translocations between the sex chromosomes can result in a number of genetic conditions, such as XX male syndrome: caused by a translocation of the SRY gene from the Y to the X chromosome The International System for Human Cytogenetic Nomenclature is used to denote a translocation between chromosomes.
The designation t is used to denote a translocation between chromosome A and chromosome B. The information in the second set of parentheses, when given, gives the precise location within the chromosome for chromosomes A and B respectively—with p indicating the short arm of the chromosome, q indicating the long arm, the numbers after p or q refers to regions and subbands seen when staining the chromosome with a staining dye. See the definition of a genetic locus; the translocation is the mechanism. In 1938, Karl Sax, at the Harvard University Biological Laboratories, published a paper entitled "Chromosome Aberrations Induced by X-rays", which demonstrated that radiation could induce major genetic changes by affecting chromosomal translocations; the paper is thought to mark the beginning of the field of radiation cytology, led him to be called "the father of radiation cytology". Accipitrida