bluuebunny/crossref_metadata_2025_split huggingface dataset:
The arginine vasopressin and corticotrophin‐releasing hormone gene transcription responses to varied frequencies of repeated stress in rats
Authors: Ma Xin‐Ming , Lightman Stafford L. 
Published: September 2004

Rats habituate to repeated exposure to homotypic stressors. The present studies were designed to define how altered frequency of exposure to a stressor affects the development of habituation and how this habituation is reflected in alterations in basal expression and responsiveness of hypothalamic corticotrophin‐releasing hormone (CRH) and arginine vasopressin (AVP) messenger and heteronuclear RNA (hnRNA).
Rats were exposed to a 60 min period of restraint stress every 7th day, every 3rd day, alternate days or daily for 2 weeks and their response to a final episode of stress on day 15 was compared with that of a control group of unstressed rats.
The response of plasma corticosterone to the final stressor on day 15 was diminished in animals which had been stressed on only two previous occasions, 7 days apart, and diminished further with increasing frequency of previous stressors until it failed to respond at all in animals stressed daily.
The pattern of CRH hnRNA and mRNA responses were similar, decreasing with increasing frequency of exposure to the stressor, while AVP mRNA responses increased in response to repeated stress.
The gradual emergence of increased AVP transcription at a time of diminishing CRH response suggests that repeated stress results in a specific facilitation of AVP gene expression, perhaps by impairment of corticosterone feedback.
Paired‐pulse magnetic stimulation of the human motor cortex: differences among I waves
Authors: Hanajima Ritsuko , Ugawa Yoshikazu , Terao Yasuo , Sakai Katsuyuki , Furubayashi Toshiaki , Machii Katsuyuki , Kanazawa Ichiro 
Published: September 2004

In paired‐pulse cortical stimulation experiments, conditioning subthreshold stimuli suppress the electromyographic (EMG) responses of relaxed muscles to suprathreshold magnetic test stimuli at short interstimulus intervals (ISIs) (1‐5 ms) and facilitate them at long ISIs (8‐15 ms).
We made paired‐pulse magnetic stimulation studies on the response of the first dorsal interosseous muscle (FDI) produced by I1 or I3 waves using our previously reported method which preferentially elicits one group of I waves when subjects make a slight voluntary contraction. In some experiments the conditioning and test stimuli were oppositely directed, in the others they were oriented in the same direction. Single motor unit responses were recorded with a concentric needle electrode, and surface EMG responses with cup electrodes.
In post‐stimulus time histograms (PSTHs) of the firing probability of motor units, the peaks produced by I3 waves were decreased by a subthreshold conditioning stimulus that preferentially elicited I1 or I3 waves at an ISI of 4 ms. The amount of decrement depended on the intensity of the conditioning stimulus. The stronger the conditioning stimulus, the greater the suppression. In contrast, the peaks produced by I1 waves were little affected by any type of subthreshold conditioning stimulus, given 4 ms prior to the test stimulus. At an ISI of 10 ms, a subthreshold conditioning stimulus slightly decreased the size of the peak produced by the I3 waves, but did not affect the peaks evoked by I1 waves.
Surface EMGs showed that a subthreshold conditioning stimulus suppressed the responses produced by I3 waves irrespective of its current direction (anterior or posterior). Both the amount and duration of suppression depended on the intensity of the conditioning stimulus, but not on its current direction. Both parameters increased when the intensity increased. At a high intensity conditioning stimulus, suppression was evoked at ISIs of 1‐20 ms, compatible with the duration of GABA‐mediated inhibition found in animal experiments. Responses produced by I1 waves were little affected by any type of subthreshold conditioning stimulus.
We conclude that a subthreshold conditioning stimulus given over the motor cortex moderately suppresses I3 waves but does not affect I1 waves. The duration of suppression of the I3 waves supports the idea that this is an effect of GABAergic inhibition within the motor cortex.
Zn2+ inhibition of recombinant GABAA receptors: an allosteric, state‐dependent mechanism determined by the γ‐subunit
Authors: Gingrich K. J. , Burkat P. M. 
Published: September 2004

The γ‐subunit in recombinant γ‐aminobutyric acid (GABAA) receptors reduces the sensitivity of GABA‐triggered Cl− currents to inhibition by Zn2+ and transforms the apparent mechanism of antagonism from non‐competitive to competitive. To investigate underlying receptor function we studied Zn2+ effects on macroscopic and single‐channel currents of recombinant α1β2 and α1β2γ2 receptors expressed heterologously in HEK‐293 cells using the patch‐clamp technique and rapid solution changes.
Zn2+ present for > 60 s (constant) inhibited peak, GABA (5 μM)‐triggered currents of α1β2 receptors in a concentration‐dependent manner (inhibition equation parameters: concentration at half‐amplitude (IC50) = 0.94 μM; slope related to Hill coefficient, S= 0.7) that was unaffected by GABA concentration. The γ2 subunit (α1β2γ2 receptor) reduced Zn2+ sensitivity more than fiftyfold (IC50= 51 μM, S= 0.86); increased GABA concentration (100 μM) antagonized inhibition by reducing apparent affinity (IC50= 322 μM, S= 0.79). Zn2+ slowed macroscopic gating of α1β2 receptors by inducing a novel slow exponential component in the activation time course and suppressing a fast component of control desensitization. For α1β2γ2 receptors, Zn2+ accelerated a fast component of apparent desensitization.
Zn2+ preincubations lasting up to 10 s markedly increased current depression and activation slowing of α1β2 receptors, but had little effect on currents from α1β2γ2 receptors.
Steady‐state fluctuation analysis of macroscopic α1β2γ2 currents (n= 5) resulted in control (2 μM GABA) power density spectra that were fitted by a sum of two Lorentzian functions (relaxation times: 37 ± 5.6 and 1.41 ± 0.15 ms, means ± s.e.m.). Zn2+ (200 μM) reduced the total power almost sixfold and accelerated the slow (23 ± 2.8 ms, P < 0.05) without altering the fast (1.40 ± 0.16 ms) relaxation time. The ratio (fast/slow) of Lorentzian areas was increased by Zn2+ (control, 3.39 ± 0.55; Zn2+, 4.9 ± 0.37, P < 0.05).
Zn2+ (500 μM) depression of previously activated current amplitudes (% control) for α1β2γ2 receptors was independent of GABA concentration (5 μM, 13.2 ± 0.72 %; 100 μM, 12.2 ± 2.9 %, P < 0.8, n= 5). Both onset and offset inhibition time courses were biexponential. Onset rates were enhanced by Zn2+ concentration. Inhibition onset was also biexponential for preactivated α1β2 receptors with current depression more than fourfold less sensitive (5 μM GABA, IC50= 3.8 μM, S= 0.84) relative to that in constant Zn2+.
The results lead us to propose a general model of Zn2+ inhibition of GABAA receptors in which Zn2+ binds to a single extracellular site, induces allosteric receptor inhibition involving two non‐conducting states, site affinity is state‐dependent, and the features of state dependence are determined by the γ‐subunit.
Motoneuronal pre‐compensation for the low‐pass filter characteristics of muscle. A quantitative appraisal in cat muscle units
Authors: Baldissera Fausto , Cavallari Paolo , Cerri Gabriella 
Published: September 2004

The relevance of motoneurone dynamic sensitivity in compensating for the low‐pass filter properties of muscle was assessed by stimulating cat muscle units (MUs) with impulse discharges generated by two current‐to‐rate converters: (i) a spinal motoneurone, sensitive to both the input intensity and its first derivative, and (ii) a linear current‐to‐rate converter, i.e. a neurone model with the same static sensitivity as the motoneurone but lacking dynamic sensitivity.
Discharges generated by injection of sine‐wave currents in three motoneurones of the ‘fast’ type and in the three related model versions were applied to the axon of forty‐six MUs. The MU isometric tension was modulated at the frequency of the current sine wave (0.5‐20 Hz). Phase and gain of the current‐to‐force transduction were measured.
When MUs were driven by the model, the force lagged the current by 90 deg at 1 Hz in slow MUs and at around 5 Hz in fast MUs. Under motoneurone drive, the 90 deg phase lag was attained at frequencies about twice as high.
The gain of the transduction (peak‐to‐peak force modulation/peak‐to‐peak current modulation) decayed when the modulation frequency was increased. In all but five units, the cut‐off frequency, Fco (gain attenuated by −3 dB), was higher when the unit was motoneurone driven (FcoCell) then when it was model driven (FcoMod). In both conditions, Fco was inversely correlated with the MU's time‐to‐peak. The advantage conferred by the motoneurone dynamic sensitivity was expressed by the Fco ratio (FcoCell/FcoMod). Across the MU population this ratio ranged from 0.6‐2.8, was inversely correlated with the time‐to peak, and was directly correlated with the half‐tension rate, i.e. the impulse rate at which MUs develop 50 % of their maximal tetanic force. The largest improvement (Fco ratio > 2.0) was found in units with mechanical features similar to those presumably coupled ‘in vivo’ to the motoneurones utilized for stimulation.
This estimate was confirmed in experiments in which trains of pulses, generated by injection of ramp currents in another motoneurone and the related model, were used to activate eight MUs, selected for being similar to that connected ‘in vivo’ to the motoneurone. As expected, for any given current slope the rising phase of isometric tension was steeper when units were motoneurone driven than when they were model driven. The gain (force slope/current slope) was plotted against the ramp slope to identify the cut‐off slope, Sco, at which the gain was attenuated by −3 dB. In this homogeneous MU sample, the ratio expressing the advantage of the motoneurone drive (ScoCell/ScoMod, equivalent to the Fco ratio), ranged from 2.62‐2.97, values comparable with those observed in sine‐wave experiments when the motoneurone and muscle units were properly matched.
Human calf precapillary resistance decreases in response to small cumulative increases in venous congestion pressure
Authors: Gamble J. , Christ F. , Gartside I. B. 
Published: September 2004

We studied human lower limbs to test the hypothesis that the application of small cumulative venous congestion pressure steps is associated with a reduction in precapillary resistance.
Strain gauge plethysmography was performed on twenty‐one young subjects (22.7 ± 0.6 years). At each of the small cumulative pressure steps, limb blood flow was estimated from the initial slope of the volume response to transient (10 s duration) elevations of venous congestion pressure to 90 mmHg, after which the congestion pressure was returned to the previous value. The blood flow at each pressure was also expressed as a percentage of the initial control value. Peak tibial arterial blood flux was assessed, in four of the subjects, using colour duplex ultrasonography and the same congestion pressure protocol.
We used Darcy's Law to predict the limb arterial blood flow and blood flux at each venous congestion pressure, assuming that both mean arterial blood pressure and precapillary resistance remained constant.
The mean ± s.e.m. control arterial blood flow at the lowest venous congestion pressure, 4.8 ± 0.1 mmHg, was 2.77 ± 0.18 ml min−1 (100 ml)−1. At the highest venous congestion pressure, 59.2 ± 0.2 mmHg, arterial blood flow was 2.45 ± 0.35 ml min−1 (100 ml)−1 (121.6 ± 16.9 % of the initial value). This did not differ significantly from the initial control value, but was significantly greater than the predicted value of 0.77 ± 0.13 ml min−1 (100 ml)−1 (28.6 ± 2.1 % of the initial value) calculated assuming constant resistance and sustained mean arterial pressure. The tibial arterial peak blood flux at 58.3 mmHg venous congestion pressure was 102.2 ± 2.3 % of the control value, which was significantly greater than the predicted 17.2 ± 1.3 % of control, calculated for this pressure, assuming constant resistance and sustained mean arterial pressure.
Our data show that lower limb arterial blood flow is sustained when venous congestion pressure is raised using small cumulative steps, even at congestion pressures approaching mean arterial blood pressure. These data support the notion that precapillary resistance is influenced by signals generated at the microvascular and post microvascular levels and transmitted via the endothelium.
Damage to human muscle from eccentric exercise after training with concentric exercise
Authors: Whitehead N. P. , Allen T. J. , Morgan D. L. , Proske U. 
Published: September 2004

It is known that a period of eccentric exercise provides protection against damage to muscle from subsequent eccentric exercise. Here we ask, does concentric exercise do the opposite, make muscle more prone to damage?
The triceps surae muscle group of one leg in each of eight human subjects was subjected to 30 min of concentric exercise per day, for 5 days. At the end of the training period there was a small but significant increase in passive torque in the exercised muscle (P < 0.05), with no changes in the untrained muscle.
After a single period of eccentric exercise, angle‐torque curves for muscles of both legs shifted in the direction of longer muscle lengths, suggestive of an increase in series compliance. The shift in the concentrically trained muscle was significantly greater over the first 48 h post‐exercise (P < 0.05).
The volume of the trained leg increased significantly more than the untrained leg for five subjects over 72 h post‐exercise (P < 0.05). Peak torque fell, passive stiffness increased and both muscles became sore, but with no significant differences between the two legs.
It is concluded that a period of concentric exercise increases the susceptibility of muscle to changes associated with the damage from eccentric exercise.
Exercise‐induced arterial hypoxaemia in healthy young women
Authors: Harms Craig A. , McClaran Steven R. , Nickele Glenn A. , Pegelow David F. , Nelson William B. , Dempsey Jerome A. 
Published: September 2004

We questioned whether exercise‐induced arterial hypoxaemia (EIAH) occurs in healthy active women, who have smaller lungs, reduced lung diffusion, and lower maximal O2 consumption rate (V̇O2,max) than age‐ and height‐matched men.
Twenty‐nine healthy young women with widely varying fitness levels (V̇O2,max, 57 ± 6 ml kg−1 min−1; range, 35‐70 ml kg−1 min−1; or 148 ± 5 %; range, 93‐188 % predicted) and normal resting lung function underwent an incremental treadmill test to VO2,max during the follicular phase of their menstrual cycle. Arterial blood samples were taken at rest and near the end of each workload.
Arterial PO2 (Pa,O2) decreased > 10 mmHg below rest in twenty‐two of twenty‐nine subjects at V̇O2,max (Pa,O2, 77.5 ± 0.9 mmHg; range, 67‐88 mmHg; arterial O2 saturation (Sa,O2), 92.3 ± 0.2 %; range, 87‐94 %). The remaining seven subjects maintained Pa,O2 within 10 mmHg of rest. Pa,O2 at VO2,max was inversely related to the alveolar to arterial O2 difference (A‐aDO2) (r= ‐0.93; 35‐52 mmHg) and to arterial PCO2 (Pa,CO2) (r= ‐0.62; 26‐39 mmHg).
EIAH was inversely related to V̇O2,max (r= ‐0.49); however, there were many exceptions. Almost half of the women with significant EIAH had VO2,max within 15 % of predicted normal values (VO2,max, 40‐55 ml kg−1 min−1); among subjects with very high VO2,max (55‐70 ml kg−1 min−1), the degree of excessive A‐aDO2 and EIAH varied markedly (e.g. A‐aDO2, 30‐50 mmHg; Pa,O2, 68‐91 mmHg).
In the women with EIAH at V̇O2,max, many began to experience an excessive widening of their A‐aDO2 during moderate intensity exercise, which when combined with a weak ventilatory response, led to a progressive hypoxaemia. Inactive, less fit subjects had no EIAH and narrower A‐aDO2 when compared with active, fitter subjects at the same VO2 (40‐50 ml kg−1 min−1).
These data demonstrate that many active healthy young women experience significant EIAH, and at a VO2,max that is substantially less than those in their active male contemporaries. The onset of EIAH during submaximal exercise, and/or its occurrence at a relatively low V̇O2,max, implies that lung structure/function subserving alveolar to arterial O2 transport is abnormally compromised in many of these habitually active subjects.
Dynamic response of human muscle spindle afferents to stretch during voluntary contraction
Authors: Kakuda Naoyuki , Nagaoka Masanori 
Published: September 2004

The response of twenty‐eight human muscle spindle afferents from m. extensor carpi radialis brevis to large amplitude ramp stretch and release at the wrist joint was recorded. The dynamic index was calculated as the difference in firing rate between that just before the end of stretch and that during the subsequent static phase of stretch. The value during steady voluntary contraction was compared with that during relaxation.
In twenty‐three primary afferents, the dynamic index increased in eleven and decreased in twelve afferents with a range of −8 to +25 impulses s−1. In five secondary afferents the change was less than 2 impulses s−1.
The primary afferents abruptly stopped firing when the stretch was released in the relaxed muscle. This cessation was prevented during contraction in seventeen primary afferents.
The results suggest the presence of dynamic and static fusimotor actions on the human muscle spindles during voluntary contraction.
Fast to slow transformation of denervated and electrically stimulated rat muscle
Authors: Windisch A. , Gundersen K. , Szabolcs M. J. , Gruber H. , Lømo T. 
Published: September 2004

Denervated fast extensor digitorum longus (EDL) muscles of adult rats were stimulated electrically for up to 4 months with a ‘slow’ pattern resembling the activity in soleus (Sol) motor units and examined with antibodies against myosin heavy chains (MHCs).
The normal EDL contained, on average, 45 % type IIB, 29 % type IIX, 23 % type IIA and 3 % type I fibres. All type IIB and almost all type IIX fibres disappeared during the first 3 weeks of stimulation. They were replaced by type IIA and type I fibres, whose percentages increased to about 75 and 15, respectively. Type IIA fibres remained at 75 % for nearly 2 months and were then gradually replaced by type I fibres during the next 2 months. The transformation occurred sequentially in the order IIB/IIX → IIA → I, the first step (IIB/IIX → IIA) occurring after a short delay (2 weeks) and the last step (IIA → I in originally IIB or IIX fibres) after a long delay (> 2 months). During the transformation coexpression of MHCs occurred.
It appears that the transformation to type I fibres occurred in pre‐existing type II fibres since no signs of fibre damage or regeneration were observed.
Normal EDL was also stimulated through an intact nerve with the same pattern for up to 37 days. The effects on fibre type distributions were identical to those observed in the denervated EDL. The result indicated that the Sol‐like pattern of evoked muscle activity, rather than nerve‐derived trophic influences or denervation per se, was primarily responsible for the fast to slow transformation.
Effects of voluntary contraction on descending volleys evoked by transcranial stimulation in conscious humans
Authors: Lazzaro V. Di , Restuccia D. , Oliviero A. , Profice P. , Ferrara L. , Insola A. , Mazzone P. , Tonali P. , Rothwell J. C. 
Published: September 2004

The spinal volleys evoked by single transcranial magnetic or electric stimulation over the cerebral motor cortex were recorded from a bipolar electrode inserted into the cervical epidural space of three conscious human subjects. These volleys were termed direct (D) and indirect (I) waves according to their latency.
We measured the size and number of volleys elicited by magnetic stimulation at various intensities with subjects at rest and during 20 or 100 % maximum contraction of the contralateral first dorsal interosseous muscle (FDI). Surface EMG activity was also recorded.
Electrical stimulation evoked a D‐wave volley. Magnetic stimulation at intensities up to about 15 % of stimulator output above threshold evoked only I‐waves. At higher intensities, a D‐wave could be seen in two of the three subjects.
At all intensities tested, voluntary contraction increased the number and size of the I‐waves, particularly during maximum contractions. However, there was only a small effect on the threshold for evoking descending activity. Voluntary contraction produced large changes in the size of EMG responses recorded from FDI.
Because the recorded epidural activity is destined for muscles other than the FDI, it is impossible to say to what extent increased activity contributes to voluntary facilitation of EMG responses. Indeed, our results suggest that the main factor responsible for enhancing EMG responses in the transition from rest to activity is likely to be increased excitability of spinal motoneurones, rather than increases in the corticospinal volley. The latter may be more important in producing EMG facilitation at different levels of voluntary contraction.
4‐Aminomethylbenzoic acid is a non‐translocated competitive inhibitor of the epithelial peptide transporter PepT1
Authors: Meredith D. , Boyd C. A. R. , Bronk J. R. , Bailey P. D. , Morgan K. M. , Collier I. D. , Temple C. S. 
Published: September 2004

4‐Aminomethylbenzoic acid, a molecule which mimics the spatial configuration of a dipeptide, competitively inhibits peptide influx in both Xenopus laevis oocytes expressing rabbit PepT1 and through PepT1 in rat renal brush border membrane vesicles.
This molecule is not translocated through PepT1 as measured both by direct HPLC analysis in PepT1‐expressing oocytes and indirectly by its failure to trans‐stimulate labelled peptide efflux through PepT1 in oocytes and in renal membrane vesicles.
However 4‐aminomethylbenzoic acid does reverse trans‐stimulation through expressed PepT1 of labelled peptide efflux induced by unlabelled peptide. Quantitatively this reversal is compatible with 4‐aminomethylbenzoic acid competitively binding to the external surface of PepT1.
4‐Aminomethylbenzoic acid (the first molecule discovered to be a non‐translocated competitive inhibitor of proton‐coupled oligopeptide transport) and its derivatives may thus be particularly useful as experimental tools.