Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years, radiolabelled monoclonal antibodies have been evaluated for their use in the diagnosis and treatment of neoplastic disease. One isotope which has not been assessed for antibody targeting is 32P, even though it has many favourable radiobiological characteristics and has been used clinically for the treatment of certain neoplastic disorders such as polycythaemia rubra vera. The main drawback so far in using 32P has been the absence of a general method for phosphorylating antibodies. We have now developed a novel process for the phosphorylation of immunoglobulins which is rapid, efficient and allows high specific activities to be achieved (greater than 10 muCi micrograms-1). The technique involves the chemical conjugation of Kemptide, a synthetic heptapeptide substrate for kinases, to immunoglobulins. The antibody-Kemptide conjugate can then be phosphorylated using protein kinases and [32P]-gamma-ATP. The procedure does not compromise the binding activity of the antibody. The 32P-labelled monoclonal antibodies were stable in human, mouse and rat plasmas in vitro, although they cleared from the bloodstream of mice with a beta-phase half life of 2 days which is approximately two times faster than that of native antibody. The application of this phosphorylation technique should allow the therapeutic potential of targeted 32P to be assessed.
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PMID:Conjugation of monoclonal antibodies to a synthetic peptide substrate for protein kinase: a method for labelling antibodies with 32P. 339 53

The induction of porcine cytokines, which are believed to be important for the regulation of T helper (Th)1- and Th2-specific immune responses of pigs, was analysed after in vitro restimulation with a herpesvirus, Suid herpes 1 (pseudorabies virus [PRV]), in peripheral blood mononuclear cells (PBMC). To this end, quantitative, competitive reverse transcription-polymerase chain reaction (RT-qcPCR) was established using constructed heterologous DNA MIMICS, which contain cytokine- or glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-specific primer-binding sites. This is a simple method that allows reliable determination of the differing regulation of cytokine mRNAs specific for porcine interleukin (IL)-2, -4 and -10, interferon gamma (IFN-gamma) and the housekeeping gene, GAPDH, as an endogenous control. PBMC derived from naive (innate response) and PRV-primed (memory response) outbred swine were analysed comparatively. The results demonstrated that restimulation with PRV significantly enhanced the transcription of Th1-type cytokines (IL-2 and IFN-gamma) but not of Th2-type cytokines (IL-4 and IL-10). This virus-specific cytokine response was only found with PBMC from swine protected against lethal PRV challenge infection, but not with naive PBMC or with PBMC from pigs immunized with plasmid DNA encoding PRV glycoprotein gC. Notably, PBMC derived from immune and naive pigs constitutively produced relatively high amounts of IL-10-specific mRNA, exceeding that of GAPDH mRNA, independently of the addition of viral antigen or the mitogen concanavalin A (Con A). The results of this work should help to provide a better understanding of the effector cell/cytokine network response to infection with, or vaccination against, PRV. Additionally, the simple, reliable and sensitive RT-qcPCR, when used to determine the porcine cytokine pattern, might be of prognostic value for the induction of protective immunity.
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PMID:T helper 1-type cytokine transcription in peripheral blood mononuclear cells of pseudorabies virus (Suid herpesvirus 1)-primed swine indicates efficient immunization. 1110 42

High expression of PRV-1 mRNA in granulocytes has been proposed as a new diagnostic marker for polycythemia vera. We used real-time reverse transcription polymerase chain reaction (RT-PCR) to measure the levels of PRV-1 mRNA, GAPDH mRNA and 18S rRNA in granulocytes obtained from blood samples processed 2, 24 and 48 hours after collection and observed a significant decrease of PRV-1 levels after 24 and 48 hours. The instability of PRV-1 mRNA may affect the diagnostic value of the PRV-1 test in blood samples stored for extended periods.
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PMID:Instability of PRV-1 mRNA: a factor to be considered in PRV-1 quantification for the diagnosis of polycythemia vera. 1519 44

The four Janus kinases (JAKs) comprise a family of intracellular, nonreceptor tyrosine kinases that first gained attention as signaling mediators of the type I and type II cytokine receptors. Subsequently, the JAKs were found to be involved in signaling downstream of the insulin receptor, a number of receptor tyrosine kinases, and certain G-protein coupled receptors. Although a number of cytoplasmic targets for the JAKs have been identified, their predominant action was found to be the phosphorylation and activation of the signal transducers and activators of transcription (STAT) factors. Through the STATs, the JAKs activate gene expression linked to cellular stress, proliferation, and differentiation. The JAKs are especially important in hematopoiesis, inflammation, and immunity, and aberrant JAK activity has been implicated in a number of disorders including rheumatoid arthritis, psoriasis, polycythemia vera, and myeloproliferative diseases. Although once thought to reside strictly in the cytoplasm, recent evidence shows that JAK1 and JAK2 are present in the nucleus of certain cells often under conditions associated with high rates of cell growth. Nuclear JAKs have now been shown to affect gene expression by activating other transcription factors besides the STATs and exerting epigenetic actions, for example, by phosphorylating histone H3. The latter action derepresses global gene expression and has been implicated in leukemogenesis. Nuclear JAKs may have a role as well in stem cell biology. Here we describe recent developments in understanding the noncanonical nuclear actions of JAK1 and JAK2.
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PMID:JAKs go nuclear: emerging role of nuclear JAK1 and JAK2 in gene expression and cell growth. 2189 41