Search PubMed⌕ Search

Biomedical subjects

M C Hernandez

Publications and source records attributed to M C Hernandez.

35 records · Page 2Linked to original sources
PubMed1995

Acute infusions of cocaine result in time- and dose-dependent effects on lymphocyte responses and corticosterone secretion in rats.

In the present study, we investigated the effect of intravenously (i.v.) administered cocaine on mitogen-induced lymphocyte proliferation and NK cytolytic activity in rats implanted with indwelling jugular cannula. To assess whether the effects of cocaine were accompanied by adrenal gland activation, plasma corticosterone concentrations were also determined. It was found that the i.v. infusion of cocaine resulted in both a time- and dose-dependent decrease in both blood and splenic Con-A-stimulated lymphocyte proliferative responses. Within 60 minutes, blood responses were maximally inhibited by more than 60% with 5 mg/kg cocaine. By 4 h, the suppression of blood lymphocyte responses was no longer significant. In contrast to these findings, there were no significant effects observed with splenic lymphocyte responses until 4 h after drug administration. At this time, cocaine at doses of 5 and 10 mg/kg inhibited splenic proliferative responses by 50 and 75%, respectively. These effects appeared to be selective, since no concurrent decreases in NK cell activity were observed with 5 mg/kg at either 2 or 4 h. Within 30 min, plasma corticosterone concentrations were maximally increased by 10-fold with 5 and 10 mg/kg doses of cocaine. At lower doses of cocaine (1 mg/kg), neither changes in lymphocyte proliferative responses, NK cytolytic activity nor plasma corticosterone levels were apparent. This study demonstrates that a single i.v. infusion of cocaine results in a selective dose- and time-dependent immunosuppression which is preceded by transient increases in circulating levels of corticosterone.

Animals↗
PubMed1995

Id gene expression during development and molecular cloning of the human Id-1 gene.

Id genes encode helix-loop-helix proteins that inhibit transcription by forming inactive heterodimers with basic helix-loop-helix (bHLH) proteins. bHLH proteins normally form either homodimers or heterodimers with other bHLH proteins and bind to a DNA sequence element activating transcription. Id-containing heterodimers are inactive because Id proteins lack the basic amino acid region necessary to form a DNA-binding domain. We have examined the relative levels of Id-1 and Id-2 mRNA during normal development and in malignant tissues. In the course of these experiments we cloned and sequenced the human Id-1 cDNA. Two related cDNA molecules encoding human Id-1 mRNAs were identified. Id-1a is a cDNA of 958 nucleotides and can encode a protein of 135 amino acids. Id-1b cDNA is 1145 nucleotides, can encode a protein of 149 amino acids, and appears to be a splice variant of Id-1a. The amino acid sequence of human Id-1 is greater than 90% homologous to that of mouse Id-1. The patterns of Id-1 and Id-2 expression during mouse development vary widely, and we detected Id-1 expression in human fetal and adult tissues from lung, liver, and brain. High Id-1 mRNA expression was found in many human tumor cell lines, including those isolated from nervous system tumors. We mapped Id-2 to human chromosome 2p25.

Amino Acid Sequence↗
PubMed1994

Enhanced susceptibility of the immune system to stress in morphine-tolerant rats.

The purpose of the present study was to determine the potential consequences to the immune system of the combined exposure of rats to stressor and morphine. Within 30 min following either morphine (5 mg/kg) injection or restraint stress (30 min) maximal analgesic responses as measured by tail-flick assay were observed. However, only morphine treatment was accompanied by a significant suppression (50%) in mitogen-stimulated lymphocyte proliferative responses. Restraint stress for either a 30-min or 2-h duration had no effect on lymphocyte responses. Exposure to a combination of restraint stress and acute morphine (5 mg/kg) resulted in a 50% suppression of lymphocyte responses which was similar in magnitude to that observed with morphine administration alone. When rats were injected twice daily for 4 days with increasing doses of morphine ranging from 10 mg/kg to 40 mg/kg, morphine (10 mg/kg) administration on Day 5 was not accompanied by either analgesia or depressed blood lymphocyte proliferative responses. These results indicated that tolerance had developed to both the analgesic and the immunosuppressive effects of morphine. However, upon exposure of morphine-tolerant animals to restraint stress, significant analgesic responses were retained. Furthermore, in contrast to the lack of suppression following restraint stress on lymphocyte responses in saline-injected animals, restraint for 30 min produced greater than a 70% suppression in morphine-tolerant animals. These data suggest that morphine tolerance may be accompanied by an enhanced susceptibility to the immunosuppressive effects of stress.

Analgesia↗
PubMed1994

In vitro effects of cocaine, lidocaine and monoamine uptake inhibitors on lymphocyte proliferative responses.

Cocaine was found to inhibit in vitro mitogen-stimulated rat B and T lymphocyte proliferation in a dose-dependent manner. The IC50 for B lymphocytes (70 microM) was 2 to 4 fold lower than that obtained with T lymphocytes. To determine whether ion channel blockade or inhibition of monoamine uptake produced a similar suppression of lymphocyte proliferation, the effects of pharmacological agents sharing each of these properties with cocaine were examined. Lidocaine (0.5 mM), a sodium channel blocker, had no significant effect on B and T cell proliferation. By comparison, cocaine inhibited lymphocyte responses by greater than 80 percent at this concentration. Monoamine uptake inhibitors were also found to suppress lymphocyte proliferation in a dose-dependent manner similar to that obtained with cocaine. Of those tested, desipramine and fluoxetine were considerably more potent than cocaine, nomifensine and nisoxetine. These data demonstrated the addition of cocaine directly to lymphocyte cultures resulted in a dose-dependent inhibition of proliferation which was not due to Na+ channel blockade. Instead, the resemblance of monoamine uptake inhibitors to the action of cocaine suggests that lymphocytes may be intrinsically sensitive to these agents.

Animals↗
PubMed1994

Acute immunosuppressive effects of morphine: lack of involvement of pituitary and adrenal factors.

We have previously reported that morphine inhibits Concanavalin A-stimulated blood lymphocyte proliferation in a dose-dependent manner. Maximal (80%) inhibition by morphine occurred with a dose of 10 mg/kg 2 hours after drug administration. Concurrent with this suppressive effect was a 2- to 4-fold increase in plasma corticosterone concentrations. In the present study, we examined the potential contribution of the hypothalamic-pituitary-adrenal axis to the suppressive effects of acute morphine exposure. To assess the role of glucocorticoids, rats were pretreated with the steroid receptor antagonist RU486 (20 mg/kg) 30 min before morphine (10 mg/kg) administration. A significant inhibition of lymphocyte activity occurred with morphine in the absence or presence of RU486 pretreatment. Consistent with a mechanism independent of glucocorticoids, adrenalectomy also failed to attenuate the inhibitory actions of morphine. To examine the potential role of pituitary hormones in the suppressive effect, similar experiments were carried out in hypophysectomized animals. In sham-operated or hypophysectomized animals, morphine was found to be equally effective in suppressing lymphocyte proliferation. These results suggest that factors elaborated from intact pituitary or adrenal glands are not required for the acute inhibitory effects of morphine on peripheral blood lymphocyte activity.

Adrenal Cortex Hormones↗
PubMed1993

Immunosuppression by morphine is mediated by central pathways.

We reported previously that a single systemic injection of morphine (10 mg/kg) to rats profoundly suppressed mitogen-induced proliferation of blood lymphocytes by a receptor-mediated mechanism. The present study examined whether this immunosuppressive effect of morphine is mediated by opioid receptors located at either peripheral or central sites. First, the effects of systemic morphine administration on analgesia, mitogen-stimulated lymphocyte proliferation and corticosterone secretion were compared to those observed after the systemic administration of N-methylmorphine, a quaternary derivative which does not readily penetrate the blood-brain barrier. In contrast to systemically administered morphine, the i.p. injection of N-methyl-morphine (20 mg/kg) was without any effect on lymphocyte proliferation, plasma corticosterone concentrations or analgesic responses. Secondly, the effects of morphine and N-methylmorphine after central administration were compared. Within 2 hr after the microinjection of either morphine (10 micrograms/2 microliters) or N-methylmorphine (15 micrograms/2 microliters) into the third ventricle, blood lymphocyte responses were inhibited by 70%, plasma corticosterone concentrations were significantly elevated and maximal analgesic responses were present. Finally, microinjection of morphine (1 microgram/0.2 microliter) into the anterior hypothalamus inhibited blood lymphocyte proliferation by 50% without producing analgesia or a significant increase in plasma corticosterone. These findings suggest that central opioid pathways are involved in the immunosuppressive effects of morphine and these pathways may be distinct from those participating in opioid-induced analgesia and adrenal activation.

Animals↗
PubMed1992

Neuronal specificity of the alpha 7 nicotinic acetylcholine receptor promoter develops during morphogenesis of the central nervous system.

A transient transfection assay has been developed to analyse promoter activity in neuronal cells freshly dissociated from the chick central nervous system. The assay enabled us to identify cis-acting regulatory elements within the 5'-flanking region of the alpha 7 nicotinic acetylcholine receptor gene. In differentiated retina, regulatory elements direct reporter gene expression to a small subset of neurons which has been identified as ganglion cells, i.e. to the population of neurons in which alpha 7 transcripts were localized by in situ hybridization. However, these promoter elements exhibit ubiquitous activity in undifferentiated neural cells and in mesodermal stem cells. Our study supports the idea that alpha 7 regulatory elements acquire their neuronal specificity in the course of embryogenesis.

Amino Acid Sequence↗
PubMed1990

Restraint stress-induced elevations in plasma corticosterone and beta-endorphin are not accompanied by alterations in immune function.

A variety of stressors activate the hypothalamic-pituitary-adrenal (HPA) axis, thereby resulting in elevated levels of circulating ACTH, beta-endorphin and corticosterone. Since these hormones have been shown previously to alter measures of immune function, we determined whether presentation of a stressor which activates the HPA axis produces a concomitant alteration in immune function. Restraint stress resulted in significantly elevated levels of corticosterone and beta-endorphin without affecting either proliferative or cytolytic activities of lymphocytes. At concentrations similar to those achieved during stress, in vivo, corticosterone exhibited a dose- and time-dependent reduction in both lymphocyte proliferation as well as natural killer cytotoxicity, in vitro. beta-Endorphin, on the other hand, was without direct or modulatory effects. These results indicate that restraint stress-induced activation of the HPA axis occurs without accompanying alterations in immune function.

Animals↗
PubMed1990

A neuronal nicotinic acetylcholine receptor subunit (alpha 7) is developmentally regulated and forms a homo-oligomeric channel blocked by alpha-BTX.

cDNA and genomic clones encoding alpha 7, a novel neuronal nicotinic acetylcholine receptor (nAChR) alpha subunit, were isolated and sequenced. The mature alpha 7 protein (479 residues) has moderate homology with all other alpha and non-alpha nAChR subunits and probably assumes the same transmembrane topology. alpha 7 transcripts transiently accumulate in the developing optic tectum between E5 and E16. They are present in both the deep and the superficial layers of E12 tectum. In Xenopus oocytes, the alpha 7 protein assembles into a homo-oligomeric channel responding to acetylcholine and nicotine. The alpha 7 channel desensitizes very rapidly, rectifies strongly above -20 mV, and is blocked by alpha-bungarotoxin. A bacterial fusion protein encompassing residues 124-239 of alpha 7 binds labeled alpha-bungarotoxin. We conclude that alpha-bungarotoxin binding proteins in the vertebrate nervous system can function as nAChRs.

Acetylcholine↗
PubMed1981

Photosensitization and the nervous system in the planarian Dugesia gonocephala. A histochemical, ultrastructural and behavioral investigation.

Photosensitization phenomena may be induced in planarias by eosin and hematoporphyrin, and as a result, dopamine agonistic behavior ("screw-like hyperkinesia") is set up in the animal. Histochemical, ultrastructural and pharmacological investigations have shown that this hyperkinesia is of post-synaptic origin in eosin photosensitization, and of pre-synaptic origin in hematoporphyrin photosensitization. The authors suggest an hypothesis to explain the different activity of the two photosensitizers, and discuss the validity of the experiment with regard to human porphyria.

Animals↗
PubMed1979

Pancreatic encephalopathy.

A prospective study was conducted on 17 cases of acute pancreatitis; encephalopathy was discovered in six patients (35%). The following parameters were studied: the usual ones in pancreatitis conditions (amylasemia, lipasemia, amylasuria, ions, glucose, pO2, pCO2, pH, etc.), and electroencephalographic changes and determinations in CSF of cells, proteins, lipase, amylase, lipides and cholesterol. A direct relationship was found to exist between the pancreatic encephalopahy condition and an increase in CSF-lipase. The electroencephalographic changes were nonspecific. The encephalopathy did not affect the course of the pancreatitis condition, and showed no relationship to type of treatment involved. The severity of the pancreatitis was not related to the presence or absence of encephalopathy.

Acute Disease↗
PubMedDate not supplied

Distinction between the in vitro and in vivo inhibitory effects of morphine on lymphocyte proliferation based on agonist sensitivity and naltrexone reversibility.

We have previously reported that administration of a single dose of morphine (25 mg/kg) to rats results in a naltrexone-sensitive suppression of mitogen-stimulated lymphocyte proliferation. To further delineate the site of action of this inhibitory effect, the in vitro and in vivo effects of morphine on mitogen-stimulated lymphocyte proliferation were examined. In vitro, concentrations of morphine exceeding 0.1 mM exhibited a dose-dependent inhibition of Concanavalin A-induced proliferation of both whole blood and splenic lymphocytes. This inhibitory effect of morphine on lymphocyte proliferation was not attenuated by co-incubation with the opioid antagonist naltrexone (0.25 mM). These data indicate that the in vitro inhibitory effects of morphine occur at only high concentrations and are not opioid receptor mediated. In vivo, a dose-dependent inhibition of blood lymphocyte proliferation was also observed 2 h following the subcutaneous injection of morphine. In contrast to these effects, proliferation of splenic lymphocyte cultures was not significantly inhibited by morphine at doses of up to 40 mg/kg. However, following morphine administration, a greater than 90% inhibition of proliferation was obtained in cultures containing either whole blood or Ficoll-separated lymphocytes, indicating that plasma was not a contributory factor in the differential sensitivity of blood and splenic lymphocyte responses to morphine. Moreover, in these experiments, significant inhibition of lymphocyte proliferation occurred at plasma concentrations that were two orders of magnitude less than those required to produce inhibition in vitro. The in vivo inhibition of lymphocyte proliferation by morphine (10 mg/kg) was completely antagonized by pretreatment with naltrexone (5 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

On the transcriptional regulation of neuronal nAChR genes.

The promoters driving transcription of the neuronal nicotinic genes alpha 7 and beta 3 have been characterized in the chicken. Although their regulatory modalities are thoroughly different, they nevertheless lead to co-expression in the same neurons.

Animals↗