PubMed Health⌕ Search

Biomedical subjects

H Norman

Publications and source records attributed to H Norman.

7 recordsLinked to original sources

A porcine model of acute quadriplegic myopathy: a feasibility study.

BACKGROUND: The mechanisms underlying acute quadriplegic myopathy (AQM) are poorly understood, partly as a result of the fact that patients are generally diagnosed at a late stage of the disease. Accordingly, there is a need for relevant experimental animal models aimed at identifying underlying mechanisms. METHODS: Pigs were mechanically ventilated and exposed to various combinations of agents, i.e. pharmacological neuromuscular blockade, corticosteroids and/or sepsis, for a period of 5 days. Electromyography and myofibrillar protein and mRNA expression were analysed using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), confocal microscopy, histochemistry and real-time polymerase chain reaction (PCR). RESULTS: A decreased compound muscle action potential, normal motor nerve conduction velocities, and intact sensory nerve function were observed. Messenger RNA expression, determined by real-time PCR, of the myofibrillar proteins myosin and actin decreased in spinal and cranial nerve innervated muscles, suggesting that the loss of myosin observed in AQM patients is not solely the result of myofibrillar protein degradation. CONCLUSION: The present porcine AQM model demonstrated findings largely in accordance with results previously reported in patients and offers a feasible approach to future mechanistic studies aimed at identifying underlying mechanisms and developing improved diagnostic tests and intervention strategies.

Adrenal Cortex Hormones↗

Impact of post-synaptic block of neuromuscular transmission, muscle unloading and mechanical ventilation on skeletal muscle protein and mRNA expression.

To analyse mechanisms of muscle wasting in intensive care unit patients, we developed an experimental model where rats were pharmacologically paralysed by post-synaptic block of neuromuscular transmission (NMB) and mechanically ventilated for 9+/-2 days. Specific interest was focused on the effects on protein and mRNA expression of sarcomeric proteins, i.e., myosin heavy chain (MyHC), actin, myosin-binding protein C (MyBP-C) and myosin-binding protein H (MyBP-H) in fast- and slow-twitch limb, respiratory and masticatory muscles. Muscle-specific differences were observed in response to NMB at both the protein and mRNA levels. At the protein level, a decreased MyHC-to-actin ratio was observed in all muscles excluding the diaphragm, whereas at the mRNA level a decreased expression of the dominating MyHC isoform(s) was observed in the hind limb and intercostal muscles, but not in the diaphragm and masseter muscles. MyBP-C mRNA expression was decreased in the limb muscles, but it otherwise remained unaffected. MyBP-H conversely increased in all muscles. Furthermore, we found myofibrillar protein and mRNA expression to be affected differently when comparing NMB animals with peripherally denervated (DEN) ambulatory rats. We report that NMB has both a larger and different impact on muscle, at the protein and mRNA levels, than DEN has.

Animals↗

Role of gammaENaC subunit in lung liquid clearance and electrolyte balance in newborn mice. Insights into perinatal adaptation and pseudohypoaldosteronism.

Genetic evidence supports a critical role for the epithelial sodium channel (ENaC) in both clearance of fetal lung liquid at birth and total body electrolyte homeostasis. Evidence from heterologous expression systems suggests that expression of the alphaENaC subunit is essential for channel function, whereas residual channel function can be measured in the absence of beta or gamma subunits. We generated mice without gammaENaC (gammaENaC -/-) to test the role of this subunit in neonatal lung liquid clearance and total body electrolyte balance. Relative to controls, gammaENaC (-/-) pups showed low urinary [K+] and high urinary [Na+] and died between 24 and 36 h, probably from hyperkalemia (gammaENaC -/- 18.3 mEq/l, control littermates 9.7 mEq/l). Newborn gammaENaC (-/-) mice cleared lung liquid more slowly than control littermates, but lung water at 12 h (wet/dry = 5.5) was nearly normal (wet/dry = 5.3). This study suggests that gammaENaC facilitates neonatal lung liquid clearance and is critical for renal Na+ and K+ transport, and that low level Na+ transport may be sufficient for perinatal lung liquid absorption but insufficient to maintain electrolyte balance by the distal nephron. The gammaENaC (-/-) newborn exhibits a phenotype that resembles the clinical manifestations of human neonatal PHA1.

Adaptation, Physiological↗

Binocular rivalry and motion perception.

In a series of experiments psychophysical techniques were used to study the relation between binocular rivalry and motion perception. An initial series of experiments confirmed that motion enhances the predominance of an eye during rivalry, although the direction of motion does not matter. The presence of an annulus of motion immediately surrounding one eye's rival target greatly enhances dominance of that target, but the influence of the annulus progressively decreases as the separation between disk and annulus increased. Opponent directions of motion in disk and annulus yield greater dominance than when dots in the disk and annulus moved in identical directions. In a second experiment that two eyes were adapted to orthogonal directions of motion, generating strong, distinctively different monocular motion aftereffects (MAEs). Even though the two eyes view physically identical random-motion displays following differential adaptation, binocular rivalry of the discrepant MAEs can occur. Finally, using a stimulus replacement technique to measure detectability of translational and rotational motion, it was found that both types of motion were readily detected during periods of dominance but went undetected during periods of suppression. Taken together, these results bear on the process responsible for rivalry and its neural locus relative to the analysis of different types of motion.

Adaptation, Ocular↗

Critical weight at menarche. Critique of a hypothesis.

The critical weight hypothesis in relation to menarche, which is known as the Frisch-Revelle model, has been examined. Since, in eight samples, girls reached menarche at weights spanning a 71.4-kg (157-lb) range, Frisch and Revelle's concept of a critical weight of 47 to 48 kg (104 to 106 lb) cannot be applied meaningfully to individuals. Neither can the suggestion of an invariant mean weight be accepted, because significant differences occur among the mean menarcheal weights for several samples of normal white girls. Finally, when stature is held constant, there is some evidence that girls who reach menarche at younger ages are heavier than those who begin menstruating at older ages. Apparent reductions in variability when the estimated amount of total body water is used instead of body weight may result from statistical artifacts associated with regression analysis.

Adolescent↗