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J Bernal

Publications and source records attributed to J Bernal.

At least 55 records · Page 3Linked to original sources
PubMed1998

Morphometry of the human splenic artery: muscular columns, morphofunctional aspects and developmental implications.

There is a paucity of studies in the literature concerning the structural characteristics of the arterial wall in the abdominal region using human material and specialized morphometric techniques. In the present study we carry out the morphometric study, describing a series of structural peculiarities in 12 segments of the human splenic artery. Among these the presence of length-wise or spiral-shaped muscular columns in the medial layer which mark and reduce the diameter of the arterial lumen is of major importance. In its underlying intima small localized thickenings appear which, with age may become generalized. We also analyze the different intimal thickenings and such indices as the Intimal Thickening Index, Lumen Reduction Index and Pathologic Thickening Index, with differences among the groups we have considered. The study of elastin in the various parietal structures help us to understand the possible pathogenesis of the thickenings, and to clarify the important morphological-functional correlation for the regulation of blood flow which exists in this arterial region.

Adolescent↗
PubMed1997

Transcriptional induction of RC3/neurogranin by thyroid hormone: differential neuronal sensitivity is not correlated with thyroid hormone receptor distribution in the brain.

RC3/neurogranin is a calmodulin-binding protein kinase C substrate, located in dendritic spines of forebrain neurons. It has been implicated in post-synaptic signal transduction events involving Ca2+ and calmodulin leading to many forms of synaptic plasticity. RC3 gene expression is under developmental and physiological regulation. The main physiological regulator appears to be thyroid gland activity. Hypothyroidism decreased RC3 mRNA concentration in the brain of post-natal day 22 rats. The affected areas included layer 6 of cerebral cortex, layers 2-3 of retrosplenial cortex, dentate gyrus and the caudate whereas others were not affected by hypothyroidism, such as upper layers of cerebral cortex, the pyramidal layer of the hippocampus and the amygdala. A single administration of triiodothyronine (T3) induced a significant transcriptional increase of RC3 mRNA in hypothyroid rats, 24 h after administration. Differential sensitivity to thyroid hormone was not related to differential expression of T3 receptor isoforms or the T3 receptor inhibitory variant alpha2. Therefore, it is likely that cell sensitivity to thyroid hormone in the brain depends on T3 receptor-associated factors.

Animals↗
PubMed1997

The type 2 iodothyronine deiodinase is expressed primarily in glial cells in the neonatal rat brain.

Thyroid hormone plays an essential role in mammalian brain maturation and function, in large part by regulating the expression of specific neuronal genes. In this tissue, the type 2 deiodinase (D2) appears to be essential for providing adequate levels of the active thyroid hormone 3,5,3'-triiodothyronine (T3) during the developmental period. We have studied the regional and cellular localization of D2 mRNA in the brain of 15-day-old neonatal rats. D2 is expressed in the cerebral cortex, olfactory bulb, hippocampus, caudate, thalamus, hypothalamus, and cerebellum and was absent from the white matter. At the cellular level, D2 is expressed predominantly, if not exclusively, in astrocytes and in the tanycytes lining the third ventricle and present in the median eminence. These results suggest a close metabolic coupling between subsets of glial cells and neurons, whereby thyroxine is taken up from the blood and/or cerebrospinal fluid by astrocytes and tanycytes, is deiodinated to T3, and then is released for utilization by neurons.

Animals↗
PubMed1997

Structure, organization, and chromosomal mapping of the human neurogranin gene (NRGN).

In this report the identification, structure, and chromosomal localization of the human neurogranin gene (NRGN) are described. NRGN is the human homolog of the rat Ng/RC3 gene, which encodes a brain-specific protein expressed in telencephalic neurons. The human NRGN gene spans approximately 12 kb and contains four exons and three introns. All splice acceptor and donor sites conform to the canonical AG/GT rule. Human neurogranin sequence predicts a 78-amino-acid protein with 5 amino acids encoded by exon 1 and the remaining 73 amino acids encoded by exon 2. The third and fourth exons contain untranslated sequences. The overall degree of homology between the human and the rat coding sequences is 90% for the nucleic acid sequence, with 96% identity and 97.5% similarity at the protein level. The NRGN gene is expressed exclusively in brain as a single 1.3-kb mature mRNA. The promoter lacks both TATA and CAAT boxes, but shows a consensus sequence for an initiator element located 234 bases upstream from the AUG initiation codon. The 5'-flanking region contains multiple putative binding sites for transcription factors such as Sp1, GCF, AP2, and PEA3. Analysis of a panel of radiation hybrids has led to localization of the NRGN gene in YAC 763A2 (CEPH), previously mapped at 11q24. This locus is contained in a region of conserved synteny with mouse chromosome 9.

Amino Acid Sequence↗
PubMed1997

Evolution of cerebral edema and its relationship with power in the theta band.

In previous papers we have proposed that in patients with space-occupying lesions, delta power was related with the volume of the lesion and theta power with the volume of the edema. In this report we analyze the evolution of 10 patients with space-occupying lesions in whom we measured the volume of the lesion and of the edema before and after treatment that produced changes in these volumes. EEGs were recorded in the leads of the 10-20 system referenced to linked earlobes. Delta and theta powers were calculated for voltage and current source densities (CSD) and compared with age-norms to compute conventional Z-maps. These maps provide probability statements about the deviation of observed values from the norm. Rank correlations between the change in the volume of the lesion before and after treatment and the change in Z-values before and after treatment were significant only in the delta band. However, rank correlations between the change in the volume of the edema and the change in EEG Z-values were only significant in the theta band. These correlations were higher for CSD than for voltage estimates. We also observed that the site of the lesion and of the edema was better represented by CSD maps than by voltage maps. These results are also in agreement with our previous reports, in which we observed more precise localization of brain lesions by CSD than by voltage estimates.

Adult↗
PubMed1997

A follow-up study of EEG coherences in children with different pedagogical evaluations.

A follow-up study on EEG coherence values was carried out with 46 school-age children divided into three pedagogical groups considering their reading and writing abilities (normal subject and children with mild and with serious reading-writing problems). EEGs were recorded at rest, with eyes closed in 15 referential derivations that gave 105 possible coherence values. Coherence was calculated after the elimination of the average reference. Repeated Measure ANOVAs were calculated to evaluate the effects of time, sex, reading-writing problems and their interactions. The second EEG recordings were taken 2-3 years after the first. The results revealed significant increase of coherence values during the time lapse studied, consisting of an increase of frontal coherences in all bands, with the exception of the theta band. The most numerous changes occurred in the alpha band. Very few differences in coherence values were observed between the two EEG recordings by pedagogical groups and by sex suggesting a similar but not igual maturation of coherences of boys and girls and of the three pedagogical groups, in this age range studied. These findings suggests an abnormal coherence development for the reading disabled group, as well as different coherence maturation for boys and girls in this time lapse studied.

Child↗
PubMed1997

Thyroid hormone-regulated expression of RC3/neurogranin in the immortalized hypothalamic cell line GT1-7.

The calmodulin-binding, protein kinase C substrate RC3/neurogranin is the product of a neuron-specific gene expressed in the forebrain that is under specific regional and temporal control by thyroid hormone (3,5,3'-triiodothyronine, T3). In vivo, some neuronal populations are sensitive and others are insensitive to T3. The goal of this study was to identify neuronal cell cultures that express RC3/neurogranin, to check whether they are sensitive to T3, and to examine the mechanism of regulation. We found that RC3 is induced by T3 in the hypothalamic cell line GT1-7 at the transcriptional level. The half-life of the mature mRNA was 20 h and was not affected by the hormone. Addition of T3 to the cell culture induces neurogranin mRNA after 6 h in the absence of new protein synthesis. These results suggest a direct transcriptional effect of T3 mediated through nuclear receptors. Indeed, GT1-7 cells express functional T3 receptors, as shown by northern blotting, nuclear T3-binding assays, and transactivation of reporter genes. The role of retinoic acid and glucocorticoids on RC3 expression was also evaluated, because we have previously noted the presence of consensus response elements for these hormones in the RC3 upstream promoter region. In contrast to T3, neither retinoic acid nor dexamethasone influences neurogranin expression despite the presence of respective functional receptors.

Animals↗
PubMed1997

Hypothyroidism alters the expression of prostaglandin D2 synthase/beta trace in specific areas of the developing rat brain.

Lipocalin-type prostaglandin D2 synthase is the enzyme responsible for the synthesis of prostaglandin D2, a major prostaglandin in the central nervous system. We analysed the effects of thyroid hormone deprivation on prostaglandin D2 synthase gene expression in the developing rat brain. By in situ hybridization, the strongest prostaglandin D2 synthase mRNA signal was detected in the leptomeninges and choroid plexus. The signal was greatly reduced in the cerebellar interlaminar meninges of hypothyroid rats aged 15 and 25 days. Immunohistochemical studies defined changes in the location of the prostaglandin D2 synthase protein. In control but not in hypothyroid animals, Cajal-Retzius neurons of cortical layer I, and pyramidal cortical plate neurons were intensely stained on postnatal day 5. Conversely, prostaglandin D2 synthase protein levels were higher in neurons of the CA1 and CA3 regions and the dentate gyrus of the hippocampus of hypothyroid animals on postnatal days 5, 15 and 25, and also in subplate neurons on postnatal days 15 and 25. In agreement with the in situ hybridization and northern blotting data, the major difference was found in the cerebellar interlaminar meninges of hypothyroid animals, where the protein was clearly down-regulated on postnatal days 15 and 25. These results show that hypothyroidism causes both age- and region-specific alterations in the expression and location of the prostaglandin D2 synthase during postnatal brain development, probably reflecting a cell-specific regulatory effect of thyroid hormone on the prostaglandin D2 synthase.

Animals↗
PubMed1997

Full reversal of Pb++ block of L-type Ca++ channels requires treatment with heavy metal antidotes.

The mechanisms of Pb++ block and unblock of L-type Ca++ channel currents were measured using ventricular myocytes or the cloned channel. The cloned channel was expressed in either Xenopus laevis oocytes or human embryonic kidney cells (HEK 293, stable transfectants). The threshold for Pb++ block was 1 nM, and the apparent IC50 value was 152 nM in oocytes and 169 nM in HEK 293 cells. Pb++ block was dependent on the composition of the external recording solution but not dependent on the subunit composition of the channel. Pb++ block was voltage dependent, with little block observed at negative test potentials using low concentrations of Pb++. Strong depolarizations (>+100 mV) reversed Pb++ block, allowing measurement of reblock kinetics. Reblock was fast (tau = 11 msec), as measured during a +20-mV test pulse. Simple washout did not completely reverse Pb++ block, especially after exposure to concentrations of >100 nM. Full recovery could only be observed after treatment with heavy metal antidotes such as meso-2,3-dimercaptosuccinic acid, 2,3-dimercapto-1-propanesulfonic acid and EDTA. These results suggest that Pb++ blocks voltage-gated Ca++ channels by two mechanisms and that full reversal of lead block requires chelator treatment.

Animals↗
PubMed1996

Thyroid hormone-dependent transcriptional repression of neural cell adhesion molecule during brain maturation.

Thyroid hormone (T3) is a main regulator of brain development acting as a transcriptional modulator. However, only a few T3-regulated brain genes are known. Using an improved whole genome PCR approach, we have isolated seven clones encoding sequences expressed in neonatal rat brain which are under the transcriptional control of T3. Six of them, including the neural cell adhesion molecule NCAM, alpha-tubulin and four other unidentified sequences (RBA3, RBA4, RBB3 and RBB5) were found to be upregulated in the hypothyroid brain, whereas another (RBE7) was downregulated. Binding sites for the T3 receptor (T3R/c-erbA) were identified in the isolated clones by gel-shift and footprinting assays. Sites in the NCAM (in an intron), alpha-tubulin (in an exon) and RBA4 clones mediated transcriptional regulation by T3 when inserted upstream of a reporter construct. However, no effect of the NCAM clone was found when located downstream of another reporter gene. Northern blotting and in situ hybridization studies showed a higher expression of NCAM in the brain of postnatal hypothyroid rats. Since NCAM is an important morphoregulatory molecule, abnormal NCAM expression is likely to contribute to the alterations present in the brain of thyroid-deficient humans and experimental animals.

Animals↗
PubMed1996

Pharmacological prevention of acute lead poisoning in Paramecium.

To understand how lead (Pb2+) and other metals and chelating agents effect living cells, behavioral experiments in the marine ciliate Paramecium calkinsi were carried out. The duration of Backward Swimming Behavior (BSB) of Paramecium was partially reduced when cells were exposed to 100 microM of Ni2+, CD2+ and Co2+. In contrast, Pb2+ increased Paramecium BSB in a dose-dependent manner. Thus, 1, 10, 20, 50 and 100 microM of Pb2+ increased the duration of BSB by 20.4, 83.9, 143.2, 163.2 and 185.2%, respectively. The naphthalenesulphonamide W-7, a calcium channel blocker in lower organisms, abolished the increase of Paramecium BSB initially produced by Pb2+. Paramecium, poisoned with 10 MicroM of Pb2+, were also treated with putative Pb2+ chelating agents, such as meso-2-3-dimercaptosuccinic acid (DMSA), Ca-Na2-EDTA and ascorbic acid. These compounds inhibited the increase of the duration of BSB initially produced by Pb2+ in a dose-dependent manner. The potency of these antidotes in blocking the effects of Pb2+ was as follows: DMSA >> Ca-Na2-EDTA > ascorbic acid. These results provide evidence for a membrane-based mechanism of lead poisoning and support the use of DMSA as a lead antidote.

Animals↗
PubMed1996

EEG delta activity: an indicator of attention to internal processing during performance of mental tasks.

In previous papers we proposed that an increase in delta EEG activity during mental tasks might be related to an increase in subjects' attention to internal processing. In this paper we have made a narrow band analysis to detect those EEG frequencies that change selectively during the performance of a mental task that requires attention to internal processing. Two different experiments were performed: (1) a difficult mental calculation task and a control stimulus with the same physical characteristics as the arithmetical symbols were presented in random order; (2) the Sternberg paradigm for the analysis of short term memory using a memory set of 5 or 3 digits was also presented in random order. Referential recordings to linked ears were obtained in all leads of the 10/20 system. In the first experiment, the increase of power from 1.56 to 5.46 Hz was observed only during the performance of the task and not during the control condition. In the Sternberg paradigm, the increase of power from 1.56 to 3.90 Hz was greater during the difficult than during the easy condition. These results support our hypothesis that an increase in delta activity may be related to attention to internal processing during the performance of a mental task.

Adult↗
PubMed1996

Treatment of actinic prurigo in Chimila Indians.

BACKGROUND: Actinic prurigo has a high prevalence in women of child-bearing age. Its treatment has been, among others, with thalidomide. To avoid the deleterious effects of this drug on the embryo, therapeutic alternatives have been sought. Among these, tetracycline and vitamin E have been investigated as to their influence on the symptoms of actinic prurigo. Both these drugs affect superoxide radicals that are thought to be involved in the pathogenesis of actinic prurigo. MATERIALS AND METHODS: Patients (Chimila Indians with a high prevalence of actinic prurigo) received either (a) tetracycline, 500 mg three times daily, for 6 months, or (b) vitamin E, 100 IU daily, for 6 months. The patients were seen once monthly. There were eight patients in each group. RESULTS: Both drugs used were effective. Pruritus was remarkably improved by either treatment. None of the side effects were severe enough to lead to interruption of treatment, but the observation period posttreatment was relatively short, 4 months for tetracycline and 2 months for vitamin E. The improvement occurred in spite of the continuation of extensive exposure to the sun. CONCLUSIONS: Tetracycline and vitamin E are efficacious in relieving the pruritus of actinic prurigo. Preliminary trials of a combination treatment with these two drugs is a new avenue which has shown in preliminary trials to yield synergistic effects which might allow the dosage of tetracycline to be reduced.

Anti-Bacterial Agents↗
PubMed1996

Results of Expedicion Humana. II. Analysis of HLA class II alleles in three African American populations from Colombia using the PCR/SSOP: identification of a novel DQB1*02 (*0203) allele.

PCR/SSOP typing methods were used to analyze the HLA Class II DRB1, DQA1, DQB1 and DPB1 loci of samples from three African American populations of Colombia. Forty samples from the Cauca (Pacific), and twenty samples each from the Choco (North Pacific Coast) and the Providencia (Caribbean island) populations, were collected and the Class II loci analyzed under the auspices of the Expedicion Humana. Despite the limited number of samples analyzed, the African Colombian populations exhibit a very high degree of class II polymorphism. A great diversity of DRB1 alleles was found, with representatives from all serological classes, including 19 DRB1 alleles in the Providencia, 16 in the Cauca and 14 in the Choco groups. In addition, a novel DQB1*02 allele (*0203) was found in two individuals from the Cauca population of the Pacific Coast. The sequence of the DQB1*0203 allele, associated with DR3, differs from DQB1*0201 by only one nucleotide substitution (C-->A) in the second position of codon 57, resulting in an Ala to Asp change. The addition of DQB1*0203 brings the total number of DQB1 alleles identified to date to 26. HLA class II diversity is much greater in these African Colombian populations than that seen in nearby Amerindian populations. Analysis of regional Colombian African American HLA population genetics is discussed with respect to the Colombian Amerindian HLA genetics described in an accompanying paper.

Alleles↗
PubMed1996

Cell-specific effects of thyroid hormone on RC3/neurogranin expression in rat brain.

To identify thyroid hormone-sensitive neuronal populations in the forebrain, we studied the effects of thyroid hormone deficiency and replacement on the expression of RC3 messenger RNA (mRNA) in the rat brain by in situ hybridization. RC3/neurogranin is a brain-specific, calmodulin-binding, protein kinase C substrate that has been implicated in postsynaptic events involving calcium as a second messenger. We have previously shown that RC3 mRNA and protein concentrations are thyroid hormone dependent in developing and adult rats. In normal developing rats, RC3 expression occurs in two phases. Before postnatal day 10 (P10), RC3 mRNA was detected mainly in layers II/III and V of cerebral cortex and the CA fields of the hippocampus. From P10 to P15, it decreased in layer V and increased in layer VI, the retrosplenial cortex, the caudate-putamen nucleus, and the dentate gyrus. Expression in the caudate followed a lateral to medial gradient. Thyroid hormone deficiency interfered with the late phase of RC3 expression, such that developing hypothyroid rats showed lower RC3 expression in layer VI, the retrosplenial cortex, the dentate gyrus, and the caudate, and increased expression in layer V. These changes were reverted by T4 treatment. Adult- onset hyperthyroidism also reversibly decreased hybridization in the striatum. In contrast to other molecular targets of thyroid hormone in the brain, such as myelin genes, expression of RC3 was also affected by long term hypothyroidism in the absence of hormone replacement, indicating that thyroid hormone is a required factor for the cell-specific control of RC3 expression. In addition to identifying thyroid hormone-sensitive neurons, our results suggest that one action of thyroid hormone during brain development is the timely coordination of gene expression among phenotypically different, region-specific neuronal populations.

Aging↗
PubMed1996

Post-transcriptional induction of beta 1-adrenergic receptor by retinoic acid, but not triiodothyronine, in C6 glioma cells expressing thyroid hormone receptors.

Thyroid hormone (triiodothyronine; T3) has been shown to control the expression of beta 1-adrenergic receptors (beta 1-AR) in cardiac myocytes, but not in C6 glioma cells. This cell specificity has been attributed to low expression of T3 receptors and high expression of the c-erbA alpha 2 splice variant that interferes with the action of T3. To check this hypothesis we have expressed the c-erbA/thyroid hormone receptor (TR) alpha 1 gene in C6 glioma cells and investigated their response to thyroid hormone. Cells expressing TR alpha 1, but not wild-type cells, were responsive to T3 as shown by increased expression of mitochrondrial hydroxymethylglutaryl CoA synthase after T3 exposure. However, T3 had no effect on beta 1-AR gene expression in either set of cells. The beta 1-AR mRNA concentrations were, however, altered by retinoic acid (RA) treatment. Retinoic acid caused a rapid up-regulation of beta 1-AR mRNA levels that was blocked by cycloheximide. Retinoic acid did not increase the beta 1-AR gene transcription rate in run-on experiments. These results indicate an indirect post-transcriptional effect of RA. Control of beta 1-AR expression in C6 cells is also exerted at the translational level, because there was no correlation between mRNA and protein induction, as determined by radioligand binding studies. We conclude that lack of responsiveness of the beta 1-AR gene in C6 cells to T3 is not due to high expression of c-erbA alpha 2 but to undefined cell-specific factors.

Animals↗