Browsing by Subject "Muscles"

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    Open Access
    Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to FAM111B mutations
    (2015) Mercier, Sandra; Küry, Sébastien; Salort-Campana, Emmanuelle; Magot, Armelle; Agbim, Uchenna; Besnard, Thomas; Bodak, Nathalie; Bou-Hanna, Chantal; Bréhéret, Flora; Brunelle, Perrine; Caillon, Florence; Chabrol, Brigitte; Cormier-Daire, Valérie; David, Albert; Eymard, Bruno; Faivre, Laurence; Figarella-Branger, Dominique; Fleurence, Emmanuelle; Ganapathi, Mythily; Gherardi, Romain; Goldenberg, Alice; Hamel, Antoine; Igual, Jeanine; Irvine, Alan D; Israël-Biet, Dominique; Kannengiesser, Caroline; Laboisse, Christian; Le Caignec, Cédric; Mahé, Jean-Yves; Mallet, Stéphanie; MacGowan, Stuart; McAleer, Maeve A; McLean, Irwin; Méni, Cécile; Munnich, Arnold; Mussini, Jean-Marie; Nagy, Peter L; Odel, Jeffrey; O’Regan, Grainne M; Péréon, Yann; Perrier, Julie; Piard, Juliette; Puzenat, Eve; Sampson, Jacinda B; Smith, Frances; Soufir, Nadem; Tanji, Kurenai; Thauvin, Christel; Ulane, Christina; Watson, Rosemarie M; Khumalo, Nonhlanhla P; Mayosi, Bongani M; Barbarot, Sébastien; Bézieau, Stéphane
    BackgroundHereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients.MethodsClinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected.ResultsKey features consist of: (i) early-onset poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes.ConclusionsHFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder.
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    Open Access
    Newborns should be receiving premedication before elective intubation
    (2014) Raban, Moegammad Shukri; Joolay, Yaseen; Horn, Alan Richard; Harrison, Michael Charles
    BACKGROUND: Intubation is a common neonatal procedure. Premedication is accepted as a standard of care, but its use is not universal and wide variations exist in practice. OBJECTIVE: To evaluate current practices for premedication use prior to elective neonatal intubation in South Africa (SA). METHOD: We invited 481 clinicians to participate in a cross-sectional web-based survey. RESULTS: We received responses from 28.3% of the clinicians surveyed; 54.1% were from the private sector and 45.9% from the state sector. Most respondents worked in medium-sized neonatal units with six to ten beds. Most paediatricians (76.0%) worked in the private sector, and 78.6% of neonatologists in the state sector. Premedication was practised by 71.9% of the respondents, but only 38.5% of neonatal units had a written policy. Sedatives were used for premedication by 63.2% of the respondents. Midazolam (41.5%), morphine (34.0%) and ketamine (20.8%) were most commonly used. Muscle relaxants and atropine were not routinely administered. Suxamethonium was the muscle relaxant of choice. Varied combinations of agents or single agents were used. Midazolam used alone was the preferred option. CONCLUSION: This first survey of premedication for neonatal intubation in SA revealed variations in practice, with a minority of clinicians following a written policy. The findings can be used to benchmark practice and inform the design of local collaborative trials aimed at determining optimal premedication prior to neonatal intubation. The survey demonstrates clinicians' reluctance to participate in surveys, suggesting a need for a national collaborative network to obtain representative data.
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    Purification and some properties of an alkaline protease from rat skeletal muscle
    (1981) Bosch, Benjamin; Gevers, Wieland
    Various alkaline proteases derived from skeletal muscle have been described by a number of researchers and have been purified to varying degrees. Such alkaline proteases may play an important role in the metabolism of myofibrillar and other muscle proteins and as such deserve to be fully characterised. In this study, a major myofibrillar alkaline protease was purified from rat skeletal muscle. The enzyme degraded both denatured casein and azocasein and had a pH optimum of 9,0. The molecular mass was 32 250 ± 650. The presence of a second, minor alkaline protease was demonstrated using three different separation techniques as well as by inhibitor studies. The major protease was insensitive to inhibition by pepstatin and leupeptin, whilst 90 % of the activity was expressed in the presence of 2 mM EGTA. A moderate degree of inhibition was observed in the presence of soybean trypsin inhibitor and the protease was markedly sensitive to chymostatin. A similar alkaline protease was partially purified from rat cardiac muscle using the same purification procedure. Incubation of washed myofibrils in the presence of sodium pyrophosphate released a factor into the supernatant, the removal of which facilitated the separation of myofibrillar alkaline protease from the myofibrils. The factor appeared to be necessary for binding of the alkaline protease to the myofibrillar proteins but its removal did not disrupt the binding of proteolytic activity already attached to the myofibrillar proteins. An inhibitor of myofibrillar alkaline protease was demonstrated which is, in principle, capable of playing an important regulatory role in controlling the activity of these enzymes and thereby of myofibrillar protein catabolism.