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Particular Tissue (particular + tissue)
Selected AbstractsDifferential expression of human Polycomb group proteins in various tissues and cell typesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue S36 2001Marco J. Gunster Abstract Polycomb group proteins are involved in the maintenance of cellular identity. As multimeric complexes they repress cell type-specific sets of target genes. One model predicts that the composition of Polycomb group complexes determines the specificity for their target genes. To study this hypothesis, we analyzed the expression of Polycomb group genes in various human tissues using Northern blotting and immunohistochemistry. We found that Polycomb group expression varies greatly among tissues and even among specific cell types within a particular tissue. Variations in mRNA expression ranged from expression of all analyzed Polycomb group genes in the heart and testis to no detectable Polycomb group expression at all in bone marrow. Furthermore, each Polycomb group gene was expressed in a different number of tissues. RING1 was expressed in practically all tissues, while HPH1 was expressed in only a few tissues. Also within one tissue the level of Polycomb group expression varied greatly. Cell type-specific Polycomb group expression patterns were observed in thyroid, pancreas, and kidney. Finally, in various developmental stages of fetal kidney, different Polycomb group expression patterns were observed. We conclude that Polycomb group expression can vary depending on the tissue, cell type, and development stage. Polycomb group complexes can only be composed of the Polycomb group proteins that are expressed. This implies that with cell type-specific Polycomb group expression patterns, cell type-specific Polycomb group complexes exist. The fact that there are cell type-specific Polycomb group targets and cell type-specific Polycomb group complexes fits well with the hypothesis that the composition of Polycomb group complexes may determine their target specificity. J. Cell. Biochem. Suppl. 36: 129,143, 2001. © 2001 Wiley-Liss, Inc. [source] Principles of pharmacodynamics and their applications in veterinary pharmacologyJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2004P. LEES Pharmacodynamics (PDs) is the science of drug action on the body or on microorganisms and other parasites within or on the body. It may be studied at many organizational levels , sub-molecular, molecular, cellular, tissue/organ and whole body , using in vivo, ex vivo and in vitro methods and utilizing a wide range of techniques. A few drugs owe their PD properties to some physico-chemical property or action and, in such cases, detailed molecular drug structure plays little or no role in the response elicited. For the great majority of drugs, however, action on the body is crucially dependent on chemical structure, so that a very small change, e.g. substitution of a proton by a methyl group, can markedly alter the potency of the drug, even to the point of loss of activity. In the late 19th century and first half of the 20th century recognition of these facts by Langley, Ehrlich, Dale, Clarke and others provided the foundation for the receptor site hypothesis of drug action. According to these early ideas the drug, in order to elicit its effect, had to first combine with a specific ,target molecule' on either the cell surface or an intracellular organelle. It was soon realized that the ,right' chemical structure was required for drug,target site interaction (and the subsequent pharmacological response). In addition, from this requirement, for specificity of chemical structure requirement, developed not only the modern science of pharmacology but also that of toxicology. In relation to drug actions on microbes and parasites, for example, the early work of Ehrlich led to the introduction of molecules selectively toxic for them and relatively safe for the animal host. In the whole animal drugs may act on many target molecules in many tissues. These actions may lead to primary responses which, in turn, may induce secondary responses, that may either enhance or diminish the primary response. Therefore, it is common to investigate drug pharmacodynamics (PDs) in the first instance at molecular, cellular and tissue levels in vitro, so that the primary effects can be better understood without interference from the complexities involved in whole animal studies. When a drug, hormone or neurotransmitter combines with a target molecule, it is described as a ligand. Ligands are classified into two groups, agonists (which initiate a chain of reactions leading, usually via the release or formation of secondary messengers, to the response) and antagonists (which fail to initiate the transduction pathways but nevertheless compete with agonists for occupancy of receptor sites and thereby inhibit their actions). The parameters which characterize drug receptor interaction are affinity, efficacy, potency and sensitivity, each of which can be elucidated quantitatively for a particular drug acting on a particular receptor in a particular tissue. The most fundamental objective of PDs is to use the derived numerical values for these parameters to classify and sub-classify receptors and to compare and classify drugs on the basis of their affinity, efficacy, potency and sensitivity. This review introduces and summarizes the principles of PDs and illustrates them with examples drawn from both basic and veterinary pharmacology. Drugs acting on adrenoceptors and cardiovascular, non-steroidal anti-inflammatory and antimicrobial drugs are considered briefly to provide a foundation for subsequent reviews in this issue which deal with pharmacokinetic (PK),PD modelling and integration of these drug classes. Drug action on receptors has many features in common with enzyme kinetics and gas adsorption onto surfaces, as defined by Michaelis,Menten and Langmuir absorption equations, respectively. These and other derived equations are outlined in this review. There is, however, no single theory which adequately explains all aspects of drug,receptor interaction. The early ,occupation' and ,rate' theories each explain some, but not all, experimental observations. From these basic theories the operational model and the two-state theory have been developed. For a discussion of more advanced theories see Kenakin (1997). [source] Methods in Nutrition Science: Cre/loxP System for Generating Tissue-specific Knockout Mouse ModelsNUTRITION REVIEWS, Issue 6 2004Claudine H. Kos Ph.D. Editor's note: From time to time, we take the opportunity in Nutrition Reviews to highlight a particularly exciting application of sophisticated methodological advances that are relevant to the nutrition research community. In the current issue of Nutrition Reviews, Dr. Claudine Kos has provide a brief review of some of the salient features of the Cre/loxP system for generating tissue-specific knockout mouse models. Hopefully, this review will provide additional background to Dr. George Wolf's Brief Critical Review (page 253) of the use of the Cre/loxP technique by investigators to gain further insight into the function of the peroxysome proliferators-activated receptor-gamma (PPAR-,), as well as promote its further use within experimental nutrition. Alteration of the mouse genome by conventional transgenic and gene-targeted approaches has greatly facilitated studies of gene function. However, a gene alteration expressed in the germ line may cause an embryonic lethal phenotype resulting in no viable mouse to study gene function. Similarly, a gene alteration may exert its effect in multiple different cell and tissue types, creating a complex phenotype in which it is difficult to distinguish direct function in a particular tissue from secondary effects resulting from altered gene function in other tissues. Therefore, methods have been developed to control conditions such as the timing, cell-type, and tissue specificity of gene activation or repression. This brief review provides an overview of the Cre/LoxP system for generating tissue-specific knockout mouse models. [source] Tissue-dependent limited pleiotropy affects gene expression in barleyTHE PLANT JOURNAL, Issue 2 2008Elena Potokina Summary Non-synonymous coding mutations in a gene change the resulting protein, no matter where it is expressed, but the effects of cis -regulatory mutations could be spatially or temporally limited , a phenomenon termed limited pleiotropy. Here, we report the genome-wide occurrence of limited pleiotropy of cis -regulatory mutations in barley (Hordeum vulgare L.) using Affymetrix analysis of 22 840 genes in a population of 139 doubled haploid lines derived from a cross between the cultivars Steptoe (St) and Morex (Mx). We identified robust cis -acting expression regulators that segregate as major genes in two successive ontogenetic stages: germinating embryo tissues and seedling leaves from the embryonic axis. We show that these polymorphisms may be consistent in both tissues or may cause a dramatic change in transcript abundance in one tissue but not in another. We also show that the parental allele that increases expression can vary with the tissue, suggesting nucleotide polymorphism in enhancer sequences. Because of the limited pleiotropy of cis -regulating mutations, the number of cis expression quantitative trait loci (cis -eQTLs) discovered by ,genetical genomics' is strongly affected by the particular tissue or developmental stage studied. Given that limited pleiotropy is a common feature of cis -regulatory mutations in barley, we predict that the phenomenon would be relevant to developmental and/or tissue-specific interactions across wide taxonomic boundaries in both plants and animals. [source] Emerging strategies for exploiting cannabinoid receptor agonists as medicinesBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2009Roger G Pertwee Mandarin translation of abstract Medicines that activate cannabinoid CB1 and CB2 receptor are already in the clinic. These are Cesamet® (nabilone), Marinol® (dronabinol; ,9 -tetrahydrocannabinol) and Sativex® (,9 -tetrahydrocannabinol with cannabidiol). The first two of these medicines can be prescribed to reduce chemotherapy-induced nausea and vomiting. Marinol® can also be prescribed to stimulate appetite, while Sativex® is prescribed for the symptomatic relief of neuropathic pain in adults with multiple sclerosis and as an adjunctive analgesic treatment for adult patients with advanced cancer. One challenge now is to identify additional therapeutic targets for cannabinoid receptor agonists, and a number of potential clinical applications for such agonists are mentioned in this review. A second challenge is to develop strategies that will improve the efficacy and/or the benefit-to-risk ratio of a cannabinoid receptor agonist. This review focuses on five strategies that have the potential to meet either or both of these objectives. These are strategies that involve: (i) targeting cannabinoid receptors located outside the blood-brain barrier; (ii) targeting cannabinoid receptors expressed by a particular tissue; (iii) targeting up-regulated cannabinoid receptors; (iv) targeting cannabinoid CB2 receptors; or (v) ,multi-targeting'. Preclinical data that justify additional research directed at evaluating the clinical importance of each of these strategies are also discussed. Mandarin translation of abstract [source] Tissue-specific mechanical microdissection of higher plantsPHYSIOLOGIA PLANTARUM, Issue 3 2006Marco Thome Higher plants are multicellular organisms, which exhibit a high degree of differentiation with respect to their anatomy, metabolism and gene expression. Analysing entire plants or organs results in an average of information of all tissues and cells included in the sample. In this way neither physiological processes nor gene expression can be attributed to particular tissues. For revealing the contributions of specific tissues to the overall metabolism and the gene expression, highly spatially resoluted cell sampling is a prerequisite. Here, mechanical microdissection (MMD), a low cost and easy to handle alternative to existing sampling techniques (e.g. laser-assisted microdissection or glass capillary,based sampling) was tested on several plant species (Arabidopsis thaliana L., Cucurbita maxima Duch., Hordeum vulgare L. and Pelargonium hybrid cultivar ,Graveolens'). The applicability and potential of MMD for separating tissues from different organs of these plants was demonstrated. Furthermore, A. thaliana samples were, as examples, tested for their RNA quality by reverse transcription,PCR and for tissue specificity by amplifying messenger RNA of tissue marker genes. [source] Whole Plant Regulation of Sulfur Nutrition of Deciduous Trees-Influences of the EnvironmentPLANT BIOLOGY, Issue 3 2003C. Herschbach Abstract: The current view of sulfur nutrition is based on the source-to-sink relationship of carbohydrates. SO42- reduction is thought to occur mainly in leaves. Surplus reduced sulfur must be transported out of the leaves, loaded into the phloem and transported to other tissues, in particular tissues assumed to be sink organs. However, it has not been proved that tissues which are sinks for carbohydrates are also sink organs for reduced sulfur. It is evident that sinks must communicate with sources, and vice versa, to signal demand and to transport the surplus of reduced sulfur that is produced. The demand-driven control model of sulfur nutrition proposes that the tripeptide glutathione is the signal which regulates S nutrition of the whole plant at the level of SO42- uptake. Acclimatization to environmental changes has been shown to result in several changes in S nutrition of deciduous trees: (i) Drought stress diminished SO42- transport into the xylem, although the GSH content in lateral roots remained unaffected, possibly due to an overall reduction in water status. (ii) Flooding decreased APS reductase activity in the anoxic roots. This may be due to enhanced GSH transport to the roots, but it is more likely to be the result of a change in metabolism leading to diminished energy gain in the roots. (iii) Mycorrhization enhanced the GSH content in the phloem, while SO42- uptake was not affected. This clearly goes against the demand-driven control model. (iv) Under both short- and long-term exposure to elevated pCO2, the APS reductase activity in leaves and lateral roots did not correlate with the GSH contents therein. Therefore, it must be assumed that, under these conditions, regulation of S nutrition goes beyond the demand-driven control model, and occurs within the network of other nutrient metabolism. (v) Atmospheric S in the form of H2S enhanced the reduced sulfur content of the phloem and lateral roots. Under these conditions, the SO42- loaded into the xylem decreased. It would appear that the demand-driven control model of sulfur nutrition is not always valid in the case of deciduous trees. [source] Hepatopancreatic and muscular distribution of oxytetracycline antibiotics in farmed pacific white shrimp (Penaeus vannamei): a physiological-based pharmacokinetic model approachAQUACULTURE RESEARCH, Issue 1 2009Damrongsak Faroongsarng Abstract Oxytetracycline (OTC) pharmacokinetic models previously used to investigate Penaeus vannamei have not addressed the specific problems related to drug distribution/disposition in particular tissues. This study aimed to provide an insight into OTC kinetics in the hepatopancreas and muscle based on a physiological model approach. Adult male P. vannamei at the C-D0 inter-moulting stage were randomly assigned to intra-sinus and oral administrations. In the intra-sinus group, shrimps were dosed via the ventral sinus at an OTC level of 10.0 ,g g,1 body weight, while in the oral one, they were force fed at a dose level of 50.2 ,g g,1. The medicated animals were sampled at various time intervals until 170 h after dosing. Haemolymph, muscle and hepatopancreas samples were taken and OTC levels were determined using the validated HPLC method. A model focused on the hepatopancreas and muscle was developed. Oxytetracycline pharmacokinetic profiles in particular tissues were fitted into the model with an R2 of between 0.6568 and 0.9904. Oxytetracycline muscular distributions were essentially identical for both groups and the drug did not accumulate in muscle. The distributions in the hepatopancreas for both groups were extensive, whereas that for oral administration was approximately 2.3 times greater than that for the intra-sinus one. It was demonstrated that hepatopancreatic OTC may undergo significant first-pass elimination with non-linear kinetics. [source] | |||||||||||||