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M2 Subtype (m2 + subtype)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Rearrangement of the MOZ gene in pediatric therapy-related myelodysplastic syndrome with a novel chromosomal translocation t(2;8)(p23;p11)

GENES, CHROMOSOMES AND CANCER, Issue 4 2003
Toshihiko Imamura
In this study, we examined a pediatric case of therapy-related myelodysplastic syndrome (tMDS). The symptoms developed 17 months after treatment for acute myeloblastic leukemia (AML, M2 subtype according to the French,American,British [FAB] classification) involving a chromosome abnormality at t(8;21)(q22;q22). Upon diagnosis of tMDS, spectral karyotyping analysis detected a new chromosomal translocation at t(2;8)(p23;p11.2). In addition, fluorescence in situ hybridization analysis suggested a rearrangement in the monocytic leukemia zinc finger (MOZ) gene, located in the 8p11 region of chromosome 8. However, no partner gene on 2p23 could be identified. To our knowledge, this is the first report of tMDS associated with a rearrangement of the MOZ gene. MOZ-linked fusion proteins such as MOZ-CBP (CREB binding protein), MOZ-TIF2 (transcriptional intermediary factor 2), and MOZ-p300 (adenoviral E1A-associated protein) are associated with AML chromosomal abnormalities at t(8;16)(p11;p13), inv(8)(p11q13), and t(8;22)(p11;q13), respectively, and are thought to account for leukemogenesis occurring through the aberrant regulation of histone acetylation. Through a similar mechanism, we believe that MOZ, fused to an unidentified partner gene at 2p23, may have caused an alteration in histone acetylation, resulting in the development of tMDS in this patient. © 2003 Wiley-Liss, Inc. [source]

Detection of muscarinic receptor subtypes in human urinary bladder mucosa: Age and gender-dependent modifications,,§

NEUROUROLOGY AND URODYNAMICS, Issue 5 2008
Nicola Arrighi
Abstract Aims Muscarinic receptor subtypes expressed in the human urinary bladder mucosa were characterized, investigating whether there were gender-dependent differences and if aging could induce changes in their expression. Methods The study was carried out on 34 subjects, 22 men and 12 women, divided in four groups, based on gender and age. Gene expression was evaluated by quantitative RT-PCR. The Western blot was performed using the 4,12% NuPAGE Bis,Tris Gel System. Results The molecular expression of each subtype of the M1 receptor family was observed and it was not influenced either by gender or age. M2 receptor family transcripts revealed that both M2 and M4 were detected and that the M2 transcripts were modified by both gender and age. Indeed, M2 mRNA was lower in old rather than adult men (P,<,0.05), but higher in rather old than adult women (P,<,0.05). Further, adult men expressed more M2 mRNA than adult women (P,<,0.05), while the opposite was detected in old age (P,<,0.05). The Western blot followed by quantification confirmed that the mRNAs were translated into proteins, and that the M2 subtype showed similar modifications found at molecular level. Discussion The selective modification of M2 receptors observed at the urinary bladder mucosa levels indicates that this anatomical structure could play an active role in the pathophysiology of micturition and supports evidence suggesting an effect of antimuscarinic drugs at this level. Whether these results may influence the age-dependent development of micturition disorders remains to be determined. Neurourol. Urodynam. 27:421,428, 2008. © 2007 Wiley-Liss, Inc. [source]

Activation of M2 muscarinic receptors leads to sustained suppression of hippocampal transmission in the medial prefrontal cortex

THE JOURNAL OF PHYSIOLOGY, Issue 21 2009
Lang Wang
Cholinergic innervation of the prefrontal cortex is critically involved in arousal, learning and memory. Dysfunction of muscarinic acetylcholine receptors and their downstream signalling pathways has been identified in mental retardation. To assess the role played by the muscarinic receptors at the hippocampal,frontal cortex synapses, an important relay in information storage, we used a newly developed frontal slice preparation in which hippocampal afferent fibres are preserved. Transient activation of muscarinic receptors by carbachol results in a long-lasting depression of synaptic efficacy at the hippocampal but not cortical pathways or local circuitry. On the basis of a combination of electrophysiological, pharmacological and anatomical results, this input-specific muscarinic modulation can be partially attributed to the M2 subtype of muscarinic receptors, possibly through a combination of pre- and postsynaptic mechanisms. [source]

Regulation of bladder muscarinic receptor subtypes by experimental pathologies

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2006
M. R. Ruggieri Sr
Summary 1 The M3 muscarinic receptor subtype is widely accepted as the receptor on smooth muscle cells that mediates cholinergic contraction of the normal urinary bladder and other smooth muscle tissues, however, we have found that the M2 receptor participates in contraction under certain abnormal conditions. The aim of this study was to determine the effects of various experimental pathologies on the muscarinic receptor subtype mediating urinary bladder contraction. 2 Experimental pathologies resulting in bladder hypertrophy (denervation and outlet obstruction) result in an up-regulation of bladder M2 receptors and a change in the receptor subtype mediating contraction from M3 towards M2. Preventing the denervation-induced bladder hypertrophy by urinary diversion prevents this shift in contractile phenotype indicating that hypertrophy is responsible as opposed to denervation per se. 3 The hypertrophy-induced increase in M2 receptor density and contractile response is accompanied by an increase in the tissue concentrations of mRNA coding for the M2 receptor subtype, however, M3 receptor protein density does not correlate with changes in M3 receptor tissue mRNA concentrations across different experimental pathologies. 4 This shift in contractile phenotype from M3 towards M2 subtype is also observed in aged male Sprague,Dawley rats but not females or either sex of the Fisher344 strain of rats. 5 Four repeated, sequential agonist concentration response curves also cause this shift in contractile phenotype in normal rat bladder strips in vitro, as evidenced by a decrease in the affinity of the M3 selective antagonist p -fluoro-hexahydro-sila-diphenidol (p -F-HHSiD). 6 A similar decrease in the contractile affinity of M3 selective antagonists (darifenacin and p -F-HHSiD) is also observed in bladder specimens from patients with neurogenic bladder as well as certain organ transplant donors. 7 It is concluded that although the M3 receptor subtype predominately mediates contraction under normal circumstances, the M2 receptor subtype can take over a contractile role when the M3 subtype becomes inactivated by, for example, repeated agonist exposures or bladder hypertrophy. This finding has substantial implications for the clinical treatment of abnormal bladder contractions. [source]