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  • 1
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Listeriotysjn O (LLO), a major virulence factor of the intracellular bacterium Listens monocytogenes, shares with other known ‘thiol-activated toxins’ a conserved undecapeptide, ECTGLAWEWWR, located in the C-terminal region of the protein and containing the unique cysteine of the molecule. Single amino acid substitutions were created in this region to study the role of cysteine and tryptophan residues in the lytic activity of LLO as well as in the virulence of the bacterium. Transformation of a transposon-induced non-haemolytic mutant with plasmids carrying the mutated genes allowed allele exchange and transfer of mutations on to the chromosome by in vivo recombination. The mutant strains secreted a full-length 59 kilodalton LLO. A decrease of 25% in the haemolytic activity in culture supernatants was observed in the case of mutation Cys-484 to Ala and of 80% for mutation Cys-484 to Ser. Mutations Trp-491 and Trp-492 to Ala decreased activity by, respectively, 95% and 99.9%. LLOs produced by the mutants, as the wild type, were active at low pH, inhibited by cholesterol, and able to bind to cell membranes. A close relationship was found between virulence of mutants in the mouse model and haemolytic activity in their culture supematants. These results demonstrate that the thiol group of Cys-484 is not essential for either haemolytic activity in vitro or virulence in vivo. In contrast, Trp-492 appears to be required for both haemolytic activity and virulence. The finding that the nearly non-haemolytic mutant Trp-492-Ala persisted in the spleen for several days after inoculation indicates that mutagenesis of a virulence determinant can attenuate virulence and provides a novel approach to the development of live vaccine strains.
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  • 2
    Electronic Resource
    Electronic Resource
    Copenhagen : International Union of Crystallography (IUCr)
    Applied crystallography online 5 (1972), S. 247-248 
    ISSN: 1600-5767
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Geosciences , Physics
    Notes: Crystals of γ. CsHCO3 are monoclinic, space group P21/c, with four molecules in a unit cell of dimensions a = 4.63, b = 11.20, c = 7.52 Å, β = 112°35′. The indexing of the X-ray powder pattern and the morphological study are given.
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  • 3
    ISSN: 1432-2013
    Keywords: Control of breathing ; Exercise ; Hypnotic drugs ; Narcotic analgesic drugs ; Propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The fast component of the ventilatory changes that occur at the transition phases of exercise was studied in awake dogs trained to run on a treadmill. Two questions were examined: firstly, is the fast ventilatory component modified by changes in venous return to the lungs, such as those consecutive either to increased work loads or to β adrenergic blockade?, and secondly, is this component altered by central ventilatory depressants? The results showed that at the onset of exercise, there is no correlation between the instantaneous increment in ventilation and the intensity of exercise, but at the end of the readmill run, the fall in ventilation is closely linked to the power of the work performed. Ventilatory transients observed either at the start or at the end of exercise remain unaffected by administration of a β-adrenergic blocking agent. But central depressant effects on ventilation caused by narcotic analgesics or hypnotic drugs altered the breathing pattern of the fast component of exercise-induced ventilatory changes. It is concluded that the instantaneous changes in ventilation occurring at the transition phases of exercise are controlled by mechanoreceptor mechanisms, but cerebral control is superimposed on the reflex control in regulating both tidal volume and breathing rate.
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  • 4
    ISSN: 1432-2013
    Keywords: Capillarization ; Endurance time to exhaustion ; Fast-and slow-twitch skeletal muscles ; Fibre type distribution ; Food restriction ; Oxidative and glycolytic enzymes ; Maximal oxygen uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to determine, in the rat, the effects of chronic exposure (7–9 weeks) to normobaric hypoxia (FIO2 = 0.13, equivalent to 3700 m altitude) on cardiac and skeletal muscle properties, on maximal oxygen uptake (VO2max), and endurance time to exhaustion (ETE). In addition, we evaluated the impact of endurance training (90 min of treadmill running per day, 5 days per week, for 9 weeks) on these parameters. The results were compared to normoxic rats fed ad libitum (NAL) and to normoxic pairweight (NPW) animals in order to take into account the influence of hypoxia on growth rate. It was found that, in sedentary rats, hypoxia results in stunted growth, adrenal atrophy, a significant reduction of cross-sectional area of fast-twitch (type II) fibres, a reduced capillary to-fibre ratio (C/F), and a reduced oxidative capacity (decreases in citrate synthase and 3-hydroxy-Acyl CoA dehydrogenase activities) of the plantaris muscle. These effects are mainly related to the anorexic effects of prolonged exposure to hypoxia. Nevertheless, hypoxic (H) rats displayed higherVO2max and ETE values when compared either to NAL or to NPW animals Endurance training resulted, in all groups (H, NAL, NPW), in a significant change of the fibre type distribution of the plantaris which displayed an increased number of type IIA fibres and a decreased proportion of type IIB fibres. In addition, the C/F ratio and cross-sectional area of fast-twitch fibres were normalized by superimposition of training on hypoxia. BothVO2max and ETE were significantly higher in trained H rats than in NAL, but these improvements were mainly related to the reduced body weight induced by hypoxia. These data suggest that the greater aerobic capacity and tolerance for prolonged exercise induced by chronic exposure to hypoxia can be mainly accounted for by the anorexic effects of hypoxia, although other factors (e.g. increase in oxygen carrying capacity induced by hypoxia acclimatization) may play a significant role in some circumstances (e.g. in sedentary rats)
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  • 5
    ISSN: 1432-2013
    Keywords: Male rats ; Fibre type distribution ; Food restriction ; Fast and slow-twitch skeletal muscles ; Oxidative and glycolytic enzymes ; Physical training
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to determine the impact of chronic treatment for 8 weeks with hydrocortisone acetate (5 mg kg−1 day−1) on skeletal muscles, and to evaluate whether sprint training can prevent glucocorticoid-induced muscle atrophy better than endurance training. Biochemical, histological and contractile properties were employed to determine the influence of this steroid on skeletal musculature, and the results were compared to pair-weight animals to take into account the influence of corticoids on growth rate. It was found that hydrocortisone acetate treatment results in a stunted growth, adrenal atrophy and depressed plasma corticosterone levels. Mild corticoid-induced losses of muscle mass and protein content (9%–13%) were observed in fast-twitch skeletal muscles. It appeared that the impact of corticoids is strictly directed toward type IIb fibres, which displayed a 12%–18% reduction in cross-sectional areas. No alterations occurred in plantaris contractile speed or tensions properties. Neither endurance training (30 m/min; 90 min/day; 5 days/week) nor sprint training (60 m/min; 15 min/day; 5 days/week) for 8 weeks was able to counteract the effects of corticoids. These data suggest that increased contractile activity, as induced by treadmill running, is not sufficient to counteract the muscular effects of glucocorticoids when administered at a dose of 5 mg kg−1 day−1.
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  • 6
    ISSN: 1432-2013
    Keywords: Key words Capillarization ; Endurance time to exhaustion ; Fast-and slow-twitch skeletal muscles ; Fibre type distribution ; Food restriction ; Oxidative and glycolytic enzymes ; Maximal oxygen uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to determine, in the rat, the effects of chronic exposure (7–9 weeks) to normobaric hypoxia (FIO2 = 0.13, equivalent to 3700 m altitude) on cardiac and skeletal muscle properties, on maximal oxygen uptake (VO2max), and endurance time to exhaustion (ETE). In addition, we evaluated the impact of endurance training (90 min of treadmill running per day, 5 days per week, for 9 weeks) on these parameters. The results were compared to normoxic rats fed ad libitum (NAL) and to normoxic pair-weight (NPW) animals in order to take into account the influence of hypoxia on growth rate. It was found that, in sedentary rats, hypoxia results in stunted growth, adrenal atrophy, a significant reduction of cross-sectional area of fast-twitch (type II) fibres, a reduced capillary-to-fibre ratio (C/F), and a reduced oxidative capacity (decreases in citrate synthase and 3-hydroxy-Acyl CoA dehydrogenase activities) of the plantaris muscle. These effects are mainly related to the anorexic effects of prolonged exposure to hypoxia. Nevertheless, hypoxic (H) rats displayed higher VO2max and ETE values when compared either to NAL or to NPW animals. Endurance training resulted, in all groups (H, NAL, NPW), in a significant change of the fibre type distribution of the plantaris which displayed an increased number of type IIA fibres and a decreased proportion of type IIB fibres. In addition, the C/F ratio and cross-sectional area of fast-twitch fibres were normalized by superimposition of training on hypoxia. Both VO2max and ETE were significantly higher in trained H rats than in NAL, but these improvements were mainly related to the reduced body weight induced by hypoxia. These data suggest that the greater aerobic capacity and tolerance for prolonged exercise induced by chronic exposure to hypoxia can be mainly accounted for by the anorexic effects of hypoxia, although other factors (e.g. increase in oxygen carrying capacity induced by hypoxia acclimatization) may play a significant role in some circumstances (e.g. in sedentary rats).
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  • 7
    ISSN: 1432-2013
    Keywords: Key words Carotid body ; Chemoreceptor pathway ; Nucleus tractus solitarius ; Noradrenergic brainstem cell groups ; Dopamine ; Polycythaemia ; Acclimatization to altitudeReceived: 12 July 1996 / Received after revision: 31 October 1996 / Accepted: 14 November 1996
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Mechanisms underlying sex-related differences in adaptation to high altitude were investigated by assessing the turnover of dopamine and noradrenaline in structures of the chemoafferent pathway, i.e. carotid body and brainstem noradrenergic cell groups (A1, A5, A6, A2 to which chemosensory fibres project). The influence of gender was assessed in male and female rats reared at an altitude of 3600 m, whereas the influence of endogenous sex hormones was evaluated by castration. Haematocrit, red blood cell count and plasma erythropoietin levels were lower in females than in males (–5%, –15%, –53%, respectively). Dopamine and noradrenaline turnover were higher in female structures (carotid body: +51%; A2: +140%; A1: +54%; A5: +27%). Dopamine and noradrenaline turnover in carotid body and brainstem cell groups were differently affected by castration, i.e. enhanced by orchidectomy (carotid body: +134%; A2: +120%; A1: +69%; A5: +67%) but inhibited by ovariectomy (carotid body: –33%; A2: –92%). Orchidectomy elicited a reduction in haematocrit (–10%), haemoglobin concentration (–8%) and red blood cell count (–24%), whereas haematological status remained unaltered after ovariectomy. Therefore, both gender and endogenous sex steroids may control catecholamine activity differently in structures involved in the chemoafferent pathway, thus providing a neurochemical basis for sex-related differences in adaptation to hypoxia.
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  • 8
    ISSN: 1432-2013
    Keywords: Key words Carotid body ; Dopamine ; Erythropoietin ; Noradrenergic cell groups ; Norepinephrine ; Polycythemia ; Sympathetic outflow ; Ventilation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In the absence of pulmonary disease, hypoventilation is considered to be the primary cause of Chronic Mountain Sickness, and there is some reason to believe that chronic administration of respiratory analeptics could be useful for treatment of this disease. The present study was intended to define comparatively the influence of two potent ventilatory stimulants, namely a combination of progesterone and estrogen and the pharmacological agent almitrine, on catecholaminergic structures implicated in the chemoreflex pathway and on hypoxia-induced polycythemia. Three groups of young male rats born and living at high altitude (3 600 m) were examined: untreated animals (n = 25), rats given ovarian steroids (progesterone plus 17β-estradiol, n = 25) or almitrine (n = 25) for 6 weeks until sacrifice. Ovarian steroids or almitrine had pronounced neurochemical effects on the afferent chemoreflex circuitry. Both treatments inhibited norepinephrine (NE) and dopamine (DA) turnover in the carotid body, but central processing of chemosensory inputs differed between the two respiratory drugs. Ovarian steroids inhibited noradrenergic activity in the projection area of the chemosensory nerve fibers within the caudal portion (A2C) of the nucleus tractus solitarius (NTS). In contrast, almitrine stimulated neurochemical activity of other brainstem noradrenergic cell groups involved in cardiorespiratory control, i.e., the rostral portion (A2R) of the NTS, the nucleus reticularis lateralis (A1), the nucleus olivaris superior (A5) and the locus ceruleus (A6). Although both treatments increased chemoreflex drive and ventilation, only sex hormones decreased erythropoietin (EPO) levels and the degree of polycythemia. These results suggest that stimulation of ventilation through activation of peripheral arterial chemoreceptors activation alone is not sufficient for reducing EPO levels and polycythemia. The better efficiency of female sex hormone treatment as compared to almitrine could be related either to the central effects of progesterone and estrogen and/or to the impact of these hormones on erythropoiesis at the kidney/bone marrow level.
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  • 9
    ISSN: 1439-6327
    Keywords: Children ; Exercise ; Catecholamines ; Glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ten prepubertal boys performed 60-min cycle exercise at about 60% of their maximal oxygen uptake as previously measured. To measure packed cell volume, plasma glucose, free fatty acids (FFA), glycerol and catecholamines, blood samples were drawn at rest using a heparinized cathether and at the 15th, 30th and 60th min of the exercise and after 30 min of recovery. At rest, the blood glucose concentrations were at the lowest values for normal. Exercise induced a small decrease of blood glucose which was combined with an abrupt increase of the noradrenaline concentration during the first 15 min. The FFA and glycerol concentrations increased throughout the exercise linearly with that of adrenaline. Compared to adults, the FFA uptake expressed per minute and per litre of oxygen uptake was greater in children. These results suggested that it is difficult for children to maintain a constant blood glucose concentration and that prolonged exercise provided a real stimulus to hypoglycaemia. An immediate and large increase in noradrenaline concentration during exercise and a greater utilization of FFA was probably used by children to prevent hypoglycaemia.
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  • 10
    ISSN: 1439-6327
    Keywords: Glucoregulation ; Exercise ; Age ; Sex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A group of 17 children, 8.5–11 years old, performed a 60-min cycle exercise at 60% of maximal oxygen uptake (VO2max) 2 h after a standardized breakfast. They were 10 young boys (pubertal stage =1) and 7 young girls (pubertal stage ⩽2) of similarVO2max (respective values were 48.5 ml min−1 kg−1, SEM 1.8; 42.1 ml min−1 kg−1, SEM 2.4). Blood samples of 5 ml were withdrawn by heparinized catheter, the subjects being in a supine position, 30 min before the test, then after 0, 15, 30 and 60 min of exercise and following 30 min recovery. Haematocrit was immediately measured. Thereafter plasma was analysed for glucose, non-esterified fatty acid, glycerol, catecholamine (noradrenaline, adrenaline), insulin and glucagon concentrations. This study showed two main results. First, the onset of exercise induced a significant glucose decrease (of about 11,4%) in all the children. Secondly, both the glycaemic and the hormonal responses were obviously different according to the sex. In boys only, the initial glucose drop was significantly correlated to the pre-exercise insulin values. Whatever the time, the glycaemic levels and the catecholamine responses were lower in girls than in boys, whereas the insulin values remained higher. However, none of these two hormonal parameters seemed to be really responsible for the lower glucose values in girls. On the one hand, the great individual variability of noradrenaline and adrenaline and differences in their relative intensity at the end of the exercise between boys and girls might contribute to the lower catecholamine levels in girls. On the other hand, the lack of a significant relationship in girls between the glucose decrease after exercise and the pre-exercise insulin values might be explained by a relative insulin insensitivity concomitant with the earlier growth spurt in girls, as demonstrated in subjects at rest by other authors. Finally the mechanisms of all these gender differences remain to be clarified and might be accounted for by a different maturation level in boys and girls.
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