Publications by authors named "Aherne A"

Objectives: Objective measures of clinical improvement in patients with acute heart failure (AHF) are lacking. The aim of this study was to determine whether repeated lung sonography could semiquantitatively capture changes in pulmonary edema (B-lines) in patients with hypertensive AHF early in the course of treatment.

Methods: We conducted a feasibility study in a cohort of adults with acute onset of dyspnea, severe hypertension in the field or at triage (systolic blood pressure ≥ 180 mm Hg), and a presumptive diagnosis of AHF.

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Background: To many physicians, hyperkalemia is the first diagnosis ascribed to any patient with end-stage renal disease and abnormal electrocardiographic morphologies or dysrhythmias.

Case Report: A 52-year-old man with end-stage renal disease presented in cardiac arrest. The patient was initially presumed to have hyperkalemia, based on the appearance of wide QRS complexes on the monitor.

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Retinitis pigmentosa, causing progressive blindness, is genetically heterogeneous. RP10, due to a defect in inosine monophosphate dehydrogenase 1 (IMPDH1), shows autosomal dominant inheritance. Recombinantly expressed clinical mutants show unaltered kinetic behaviour.

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Mutations within the inosine 5'-monophosphate dehydrogenase 1 (IMPDH1) gene cause the RP10 form of autosomal dominant retinitis pigmentosa (adRP), an early-onset retinopathy resulting in extensive visual handicap owing to progressive death of photoreceptors. Apart from the prevalence of RP10, estimated to account for 5-10% of cases of adRP in United States and Europe, two observations render this form of RP an attractive target for gene therapy. First, we show that while recombinant adeno-associated viral (AAV)-mediated expression of mutant human IMPDH1 protein in the mouse retina results in an aggressive retinopathy modelling the human counterpart, expression of a normal human IMPDH1 gene under similar conditions has no observable pathological effect on retinal function, indicating that over-expression of a therapeutic replacement gene may be relatively well tolerated.

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Intraoperative neurophysiological monitoring (IONM) during corrective spinal surgery is widely used. Because of the possible interference with the recording of evoked potentials by inhalational anesthetics, total intravenous anesthetic (TIVA) regimens have been advocated. TIVA regimens may be difficult to use in pediatric populations due to metabolic factors.

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Article Synopsis
  • The challenge of intragenic heterogeneity in dominant disease-causing genes complicates the development of effective and affordable treatments, as seen in autosomal dominant retinitis pigmentosa caused by numerous rhodopsin mutations.
  • An RNA interference (RNAi)-based method is proposed that can target the problematic native transcripts without affecting engineered replacement genes, suggesting a mutation-independent therapeutic strategy.
  • Experiments show that this RNAi approach can reduce murine rhodopsin levels by up to 90% while still allowing the expression of the replacement genes, validating its effectiveness in cell cultures and live mouse models.
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Retinitis pigmentosa (RP) is one of the most genetically heterogeneous inherited disorders. Twelve genes have now been identified in the autosomal dominant form of the disease, including some recently characterized genes that show unprecedented and fascinating traits in both their function and in their expression profiles. These include many widely expressed genes encoding components of the spliceosome and a guanine nucleotide synthesis gene.

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Article Synopsis
  • Retinitis pigmentosa (RP), a hereditary eye disease, significantly contributes to blindness in working-age individuals in developed countries, with specific mutations in the IMPDH1 gene linked to a severe form known as RP10.
  • Research shows that the majority of GTP necessary for photoreceptor function is produced by the IMPDH1 enzyme, while mice lacking IMPDH1 exhibit gradual retinal degeneration but retain some photoreceptor integrity.
  • The study indicates that RP10's severity is likely due to the misfolding and aggregation of mutant IMPDH1 proteins rather than reduced enzyme activity, suggesting potential therapeutic strategies could involve targeting both normal and mutant IMPDH1 alleles while increasing GTP levels in retinas.
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Comparative analysis of the transcriptional profiles of approximately 6000 genes in the retinas of wild-type mice with those carrying a targeted disruption of the rhodopsin gene was undertaken by microarray analysis. This revealed a series of transcripts, of which some were derived from genes known to map at retinopathy loci, levels of which were reduced or elevated in the retinas of Rho(-/-) mice lacking functional photoreceptors. The human homologue of one of these genes, encoding inosine monophosphate dehydrogenase type 1 (IMPDH1), maps to the region of 7q to which an adRP gene (RP10) had previously been localized.

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Dopamine (DA) is regarded as an important modulator of enteric function. Recent experiments have suggested that newly cloned DA receptor subtypes are widely expressed in peripheral organs, including the gastrointestinal tract. In the present studies, the D(1A) receptor subtype was identified in rat gut regions through localization of receptor protein by means of light microscopic immunohistochemistry and Western blot analysis and receptor mRNA by RT-PCR and in situ amplification and hybridization (3SR in situ).

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Dopamine (DA) has been shown to influence kidney function through endogenous synthesis and subsequent interaction with locally expressed dopamine receptor subtypes (D1, D5 as D1-like and D2, D3, and D4 as D2-like). DA, and DA-receptor specific agonists and antagonists can alter renal water and electrolyte excretion along with renin release when infused systemically or intrarenally. Such effects are brought about by a combination of renal hemodynamic and direct tubular effects evoked along the full length of the nephron.

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The dopamine D3 receptor subtype was identified in rat kidney using both light microscopic immunohistochemistry and electron microscopic immunocytochemistry. Antipeptide polyclonal antisera were directed to both extracellular and intracellular regions of the native D3 receptor. Selectivity of the antipeptide antisera was validated by their ability to recognize native receptor protein expressed in permanently transfected mouse LTK- cells or Spodoptera fragiperda (Sf9) cell membranes.

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In recent years, both molecular biological and immunohistochemical techniques, utilizing receptor subtype-specific probes and antibodies to cloned central nervous system dopamine receptors, have revealed their presence in a number of peripheral organs and tissues. Molecular techniques have been hindered by the low abundance of receptor mRNA in these sites, and reverse transcription-polymerase chain reaction (RT-PCR) has been utilized to address this problem. However, RT-PCR is most often employed on either isolated mRNA or microdissected tissue samples, thereby limiting interpretation of whole tissue distribution.

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Pharmacological, physiological, and autoradiographic studies have suggested the presence of dopamine receptors in the adrenal gland. Dopaminergic ligands have been shown to modulate adrenocortical aldosterone biosynthesis and secretion as well as adrenomedullary catecholamine production and release. Using a combination of light microscopic immunochemistry and in situ amplification and hybridization, the present study sought to determine the site-specific expression of the recently cloned D1A receptor subtype in rat adrenal gland.

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The growth responses of a vegetative inoculum of Bacillus cereus as influenced by varying conditions of temperature, pH value and sodium chloride concentration (% w/v) and carbondioxide concentration (% v/v) were determined in laboratory medium. Growth curves in concentrations of NaCl in the range 0.5-10.

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Jumping and linking libraries have been constructed in order to have more information of chromosome 4. Two types of jumping libraries (Not I and Xma III jumping) and one linking library were prepared. The jumping clones represent DNA regions between two rare-cutting enzymes sites (such is Not I or Xma III) whereas linking clones represent only the area which surrounds the rare-cutting site.

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