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Biomedical subjects

J Aguilar

Publications and source records attributed to J Aguilar.

At least 37 records · Page 2Linked to original sources
PubMed2000

Sensorimotor cortical influences on cuneate nucleus rhythmic activity in the anesthetized cat.

This work aimed to study whether the sensorimotor cerebral cortex spreads down its rhythmic patterns of activity to the dorsal column nuclei. Extracellular and intracellular recordings were obtained from the cuneate nucleus of chloralose-anesthetized cats. From a total of 140 neurons tested (106 cuneolemniscal), 72 showed spontaneous rhythmic activity within the slow (< 1 Hz), delta (1-4 Hz), spindle (5-15 Hz) and higher frequencies, with seven cells having the delta rhythm coupled to slow oscillations. The spindle activity recorded in the cuneate was tightly coupled to the thalamo-cortico-thalamic spindle rhythmicity. Bilateral or contralateral removal of the frontoparietal cortex abolished the cuneate slow and spindle oscillations. Oscillatory paroxysmal activity generated by fast electrical stimulation (50-100 Hz/1-2 s) of the sensorimotor cortex induced burst firing synchronized with the paroxysmal cortical "spike" on all the non-lemniscal neurons, and inhibitory responses also coincident with the cortical paroxysmal "spike" in the majority (71%) of the cuneolemniscal cells. The remaining lemniscal-projecting neurons showed bursting activity (11%) or sequences of excitation-inhibition (18%) also time-locked to the cortical paroxysmal "spike". Additionally, the cerebral cortex induced coherent oscillatory activity between thalamic ventroposterolateral and cuneate neurons. Electrolytic lesion of the pyramidal tract abolished the cortically induced effects on the contralateral cuneate nucleus, as well as on the ipsilateral medial lemniscus. The results demonstrate that the sensorimotor cortex imposes its rhythmic patterns on the cuneate nucleus through the pyramidal tract, and that the corticocuneate network can generate normal and abnormal patterns of synchronized activity, such as delta waves, spindles and spike-and-wave complexes. The cuneate neurons, however, are able to generate oscillatory activity above 1 Hz in the absence of cortical input, which implies that the cerebral cortex probably imposes its rhythmicity on the cuneate by matching the intrinsic preferred oscillatory frequency of cuneate neurons.

Animals↗
PubMed2000

Chronic liver injury related to use of bentazepam: an unusual instance of benzodiazepine hepatotoxicity.

Liver injury induced by benzodiazepines is rare and is classified as an unpredictable or idiosyncratic hepatotoxic reaction. Early reports indicated that in most cases the pattern of liver injury was cholestatic. We describe three patients with persistent increases in liver transaminase levels after several weeks of treatment with bentazepam, a benzodiazepine marketed in Spain for anxiety disorders. In all cases withdrawal of the drug was followed by resolution of transaminase level abnormalities. A liver biopsy (done in one patient only) showed histological evidence of severe chronic active hepatitis. In conclusion, these findings, together with two previously published case reports, suggest that a benzodiazepine can cause chronic hepatitis and argue in favor of using liver function tests to monitor all patients taking bentazepam.

Administration, Oral↗
PubMed2000

Spatial and cortical influences exerted on cuneothalamic and thalamocortical neurons of the cat.

This work aimed to study the responses of cuneothalamic and thalamocortical cells to electrical stimulation of the body surface in alpha-chloralose-anaesthetized cats. It was found that both classes of cells had a central excitatory receptive field, an edge overlapping the field centre whose stimulation elicited inhibitory-excitatory (cuneothalamic cells) and excitatory-inhibitory (thalamocortical cells) sequences, and a surrounding or peripheral area usually being inhibitory. Manipulating the descending corticofugal activity by removing the fronto-parietal cortex, electrical stimulation, or by placing picrotoxin or muscimol over the sensorimotor cortex demonstrated that the cortical feedback potentiated effects driven from the field centre and the surround. In particular this potentiated centre-driven excitation and surround-driven inhibition, but some of the data points to more complex patterns. The inhibition elicited in cuneothalamic cells from the edge and the surround of the field was faster than the excitation induced from the field centre. Effects at the edge of the field centre included late excitatory responses relayed via the cerebral cortex. There were also direct corticofugal excitatory inputs to the field centre. Excitatory surrounds were occasionally observed, the assumption being that in most cases these were suppressed by the enhanced inhibition driven from the cortex. The data indicate that the cortico-subcortical feedback contributes not only to enhance the surround antagonism of a centre response but also to increase the time resolution of thalamic and cuneate relay somesthetic neurons.

Action Potentials↗
PubMed2000

Regulation of expression of the yiaKLMNOPQRS operon for carbohydrate utilization in Escherichia coli: involvement of the main transcriptional factors.

The yiaKLMNOPQRS (yiaK-S) gene cluster of Escherichia coli is believed to be involved in the utilization of a hitherto unknown carbohydrate which generates the intermediate L-xylulose. Transcription of yiaK-S as a single message from the unique promoter found upstream of yiaK is proven in this study. The 5' end has been located at 60 bp upstream from the ATG. Expression of the yiaK-S operon is controlled in the wild-type strain by a repressor encoded by yiaJ. No inducer molecule of the yiaK-S operon has been identified among over 80 carbohydrate or derivative compounds tested, the system being expressed only in a mutant strain lacking the YiaJ repressor. The lacZ transcriptional fusions in the genetic background of the mutant strain revealed that yiaK-S is modulated by the integration host factor and by the cyclic AMP (cAMP)-cAMP receptor protein (Crp) activator complex. A twofold increase in the induction was observed during anaerobic growth, which was independent of ArcA or Fnr. Gel mobility shift assays showed that the YiaJ repressor binds to a promoter fragment extending from -50 to +121. These studies also showed that the cAMP-Crp complex can bind to two different sites. The lacZ transcriptional fusions of different fragments of the promoter demonstrated that binding of cAMP-Crp to the Crp site 1, centered at -106, is essential for yiaK-S expression. The 5' end of the yiaJ gene was determined, and its promoter region was found to overlap with the divergent yiaK-S promoter. Expression of yiaJ is autogenously regulated and reduced by the binding of Crp-cAMP to the Crp site 1 of the yiaK-S promoter.

Amino Acid Sequence↗
PubMed2000

Role of the yiaR and yiaS genes of Escherichia coli in metabolism of endogenously formed L-xylulose.

Genes yiaP and yiaR of the yiaKLMNOPQRS cluster of Escherichia coli are required for the metabolism of the endogenously formed L-xylulose, whereas yiaS is required for this metabolism only in araD mutants. Like AraD, YiaS was shown to have L-ribulose-5-phosphate 4-epimerase activity. Similarity of YiaR to several 3-epimerases suggested that this protein could catalyze the conversion of L-xylulose-5-phosphate into L-ribulose-5-phosphate, thus completing the pathway between L-xylulose and the general metabolism.

Carbohydrate Epimerases↗
PubMed2000

A common regulator for the operons encoding the enzymes involved in D-galactarate, D-glucarate, and D-glycerate utilization in Escherichia coli.

Genes for D-galactarate (gar) and D-glucarate (gud) metabolism in Escherichia coli are organized in three transcriptional units: garD, garPLRK, and gudPD. Two observations suggested a common regulator for the three operons. (i) Their expression was triggered by D-galactarate, D-glucarate, and D-glycerate. (ii) Metabolism of the three compounds was impaired by a single Tn5 insertion mapped in the yaeG gene (proposed name, sdaR), outside the D-galactarate and D-glucarate systems. Expression of the sdaR gene is autogenously regulated.

Chromosome Mapping↗
PubMed2000

[Nutritional evaluation of Lepidium meyenii (MACA) in albino mice and their descendants].

The Maca (Lepidium meyenii) is a Peruvian hypocotyl that grows exclusively between the 3700 and 4500 masl at the Peruvian Andes. Traditionally it is attributed nutritional, energizing, fertilizing properties among others. With the purpose of evaluate scientifically the nutritional property of Maca, we carried out a controlled study in two generations of albino Swiss mice (parents and breeding). The parents were aleatorily assigned to one of three nutritional schedules. The food of each group was prepared based on powder from a commercial balanced food (CBF) of which 30% was replaced by raw or cooked Maca according to the corresponding group or pure CBF in the control group. The groups were this way: 1) Raw Maca Group; 2) Cooked Maca Group; and, 3) Control Group. The results showed that the curves of growth were similar and adequate for the three groups. However, the cooked Maca group showed the best curve. These data were better observable in the second generation of animals, with significant statistical difference (p < 0.05). The CBF group had a better growth than raw Maca group. No signs of malnutrition nor overweight were observed in none of the groups. The serum values of total proteins and albumin were statistically superior for the mice group eating cooked Maca than that of the raw Maca and CBF groups. This study demonstrates, in a scientifical evaluation, one of the traditionally attributed properties of Maca, the nutritional capability.

Animal Nutritional Physiological Phenomena↗
PubMed2000

Multicenter retrospective study of response to interferon in chronic hepatitis B.

AIM: The only agent known to have a lasting beneficial effect in chronic hepatitis B is interferon alpha, which achieves long-term remission in 25-40% of the patients. The goals of treatment are to induce clearance of HBV DNA from serum, to return serum aminotransferases to normal, and to improve histological findings in the liver. The most important factors predictive of response to treatment are high serum aminotranferases levels, low serum HBV DNA concentrations, and active histologic changes on liver biopsy. The aim of this study was to assess the response to interferon alpha in patients with chronic hepatitis B and to analyze the factors predictive of response. METHODS: We conducted a multicenter retrospective study to investigate the effect of interferon treatment in 132 patients with chronic hepatitis B in overall terms and based on HBeAg, and factors predictive of response. RESULTS: A overall sustained response was noted in 59 of 132 interferon-treated patients (45%) and 61 patients were nonresponders (46%). 12 patients relapsed (9%). None of the patients had negative HBsAg. No difference was observed in the response rate between the two treatment groups (HBeAg-positive and HBeAg-negative patients). Overall, high initial levels of serum AST and ALT predicted a good response. Age and liver biopsy findings were factors predictive of response in HBeAg-positive and HBeAg-negative patients respectively. Sex, epidemiological factors, treatment and type of virus did not correlate with the response to interferon. CONCLUSIONS: A sustained response to interferon alpha was observed in 45% of the patients with chronic hepatitis B. HBeAg seroconversion was found in up to 50% of HBeAg-positive patients. None of the patients had negative HBsAg. Overall, the response rate was higher in patients with high pretreatment serum aminotransferase levels. Age was the predictive factor in HBeAg-positive patients, and histological features were predictive in the HBeAg-negative group. However, further studies in a larger patient population are necessary to obtain well-substantiated conclusions.

Adolescent↗
PubMed1999

Pollution of soils by the toxic spill of a pyrite mine (Aznalcollar, Spain).

On 25 April 1998 the retention walls broke open in a pond containing the residues from a pyrite mine of Aznalcollar (southern Spain), spilling some 45 x 10(5) m3 of polluted water and toxic tailings into the Agrio and Guadiamar River basin, affecting some 55 km2. On 5 May, seven sectors in the affected area were studied, analysing tailings, polluted water, and contaminated as well as uncontaminated soils. The principal pollutants were: Zn, Pb, Cu, As, Sb, Bi, Cd and Tl. The range of total contamination of each element was extremely broad, as penetration of the tailings depended on the soil characteristics. Most of the Cu, Zn and Cd penetrated the soil in the solution phase of the spill, while the other elements penetrated mostly as part of the solid phase. Zn exceeded the maximum concentrations permitted by the international community in four of the seven sectors studied, As in three, and the other elements only in one sector. Drying and consequent aeration of the tailings rapidly oxidized sulphides to sulphates, lowered the pH and solubilized the pollutants. Therefore, future rains could aggravate the pollution problem, if the tailings are not quickly removed.

Accidents, Occupational↗
PubMed1999

Cytidine diphosphate choline administration activates brain cytidine triphosphate: phosphocholine cytidylytransferase in aged rats.

Beneficial effects of cytidine (5') diphosphocholine (CDP-choline) administration on several diseases including brain aging, ischemia and stroke are based on an increase in membrane phospholipid turnover. We have studied the possible involvement of CTP:phosphocholine cytidylyltransferase (CT) in this mechanism by measuring its gene expression and enzyme activity in the brains of young and aged rats treated with 500 mg/kg per day of CDP-choline. Older animals showed higher (57%) of total CT activity in particulate (active) fraction than younger animals (46%). Treatment of aged animals for 8, 16, or 60 days had no effect on the CT gene expression but increased activation of the CT by translocation to membranes. The particulate fraction rose from 57% of total activity to more than 65% after 2 months of treatment. This may explain the long-term repairing effects of CDP-choline on damaged membranes of aged animals.

Age Factors↗
PubMed1999

Cross-induction of glc and ace operons of Escherichia coli attributable to pathway intersection. Characterization of the glc promoter.

The metabolic pathways specified by the glc and ace operons in Escherichia coli yield glyoxylate as a common intermediate, which is acted on by two malate synthase isoenzymes: one encoded by glcB and the other by aceB. Null mutations in either gene exhibit no phenotype, because of cross-induction of the ace operon by glycolate and the glc operon by acetate. In this study, the regulation of the glc operon, comprising the structural genes glcDEFGB, was analyzed at the molecular level. This operon, activated by growth on glycolate, is transcribed as a single message and is under the positive control of GlcC encoded by a divergent gene. Expression of the glc operon is strongly dependent on the integration host factor (IHF) and is repressed by the global respiratory regulator ArcA-P. In vitro gel-shift experiments demonstrated direct binding of the promoter DNA to IHF and ArcA-P. Mutant analysis indicated that cross-induction of the glc operon by acetate is mediated by the GlcC protein that recognizes the compound as an alternative effector. The similar pattern of regulation of the Glc and Ace systems by IHF and ArcA-P ensures their effective cross-induction.

Acetic Acid↗
PubMed1999

A mutational study of the ArcA-P binding sequences in the aldA promoter of Escherichia coli.

The aldA gene (encoding aldehyde dehydrogenase) of Escherichia coli is anaerobically repressed by ArcA-P, the phosphorylated response regulator of the ArcB/A two-component signal transduction system. The promoter region of aldA contains two 10-bp sequences (5'-TGTTAATTAA-3') that perfectly match the proposed ArcA-P binding consensus (5'-[A/T]GTTAATTA[A/T]-3'). One consensus sequence is on the coding strand (-13 to -4 from the transcriptional start point), whereas the other is on the template strand (position -2 to -11). In this study we used the aldA promoter to test the validity of the proposed consensus sequence. DNase I protection experiments confirmed the 10-bp sequence to be a strong ArcA-P binding site. Alteration of the wild-type sequence from 5'-TGTTAATTAAC-3' to 5'-TCTTAATTAAG-3' or 5'-TATTAATTAAT-3' by site-directed mutagenesis markedly decreased the in vitro affinity of the promoter region for ArcA-P, and abolished the anaerobic repression of mutant att lambda::phi (aldA'-lacZ) transcriptional reporter constructs. Both the in vitro and in vivo results therefore support the proposed consensus sequence.

Aldehyde Dehydrogenase↗
PubMed1999

Cortico-subcortical synchronization in the chloralose-anesthetized cat.

The spontaneous and paroxysmal cerebral cortical synchronized activity was used as reference to study the cortical impact exerted on subcortical neurons. The sensorimotor cortical synchronized activity spread down to subcortical structures receiving direct cortical input, including neuronal populations that originate descending rubrospinal, tectospinal and reticulospinal motor axons, and to a somatosensory relay station, the cuneate nucleus. Lesion of the pyramidal tract abolished the cortically induced synchronization of the activity of contralateral cuneate nucleus neurons.

Anesthesia, Intravenous↗
PubMed1999

Safety and immunogenicity of heptavalent pneumococcal CRM197 conjugate vaccine in infants and toddlers.

OBJECTIVES: The objectives of this study were (1) to determine the safety and immunogenicity of heptavalent pneumococcal CRM197 conjugate (PNCRM7) vaccine in infants and (2) to determine the effect of concurrent hepatitis B immunization during the primary series and the effect of concurrent diphtheria and tetanus toxoid and acellular pertussis [DTaP (ACEL-IMUNE)] and conjugate CRM197 Haemophilus influenzae type b [HbOC (HibTITER) immunization at time of the booster dose on the safety and immunogenicity of PNCRM7and these other concurrently administered vaccines. METHODS: This was a randomized double-blinded study in 302 healthy infants in the Northern California Kaiser Permanente (NCKP) Health Plan. Infants received either PNCRM7 vaccine or meningococcal group C conjugate vaccine as a control at 2, 4 and 6 months of age and a booster at 12 to 15 months of age. Study design permitted the evaluation of immunology and safety of concurrent administration of routine vaccines. Antibody titers were determined on blood samples drawn before and 1 month after the primary series and the booster dose. RESULTS: After the third dose of PNCRM7 geometric mean concentrations (GMCs) ranged from 1.01 for serotype 9V to 3.72 microg/ml for serotype 14. More than 90% of all subjects had a post-third dose titer of > or =0.15 microg/ml for all serotypes, and the percentage of infants with a post-third dose titer of > or =1.0 microg/ml ranged from 51% for type 9V to 89% for type 14. After the PNCRM7 booster dose, the GMCs of all seven serotypes increased significantly over both post-Dose 3 and pre-Dose 4 antibody levels. In the primary series there were no significant differences in GMCs of pneumococcal antibodies between the subjects given PN-CRM7 alone or concurrently with hepatitis B vaccine. At the toddler dose concurrent administration of PNCRM7 and DTaP and HbOC resulted in a near conventional threshold for statistical significance of a post-Dose 4 GMC for serotype 23F [alone 6.75 mirog/ml vs. concurrent 4.11 microg/ml (P = 0.057)] as well as significantly lower antibody GMCs for H. influenza polyribosylribitol phosphate, diphtheria toxoid, pertussis toxin and filamentous hemagglutinin. For all antigens there were no differences between study groups in defined antibody titers that are considered protective. CONCLUSION: We conclude that PNCRM7 vaccine was safe and immunogenic. When this vaccine was administered concurrently at the booster dose with DTaP and HbOC vaccines, lower antibody titers were noted for some of the antigens when compared with the antibody response when PNCRM7 was given separately. Because the GMCs of the booster responses were all generally high and all subjects achieved similar percentages above predefined antibody titers, these differences are probably not clinically significant.

Antibodies, Bacterial↗
PubMed1999

Genetic analysis of a chromosomal region containing genes required for assimilation of allantoin nitrogen and linked glyoxylate metabolism in Escherichia coli.

Growth experiments with Escherichia coli have shown that this organism is able to use allantoin as a sole nitrogen source but not as a sole carbon source. Nitrogen assimilation from this compound was possible only under anaerobic conditions, in which all the enzyme activities involved in allantoin metabolism were detected. Of the nine genes encoding proteins required for allantoin degradation, only the one encoding glyoxylate carboligase (gcl), the first enzyme of the pathway leading to glycerate, had been identified and mapped at centisome 12 on the chromosome map. Phenotypic complementation of mutations in the other two genes of the glycerate pathway, encoding tartronic semialdehyde reductase (glxR) and glycerate kinase (glxK), allowed us to clone and map them closely linked to gcl. Complete sequencing of a 15.8-kb fragment encompassing these genes defined a regulon with 12 open reading frames (ORFs). Due to the high similarity of the products of two of these ORFs with yeast allantoinase and yeast allantoate amidohydrolase, a systematic analysis of the gene cluster was undertaken to identify genes involved in allantoin utilization. A BLASTP search predicted four of the genes that we sequenced to encode allantoinase (allB), allantoate amidohydrolase (allC), ureidoglycolate hydrolase (allA), and ureidoglycolate dehydrogenase (allD). The products of these genes were overexpressed and shown to have the predicted corresponding enzyme activities. Transcriptional fusions to lacZ permitted the identification of three functional promoters corresponding to three transcriptional units for the structural genes and another promoter for the regulatory gene allR. Deletion of this regulatory gene led to constitutive expression of the regulon, indicating a negatively acting function.

Allantoin↗
PubMed1999

Inactive and temperature-sensitive folding mutants of aldehyde dehydrogenase of Escherichia coli.

Aldehyde dehydrogenase, encoded by the aldA gene in Escherichia coli, is inactive in nitrosoguanidine induced mutant strain ECL40 and temperature-sensitive in spontaneous mutant strain JA104. Both mutants were proven, by complementation experiments, to have a functional aldA regulator and promoter. In spite of no immunodetection of the aldA product, its specific transcript was present in the mutant extracts. It was subsequently proven that the immunodetection of aldehyde dehydrogenase in these mutants required denaturation, revealing that cells lacking the enzyme activity had the inactive protein in their extracts. Thus, the mutations seemed to affect the protein conformation. The temperature-sensitive aldehyde dehydrogenase did not show, neither in vivo nor in vitro, a different thermal stability compared to the wild type enzyme. In this temperature-sensitive strain, the recovery of active aldehyde dehydrogenase, in the presence of rifampicin but not of chloramphenicol, when cells grown at 37 degrees C were shifted to 30 degrees C indicated that this mutation affected the folding process of the protein at the restrictive temperature. Sequencing of the two mutant aldA corresponding genes determined a single amino acid change of Pro to Leu at position 182 for strain ECL40, and of Val to Met at position 145 for strain JA104. These mutations were thought to possibly promote changes in the local flexibility in the first case, and to perturb the packing of residues by steric hindrance in the second case.

Aldehyde Dehydrogenase↗
PubMed1998

Site-directed mutagenesis studies of the metal-binding center of the iron-dependent propanediol oxidoreductase from Escherichia coli.

The amino acid residues involved in the metal-binding site in the iron-containing dehydrogenase family were characterized by the site-directed mutagenesis of selected candidate residues of propanediol oxidoreductase from Escherichia coli. Based on the findings that mutations H263R, H267A and H277A resulted in iron-deficient propanediol oxidoreductases without catalytic activity, we identified three conserved His residues as iron ligands, which also bind zinc. The Cys362, a residue highly conserved among these dehydrogenases, was considered another possible ligand by comparison with the sequences of the medium-chain dehydrogenases. Mutation of Cys362 to Ile, resulted in an active enzyme that was still able to bind iron, with minor changes in the Km values and decreased thermal stability. Furthermore, in an attempt to produce an enzyme specific only for the zinc ion, three mutations were designed to mimic the catalytic zinc-binding site of the medium-chain dehydrogenases: (1) V262C produced an enzyme with altered kinetic parameters which nevertheless retained a significant ability to bind both metals, (2) the double mutant V262C-M265D was inactive and too unstable to allow purification, and (3) the insertion of a cysteine at position 263 resulted in a catalytically inactive enzyme without iron-binding capacity, while retaining the ability to bind zinc. This mutation could represent a conceivable model of one of the steps in the evolution from iron to zinc-dependent dehydrogenases.

Alcohol Oxidoreductases↗