"Staining Solutions"

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CD45R, also designated CD45 and PTPRC, has been identified as a transmembrane glycoprotein, broadly expressed among hematopoietic cells. Multiple isoforms of CD45R are distributed throughout the immune system according to cell type. These isoforms arise because of alternative splicing of exons 4, 5, and 6. The corresponding protein domains are characterised by the binding of monoclonal antibodies specific for CD45RA (exon 4), CD45RB (exon 5), CD45RC (exon 6) and CD45RO (exons 4 to 6 spliced out). The variation in these isoforms is localized to the extracellular domain of CD45R, while the intracellular domain is conserved. CD45R functions as a phosphor-tyrosine phosphatase. Antibody to CD45 is useful in differential diagnosis of lymphoid tumors from non-hematopoietic undifferentiated neoplasms.

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This mAb reacts with a protein of 20-30 kDa, identified as PGP9.5, also known as ubiquitin carboxyl-terminal hydrolase-1 (UchL1). Initially, PGP9.5 expression in normal tissues was reported in neurons and neuroendocrine cells but later it was found in distal renal tubular epithelium, spermatogonia, Leydig cells, oocytes, melanocytes, prostatic secretory epithelium, ejaculatory duct cells, epididymis, mammary epithelial cells, Merkel cells, and dermal fibroblasts. Furthermore, immunostaining for PGP9.5 has been shown in a wide variety of mesenchymal neoplasms as well. A mutation in PGP9.5 gene is believed to cause a form of Parkinson's disease.

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This antibody recognises a protein of 25 to 26 kDa, identified as the Bcl-2 alpha oncoprotein. It shows no cross-reaction with Bcl-x or Bax protein. Expression of bcl-2 alpha oncoprotein inhibits the programmed cell death (apoptosis). In most follicular lymphomas, neoplastic germinal centers express high levels of bcl-2 alpha protein, whereas the normal or hyperplastic germinal centers are negative. Consequently, this antibody is valuable when distinguishing between reactive and neoplastic follicular proliferation in lymph node biopsies. It may also be used in distinguishing between those follicular lymphomas that express bcl-2 protein and the small number in which the neoplastic cells are bcl-2 negative.

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CD45RO is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitosis, and oncogenic transformation. CD45RO contains an extracellular domain, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus is classified as a receptor type PTP. It has been shown to be an essential regulator of T- and B-cell antigen receptor signaling. It functions through either direct interaction with components of the antigen receptor complexes, or by activating various Src family kinases required for the antigen receptor signaling. It also suppresses JAK kinases, and thus functions as a regulator of cytokine receptor signaling. [RefSeq].

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CD79a is required in cooperation with CD79b for initiation of the signal transduction cascade activated by binding of antigen to the B-cell antigen receptor complex (BCR) which leads to internalization of the complex, trafficking to late endosomes and antigen presentation. Also required for BCR surface expression and for efficient differentiation of pro- and pre-B-cells. Stimulates SYK autophosphorylation and activation. Binds to BLNK, bringing BLNK into proximity with SYK and allowing SYK to phosphorylate BLNK. Also interacts with and increases activity of some Src-family tyrosine kinases. Represses BCR signaling during development of immature B-cells. [UniProt].

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Multiple isoelectric variants of calponin have been identified, however only two molecular weight isoforms exist; a 34 kDa form and a 29 kDa form. Expression of the 29 kDa form, I-calponin, is primarily restricted to muscle of the urogenital tract, whereas the higher molecular weight variant has been demonstrated in vascular and visceral smooth muscle. Calponin is a calmodulin, F-actin and tropomyosin binding protein, which is thought to be involved in the regulation of smooth muscle contraction. Calponin expression is restricted to smooth muscle cells and has been shown to be a marker of the differentiated (contractile) phenotype of developing smooth muscle.

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This antibody is specific to lambda light chain of immunoglobulin and shows no cross-reaction with lambda light chain or any of the five heavy chains. In mammals, the two light chains in an antibody are always identical, with only one type of light chain, kappa or lambda. In general the ratio of Kappa to Lambda is 3:1. However, with the occurrence of multiple myeloma or other B-cell malignancies this ratio is disturbed. Antibody to the lambda light chain is reportedly useful in the identification of leukemias, plasmacytomas, and certain non-Hodgkin's lymphomas. Demonstration of clonality in lymphoid infiltrates indicates that the infiltrate is malignant.

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It recognises a protein of 36 kDa, identified as Thymidylate Synthase (TS). TS converts deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), which is essential for DNA biosynthesis. TS is also a critical target for the fluoropyrimidines, an important group of antineoplastic drugs that are widely used in the treatment of solid tumors. Both 5-FU and fluorodeoxyuridine are converted in tumor cells to FdUMP which inactivates TS by formation of a ternary covalent complex in the presence of the folate cofactor 5,10-methylenetetrahydrofolate. Expression of TS protein is associated with response to 5-fluorouracil (5-FU) in human colorectal, gastric, head and neck, and breast carcinomas.

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TIMP3 (tissue inhibitor of metalloproteinases 3), along with family members TIMP1, TIMP2, and TIMP4, are inhibitors of the matrix metalloproteinases (MMPs), a group of peptidases involved in degradation of the extracellular matrix (ECM). An imbalance between MMPs and the associated TIMPs may play a significant role in the invasive phenotype of malignant tumors. TIMP’s inhibit the proteolytic invasiveness of tumor cells and normal placental trophoblast cells. TIMP3 may be involved in regulating trophoblastic invasion of the uterus as well as in regulating remodeling of the extracellular matrix during the folding of epithelia, and in the formation, branching and expansion of epithelial tubes.

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CD271/NGFR pays a role in the regulation of the translocation of GLUT4 to the cell surface in adipocytes and skeletal muscle cells in response to insulin, probably by regulating RAB31 activity, and thereby contributes to the regulation of insulin-dependent glucose uptake (By similarity). Low affinity receptor which can bind to NGF, BDNF, NT-3, and NT-4. Can mediate cell survival as well as cell death of neural cells. Necessary for the circadian oscillation of the clock genes ARNTL/BMAL1, PER1, PER2 and NR1D1 in the suprachiasmatic nucleus (SCN) of the brain and in liver and of the genes involved in glucose and lipid metabolism in the liver. [UniProt].

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Expression of DOG-1/ANO1/TMEM16A protein is elevated in the gastrointestinal stromal tumors (GISTs), c-kit signaling-driven mesenchymal tumors of the GI tract. ANO1 is rarely expressed in other soft tissue tumors, which, due to appearance, may be difficult to diagnose. Immunoreactivity has been reported in 97.8 percent of scorable GISTs, including all c-kit negative GISTs. Overexpression has been suggested to aid in the identification of GISTs, including Platelet-Derived Growth Factor Receptor Alpha mutants that fail to express c-kit antigen. The overall sensitivity of DOG-1/ANO1 and c-kit in GISTs is nearly identical: 94,4% vs. 94,7%.

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Recognises a protein of 75 kDa, identified as gamma heavy chain of human immunoglobulins. Its epitope maps in CH2 domain of Fc region of IgG. It reacts with all sub-classes of gamma chain of human immunoglobulins. It does not cross-react with alpha (IgA), mu (IgM), epsilon (IgE), or delta (IgD), heavy chains, T-cells, monocytes, granulocytes, or erythrocytes. This mAb is useful in the identification of leukemias, plasmacytomas, and certain non-Hodgkins lymphomas. The most common feature of these malignancies is the restricted expression of a single heavy chain class. Demonstration of clonality in lymphoid infiltrates indicates that the infiltrate is clonal and therefore malignant.

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This cytokeratin 18 antibody reacts with a wide variety of simple epithelia. It does not react with stratified squamous epithelia. It reacts with epithelial tumors of the gastrointestinal tract, lung, breast, pancreas, ovary, and thyroid. Cytokeratin 18, which belongs to the type A (acidic) subfamily of low molecular weight keratins, exists in combination with cytokeratin 8. It is reported that tissues from gastrointestinal tract are positive for both cytokeratin 18 and 8 but do not contain cytokeratin 14. Tissues from gastrointestinal tract, respiratory tract and urogenital tract, as well as endocrine and exocrine tissues and mesothelial cells are positive for cytokeratin 18.

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Retinol binding protein a single-chain glycoprotein belonging to the superfamily of hydrophobic molecule transporter proteins, which is responsible for transport of retinol (vitamin A1) from the liver to peripheral target tissues, like the eye, where it mediates the cellular uptake. RBP1 is synthesised by hepatic parenchymal cells where it becomes bound to its ligand retinol and is then released into the circulation, where it binds further to the protein transthyretin, to form a transporting complex, which is big enough not to be lost by filtration through the kidney glomeruli. It is detected in nearly all tissues with higher expression in adult ovary, pancreas, pituitary gland, adrenal gland, and fetal liver.

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CK10 is expressed in all suprabasal layers of the epidermis. In the epidermis, expression of CK10 strictly parallels the extent of differentiation; it is absent in the basal layer, appears in the first suprabasal layers and increases in concentration towards the granular layer. However, CK10 is rarely detected in early stages of vulvar squamous carcinomas (tumors less than 2 cm, clinical stage I) regardless of the tumor grade. In larger and more advanced tumors (greater than 2 cm, clinical stages II and III), CK10 is detected very frequently. Expression of CK10 is related to maturation of malignant keratinocytes, being preferentially detected in more-differentiated parts.

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This mAb recognises basic (Type II or HMW) cytokeratins, which include 67 kDa (CK1); 64 kDa (CK3); 59 kDa (CK4); 58 kDa (CK5); 56 kDa (CK6); 52 kDa (CK8). Twenty human keratins are resolved with two-dimensional gel electrophoresis into acidic (pI 6.0) subfamilies. The acidic keratins have molecular weights (MW) of 56.5, 55, 51, 50, 50 , 48, 46, 45, and 40 kDa. Many studies have shown the usefulness of keratins as markers in cancer research and tumor diagnosis.