Biomedical subjects

J Bernal

Publications and source records attributed to J Bernal.

At least 37 records · Page 2Linked to original sources

PubMed2000

Auditory event-related potentials in poor readers.

Although poor readers (PR) are considered the major group among reading-disabled children, there are not event-related potentials (ERP) studies reported of PR on the subject. In this study, attentional and memory processes were studied in an auditory oddball task in PR and normal controls. ERP to auditory stimuli were recorded in 19 leads of the 10/20 system, using linked earlobes as references, in 20 normal children (10 female) and 20 PR (10 female) of the same age (10-12 years old). Two pure tones (1000 and 3000 Hz) were used in an oddball paradigm. No significant differences were observed in the amplitudes and latencies of N100 between the groups. However, N200 to frequent stimuli and P200 to both frequent and infrequent stimuli were of higher amplitude in poor readers than in normal children. There were no differences between groups in the latency and amplitude of P300. The results suggest that PR use more attentional resources in the components occurring before P300 to both frequent and infrequent stimuli than the normal children, and this finding is particularly marked for PR girls.

Child↗

PubMed2000

Primary task demands modulate P3a amplitude.

Auditory event-related brain potentials (ERPs) were recorded from 10 subjects in two different conditions: (1) subjects were required to reorder five visually presented letters in order to form a word and provide a verbal response (task condition); (2) subjects were presented with a control stimulus with the same physical characteristics as the experimental stimulus, but containing just one type of letter (i.e., AAAAA). Subjects had to verbally respond to such stimuli by saying "A" (control condition). Tones of 1000 Hz (standard) and 1050 Hz (deviant) were also presented to the subjects in a 85%-15% probability paradigm 2 s before, during and 8 s after the presentation of the visual stimuli. Recordings were obtained from Fpz, Fz, Cz and Pz vs. linked ears. Auditory ERPs to the auditory stimuli after the presentation of the visual letter string and during the performance of the task were averaged for the standard and deviant tones in both conditions. Only correct responses were considered for the averages. The N100 was affected by stimulus type (standard vs. deviant) but not by condition (task vs. control); however, larger P3a waves were observed during the control than during the task condition. No significant differences between conditions were observed in the mismatch negativity (MMN) latency range. These results suggest that primary task demands modulate involuntary attention processing.

Acoustic Stimulation↗

PubMed1999

Identification of a cis-acting element that interferes with thyroid hormone induction of the neurogranin (NRGN) gene.

The neuron-specific RC3/neurogranin gene is regulated by thyroid hormone at the transcriptional level in brain and in cultured neuronal cells. Regulation in vivo displays exquisite regional selectivity which is not due to differential distribution of thyroid receptors and is most probably related to region-specific trans-acting elements. We have previously identified an intronic thyroid hormone responsive element in the human RC3 gene homolog, NRGN. In a search for cis-acting elements that might contribute to the specificity of thyroid regulation, we have identified a novel sequence, TTCCAAAATGG, which binds to a developmentally regulated protein, and interferes with T3 transactivation.

Animals↗

PubMed1999

Rhes: A striatal-specific Ras homolog related to Dexras1.

We have characterized an apparently full-length cDNA corresponding to a rat mRNA, SE6C, previously identified by subtractive hybridization as being expressed predominantly in the striatal region of the brain. The SE6C mRNA encodes a 266 amino acid protein with significant similarity to members of the Ras-like GTP-binding protein family; thus, we have chosen the name Rhes, for Ras homolog enriched in striatum. The human homolog was found in a genomic sequence from human chromosome 22q13.1 and shares 95% identity with rat Rhes. Among the family of small G-proteins, Rhes shares 62% identity with Dexras1, a mouse dexamethasone-inducible Ras-like protein. Both Rhes and Dexras1 have substantially longer C-termini than other members of the Ras-like small G-protein family. Divergence between the C-terminal sequences of Rhes and Dexras1 suggests that, although their functions are probably similar, they have unique properties. Bacterially expressed Rhes binds GTP, suggesting that the protein indeed has GTPase functionality. Although Rhes was not induced by dexamethasone, its full expression is dependent upon thyroid hormone availability. Its accumulation is postnatal, consistent with the dependence upon thyroid hormone. It is noteworthy that most striatum-"specific" mRNAs characterized to date encode components of signal transduction cascades.

Amino Acid Sequence↗

PubMed1999

Identification of the mammalian homolog of the splicing regulator Suppressor-of-white-apricot as a thyroid hormone regulated gene.

Mammalian brain development is controlled by thyroid hormone through the regulation of target genes. In this study, we describe for the first time that a splicing regulator gene is under thyroid hormone control in the rat brain during the critical period of neuronal differentiation. By differential display, we have identified the mammalian homolog of the Drosophila splicing regulator Suppressor-of-white-apricot (SWAP) as a thyroid hormone-regulated gene in an immortal line of rat neuroblasts, E18 cells. Using Northern blotting and in situ hybridization, we found that expression of SWAP is under thyroid control in the developing rat brain. SWAP gene expression is highest during the first 10 days of life (P0-P10), preferentially in cerebral cortex, cerebellum, subventricular epithelium, piriform cortex, hippocampus, amygdala, and caudate putamen. At later stages (P15-P30) SWAP expression decreases, being detectable only in the cerebellum, hippocampus, and layers II/III of cerebral and piriform cortexes. We found that hypothyroidism causes an abnormal high level of SWAP RNA expression at P5-P15 throughout the brain except the cerebellum. Significantly, thyroid hormone treatment in vivo of hypothyroid animals led to a normalization of SWAP RNA expression. Furthermore, similar hormone treatment caused a decrease in SWAP expression in control rats. By modulating the expression of SWAP and perhaps other splicing regulators thyroid hormone may exert wide regulatory effects on multiple genes. The regulation of SWAP gene defines a novel mechanism of action of thyroid hormone which can be important for its effects in the developing brain.

Amino Acid Sequence↗

PubMed1999

Thyroid hormone regulates reelin and dab1 expression during brain development.

The reelin and dab1 genes are necessary for appropriate neuronal migration and lamination during brain development. Since these processes are controlled by thyroid hormone, we studied the effect of thyroid hormone deprivation and administration on the expression of reelin and dab1. As shown by Northern analysis, in situ hybridization, and immunohistochemistry studies, hypothyroid rats expressed decreased levels of reelin RNA and protein during the perinatal period [embryonic day 18 (E18) and postnatal day 0 (P0)]. The effect was evident in Cajal-Retzius cells of cortex layer I, as well as in layers V/VI, hippocampus, and granular neurons of the cerebellum. At later ages, however, Reelin was more abundant in the cortex, hippocampus, cerebellum, and olfactory bulb of hypothyroid rats (P5), and no differences were detected at P15. Conversely, Dab1 levels were higher at P0, and lower at P5 in hypothyroid animals. In line with these results, reelin RNA and protein levels were higher in cultured hippocampal slices from P0 control rats compared to those from hypothyroid animals. Significantly, thyroid-dependent regulation of reelin and dab1 was confirmed in vivo and in vitro by hormone treatment of hypothyroid rats and organotypic cultures, respectively. In both cases, thyroid hormone led to an increase in reelin expression. Our data suggest that the effects of thyroid hormone on neuronal migration may be in part mediated through the control of reelin and dab1 expression during brain ontogenesis.

Animals↗

PubMed1999

Expression of type 2 iodothyronine deiodinase in hypothyroid rat brain indicates an important role of thyroid hormone in the development of specific primary sensory systems.

Thyroid hormone is an important epigenetic factor in brain development, acting by modulating rates of gene expression. The active form of thyroid hormone, 3,5,3'-triiodothyronine (T3) is produced in part by the thyroid gland but also after 5'-deiodination of thyroxine (T4) in target tissues. In brain, approximately 80% of T3 is formed locally from T4 through the activity of the 5'-deiodinase type 2 (D2), an enzyme that is expressed mostly by glial cells, tanycytes in the third ventricle, and astrocytes throughout the brain. D2 activity is an important point of control of thyroid hormone action because it increases in situations of low T4, thus preserving brain T3 concentrations. In this work, we have studied the expression of D2 by quantitative in situ hybridization in hypothyroid animals during postnatal development. Our hypothesis was that those regions that are most dependent on thyroid hormone should present selective increases of D2 as a protection against hypothyroidism. D2 mRNA concentration was increased severalfold over normal levels in relay nuclei and cortical targets of the primary somatosensory and auditory pathways. The results suggest that these pathways are specifically protected against thyroid failure and that T3 has a role in the development of these structures. At the cellular level, expression was observed mainly in glial cells, although some interneurons of the cerebral cortex were also labeled. Therefore, the T3 target cells, mostly neurons, are dependent on local astrocytes for T3 supply.

Animals↗

PubMed1999

Iodine and brain development.

The development of the brain is critically dependent on an adequate supply of iodine. Iodine is an integral part of thyroid hormone, which acts on brain development by regulating the expression of target genes. The active thyroid hormone, T3, is generated in part in the thyroid gland, but about 80% of T3 in brain is formed locally from T4 deiodination mainly by the action of a specific iodothyronine deiodinase. This enzyme is highly expressed in astrocytes, which take up T4 from the blood and deliver T3 for neuronal use. In the target cells T3 binds to nuclear receptors which are transcription factors. The T3 receptors are expressed in the brain before fetal thyroid gland function and may be activated by maternal thyroid hormone during midgestation. Although a group of thyroid hormone target genes has been identified in recent years, many basic questions of thyroid hormone action in the brain remain to be elucidated.

Animals↗

PubMed1999

N400 and lexical decisions: automatic or controlled processing?

OBJECTIVE: To investigate whether the N400 effect is sensitive to automatic or controlled processes. METHODS: Two experiments were performed. In one experiment, directly related word pairs were used. In the other experiment, mediated-related word pairs were used. In order to reduce controlled processes, each experiment consisted of 3 tasks: Low- and high-proportion of related pairs, and single presentation lexical decision task. RESULTS: In the first experiment, the amount of priming was equivalent for the 3 tasks. The N400 effect appeared in the high and low proportion of directly related words, but not in the single presentation task. In the second experiment, behavioral priming was also found in the 3 tasks. However, the N400 effect was observed only in the task with low proportion of related pairs. CONCLUSION: These results suggest that the N400 effect may be related to controlled processes.

Adult↗

PubMed1999

Identification of a mammalian homologue of the fungal Tom70 mitochondrial precursor protein import receptor as a thyroid hormone-regulated gene in specific brain regions.

Thyroid hormone is an important regulator of mammalian brain maturation. By differential display PCR, we isolated a cDNA clone (S2) that is specifically up-regulated in the striatum of neonatal hypothyroid rats. S2 was identified as KIAA0719, the first human gene distantly homologous to the fungal Tom70, which encodes a member of the translocase mitochondrial outer membrane complex involved in the import of preproteins into the mitochondria. By northern and in situ hybridization studies, KIAA0719 was found to be up-regulated in the striatum, nucleus accumbens, and discrete cortical layers of 15-day-old hypothyroid rats. In contrast, lower expression was found in the olfactory tubercle, whereas no differences were detected in other brain regions. Significantly, treatment of hypothyroid animals with single injections of thyroxine restored the normal levels of KIAA0719 expression. Moreover, treatment of control animals with thyroxine led to a reduced expression, demonstrating a negative hormonal regulation in vivo. Thus, KIAA0719 gene expression is regulated by thyroid hormone in the neonatal rat brain in a region-specific fashion. Given the role of the homologous Tom70 gene, the alteration of KIAA0719 expression may contribute to the changes in mitochondrial morphology and physiology caused by hypothyroidism in the developing rat brain.

Amino Acid Sequence↗

PubMed1999

The human RC3 gene homolog, NRGN contains a thyroid hormone-responsive element located in the first intron.

NRGN is the human homolog of the neuron-specific rat RC3/neurogranin gene. This gene encodes a postsynaptic 78-amino acid protein kinase substrate that binds calmodulin in the absence of calcium, and that has been implicated in dendritic spine formation and synaptic plasticity. In the rat brain RC3 is under thyroid hormone control in specific neuronal subsets in both developing and adult animals. To evaluate whether the human gene is also a target of thyroid hormone we have searched for T3-responsive elements in NRGN cloned genomic fragments spanning the whole gene. Labeled DNA fragments were incubated with T3 receptors (T3R) and 9-cis-retinoic acid receptors and immunoprecipitated using an anti T3R antibody. A receptor-binding site was localized in the first intron, 3000 bp downstream from the origin of transcription. Footprinting analysis revealed the sequence GGATTAAATGAGGTAA, closely related to the consensus T3-responsive element of the direct repeat (DR4) type. This sequence binds the T3R-9-cis-retinoic acid receptors heterodimers, but not T3R monomers or homodimers, and is able to confer regulation by T3R and T3 when fused upstream of the NRGN or thymidine kinase promoters. The data reported in this work suggest that NRGN is a direct target of thyroid hormone in human brain, and that control of expression of this gene could underlay many of the consequences ofhypothyroidism on mental states during development as well as in adult subjects.

Animals↗

PubMed1999

Type 3 iodothyronine deiodinase is selectively expressed in areas related to sexual differentiation in the newborn rat brain.

Thyroid hormone (T4 and T3) concentrations in target tissues are greatly influenced by the activity of iodothyronine deiodinases. Type 1 and 2 deiodinases generate T3 from T4, while deiodinase type 3 (D3) transforms T4 and T3 to inactive metabolites. Coordination of the expression and activity of these enzymes is postulated to play an important role in physiology and development, making it possible that individual cells and tissues regulate the concentrations of the active hormone according to specific needs. We have analyzed the expression of D3 in the neonatal rat brain by in situ hybridization using a specific 35S-labelled riboprobe. At postnatal day 0 D3 transcripts were unexpectedly found to be selectively expressed in areas involved in sexual differentiation of the brain such as the bed nucleus of the stria terminalis and preoptic nuclei. Expression in these areas was transient and was no longer observed at postnatal day 10. These observations suggest that D3 expression is linked to the early mechanism determining sexual function and behavior.

Animals↗

PubMed1999

Broad band spectral EEG parameters correlated with different IQ measurements.

The relationship of IQ (measured by WAIS and all its subscales) and EEG broad band spectral parameters were studied in 40 right-handed, male volunteers ranging in age from 20 to 25 years old. EEGs were recorded in 20 derivations during rest with eyes opened. The results obtained reveal positive and negative correlations with abundant frontal participation in all bands. Mean frequency data show a frequency shift in a very narrow range suggesting that more relations in narrow band could be achieved. These results highlight the need of psychological tests that measure more homogeneous abilities and finer measurement technique to reveal clearly explainable correlations and demonstrate that EEG recordings do reflect intellectual abilities.

Adult↗

PubMed1998

Trifluoperazine enhancement of Ca2+-dependent inactivation of L-type Ca2+ currents in Helix aspersa neurons.

The effects of trifluoperazine hydrochloride (TFP), a calmodulin antagonist, on L-type Ca2+ currents (L-type ICa2+) and their Ca(2+)-dependent inactivation, were studied in identified Helix aspersa neurons, using two microelectrode voltage clamp. Changes in [Ca2+]i were measured in unclamped fura-2 loaded neurons. Bath applied TFP produced a reversible and dose-dependent reduction in amplitude of L-type ICa2+ (IC50 = 28 microM). Using a double-pulse protocol, we found that TFP enhances the efficacy of Ca(2+)-dependent inactivation of L-type ICa2+. Trifluoperazine sulfoxide (50 microM), a TFP derivative with low calmodulin-antagonist activity, did not have any effects on either amplitude or inactivation of L-type ICa2+. TFP (20 microM) increased basal [Ca2+]i from 147 +/- 37 nM to 650 +/- 40 nM (N = 7). The increase in [Ca2+]i was prevented by removal of external Ca2+ and curtailed by depletion of caffeine-sensitive intracellular Ca2+ stores. Since TFP may also block protein kinase C (PKC), we tested the effect of a PKC activator (12-C-tetradecanoyl-phorbol-13-acetate) on L-type Ca2+ currents. This compound produced an increase in L-type ICa2+ without enhancing Ca(2+)-dependent inactivation. The results show that 1) TFP reduces L-type ICa2+ while enhancing the efficacy of Ca(2+)-dependent inactivation. 2) TFP produces an increase in basal [Ca2+]i which may contribute to the enhancement of Ca(2+)-dependent inactivation. 3) PKC up-regulates L-type ICa2+ without altering the efficacy of Ca(2+)-dependent inactivation. 4) The TFP effects cannot be attributed to its action as PKC blocker.

Animals↗

PubMed1998

Vitamin D3 inhibits proliferation and increases c-myc expression in fibroblasts from psoriatic patients.

Fibroblast cultures were established from the skin of normal and psoriatic subjects. The response to 1 alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] of each kind of cells was assessed by measuring tritiated thymidine incorporation into DNA as an index of cell proliferation. We found that both types of cells responded with a similar dose- and time-dependent inhibition of thymidine incorporation. We also studied the response of the mRNA encoding the proto-oncogene c-myc, since its level is associated to the proliferative state in many cell types. Psoriatic fibroblasts contained higher basal amounts of c-myc RNA than control fibroblasts. Addition of 1,25-(OH)2D3 to the culture medium induced a time-dependent increase of c-myc RNA in psoriatic fibroblasts but not in controls. As a control, retinoic acid had no effect in any of the two cell types. It is concluded that in primary normal human fibroblasts, c-myc RNA levels are not correlated with the proliferative state, and that there is an altered expression of this proto-oncogene in psoriasis.

Adult↗

PubMed1998

Identification of a thyroid hormone response element in the promoter region of the rat lipocalin-type prostaglandin D synthase (beta-trace) gene.

We have previously reported that mRNA levels for the rat lipocalin-type prostaglandin (PG) D synthase/beta-trace (PGDS) gene, the enzyme responsible for the production of PGD2 in the central nervous system, are regulated by thyroid hormone in vivo. In this study, we describe the identification of a thyroid hormone (T3) response element (T3RE) in the 5'-flanking region of the rat PGDS gene. By radioimmunoprecipitation of genomic fragments using thyroid hormone receptor (TR) protein and specific anti-TR antibodies, gel-shift, foot-printing, mutational analysis, and transactivation assays we have identified a spaced four imperfect direct repeat (DR4) element, GGTTCACTTCAGGGTA (positions -586/-571), which functions as a T3RE when fused to a heterologous promoter. Our results suggest that thyroid hormone regulates the expression of the rat lipocalin-type PGDS gene through this element. Remarkably, the element identified also confers regulation by retinoic acid. Giving the important roles proposed for the PGDS enzyme and its product, PGD2, the major PG in the mammalian brain, the altered expression of the PGDS gene may contribute to the deleterious effects of hypothyroidism in the central nervous system.

5' Untranslated Regions↗

PubMed1998

Developmental expression of the tenascin-C is altered by hypothyroidism in the rat brain.

Tenascin-C is an extracellular matrix glycoprotein involved in cell adhesion and migration, and neurite outgrowth. Since these processes have been found to be under thyroid control in the developing rat brain, we have investigated the effect of congenital hypothyroidism on tenascin-C expression. At birth, in situ hybridization studies in hypothyroid rats show an abnormal up-regulation of tenascin-C in some areas (caudate-putamen, geniculate nuclei, ependymal epithelium of the lateral ventricles, hippocampus) and down-regulation in others (occipital and retrosplenial cortex, subiculum). With subsequent development, hypothyroid animals show higher tenascin-C expression also in the upper layers of the cerebral cortex and subplate, and the Bergmann glia of the cerebellum. Significantly, thyroxine treatment of hypothyroid rats led to normalization of tenascin-C levels in most areas. In agreement with the messenger RNA data, hypothyroid rats contain an uniformly higher level of immunoreactive tenascin-C protein throughout the brain, particularly in the cerebellum. Suggesting a direct cellular effect, thyroid hormone also decreases tenascin-C expression in two glial cell lines (C6, B3.1) expressing thyroid receptors. Our results show that congenital hypothyroidism causes specific alterations in the pattern of tenascin-C expression in the rat brain which may at least partially be responsible for some of the developmental disturbances observed in this syndrome.

Aging↗

PubMed1998

Pericardial fluid postmortem: Comparative study of natural and violent deaths.

Thanatochemistry is an increasingly important ancillary procedure in forensic practice. Alterations are known to take place in biochemical components during the postmortem period, particularly in the blood, and both research results and their interpretation have been the object of some controversy. For that reason, emphasis has been placed on the examination of fluids that are neither altered nor contaminated as rapidly as blood after death. This study tested the hypothesis that pericardial fluid (PF) may be a suitable medium for biochemical analysis in corpses. The study sought to determine concentrations of urea, creatinine, glucose, creatinine kinase 2, proteins, calcium, sodium, and potassium, in the pericardial fluid of corpses. The study sample was divided into two groups, natural deaths and violent deaths. Intergroup results were compared, using Mann-Whitney's U test for paired data. No significant differences were obtained between the natural death and violent death groups for the parameters studied, with the exception of urea (p < .05). Further studies are required to compare these results and create the possibility for new conclusions.

Autopsy↗