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Various Mammalian Species (various + mammalian_species)
Selected AbstractsThree novel thiopurine S-methyltransferase allelic variants (TPMT*20, *21, *22) , association with decreased enzyme function,,HUMAN MUTATION, Issue 9 2006Elke Schaeffeler Abstract The genetic polymorphism of the thiopurine S-methyltransferase, TPMT, comprises at least 21 alleles causing three distinct drug metabolism phenotypes termed normal/high, intermediate, and deficient methylators. In consequence, adverse drug reactions may occur if standard doses of thiopurines are applied routinely. Genetic prediction of the methylator phenotype as a basis for dose selection requires the extensive knowledge of single nucleotide polymorphisms occurring naturally in the population. Here we describe three novel missense variants in the TPMT gene which were associated with an intermediate red blood cell TPMT activity in three Caucasians. The following alleles were designated: TPMT*20 (c.712A>G), *21 (c.205C>G), and *22 (c.488G>C). No further genetic variations in remaining coding regions as well as the 5,flanking region of TPMT were identified. These sequence variants are present in highly conserved nucleotide positions of the TPMT gene throughout various mammalian species and in zebra fish, and are predicted to be intolerant when the functional consequences of variations were analyzed using SIFT (Sorting Intolerant From Tolerant) algorithm. In Caucasians the occurrence of these genetic variants appears to be extremely rare since none of these alleles were identified in a randomly selected control population of 1048 individuals. © 2006 Wiley-Liss, Inc. [source] Transcriptional inactivation of amphotropic murine leukemia virus replication in human cellsJOURNAL OF MEDICAL VIROLOGY, Issue 2 2003Martin Ploss Abstract Amphotropic murine leukemia virus (MLV) replicates in cells from various mammalian species including humans and is a potential contaminant in MLV vector preparations for human gene transfer studies. Because MLV replication proceeds through an RNA genome that is generated under the control of viral enhancer and promoter elements, vectors were developed that delete such elements during transduction to reduce the generation of replication-competent virus. It was shown recently that replication of amphotropic MLV in certain human cells is possible without the 75 bp transcription enhancers. It is now demonstrated that enhancer-independent replication requires functional elements within U3 and is repressed by an extended deletion in the U3 region comprising enhancers, promoter and flanking sequences. It is concluded that the transcriptional inactivation of amphotropic MLV in human cells requires the combined deletion of enhancers and of additional elements in U3. J. Med. Virol. 69:267,272, 2003. © 2003 Wiley-Liss, Inc. [source] EGF-induced EGF-receptor and MAP kinase phosphorylation in goat cumulus cells during in vitro maturationMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2005Laurence Gall Abstract EGF has been shown to influence meiotic maturation and development competence of oocyte in various mammalian species. We previously reported, in goat, that the EGF receptor (EGF-R) was present both on cumulus cells and oocytes. Here, EGF-induced signaling was investigated during the in vitro maturation process in goat cumulus,oocyte complexes (COCs). Cumulus cells and oocytes were subjected to Western immunoblotting analysis using anti-MAP kinase, anti-phosphotyrosine, anti-phospho MAP kinase, and anti-phospho EGF-R antibodies. We demonstrated that treatment with EGF during the in vitro maturation process induced rapid tyrosine phosphorylation of EGF-R in a time and concentration dependent manner in cumulus cells. A similar pattern of activation by phosphorylation was observed for MAP kinase upon EGF stimulation. AG 1478, an inhibitor of the EGF kinase, suppressed EGF-stimulated phosphorylation of EGF-R and also affected the MAP kinase activation. Treatment with the MEK inhibitor PD 98059 abolished EGF-induced MAP kinase activation. We did not observe oocyte EGF-R phosphorylation in our experiments during the in vitro maturation process. Our data indicate, in goat cumulus cells, that activation of EGF-R by EGF triggers signaling through the MAP kinase pathway during in vitro maturation. This supports the hypothesis that the major site of action for EGF, that regulates oocyte maturation, is the cumulus cell. Mol. Reprod. Dev. © 2005 Wiley-Liss, Inc. [source] The physiological role of hormones in salivaBIOESSAYS, Issue 8 2009Michael Gröschl Abstract The assessment of hormones in saliva has gained wide acceptance in clinical endocrinology. To date, there is no hypothesis as to why some hormones can be found in saliva, while others cannot, and whether there is a physiological consequence of this fact. A number of carefully performed studies give examples of important physiological hormonal activity in saliva. Steroids, such as androgens, act as pheromones in olfactory communication of various mammalian species, such as facilitating mating behavior in swine or serving as odor cues for rodent nestlings. Salivary peptide hormones, such as epidermal growth factor (EGF) and transforming growth factor-, (TGF-,), and amines such as melatonin, are involved in the regulation of inflammatory processes and in the promotion of cell proliferation, and contribute to a rapid wound healing in the oropharyngeal epithelia. Current data provide evidence of the involvement of salivary cytokines, such as interleukin-8 and leptin, in tumorgenesis in the oral cavity and the salivary glands. The tumor tissues express and release significantly more of these cytokines than healthy glands. Consequently, the assessment of salivary hormone profiles may provide promising targets for diagnostic tumor markers. [source] Pharmacological characterization of F-180: a selective human V1a vasopressin receptor agonist of high affinityBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2002Miriam Andrés The pharmacological properties of F-180, a vasopressin (VP) structural analogue, were determined on CHO cells expressing the different human vasopressin and oxytocin (OT) receptor subtypes. Binding experiments revealed that F-180 exhibited a high affinity for the human V1a receptor subtype (Ki=11 nM) and was selective for this receptor subtype. Functional studies performed on CHO cells expressing human V1a receptors indicate that similarly to AVP, F-180 can stimulate the accumulation of inositol phosphate. The activation constant (Kact) for both F-180 and AVP was 1.7 nM. F-180 was also an agonist for the human V2 and V1b receptor subtypes and an antagonist for the human OT receptor. Since marked species pharmacological differences for vasopressin receptors have been described, we studied the properties of F-180 on various mammalian species. F-180 showed high affinity and good selectivity for human and bovine V1a receptors, but weak affinity and non selective properties for rat V1a receptors. To assess the functional properties of F-180 on a native biological model, we performed studies on primary cultures of cells from bovine zona fasciculata (ZF). As AVP, F-180 stimulated inositol phosphate accumulation and cortisol secretion with similar efficiency. In conclusion, we demonstrate that F-180 is the first selective V1a agonist described for human and bovine vasopressin receptors. Therefore F-180 can be used as a powerful pharmacological tool to characterize the actions of vasopressin that are mediated by V1a receptor subtypes. British Journal of Pharmacology (2002) 135, 1828,1836; doi:10.1038/sj.bjp.0704634 [source] | ||||||||||