Analyses of the differentiation potential of satellite cells from <Emphasis Type="Italic">myoD</Emphasis><Superscript>-/-</Superscript>, <Emphasis Type="Italic">mdx</Emphasis>, and <Emphasis Type="Italic">PMP22</Emphasis> C22 mice

Background  

Sporadic and sometimes contradictory studies have indicated changes in satellite cell behaviour associated with the progressive nature of human Duchenne muscular dystrophy (DMD). Satellite cell proliferation and number are reportedly altered in DMD and the mdx mouse model. We recently found that satellite cells in MSVski transgenic mice, a muscle hypertrophy model showing progressive muscle degeneration, display a severe ageing-related differentiation defect in vitro. We tested the hypothesis that similar changes contribute to the gradual loss of muscle function with age in mdx and PMP22 mice, a model of human motor and sensory neuropathy type 1A (HMSN1A).     

Influence of weight and weight change on bone loss in perimenopausal and early postmenopausal Scottish women

Weight is recognized as an important factor in determining an individuals risk of osteoporosis. However, little is known about whether weight or weight change influences bone loss around the time of the menopause, and the relationship with energy intake and physical activity level remains largely undefined. Healthy premenopausal women (1,064 selected from a random population of 5,119 women aged 45–54 years at baseline) each had bone mineral density (BMD), weight and height measurements, and completed a food frequency and physical activity questionnaire. Of the original participants, 907 women (85.2%) returned 6.3 ± 0.6 years later for repeat BMD measurements, and 896 women completed the questionnaires. Bone loss at the hip (FN) and spine (LS) occurred before the menopause. Weight change rather than weight was associated with FN BMD loss (r=0.102, p=0.002), but weight at follow-up was associated with LS BMD change (r=0.105, p=0.002). Although an increase in physical activity level (PAL) appeared to be beneficial for FN BMD in women who were heavy weight gainers, PAL was associated with increased LS BMD loss in women who lost weight. For current HRT users, neither weight nor weight change was associated with change in BMD. Postmenopausal women not taking HRT should be made aware that low body weight or losing weight during this particularly vulnerable period may worsen bone loss.     

Extrafacial indolent CD8‐positive cutaneous lymphoid proliferation with unusual symmetrical presentation involving both feet

Indolent CD8+ cutaneous lymphoid proliferation represents a recently described entity among cutaneous T‐cell lymphomas that typically presents with solitary skin lesions on the face or at acral sites and usually follows an indolent clinical course. Histopathologically, this entity is characterized by a dense dermal infiltrate of non‐epidermotropic, small‐ to medium‐sized pleomorphic CD8+ T‐cells of the non‐activated cytotoxic phenotype showing a clear‐cut grenz zone and a low proliferation index. Distinction from otherwise aggressive T‐cell lymphomas bearing a cytotoxic CD8+ phenotype is fundamental. We herein present an unusual case of indolent CD8+ cutaneous lymphoid proliferation presenting in bilateral symmetrical distribution on both feet and lacking the otherwise described grenz zone. Our case widens the spectrum of possible clinical and histomorphological variations of this entity. Taking into account the distinctive and unique clinical and microscopic features of all hitherto published cases of indolent CD8+ cutaneous lymphoid proliferation we suppose that this lymphoma subtype has to be included as a new and distinct entity in the World Health Organisation (WHO)‐/European Organisation for Research and Treatment of Cancer (EORTC)‐classification of cutaneous lymphomas.     

Spatial heterogeneity of myocardial perfusion predicts local potassium channel expression and action potential duration

AIMS: In the heart, there is not only a transmural gradient of left ventricular perfusion and action potential duration (APD), but also spatial heterogeneity within each myocardial layer, where local blood flow and energy turnover vary more than three-fold between individual regions. We analysed at high spatial resolution whether a corresponding heterogeneity also extends to ion channel gene expression and APD. METHODS AND RESULTS: In the open-chest beagle dog, left ventricular 300 microL samples of very low or high flow were identified by radioactive microspheres and expression levels determined by quantitative PCR. The distribution of epicardial APD was assessed by mapping local activation repolarization intervals (ARIs) and QT interval (QT). ERG, the potassium channel mediating IKr, and KChIP2, the interacting protein modulating Ito, were increased in Low flow (3.3- and 2.5-fold, P < 0.001 and <0.05, respectively; n = 6 hearts, 30-31 samples each) as compared with High flow areas. This suggested enhanced repolarizing currents in Low flow areas, and in consequence, mathematical model analysis predicted a shorter local APD upon enhanced ERG and IKr. Epicardial mapping revealed a patchy, temporally stable APD pattern (n = 11), a small apico-basal gradient and an APD prolongation induced by the ERG blocker dofetilide predominantly in areas of short basal ARI or QT, respectively (n = 9). In addition, in Short QT areas, ERG expression was three-fold increased (P < 0.05, n = 4). CONCLUSION: The spatial pattern of perfusion is matched by the novel patterns of K+ channel expression and APD. Whenever this newly recognized intramural dispersion of APD increases, it may contribute to arrhythmogenesis.     

Reversibility of deficient sleep entrained growth hormone secretion in a boy with achondroplasia and obstructive sleep apnea

Obstructive sleep apnea may lead to disordered sleep architecture and impair the physiologic slow wave sleep related growth hormone release. Obstructive sleep apnea occurs with craniofacial syndromes and in children with airway narrowing, pharyngeal hypoplasia, tonsillar adenoidal hypertrophy, micrognathia and achondroplasia. To examine the relationship between disordered sleep and growth hormone release we studied a 9 year old male with achondroplasia, growth failure (3 cm/year) and obstructive sleep apnea. Polysomnography data and a 20 min sampling for sleep entrained growth hormone showed before therapeutic tracheostomy numerous apneic episodes, absent slow wave sleep and abnormal low growth hormone secretion during sleep. Normalized slow wave sleep entrained growth hormone secretion after tracheostomy led to a sustained increase in growth rate. Normal growth rate (greater than 5 cm/year) continues 2 years after tracheostomy. We conclude that obstructive sleep apnea may impair sleep related growth hormone release. Obstructive sleep apnea may be a useful model for other diseases in which growth failure and sleep disturbances are linked.