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  • 1
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    Identification of FHL1 as a therapeutic target for Duchenne muscular dystrophy (2014)
    Oxford University Press
    Details
    Publication Date: 2014-01-11
    Description: Utrophin is a potential therapeutic target for the fatal muscle disease, Duchenne muscular dystrophy (DMD). In adult skeletal muscle, utrophin is restricted to the neuromuscular and myotendinous junctions and can compensate for dystrophin loss in mdx mice, a mouse model of DMD, but requires sarcolemmal localization. NFATc1-mediated transcription regulates utrophin expression and the LIM protein, FHL1 which promotes muscle hypertrophy, is a transcriptional activator of NFATc1. By generating mdx /FHL1-transgenic mice, we demonstrate that FHL1 potentiates NFATc1 activation of utrophin to ameliorate the dystrophic pathology. Transgenic FHL1 expression increased sarcolemmal membrane stability, reduced muscle degeneration, decreased inflammation and conferred protection from contraction-induced injury in mdx mice. Significantly, FHL1 expression also reduced progressive muscle degeneration and fibrosis in the diaphragm of aged mdx mice. FHL1 enhanced NFATc1 activation of the utrophin promoter and increased sarcolemmal expression of utrophin in muscles of mdx mice, directing the assembly of a substitute utrophin–glycoprotein complex, and revealing a novel FHL1-NFATc1-utrophin signaling axis that can functionally compensate for dystrophin.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 2
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    Inhibition of purine nucleoside phosphorylase by 8-aminoguanosine: selective toxicity for T lymphoblasts (1981)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1981-12-04
    Description: The guanosine analog 8-aminoguanosine is an effective inhibitor of the purine degradative enzyme purine nucleoside phosphorylase, both in vitro and in intact lymphoid cells. In a human lymphoblast tissue culture system, 8-aminoguanosine, in combination with low concentrations of 2'-deoxyguanosine, causes toxicity toward T cells but not B cells. The selective T cell toxicity correlates with increased accumulation of deoxyguanosine triphosphate in the treated T lymphoblasts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kazmers, I S -- Mitchell, B S -- Dadonna, P E -- Wotring, L L -- Townsend, L B -- Kelley, W N -- AM 19045/AM/NIADDK NIH HHS/ -- CA 26032/CA/NCI NIH HHS/ -- CA 26284/CA/NCI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1981 Dec 4;214(4525):1137-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6795718" target="_blank"〉PubMed〈/a〉
    Keywords: B-Lymphocytes/enzymology ; Cell Line ; Deoxyguanosine/pharmacology ; Guanosine/*analogs & derivatives/pharmacology ; Humans ; Kinetics ; Pentosyltransferases/*antagonists & inhibitors ; Purine-Nucleoside Phosphorylase/*antagonists & inhibitors ; T-Lymphocytes/drug effects/*enzymology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
    Electronic Resource
    Electronic Resource
    The use of proteolytic enzymes to improve immunoglobulin staining by the PAP technique (1979)
    Springer
    Journal of molecular histology 11 (1979), S. 345-357 
    Details
    ISSN: 1573-6865
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Synopsis Proteolytic enzymes, protease and trypsin have recently been introduced to reduce the inconsistency hitherto encountered in the unlabelled antibody-enzyme method using PAP. This study investigated factors determining the optimum conditions for use of such enzymes in order to establish which one is most suitable. Trypsin was the most effective enzyme; however, its activity decreased over 3 h, a feature paralleled immunocytochemically. Method and duration of fixation appears to influence the required time of exposure to trypsin in order that consistent immunostaining may be produced. Treatment of sections with trypsin prior to the use of the unlabelled antibody-enzyme method using PAP renders the technique reliable, provided the enzyme is used in a carefully controlled manner.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01005033
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  • 4
    Electronic Resource
    Electronic Resource
    An immunohistochemical study of the catecholamine synthesizing enzymes and neuropeptides in the female guinea-pig uterus and vagina (1992)
    Springer
    Journal of molecular histology 24 (1992), S. 361-367 
    Details
    ISSN: 1573-6865
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The uterus and vagina of the guinea pig have been examined, region by region, for acetylcholinesterase, tyrosine hydroxylase, dopamine β-hydroxylase and aromatic amino acid decarboxylase activity, as well as for the neuropeptides, neuropeptide Y, vasoactive intestinal peptide, substance P, enkephalin and somatostatin. No acetylcholinesterase activity was localized in the uterus, though it was present in associated paracervical ganglion tissues. Of the catecholamine-synthesizing enzymes, tyrosine hydroxylase and dopamine β-hydroxylase activity was found virtually throughout the reproductive tract, whereas aromatic amino acid decarboxylase activity was restricted in its distribution. Neuropeptide distribution was quite varied. Neuropeptide Y was found throughout the endometrium/submucosa but only in the muscularis of the vagina and not in the myometrium. Substance P was localized in the vagina and uterine horn, though not the body of the uterus. Vasoactive intestinal peptide was present in all regions of the endometrium/submucosa, but not in the myometrium of the uterine horn. Enkephalin and somatostatin were not localized in any part of the reproductive tract examined, apart from paracervical ganglion tissues. The types and significance of the nerves supplying the reproductive tract are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01046168
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  • 5
    Electronic Resource
    Electronic Resource
    Localization of substance P and leucine enkephalin in the nerve terminals of the guinea pig paracervical ganglion (1993)
    Springer
    Journal of molecular histology 25 (1993), S. 144-149 
    Details
    ISSN: 1573-6865
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Immunoreactivities (IR) of substance P and leucine enkephalin have been demonstrated in the guinea-pig paracervical ganglion by an immunogold electron microscope method. Both substance P-IR and leucine enkephalin-IR were detected in large synaptic vesicles with electron-dense cores. The former neuropeptide was detected in nerve terminals and varicosities comprised mainly of large vesicles with electron-dense cores; the latter was detected in nerve terminals and varicosities that also included small, clear synaptic vesicles. In a minority of nerve terminals and varicosities coexistence of both immunoreactivities could be demonstrated within vesicles with an electron-dense core. Also present in these nerve terminals and varicosities were small, clear synaptic vesicles, though these were unreactive.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00157987
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  • 6
    Electronic Resource
    Electronic Resource
    Corrigendum (1979)
    Springer
    Journal of molecular histology 11 (1979), S. ii 
    Details
    ISSN: 1573-6865
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01002764
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  • 7
    Electronic Resource
    Electronic Resource
    Projections of the guinea-pig paracervical ganglion to pelvic viscera (1993)
    Springer
    Journal of molecular histology 25 (1993), S. 51-56 
    Details
    ISSN: 1573-6865
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The uterine cervix, urinary bladder and rectum of guinea pigs were injected with Fast Blue dye for retrograde transport studies. Dye-laden neuronal perikarya were detected for each viscus in the paracervical ganglion. These same perikarya also exhibited immunoreactivities for tyrosine hydroxylase, aromatic amino acid decarboxylase, dopamine β-hydroxylase, neuropeptide Y, or vasoactive intestinal peptide, though the perikarya projecting to the urinary bladder did not exhibit immunoreactivity for aromatic amino acid decarboxylase. The results of this study indicate that the guinea-pig paracervical ganglion projects to viscera in addition to the uterus, and that the ganglion contains a range of immunoreactivities related to adrenergic and non-adrenergic neurotransmitters.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00161044
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  • 8
    Electronic Resource
    Electronic Resource
    An immunohistochemical and electron microscopic study of the peri-ureteric ganglia of the guinea-pig (1993)
    Springer
    Journal of molecular histology 25 (1993), S. 509-515 
    Details
    ISSN: 1573-6865
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The neuropeptide- and catecholamine-synthesizing enzyme content and ultrastructure of the peri-ureteric ganglia of guinea-pigs were investigated. Small numbers of neuronal perikarya were present at frequent intervals forming ganglia close to, and along the entire length of, the ureter. Each of these ganglia was surrounded by a connective tissue capsule, and was located in the peri-ureteric connective tissues. Within each ganglion were typical nerve terminals and varicosities containing small, clear synaptic vesicles or synaptic vesicles with an electron-dense core, or a mixture of the two. In the ganglia, immunoreactivity to tyrosine hydroxylase, dopamine β hydroxylase, neuropeptide tyrosine, or vasoactive intestinal peptide was present in neuronal perikarya; immunoreactivity to substance P or leucine enkephalin was present in nerve terminals and varicosities. Electron-microscopic immunogold studies indicated that there was no coexistence of substance P and enkephalin in the nerve terminals, unlike related ganglia in the pelvis of guinea-pigs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00159287
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  • 9
    Electronic Resource
    Electronic Resource
    Chemical coding of neurons projecting to pelvic viscera in the male guinea pig: a study by retrograde transport and immunohistochemistry (1994)
    Springer
    Journal of molecular histology 26 (1994), S. 262-270 
    Details
    ISSN: 1573-6865
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Retrograde transport studies using Fast Blue dye demonstrated that the ductus deferens, seminal vesicle, prostate and rectum, but not the urinary bladder of the male guinea pig are at least in part innervated by the anterior major pelvic ganglion. In the ductus deferens, seminal vesicle and prostate innervation is derived from ipsilateral and contralateral ganglia. In addition to retrograde studies, dye-filled neurons were analysed immunohistochemically for neuronal markers and associations with specifically identified neuronal projections. Neurons of the ganglion projecting to the ductus deferens either contained tyrosine hydroxylase alone, tyrosine hydroxylase and neuropeptide Y, neuropeptide Y alone, neuropeptide Y and vasoactive intestinal peptide, or vasoactive intestinal peptide alone. These neurons were associated with three classes of neuronal projections, substance P-, leucine-enkephalin-, and methionine-enkephalin-immunoreactive. Neurons projecting to the seminal vesicles were similar to the neurons supplying the ductus deferens, except none of the seminal vesicle-specific neurons exhibited vasoactive intestinal peptide immunoreactivity. Neurons supplying the prostate were immunoreactive for either tyrosine hydroxylase or neuropeptide Y; these neurons were infrequently associated with the three classes of varicose neuronal projections. Neurons projecting to the rectum contained neuropeptide Y and were only associated with methionine-enkephalin immunoreactive neuronal projections in one animal.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00166107
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  • 10
    Electronic Resource
    Electronic Resource
    Chemical coding of neurons projecting to pelvic viscera in the male guinea pig: a study by retrograde transport and immunohistochemistry (1994)
    Springer
    Journal of molecular histology 26 (1994), S. 262-270 
    Details
    ISSN: 1573-6865
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Retrograde transport studies using Fast Blue dye demonstrated that the ductus deferens, seminal vesicle, prostate and rectum, but not the urinary bladder of the male guinea pig are at least in part innervated by the anterior major pelvic ganglion. In the ductus deferens, seminal vesicle and prostate innervation is derived from ipsilateral and contralateral ganglia. In addition to retrograde studies, dye-filled neurons were analysed immunohistochemically for neuronal markers and associations with specifically identified neuronal projections. Neurons of the ganglion projecting to the ductus deferens either contained tyrosine hydroxylase alone, tyrosine hydroxylase and neuropeptide Y, neuropeptide Y alone, neuropeptide Y and vasoactive intestinal peptide, or vasoactive intestinal peptide alone. These neurons were associated with three classes of neuronal projections, substance P-, leucine-enkephalin-, and methionine-enkephalin-immunoreactive. Neurons projecting to the seminal vesicles were similar to the neurons supplying the ductus deferens, except none of the seminal vesicle-specific neurons exhibited vasoactive intestinal peptide immunoreactivity. Neurons supplying the prostate were immunoreactive for either tyrosine hydroxylase or neuropeptide Y; these neurons were infrequently associated with the three classes of varicose neuronal projections. Neurons projecting to the rectum contained neuropeptide Y and were only associated with methionine-enkephalin immunoreactive neuronal projections in one animal.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02388441
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