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M Vendrell

Publications and source records attributed to M Vendrell.

31 records · Page 2Linked to original sources
PubMed1993

Nuclear calmodulin-binding proteins in rat neurons.

By using a 125I-calmodulin overlay assay, three major high-affinity calmodulin-binding proteins, showing apparent molecular masses of 135, 60, and 50 kDa, have been detected in purified nuclear fractions isolated from rat neurons. It has been shown that after extraction of the nuclei with nucleases and high salt, all these proteins remain strongly associated with the nuclear matrix. The 60- and 50-kDa proteins have been previously identified as subunits of the calmodulin-dependent protein kinase II. We report here the immunoblot identification of the 135-kDa calmodulin-binding protein as myosin light chain kinase. We also show that the calmodulin-dependent protein phosphatase calcineurin is present in the neuronal nuclei and associated with the nuclear matrix. The nuclear localization of both calcineurin and myosin light chain kinase has been confirmed by immunocytochemical studies.

Animals↗
PubMed1993

Diagnostic value of bronchoalveolar lavage in peripheral lung cancer.

A prospective study has been performed to assess the value of the addition of bronchoalveolar lavage (BAL) to the routine bronchoscopic exploration with bronchial washing (BW) and postbronchoscopy sputum (PBS) procedures in the diagnosis of peripheral primary lung cancer not visible through bronchoscope when fluoroscopic guidance is not available. BW, BAL, and PBS were performed in 67 patients with suspected primary lung cancer by peripheral lung lesion on chest radiograph (39 nodules and 28 infiltrates) and nonendoscopically visible lesion. The sequence of procedures was in all cases BW, BAL, and post-bronchoalveolar lavage bronchoaspirate (PBBA). An attempt was made to collect early morning postbronchoscopy samples of sputum (PBS) on 3 consecutive days. BW and PBBA were collected in the same test tube, and the cytologic result was considered as BW diagnostic yield. If there were negative bronchoscopic results, either percutaneous fine-needle aspiration or open-lung biopsy were performed for diagnosis. Fifty-five patients were found to have malignant disease (23 adenocarcinomas, 22 squamous cell carcinomas, six small cell carcinomas, and four bronchioloalveolar cell carcinomas). BAL was positive in 18 of the 55 (33%) carcinomas, and it gave the only positive result in six (11%). BW was also positive in 18 of the 55 (33%), but it gave positive results in only 3 (5%). PBS was positive in 13 of the 43 (30%) patients from whom samples could be spontaneously obtained and were suitable for cytologic examination (not consisting of saliva), and gave the only positive result in three (7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Lindane-induced convulsions in NMRI and OF1 mice: antagonism with (+)MK-801 and voltage-dependent calcium channel blockers.

The convulsant profile of lindane was investigated in OF1 and NMRI mice lines in relation to other convulsants acting at the GABAA and NMDA receptor complexes. Thus, a specific GABA-gated chloride channel blocker, PTX, a GABAA receptor antagonist, PTZ, and an excitatory amino acid receptor agonist, NMDA, were used. Antagonism of the convulsant effects of each of these drugs was investigated with (+)MK-801, a blocker of the NMDA-operated cation channel, and with nifedipine, a voltage-dependent calcium channel antagonist. While no differences in potency for PTX or PTZ to induce seizures were observed between OF1 and NMRI mice, lindane was approximately 80 and 90% more potent in its ability to induce seizures and lethality, respectively, in OF1 than in NMRI mice. Brain lindane concentrations at the moment of convulsion, measured after ED100 doses of lindane (400 and 200 mg/kg for NMRI and OF1 mice, respectively), did not differ between OF1 and NMRI mice, suggesting that the different potency of lindane between these mouse lines is a consequence of pharmacokinetic factors. Furthermore, (+)MK-801 antagonized seizures induced by either lindane, PTX or PTZ with similar potencies in both mouse lines. These results, coupled with the different pharmacokinetics of lindane in OF1 and NMRI mice, suggest that the distinct effects of lindane in these mice are not mediated by different activities at either NMDA or GABAA receptor complexes. Nonetheless, nifedipine antagonized lindane-induced seizures with a three-fold higher potency in NMRI than in OF1 mice. In contrast, nifedipine failed to antagonize PTX and PTZ convulsions in both OF1 and NMRI mice. These results suggest that besides the GABAA receptor complex other mechanisms related to calcium mobilization may be involved in the convulsant action of lindane.

Animals↗
PubMed1992

Effect of different convulsants on calmodulin levels and proto-oncogene c-fos expression in the central nervous system.

In the present study, a relationship between convulsant activity and two cellular events, changes in calmodulin (CaM) concentration and proto-oncogene c-fos expression has been considered. c-fos has been found activated after the administration of the organochlorine insecticide lindane, the Ca2+ channel agonist Bay K, and N-methyl-D-aspartate (NMDA). The administration of the voltage-dependent Ca2+ channel antagonist nifedipine was able to block the expression elicited by lindane. The effect of lindane on c-fos expression could not be blocked by prior administration of MK-801, a non-competitive antagonist of the NMDA receptor. These results suggest a possible role for the voltage-dependent Ca2+ channels in the mechanism of action of lindane. By means of in situ hybridization, the different patterns of c-fos expression after the administration of the mentioned compounds have been described. A possible modification of the levels of CaM has also been investigated. Among all the subcellular fractions considered, only levels of nuclear CaM appeared to be affected after the different treatments. The changes observed seemed to follow a similar pattern to that described for c-fos induction. Calcium entry through these voltage-dependent calcium channels would be the link between membrane depolarizing events and expression of c-fos and/or increase in nuclear CaM.

Animals↗
PubMed1992

c-fos expression as a model for studying the action of hexachlorocyclohexane isomers in the CNS.

The induction of protooncogene c-fos in the CNS after administration of several convulsants has been studied. The organochlorine insecticide gamma-hexachlorocyclohexane (gamma-HCH, lindane) has been shown to induce c-fos expression in different brain areas. Pentylenetetrazole and picrotoxin, a known gamma-aminobutyric acid-receptor antagonist, have also been considered. The administration of two nonconvulsant isomers of gamma-HCH, alpha-HCH, and delta-HCH, before the mentioned toxicants, affects the protooncogene expression in different ways. The differential pattern of expression displayed by c-fos after these treatments suggests the presence of diverse mechanisms of action for the compounds studied.

Animals↗
PubMed1992

Effect of gamma-hexachlorocyclohexane and its isomers on proto-oncogene c-fos expression in brain.

By means of in situ hybridization, the induction of proto-oncogene c-fos in rat brain after administration of several convulsants has been studied. The organochlorine insecticide gamma-hexachlorocyclohexane (lindane) has been shown to induce c-fos expression in a dose dependent manner. 30 mg/kg of lindane increased c-fos expression in cortical and hippocampal areas. The two non convulsant isomers of lindane, alpha- and delta-HCH, were not able to induce the expression of the proto-oncogene, but blocked that elicited by lindane. Pentylenetetrazole (PTZ) and picrotoxin (PTX), a known GABAA-receptor antagonist, have also been considered. Both of them were able to induce c-fos, although the pattern of expression was not the same in each case. alpha- and delta-HCH, were administered prior to the mentioned toxicants, affecting the proto-oncogene expression in different ways. We propose here that the distribution of c-fos mRNA after different treatments can be used as a marker of neurotoxic action.

Animals↗
PubMed1991

c-fos and ornithine decarboxylase gene expression in brain as early markers of neurotoxicity.

An increase of proto-oncogene c-fos expression in cerebral cortex of rats treated with subconvulsant doses of the pesticide organochlorine lindane (gamma-hexachlorocyclohexane) has been detected using Northern blots. Immunohistochemical studies show that Fos protein was already increased in neuronal nuclei 3 h after treatment. The administration of the benzodiazepine diazepam prior to lindane totally blocked the activation of this proto-oncogene expression. Parallel to this increased expression of c-fos an activation of the ornithine decarboxylase (ODC) gene and enzyme was also observed. High levels of ODC mRNA and increased enzyme activity in cortex were found in rats following lindane treatment. These changes were attenuated by prior treatment of animals with diazepam. The co-induction of c-fos and ODC suggests a potential link between the ODC/polyamine system and the short-acting proto-oncogenes in stimulus-transcription coupling events.

Animals↗
PubMed1991

Presence of calmodulin and calmodulin-binding proteins in the nuclei of brain cells.

The nuclear calmodulin levels have been measured in rat neurons and glial cells. The values are 1.0 and 1.1 micrograms/mg of protein, respectively. These levels are about threefold higher than those in the nuclei of rat liver cells. We have also investigated the presence of several calmodulin-binding proteins in the nuclei of both brain cellular types. As similarly observed in the nuclei of liver cells, we detected the presence of alpha-spectrin and a 62-kDa calmodulin-binding protein (p62) in the nuclei of neurons and glial cells by immunoblotting and immunocytochemical methods. Both proteins are enriched in the purified nuclear matrix samples from both cellular types. In contrast to that occurring in rat hepatocytes, we have not been able to detect, by immunoblotting methods, caldesmon in the nuclear matrices of neurons and glial cells. The immunocytochemical studies suggest, however, that caldesmon can be present in the nuclei but in a fraction distinct from the nuclear matrices.

Animals↗
PubMed1988

An improved procedure for the isolation of rat brown adipose tissue cells.

A method for the isolation of brown adipocytes free of fat interferences and sensitive to noradrenalin is presented. The cells were isolated from pieces of brown adipose tissue with a collagenase treatment. The cells were obtained in the presence of heparin, in order to free the lipoprotein lipase attached to the cell surface. The cells were isolated in the presence of Amberlite XAD-2 [polymeric hydrophobic absorbent beads], which retained most of the fat droplets, formed from broken cells, during the process of disaggregation. The combined use of heparin and Amberlite XAD-2 during the isolation procedure resulted in a lowered cell basal oxygen consumption rate when compared with that of cells isolated with standard methods. The treatment presented lowered the availability of extracellular fatty acids for the isolated brown fat cells, resulting in lower operation of the thermogenin shunt, and thence in decreased basal oxygen consumption and higher sensitivity to glucose and noradrenalin stimulation.

Adipose Tissue, Brown↗
PubMedDate not supplied

Effect of lindane on the myelination process in the rat.

After lindane administration at several doses, brain myelin fractions of litters of male and female Wistar rats show a significant diminution of CNP (2',3'-cyclic nucleotide 3'-phosphodiesterase) activity. Furthermore, the immunohistochemical study of brains by means of a MBP (myelin basic protein) specific antibody reveals myelin deficits in some brain regions after lindane treatment. This loss of myelin protein is dose dependent. The deficit in myelin cannot be attributed to undernourishment of lindane-administered rats. This work shows the vulnerability of the developing central nervous system (CNS) to lindane and the correlation between a decrease in the CNPase activity and a deficit of MBP during the period of study of these animals.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMedDate not supplied

Behavioral and monoaminergic changes after lindane exposure in developing rats.

The effects of lindane on behavior and central monoaminergic systems were studied in rat pups at 15 days of postnatal age. Pups were previously given nonconvulsant lindane PO doses, either a single 20 mg/kg or 7-day repeated 10 mg/kg doses. Both treatment schedules improved the passive avoidance acquisition but only the acute administration prolonged the step-through latency. Acute lindane decreased the motor activity, whereas the repeated dosing increased it. Increases of the ratio 5-HIAA/serotonin in several brain regions and of the ratio DOPAC/dopamine in the mesencephalon after a single dose of lindane suggest an enhanced monoaminergic turnover. In contrast, repeated lindane doses decreased monoamine/metabolite ratios excluding the striatum, where an increase of DOPAC/dopamine ratio correlates with the higher motor activity of these animals. It is postulated that both the imbalance of the central monoaminergic systems and the lindane-induced GABAergic blockade may be the basis of the behavioral alterations.

Animals↗