A role for CD147 in thymic development.

We have previously identified a mAb that binds to a molecule expressed preferentially on the surface of cycling thymocytes. In this study the molecule recognized by this mAb has been identified in the mouse as CD147 (basigin) by expression cloning. We show that CD147 expression correlates with cycling of immature thymocytes even in the absence of TCRbeta selection and that ligation of this molecule on immature fetal thymocytes inhibits their further development into mature T cells.

Cefotaxime acts synergistically with levofloxacin in experimental meningitis due to penicillin-resistant pneumococci and prevents selection of levofloxacin-resistant mutants in vitro.

Cefotaxime, given in two doses (each 100 mg/kg of body weight), produced a good bactericidal activity (-0.47 Deltalog(10) CFU/ml. h) which was comparable to that of levofloxacin (-0.49 Deltalog(10) CFU/ml. h) against a penicillin-resistant pneumococcal strain WB4 in experimental meningitis. Cefotaxime combined with levofloxacin acted synergistically (-1.04 Deltalog(10) CFU/ml. h). Synergy between cefotaxime and levofloxacin was also demonstrated in vitro in time killing assays and with the checkerboard method for two penicillin-resistant strains (WB4 and KR4). Using in vitro cycling experiments, the addition of cefotaxime in sub-MIC concentrations (one-eighth of the MIC) drastically reduced levofloxacin-induced resistance in the same two strains (64-fold increase of the MIC of levofloxacin after 12 cycles versus 2-fold increase of the MIC of levofloxacin combined with cefotaxime). Mutations detected in the genes encoding topoisomerase IV (parC and parE) and gyrase (gyrA and gyrB) confirmed the levofloxacin-induced resistance in both strains. Addition of cefotaxime in low doses was able to suppress levofloxacin-induced resistance.

Are oxygen uptake kinetics modified when using a respiratory snorkel?

PURPOSE: The aim of this study was to compare VO2 kinetics during constant power cycle exercise measured using a conventional facemask (CM) or a respiratory snorkel (RS) designed for breath-by-breath analysis in swimming. METHODS: VO2 kinetics parameters-obtained using CM or RS, in randomized counterbalanced order-were compared in 10 trained triathletes performing two submaximal heavy-intensity cycling square-wave transitions. These VO2 kinetics parameters (ie, time delay: td1, td2; time constant: τ1, τ2; amplitude: A1, A2, for the primary phase and slow component, respectively) were modeled using a double exponential function. In the case of the RS data, this model incorporated an individually determined snorkel delay (ISD). RESULTS: Only td1 (8.9 ± 3.0 vs 13.8 ± 1.8 s, P < .01) differed between CM and RS, whereas all other parameters were not different (τ1 = 24.7 ± 7.6 vs 21.1 ± 6.3 s; A1 = 39.4 ± 5.3 vs 36.8 ± 5.1 mL x min(-1) x kg(-1); td2 = 107.5 ± 87.4 vs 183.5 ± 75.9 s; A2' (relevant slow component amplitude) = 2.6 ± 2.4 vs 3.1 ± 2.6 mL x min(-1) x kg(-1) for CM and RS, respectively). CONCLUSIONS: Although there can be a small mixture of breaths allowed by the volume of the snorkel in the transition to exercise, this does not appear to significantly influence the results. Therefore, given the use of an ISD, the RS is a valid instrument for the determination of VO2 kinetics within submaximal exercise.

Vibration training elicits a mixed aerobic and resistance-type exercise in sedentary subjects.

Objective. Vibration training (VT) is a new exercise method, with good acceptance among sedentary subjects, due to its passive principle: the machine moves the subject, not the opposite. We hypothesize that untrained subjects can benefit from a greater cardiovascular and metabolic stimulation than trained athletes, resembling classical aerobic-type activity, in addition of eliciting strength gains shown in diverse studies. Methods. 3 group of male subjects, inactive (SED), endurance trained athletes (END) and strength trained athletes (STR) underwent fitness (VO2max) and lower-body strength tests (isokinetic). Subjects were submitted to a session of oscillating VT, composed of 3 exercises (isometric half-squat, dynamic squat, dynamic squat with added load), each of 3 minutes duration, and repeated at 3 frequencies. VO2, heart rate and Borg scale were monitored. Results. 27 healthy subjects (10 SED, 9 END and 8 STR), mean age 24.5 (SED), 25.0 (STR) and 29.8 (END) were included. VO2max was significantly different as expected (47.9 vs. 52.9 vs. 63.9 ml/kg/min, resp. for SED, STR and END). Isokinetic dominant leg extensors strength was higher in STR (3.32 Nm/kg vs. 2.60 and 2.74 in SED and END). During VT, peak oxygen consumption (% of VO2max) attained was 59.3 in SED, 50.8 in STR and 48.0 in END (P<0.001 between SED and other subjects). Peak heart rate (% of heart rate max) was 82.7 in SED, 80.4 in STR and 72.4 in END. In SED, dynamic exercises without extra load elicited 51.0% of VO2max and 72.1% of heart rate max, and perceived effort reached 15.1/20. Conclusions. VT is an unconventional type of exercise, which has been shown to enhance strength, bone density, balance and flexibility. Users are attracted by the relative passivity. In SED, we show that VT elicits sufficient cardiovascular response to benefit overall fitness in addition to the known strength effects. VT's higher acceptance as an exercise in sedentary people, compared to jogging or cycling for example, can lead to better adherence to physical activity. Although long-term effects of VT on health are not avalaible, we believe this type of combination of aerobic and resistance-type exercise can be beneficial on multiple health parameters, especially cardiovascular health.

Ceftriaxone acts synergistically with levofloxacin in experimental meningitis and reduces levofloxacin-induced resistance in penicillin-resistant pneumococci.

Ceftriaxone acted synergistically with levofloxacin in time-killing assays in vitro over 8 h against two penicillin-resistant pneumococcal strains (WB4 and KR4; MIC of penicillin: 4 mg/L). Synergy was confirmed with the chequerboard method, showing FIC indices of 0.25. In the experimental rabbit meningitis model, ceftriaxone (1x 125 mg/kg) was slightly less bactericidal (-0.30 Deltalog(10) cfu/mL(.)h) compared with levofloxacin (-0.45 Deltalog(10) cfu/mL(.)h) against the penicillin-resistant strain WB4. The combination therapy (levofloxacin and ceftriaxone) was significantly superior (-0.64 Deltalog(10) cfu/mL(.)h) to either monotherapy. In cycling experiments in vitro, the addition of ceftriaxone at a sub-MIC concentration (1/16 MIC) reduced levofloxacin-induced resistance in the two strains KR4 and WB4. After 12 cycles with levofloxacin monotherapy, the MIC increased 64-fold in both strains versus a 16-fold increase with the combination (levofloxacin + ceftriaxone 1/16 MIC). In both strains, levofloxacin-induced resistance was confirmed by mutations detected in the genes parC and gyrA, encoding for subunits of topoisomerase IV and gyrase, respectively. The addition of ceftriaxone suppressed mutations in parC but led to a new mutation in parE in both strains.

Location of corneal epithelial stem cells Reply

The longstanding concept that corneal epithelial stem cells reside mainly in the limbus is supported by the absence of major corneal epithelial differentiation markers, that is, K3 and K12 keratins, in limbal basal cells (these markers are expressed, however, in corneal basal cells, thus distinguishing the mode of keratin expression in corneal epithelium from that of all other stratified epithelia), the centripetal migration of corneal epithelial cells, the exclusive location of slow-cycling cells in the limbal basal layer, the superior in vitro proliferative potential of limbal epithelial cells, and the transplanted limbal cells' ability to reconstitute corneal epithelium in vivo (reviewed in refs 1-4). Moreover, previous data indicate that corneal and conjunctival epithelia represent two separate cell lineages (reviewed in refs 1-4). Majo et al. suggested, however, that corneal and conjunctival epithelia are equipotent, and that identical oligopotent stem cells are present throughout the corneal, limbal and conjunctival epithelia. We point out here that these suggestions are inconsistent with many known growth, differentiation and cell migration properties of the anterior ocular epithelia.

Mechanical properties of rat cardiac skinned fibers are altered by chronic growth hormone hypersecretion.

Chronic growth hormone (GH) hypersecretion in rats leads to increased isometric force without affecting the unloaded shortening velocity of isolated cardiac papillary muscles, despite a marked isomyosin shift toward V3. To determine if alterations occurred at the level of the contractile proteins in rats bearing a GH-secreting tumor (GH rats), we examined the mechanical properties of skinned fibers to eliminate the early steps of the excitation-contraction coupling mechanism. We found that maximal active tension and stiffness at saturating calcium concentrations (pCa 4.5) were markedly higher in GH rats than in control rats (tension, 52.9 +/- 5.2 versus 38.1 +/- 4.6 mN.mm-2, p < 0.05; stiffness, 1,105 +/- 120 versus 685 +/- 88 mN.mm-2.microns-1, p < 0.01), whereas values at low calcium concentrations (pCa 9) were unchanged. In addition, the calcium sensitivity of the contractile proteins was slightly but significantly higher in GH rats than in control rats (delta pCa 0.04, p < 0.001). The crossbridge cycling rate, reflected by the response to quick length changes, was lower in GH rats than in control rats (62.0 +/- 2.6 versus 77.4 +/- 6.6 sec-1, p < 0.05), in good agreement with a decrease in the proportion of alpha-myosin heavy chains in the corresponding papillary muscles (45.5 +/- 2.0% versus 94.6 +/- 2.4%, p < 0.001). The changes in myosin heavy chain protein phenotype were paralleled by similar changes of the corresponding mRNAs, indicating that the latter occurred mainly at a pretranslational level. These results demonstrate that during chronic GH hypersecretion in rats, alterations at the myofibrillar level contribute to the increase in myocardial contractility observed in intact muscle.

Coevolution of adaptive technology, maladaptive culture and population size in a producer-scrounger game.

Technology (i.e. tools, methods of cultivation and domestication, systems of construction and appropriation, machines) has increased the vital rates of humans, and is one of the defining features of the transition from Malthusian ecological stagnation to a potentially perpetual rising population growth. Maladaptations, on the other hand, encompass behaviours, customs and practices that decrease the vital rates of individuals. Technology and maladaptations are part of the total stock of culture carried by the individuals in a population. Here, we develop a quantitative model for the coevolution of cumulative adaptive technology and maladaptive culture in a 'producer-scrounger' game, which can also usefully be interpreted as an 'individual-social' learner interaction. Producers (individual learners) are assumed to invent new adaptations and maladaptations by trial-and-error learning, insight or deduction, and they pay the cost of innovation. Scroungers (social learners) are assumed to copy or imitate (cultural transmission) both the adaptations and maladaptations generated by producers. We show that the coevolutionary dynamics of producers and scroungers in the presence of cultural transmission can have a variety of effects on population carrying capacity. From stable polymorphism, where scroungers bring an advantage to the population (increase in carrying capacity), to periodic cycling, where scroungers decrease carrying capacity, we find that selection-driven cultural innovation and transmission may send a population on the path of indefinite growth or to extinction.

Effects of two types of fatigue on the VO(2) slow component.

The aim of the study was to test the hypothesis of the involvement of type II fibres in the V.O (2) slow component phenomenon by using two prior fatiguing protocols on the knee extensor muscles. Nine subjects performed three constant-load cycling exercises at a work rate corresponding to 80 % of their V.O (2) max: (i) preceded by a 20-min fatiguing protocol using electromyostimulation (EMS), (ii) preceded by a 20-min fatiguing protocol using voluntary contractions (VOL), and (iii) without fatiguing protocol (NFP). Voluntary and evoked neuromuscular properties of the knee extensor muscles were tested before (PRE) and after (POST) the two fatiguing protocols. Results show a significant reduction in voluntary force after both fatiguing protocols (-19.9 % and -11.8 %, in EMS and VOL, respectively p<0.01). After EMS, this decrease was greater than after VOL (p<0.05) and was combined with a slackening of muscle contractile properties which was absent after VOL (p<0.05). Regarding the effects on oxygen uptake kinetics, the appearance of the slow component was delayed after EMS and its amplitude was lower than those obtained in VOL and NFP conditions (0.48+/-0.07 vs. 0.75+/-0.09 and 0.69+/-0.08 L . min (-1), respectively; p<0.05). It can thus be concluded that exercises dedicated to preferentially fatiguing type II fibres may alter V.O (2) kinetics.

Dynamic responses of oxygen uptake at the onset and end of moderate and heavy exercise in trained subjects.

Inconsistencies about dynamic asymmetry between the on- and off-transient responses in VO2 are found in the literature. Therefore the purpose of this study was to examine VO2 on- and off-transients during moderate- and heavy-intensity cycling exercise in trained subjects. Ten men underwent an initial incremental test for the estimation of ventilatory threshold (VT) and, on different days, two bouts of square-wave exercise at moderate (<VT) and heavy (>VT) intensities. VO2 kinetics in exercise and recovery were better described by a single exponential model (<VT), or by a double exponential with two time delays (>VT). For moderate exercise, we found a symmetry of VO2 kinetics between the on- and off-transients (i.e., fundamental component), consistent with a system manifesting linear control dynamics. For heavy exercise, a slow component superimposed on the fundamental phase was expressed in both the exercise and recovery, with similar parameter estimates. But the on-transient values of the time constant were appreciably faster than the associated off-transient, and independent of the work rate imposed (<VT and >VT). Our results do not support a dynamically linear system model of VO2 during cycling exercise in the heavy-intensity domain.

Dynamic responses of O2 uptake at the onset and end of exercise in trained subjects.

Inconsistencies about dynamic asymmetry between the on- and off-transient responses in .VO2 are found in the literature. Therefore the purpose of this study was to examine .VO2on- and off-transients during moderate- and heavy-intensity cycling exercise in trained subjects. Ten men underwent an initial incremental test for the estimation of ventilatory threshold (VT) and, on different days, two bouts of square-wave exercise at moderate (<VT) and heavy (>VT) intensities. .VO2 kinetics in exercise and recovery were better described by a single exponential model (<VT) or by a double exponential with two time delays (>VT). For moderate exercise, we found a symmetry of .VO2 kinetics between the on- and off-transients (i.e., fundamental component), consistent with a system manifesting linear control dynamics. For heavy exercise, a slow component superimposed on the fundamental phase was expressed in both the exercise and recovery, with similar parameter estimates. But the on-transient values of the time constant were appreciably faster than the associated off-transient, and independent of the work rate imposed (<VT and >VT). Our results do not support a dynamically linear system model of .VO2 during cycling exercise in the heavy-intensity domain.

Addition of inspiratory resistance increases the amplitude of the slow component of O2 uptake kinetics.

The contribution of respiratory muscle work to the development of the O(2) consumption (Vo(2)) slow component is a point of controversy because it has been shown that the increased ventilation in hypoxia is not associated with a concomitant increase in Vo(2) slow component. The first purpose of this study was thus to test the hypothesis of a direct relationship between respiratory muscle work and Vo(2) slow component by manipulating inspiratory resistance. Because the conditions for a Vo(2) slow component specific to respiratory muscle can be reached during intense exercise, the second purpose was to determine whether respiratory muscles behave like limb muscles during heavy exercise. Ten trained subjects performed two 8-min constant-load heavy cycling exercises with and without a threshold valve in random order. Vo(2) was measured breath by breath by using a fast gas exchange analyzer, and the Vo(2) response was modeled after removal of the cardiodynamic phase by using two monoexponential functions. As anticipated, when total work was slightly increased with loaded inspiratory resistance, slight increases in base Vo(2), the primary phase amplitude, and peak Vo(2) were noted (14.2%, P < 0.01; 3.5%, P > 0.05; and 8.3%, P < 0.01, respectively). The bootstrap method revealed small coefficients of variation for the model parameter, including the slow-component amplitude and delay (15 and 19%, respectively), indicating an accurate determination for this critical parameter. The amplitude of the Vo(2) slow component displayed a 27% increase from 8.1 +/- 3.6 to 10.3 +/- 3.4 ml. min(-1). kg(-1) (P < 0.01) with the addition of inspiratory resistance. Taken together, this increase and the lack of any differences in minute volume and ventilatory parameters between the two experimental conditions suggest the occurrence of a Vo(2) slow component specific to the respiratory muscles in loaded condition.

Neonatal and adult ICU ventilators to provide ventilation in neonates, infants, and children: a bench model study.

BACKGROUND: Using a bench test model, we investigated the hypothesis that neonatal and/or adult ventilators equipped with neonatal/pediatric modes currently do not reliably administer pressure support (PS) in neonatal or pediatric patient groups in either the absence or presence of air leaks. METHODS: PS was evaluated in 4 neonatal and 6 adult ventilators using a bench model to evaluate triggering, pressurization, and cycling in both the absence and presence of leaks. Delivered tidal volumes were also assessed. Three patients were simulated: a preterm infant (resistance 100 cm H2O/L/s, compliance 2 mL/cm H2O, inspiratory time of the patient [TI] 400 ms, inspiratory effort 1 and 2 cm H2O), a full-term infant (resistance 50 cm H2O/L/s, compliance 5 mL/cm H2O, TI 500 ms, inspiratory effort 2 and 4 cm H2O), and a child (resistance 30 cm H2O/L/s, compliance 10 mL/cm H2O, TI 600 ms, inspiratory effort 5 and 10 cm H2O). Two PS levels were tested (10 and 15 cm H2O) with and without leaks and with and without the leak compensation algorithm activated. RESULTS: Without leaks, only 2 neonatal ventilators and one adult ventilator had trigger delays under a given predefined acceptable limit (1/8 TI). Pressurization showed high variability between ventilators. Most ventilators showed TI in excess high enough to seriously impair patient-ventilator synchronization (> 50% of the TI of the subject). In some ventilators, leaks led to autotriggering and impairment of ventilation performance, but the influence of leaks was generally lower in neonatal ventilators. When a noninvasive ventilation algorithm was available, this was partially corrected. In general, tidal volume was calculated too low by the ventilators in the presence of leaks; the noninvasive ventilation algorithm was able to correct this difference in only 2 adult ventilators. CONCLUSIONS: No ventilator performed equally well under all tested conditions for all explored parameters. However, neonatal ventilators tended to perform better in the presence of leaks. These findings emphasize the need to improve algorithms for assisted ventilation modes to better deal with situations of high airway resistance, low pulmonary compliance, and the presence of leaks.

Could a satellite-based navigation system (GPS) be used to assess the physical activity of individuals on earth?

OBJECTIVES: To test whether the Global Positioning System (GPS) could be potentially useful to assess the velocity of walking and running in humans. SUBJECT: A young man was equipped with a GPS receptor while walking running and cycling at various velocity on an athletic track. The speed of displacement assessed by GPS, was compared to that directly measured by chronometry (76 tests). RESULTS: In walking and running conditions (from 2-20 km/h) as well as cycling conditions (from 20-40 km/h), there was a significant relationship between the speed assessed by GPS and that actually measured (r = 0.99, P < 0.0001) with little bias in the prediction of velocity. The overall error of prediction (s.d. of difference) averaged +/-0.8 km/h. CONCLUSION: The GPS technique appears very promising for speed assessment although the relative accuracy at walking speed is still insufficient for research purposes. It may be improved by using differential GPS measurement.

Steroid hormone pulsing drives cyclic gene expression.

Transcriptional cycling of activated glucocorticoid receptor (GR) and ultradian glucocorticoid secretion are well established processes. Ultradian hormone release is now shown to result in pulsatile gene transcription through dynamic exchange of GR with the target-gene promoter and GR cycling through the chaperone machinery.