Neuromuscular changes after long-lasting mechanically and electrically elicited fatigue

Central fatigue was investigated under an isolated active condition whereby the possible effects of supraspinal fatigue were minimized. Therefore, ten subjects were fatigued by simultaneously and repeatedly mechanically stretching and electrically stimulating their calf muscles for 1 h. This was performed using an ankle ergometer. The active fatigue task included a total of 2400 muscle stretches with an intensity of 10% of the maximal voluntary contraction (MVC). This protocol clearly impaired neuromuscular function, as revealed by a significant reduction in MVC (<i>P</i><0.01) and the neural input to the muscle (average EMG) (<i>P</i><0.01–0.001). The interpolated nerve stimulation compensated for this force loss by 4.28% (<i>P</i><0.05). Stretch-reflex recordings revealed a notable post-fatigue reduction in the peak-to-peak amplitude (59.1%, <i>P</i><0.01) and stretch-resisting force of the muscle (14.1%, <i>P</i><0.01). The maximal H-reflex declined by 50.5% (<i>P</i><0.001) and did not recover while the leg was kept ischemic. It is suggested that the existing protocol with minor metabolic loading can induce central fatigue, which seems to be of reflex origin from the fatigued muscle. Although the role of presynaptic inhibition of Ia terminals is possibly reinforced, disfacilitation via reduced spindle sensitivity cannot be excluded. Electronic Publication     

A novel fungal prenyl diphosphate synthase in the dimorphic zygomycete Mucor circinelloides

Two <i>Mucor circinelloides</i> structural genes involved in isoprenoid biosynthesis were isolated and characterised. The <i>isoA</i> gene encodes a typical eukaryotic farnesyl diphosphate synthase (EC 2.5.1.10), whereas the <i>isoB</i> gene deduced amino acid sequence shows similarity to fungal medium-chain prenyl diphosphate synthases. By functional complementation in <i>Escherichia coli</i>, the <i>isoB</i> gene product was shown to be a solanesyl diphosphate synthase (EC 2.5.1.11), which is the first fungal enzyme reported having this specificity. In addition, a <i>M. circinelloides</i> one-marker-per-chromosome map was completed by contour-clamped homogeneous electric field localisation of <i>isoA</i>, <i>isoB</i> and three other isoprenoid biosynthesis genes to individual chromosomes.Abbreviations FPP farnesyl diphosphate (or pyrophosphate) - GGPP geranylgeranyl diphosphate - PrenylPP prenyl diphosphate - DPP decaprenyl diphosphate - HPP hexaprenyl diphosphate - SPP solanesyl diphosphate     

Impaired responses to toll-like receptor 4 and toll-like receptor 3 ligands in human cord blood

Toll-like receptor (TLR)-4 signaling pathway plays an essential role in host defense against gram-negative bacteria while TLR-3-mediated signaling is critically involved in anti-viral immunity. To gain insight into the defects responsible for impaired Th1 responses in human newborns, we investigated the responses of human cord blood cells to lipopolysaccharide, LPS, and to polyinosinic-polycytidylic acid, Poly (I:C), ligands of TLR-4 and TLR-3, respectively. Measurement of cytokine levels revealed a profound defect in IL-12 (p70) synthesis and an increased release of IL-10 in cord blood exposed to LPS or Poly (I:C), as compared to adult blood. Moreover, Poly (I:C)-induced IFN-alpha production was found to be significantly impaired in cord blood. Phenotypic maturation of myeloid DC in response to LPS or Poly (I:C) was next compared in cord and adult blood. We observed that neonatal myeloid DC displayed decreased upregulation of CD40, CD80 whereas CD86 and HLA-DR upregulation did not differ significantly between adults and neonates. Taken together, these findings might be relevant to the increased vulnerability of human newborns to intracellular pathogens and to their inability to develop efficient Th1-type responses.     

Characterization of T lymphocyte subsets in hairy cell leukaemia: influence of splenectomy and correlations with the clinical stage of the disease.

Peripheral blood mononuclear cell surface markers were studied in a series of 26 hairy cell leukaemia patients 19 of whom were splenectomized previously. Patients with non-symptomatic and stable disease were distinguished from those with symptomatic and/or progressive disease (also termed "active" clinical stages). In all HCL patients as a group, the absolute number of CD4+ MN cells did not differ statistically from that of the controls, while the number of CD8+ MN cells was significantly increased. The reduction of the CD4/CD8 ratio in the peripheral blood of HCL patients as compared to the controls was explained by the reduction of this ratio in patients with "active disease", while the CD4/CD8 ratio of patients with non-symptomatic and stable disease did not differ statistically from that of the controls. The CD4/CD8 ratio was found to be influenced mainly by the clinical stage of the disease, and not by the effect of splenectomy.     

Histamine liberation and membrane fluidisation of mast cells exposed to the beta-adrenoceptor blocking drug propranolol

Propranolol liberates histamine from isolated mast cells and decreases the uptake of extracellular histamine in a dose-dependent way. Histamine liberation due to propranolol is accompanied by calcium displacement from intracellular storage sites. The significant increase in membrane fluidity due to propranolol is temperature dependent. The perturbation of membranes is most probably the explanation of propranolol's interaction with isolated rat mast cells which results in altered histamine transportation.     

Proprioception does not quickly drift during visual occlusion

Several perceptual studies have shown that the ability to estimate the location of the arm degrades quickly during visual occlusion. To account for this effect, it has been suggested that proprioception drifts when not continuously calibrated by vision. In the present study, we re-evaluated this hypothesis by isolating the proprioceptive component of position sense (i.e., the subjects were forced to rely exclusively on proprioception to locate their hand, which was not the case in earlier studies). Three experiments were conducted. In experiment 1, subjects were required to estimate the location of their unseen right hand, at rest, using a visual spot controlled by the left hand through a joystick. Results showed that the mean accuracy was identical whether the localization task was performed immediately after the positioning of the hand or after a 10-s delay. In experiments 2 and 3, subjects were required to point, without vision of their limb, to visual targets. These two experiments relied on the demonstration that biases in the perception of the initial hand location induced systematic variations of the movement characteristics (initial direction, final accuracy, end-point variability). For these motor tasks, the subjects did not pay attention to the initial hand location, which removed the possible occurrence of confounding cognitive strategies. Results indicated that movement characteristics were, on average, not affected when a 15-s or 20-s delay was introduced between the positioning of the arm at the starting point and the presentation of the target. When considered together, our results suggest that proprioception does not quickly drift in the absence of visual information. The potential origin of the discrepancy between our results and earlier studies is discussed.     

Competing functions encoded in the allergy-associated F(c)epsilonRIbeta gene

Allergic reactions are triggered via crosslinking of the high-affinity receptor for immunoglobulin E, F(c)epsilonRI. In humans, F(c)epsilonRI is expressed as a tetramer (alphabetagamma(2)) and a trimer (alphagamma(2)). The beta subunit is an amplifier of F(c)epsilonRI surface expression and signaling. Here, we show that as a consequence of alternative splicing, the F(c)epsilonRIbeta gene encodes two proteins with opposing and competing functions. One isoform is the full-length classical beta, the other a novel truncated form, beta(T). In contrast to beta, beta(T) prevents F(c)epsilonRI surface expression by inhibiting alpha chain maturation. Moreover, beta(T) competes with beta to control F(c)epsilonRI surface expression in vitro. We propose that the relative abundance of the products of the beta gene may control the level of F(c)epsilonRI surface expression and thereby influence susceptibility to allergic diseases.