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J Gallego

Publications and source records attributed to J Gallego.

At least 73 records · Page 4Linked to original sources
PubMed1995

Phenytoin-induced glutathione depletion in rat peripheral nerve.

Administration of high doses (150-250 mg/kg body weight) of phenytoin (DPH) promote a 40% decrease in glutathione (GSH) content of rat sciatic nerve. This DPH-induced GSH depletion is accompanied with an electrophysiological impairment of peripheral neuromuscular function. H7 (20 mg/kg body weight IP, 30 min prior to DPH), a protein kinase C inhibitor, was able to prevent the DPH-induced GSH depletion only at the lower DPH dose used. This same inhibitor completely prevented the electrophysiological impairment at the lower DPH dose, and only partially at the higher DPH dose used. These results confirm the hypothesis of a DPH-dependent activation of PKC (that might be triggered by, or be the consequence of, the reduction of the intracellular antioxidant GSH), as one of the pathophysiological mechanisms involved in DPH-induced neurotoxicity.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

DNA sequence-specific reading by echinomycin: role of hydrogen bonding and stacking interactions.

The binding of echinomycin to DNA hexamers of the form GpApXpZpTpC, where the central XpZ step can be CpG, TpA, GpC, or ApT, has been studied by molecular modeling and molecular mechanics techniques. Interaction energies have also been calculated for the complexation of echinomycin with sequences containing the preferred central CpG step and different flanking base pairs. Besides, two more sets of sequences incorporating either 2,6-diaminopurine (DAP) or hypoxanthine in place of adenine or guanine, respectively, have been examined. The aim of this work was to evaluate the relative importance of hydrogen-bonding and stacking interactions in the association of echinomycin with DNA and further rationalize the experimental evidence. The results of these calculations are in consonance with available data from footprinting experiments and appear to support our previous hypothesis that, in addition to the crucial intermolecular hydrogen bonds in the central region, the stacking interactions involving the quinoxaline-2-carboxamide chromophores of the drug and the DNA base pairs play an important role in modulating the binding specificity of this bisintercalating antitumor antibiotic. This is most clearly seen when sequences with similar minor-groove environments are compared (e.g. CpI vs TpA or CpG vs TpDAP). The dipole moment of N-methylquinoxaline-2-carboxamide has been measured (mu = 4.15 +/- 0.03 D) and compares very well with the calculated value (mu = 4.14 D). The fact that G:C, I:C, A:T, and DAP:T base pairs are shown to be endowed with distinct van der Waals and electrostatic stacking properties with respect to this heteroaromatic ring system could have important implications for the design of novel DNA mono- and bis-intercalating agents.

2-Aminopurine↗
PubMed1994

Ventilatory conditioning by self-stimulation in rats: a pilot study.

This article describes an experimental attempt to condition breathing pattern in rats. In this experiment, a freely moving rat was first rewarded by an electrical stimulation of the medial forebrain bundle whenever inspiratory duration (TI) exceeded 300 ms. A bidirectional control was then used: TIs longer than 400 ms were rewarded, and then TIs shorter than 300 ms were rewarded. The frequency of TIs longer than 300 ms increased when this event was rewarded, further increased when TIs above 400 ms were rewarded, and decreased during reversal conditioning (TI < 300 ms). At the beginning of the experiment, stimulation caused increased arousal and motor activity, but after prolonged conditioning, the brain stimulation was associated with quiet wakefulness. Although the general procedure appears to be well-suited to the experimental study of voluntary breathing, some possible improvements are suggested for further, more extensive investigations.

Animals↗
PubMed1994

Do voluntary changes in inspiratory-expiratory ratio prevent exercise-induced asthma?

It is often admitted that heat exchange in the airways is a major cause of exercise-induced asthma. Because a decrease in the inspiratory time/expiratory time ratio (TI/TE) decreases these exchanges, we postulated that it might decrease bronchoconstriction as well. Twenty-four asthmatic children, divided into three groups, underwent two exercise provocation tests, 24 hours apart (outdoor running for 6 min). The first test was identical for all the subjects. In the second test, the first group did not receive any instruction concerning breathing pattern. The second group was instructed to adopt equal inspiratory and expiratory times (TI/TE = 1). The third group had to adopt an expiratory time three times longer than inspiratory time (TI/TE = 1/3). The three groups displayed similar pulmonary function tests (FEV1 and FVC), cardiac frequency, and running performances. However, FEV1 significantly improved in the second session. This suggested that familiarization with the task and related psychological factors may influence asthma more than voluntary changes in TI/TE.

Adolescent↗
PubMed1994

Measurement of respiratory times in freely moving rats.

A catheter was threaded beneath the skin from the trachea to an opening on the top of the skull. It conducted a small fraction of the ventilatory flow to an external miniaturized transducer, which was composed of a heating element surrounded by two thermocouples. During inspiration, the heating element heated the inner thermocouple, whereas during expiration it heated the outer one. A square signal synchronous with breathing was obtained from the difference in temperature at the two probing sites. Inspiratory and expiratory times were calculated from this signal. This device has been tested with calibrated flows, and compared with head-out plethysmography. It may be easily adapted for ventilatory measurements in any small mammal.

Animals↗
PubMed1994

Performance and learning during voluntary control of breath patterns.

Fourteen subjects learned to adjust their breath pattern to two target breaths displayed on a video screen, by using visual feedback, during two sessions 24 h apart. These two targets were respectively the smallest and the largest breaths of a ten-breath sample previously recorded from each subject's resting spontaneous breathing. Performances were significantly better for the large than for the small target breath. This cannot be directly inferred from current knowledge related to the control of movement time and amplitude, but rather it may be inferred from the periodic character of breathing, to the higher mental load during the small breath task, or to the presumably different frequencies of target breaths in the whole span of spontaneous breathing. In the second session, performance on the two targets levelled out as a result of learning.

Adult↗
PubMed1994

Binding of echinomycin to d(GCGC)2 and d(CCGG)2: distinct stacking interactions dictate the sequence-dependent formation of Hoogsteen base pairs.

Molecular dynamics simulations have been used to explore the behavior of the complexes of echinomycin with the DNA tetramers d(GCGC)2 and d(CCGG)2 in which the terminal bases have been paired according to either a Hoogsteen or a Watson-Crick hydrogen bonding scheme. The energy of the four resulting complexes has been monitored along the dynamics trajectories and the interaction energy between echinomycin and DNA has been decomposed into contributions arising from the planar aromatic systems and the depsipeptide part of the antibiotic. Our calculations predict a large increase in overall stabilization upon protonation of the terminal cytosines and subsequent Hoogsteen pair formation in the complex of echinomycin with d(GCGC)2 but not with d(CCGG)2, in agreement with the experimental evidence [Gao and Patel, Quart. Rev. Biophys. 22, 93-138 (1989)]. The conformational preferences appear to arise mainly from differential stacking interactions in which the electrostatic component is shown to play a dominant role. Differences in hydrogen bonding patterns are also found among the complexes and these are compared in relation to available crystal structures. The binding of echinomycin to DNA appears as a complex process involving many interrelated variables.

Base Composition↗
PubMed1994

Chronic eosinophilic pneumonia as a presenting feature of Churg-Strauss syndrome.

We report on a case of Churg-Strauss syndrome in a 30 year old male with a history of perennial rhinitis. The syndrome began nine months earlier with clinico-radiological features typical of chronic eosinophilic pneumonia. Diagnosis of vasculitis was made by skin biopsy, and at that time there was multisystemic involvement with pulmonary, cardiac, renal, cutaneous and muscular disease, and right vocal chord paralysis, which improved with corticosteroids and cyclophosphamide. This case report illustrates the possible overlap of chronic eosinophilic pneumonia and the Churg-Strauss syndrome.

Adult↗
PubMed1993

A molecular dynamics study of the bis-intercalation complexes of echinomycin with d(ACGT)2 and d(TCGA)2: rationale for sequence-specific Hoogsteen base pairing.

The behavior of the complexes of echinomycin with the DNA tetramers d(ACGT)2 and d(TCGA)2, in which the terminal AT base pairs are in either a Hoogsteen or a Watson-Crick conformation, has been explored by molecular dynamics taking into account experimental data from NMR studies (Gao and Patel. Biochemistry 1988, 27, 1744-1751). The DNA binding specificity of echinomycin appears to be the result of a subtle balance between stabilizing and destabilizing forces. Among the former is a number of hydrogen bonds between the alanine residues of echinomycin and both the N3 and 2-amino groups of the guanine bases which decisively determine the strong affinity of the antibiotic for CpG steps. On the other hand, there appears to be an unfavorable dipolar interaction between the chromophores of the antibiotic and the CpG step. This electrostatic component of the stacking interactions also contributes to explaining the conformational preferences of the flanking sequences: upon Hoogsteen pairing, the dipole moment of an AT base pair is found to increase significantly and alter its relative orientation. In the d(ACGT)2:echinomycin complex, this arrangement helps to improve the stacking interactions with the quinoxaline-2-carboxamide system, but would lead to unfavorable dipolar interactions in the d(TCGA)2 complex. The bearing of these findings on the binding of echinomycin to several sequences as well as on the altered binding selectivity of other members of the quinoxaline family of antibiotics is also discussed.

Amino Acid Sequence↗
PubMed1993

The effect of voluntary breathing on reaction time.

The effect of voluntary changes in inspiratory duration on reaction time was studied in 17 normal subjects. All received a visual feedback on inspiratory duration and successively adjusted this variable to two target values which were respectively higher and slightly lower than resting level. The order of the two tasks was counterbalanced across subjects. Reaction times to auditory stimuli were measured during a key-pressing task immediately after voluntary breathing. Voluntary control of inspiration induced concomitant changes in breathing period and minute ventilation. Per cent changes in these breathing variables and in reaction times under the two conditions were analysed. Correlations were significant for period not for minute ventilation. This effect was probably due to neuromuscular rather than humoral factors.

Adolescent↗
PubMed1993

Learned activation of thoracic inspiratory muscles in tetraplegics.

The aim of this study was to determine whether tetraplegics can learn to activate accessory inspiratory muscles of the upper rib cage, and how this learning affects respiratory motion. Ten tetraplegics with lesional levels ranging from C5 to C7 were trained to increase the upper rib cage expansion during nine 20-min sessions. They were shown an electromyogram (EMG) feedback of the inspiratory muscles of the upper thorax and a signal indicating their current breathing phase (inspiration or expiration). The subjects were instructed to increase EMG during inspiration and to decrease it during expiration. Analysis of variance with session and respiratory phase as factors showed that the subjects progressively learned to increase inspiratory EMG. Thoracic motion, tidal volume and minute ventilation were correlated with inspiratory EMG and tended to increase as a function of practice. These preliminary results lend some support to the clinical use of EMG feedback in breathing therapy aimed at increasing thoracic motion and preventing or reducing paradoxical breathing in tetraplegics.

Adult↗
PubMed1993

Abstraction of covariation in category learning: a critical note on K. Richardson's studies.

Several studies directed by K. Richardson (Richardson, 1986, 1987; Richardson & Carthy, 1989, 1990) claimed that people are able to abstract imperfect covariations among feature variables defining artificial categories, and to use that information in various subsequent tasks. We challenge this claim on a twofold basis. First, a large part of the performance variance Richardson attributed to covariation knowledge may be accounted for by a very simple exemplar model, which assumes no abstractive processes. Second, the residual influence of relational information on performance may be attributed to the knowledge subjects have acquired in real-world situations before their training with the study exemplars.

Analysis of Variance↗
PubMed1992

Prevention of the acute neurotoxic effects of phenytoin on rat peripheral nerve by H7, an inhibitor of protein kinase C.

The neurotoxic effects of a single dose of phenytoin (150 mg/kg body weight) alone or 30 min after H7 (a protein kinase C inhibitor) injection (20 mg/kg body weight) were investigated in terms of peripheral neuromuscular function and Na+,K(+)-ATPase activity of the sciatic nerve. This intraperitoneal injection of phenytoin induced complete blockade of muscle action potentials in the dorsal segmental muscles of the rat tail evoked by electric stimulation of the caudal nerve and a 40% decrease in the Na+,K(+)-ATPase activity of the rat sciatic nerve when compared with control values, measured as the difference between total and ouabain-insensitive ATPase activity. Prior administration of H7 resulted in the complete prevention of both effects. Implications of protein kinase C inhibition in phenytoin neurotoxicity are discussed.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Implications of a consensus recognition site for phosphatidylcholine separate from the active site in cobra venom phospholipases A2.

A model structure of Naja naja kaouthia cobra venom phospholipase A2 has been constructed by utilizing molecular modeling techniques. Analysis of the model and available biochemical data reveal the presence in this enzyme of a putative recognition site for choline derivatives in loop 57-70 made up of residues Trp-61, Tyr-63, Phe-64, and Lys-65, together with Glu-55. The magnitude and shape of the electrostatic potential in this binding site are approximately 80% similar to that in the McPC603 antibody binding site specifically recognizing phosphocholine. Docking studies indicate that the recognition site we now describe and the phosphocholine head of an n-alkylphosphocholine molecule are complementary both sterically and electronically, mainly due to anion-cation and cation-pi interactions. Moreover, binding enthalpies of n-heptylphosphocholine to this site are found to parallel the catalytic rate of pancreatic, mutant pancreatic, and cobra venom phospholipase A2 enzymes acting on dihexanoylphosphatidylcholine micelles, suggesting that it behaves as an activator site. This proposal is in keeping with the "dual phospholipid" model put forward to account for the phenomenon of interfacial activation. This novel site is also shown to be able to discriminate choline derivatives from ethanolamine derivatives, in accord with experimental data. On the basis of the results obtained, two functions are assigned to this putative activator site: (i) desolvation of the lipid-enzyme interface, particularly the surroundings of tyrosine at position 69 (Tyr-63), and (ii) opening of the entrance to the active site by means of a conformational change of Tyr-63 whose chi 2 angle rotates nearly 60 degrees.

Amino Acid Sequence↗
PubMed1991

Effect of practice on the voluntary control of a learned breathing pattern.

Changes in orientation of attention and ventilatory data were examined in three normal volunteers who practiced a learned ventilatory pattern over eight training sessions. The breathing task was a voluntary increase of inspiratory duration up to a given target with the aid of informative feedback on this variable. The orientation of attention was investigated through reaction time (RT) to auditory stimuli presented at different points in inspiration and expiration, during either automatic or voluntary control of breathing. Findings show that RTs are longer during voluntary than automatic breathing throughout the experiment, and that they decrease across sessions in both conditions. In the first sessions, RTs were longer during expiration than inspiration but this difference cancels out in the last sessions. The results are discussed in terms of attentional demands of control of breathing, automatization, and the connection between automatic and voluntary control of breathing. This work shows that after eight practice sessions, the orientation of attention displays significant changes; however, the control of breathing remains attention demanding.

Animals↗
PubMed1991

Electromyographic feedback for learning to activate thoracic inspiratory muscles.

The utility of EMG feedback for modifying the muscular pattern of breathing was investigated in twenty-four subjects divided into two groups (feedback, no feedback. Each took part in three 20-min training sessions, 24 h apart. All the subjects were instructed to increase the thoracic contribution of inspired gas. The feedback subjects were shown an EMG signal of the inspiratory muscles of the upper thorax and a signal indicating their current breathing phase (inspiration or expiration). The no feedback subjects only saw the breathing phase signal. The subjects' ability to control muscular activity was assessed as the relative increase in EMG from expiration to the subsequent inspiration. Analysis of variance with group and session as factors showed that feedback subjects performed significantly better, although the improvement in performance over the sessions by the two groups was not significantly different. These results lend some support to the clinical use of EMG feedback in breathing therapy aimed at changing the thoracoabdominal distribution of ventilation. However, further research for improving learning is necessary.

Adult↗