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Biomedical subjects

D Levesque

Publications and source records attributed to D Levesque.

At least 19 recordsLinked to original sources
PubMed1998

Tyrosine kinase and MAPK inhibition of TNF-alpha- and EGF-stimulated IEC-6 cell growth.

The role of TNF-alpha in modulating intestinal crypt cell growth was examined, in comparison with EGF. Both significantly increased IEC-6 cell proliferation. Neither EGF nor TNF-alpha overcame the inhibitory effect on growth exerted by the tyrosine kinase inhibitor genistein. Immunoblots with phosphotyrosine antibodies showed increased tyrosine phosphorylation of IEC-6 cell proteins in response to EGF and TNF-alpha stimulation. TNF-alpha increased ERK1 and ERK2 MAPK phosphorylation. A MAPK assay confirmed the increased activity upon TNF-alpha stimulation. Selective inhibition of MAPK activation by PD98059 resulted in a dose dependent inhibition of TNF-alpha or EGF-induced IEC-6 cell growth. These findings suggest a role for TNF-alpha in the regulation of intestinal epithelial cell growth and that the mitogenic effect of TNF-alpha requires protein tyrosine phosphorylation and MAPK activation.

Animals↗
PubMed1996

Pneumocystis carinii infection in transgenic B cell-deficient mice.

Pneumocystis carinii is an important cause of pneumonia in immunocompromised hosts. Both cellular and humoral immunity seem important in resistance to this pathogen, but the specific role of each component is poorly understood. An outbreak of P. carinii pneumonia in transgenic B cell-deficient mice (muMT) was studied. Over 4 months, >50% of 41 muMT/muMT mice maintained in a sterile environment died of pneumonia. Some mice had concurrent infection with Pasteurella pneumotropica. Homozygous muMT/muMT mice had no detectable serum immunoglobulins, while their heterozygous muMT/+ counterparts had normal levels of IgM, IgG, and IgA and did not develop pneumonia. The infection was controlled by treating the mice with trimethoprim-sulfamethoxazole, and the pathogen was eliminated by cesarean rederivation. These observations suggest an important role for B cells in the host defense against P. carinii.

Animals↗
PubMed1996

Caco-2 cell disaccharidase activities are unaffected by gestational hormones.

We previously reported that lactose handling was significantly improved during late-phase pregnancy in women with a genetically determined adult-type hypolactasia. However, the adaptive mechanisms underlying the enhanced lactose digestion during pregnancy are not clear. Progesterone therapy has been associated in animals with increased intestinal lactase activity. To investigate the potential role of progesterone and estrogen as modulators of human lactase activity during pregnancy, we employed the human-derived intestinal epithelial Caco-2 cell line. Measurements of lactase and sucrase activities were performed in parallel with DNA content in progesterone- and estrogen-treated cells after 5, 10, and 30 days of confluency. Caco-2 monolayer DNA content was observed to increase with duration of culture to an equivalent extent in both hormone-treated and control cultures. Lactase and sucrase activities were similarly unaltered by incubation with either progesterone or estrogen, at any time point tested. These data demonstrate that gestational hormones do not influence intestinal cell number nor disaccharidase activity in Caco-2 cells, at the doses tested. Although these studies were carried out in a malignant cell line, our data suggest that the improved lactose handling observed during pregnancy is probably related to prolonged intestinal transit.

Caco-2 Cells↗
PubMed1995

The D3 receptor and its relevance in psychiatry.

A large fraction of neurotensin neurons in the ventromedial shell subdivision of nucleus accumbens express D3 receptors. Blockade of D2/D3 receptors by antipsychotic agents paradoxically decreases neurotensin gene expression in these neurons whereas it enhances it in other striatal areas expressing the D2 receptor. This suggests that D2 and D3 receptors mediate opposite actions of dopamine. In support of this view low doses of nafadotride, a novel D3 receptor-preferring antagonist, enhances locomotor activity in rodents, a behavioral response opposite to that of current neuroleptics. The action of D3 receptor-preferring agonists was characterized by the mitogenic response they elicit in transfected NG 108-15 cells. Finally, gene expression of the D3 receptor is in opposition to that of the D2 receptor, being decreased by denervation and unaffected by chronic blockade by neuroleptics.

Antipsychotic Agents↗
PubMed1994

Multiple dopamine receptors: the D3 receptor and actions of substances of abuse.

Our knowledge of dopamine receptor diversity has markedly increased during the past few years as a result of discovery of five distinct genes, splice variants and polymorphic receptors. The genes can be classified in two subfamilies: the intronless genes that encode the D1 and D5 receptors positively linked to adenylyl cyclase and genes with introns that encode the two isoforms of the D2 receptor and the D3 and D4 receptors. The various dopamine receptor subtypes can be distinguished by their sequence, intracellular signalling systems, pharmacology and localisation. The localisation of the D3 receptor in the shell of nucleus accumbens suggests its participation in brain reward circuits and actions of substances of abuse.

Animals↗
PubMed1993

The potentiating effects of restraint stress and continuous naloxone infusion on the analgesic potency or morphine are additive.

The analgesic potency of morphine in the rat can be increased by either continuous administration of an opiate antagonist, which also increases the number of mu-opioid receptors in the brain, or by immobilization stress. To examine further the plasticity of brain opioid mechanisms, this study assessed the combined effects of continuous naloxone treatment and physical restraint on the analgesic potency of morphine. Osmotic pumps releasing 0.3 mg/kg/h of naloxone were implanted subcutaneous (SC) in two groups of rats for 7 days and empty (SHAM) pumps were implanted in two other groups. Twenty-four hours after the pumps were removed, all animals were injected with morphine in cumulative doses and tested in the tail-flick procedure. One group of naloxone-treated rats and one group of SHAM-treated rats were tested while restrained; the other two groups were tested while unrestrained. Naloxone infusion alone and restraint alone each increased significantly the analgesic potency of morphine by 1.4-fold whereas the combination of these two treatments increased analgesic potency by almost 2-fold, significantly more than either treatment alone. All animals were retested with morphine 6 days later; the analgesic potency of morphine in the SHAM groups was still potentiated by stress but the potentiating effect of the earlier naloxone infusion was no longer evident. It appears that the opioid receptors mediating stress-induced potentiation of morphine-induced analgesia can be upregulated transiently by 7-day infusion of naloxone.

Animals↗
PubMed1993

Differential cholinergic and non-cholinergic actions of acetylcholinesterase in the substantia nigra revealed by fasciculin-induced inhibition.

The effects of the peptide fasciculin (FAS), a potent inhibitor of acetylcholinesterase (AChE) have been examined, following unilateral microinfusion, on tissue levels of monoamines in the rat substantia nigra and concomitant circling behaviour. Although FAS inhibited 87% of total AChE, the levels of dopamine and its metabolites remained unchanged. Furthermore, the treatment induced modest contraversive rotation which was markedly enhanced in the presence of a systemic challenge with apomorphine. This behavioural effect of FAS was partially reversed by systemically administered atropine. Any possible interaction of FAS with nigral dopamine systems was further investigated by testing the peptide in animals that five days earlier had undergone a 6-hydroxydopamine (6-OHDA) lesion of the SN such that dopamine and AChE were significantly but not completely reduced. In a majority of these animals, FAS treatment caused a reversal of the lesion induced ipsiversive rotation, ie restored contraversive rotation. It is concluded that in the SN, FAS can have biochemical and behavioural actions independent of local dopamine systems and linked to cholinergic transmission. In addition, treatment with FAS in the substantia nigra also reveals the possible existence of at least two distinct pools of AChE with, respectively, non-cholinergic and cholinergic actions.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Elimination of polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) from human blood in the Yusho and Yu-Cheng rice oil poisonings.

The pharmacokinetics of polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) in humans was studied by monitoring the blood concentrations of individuals who ingested a contaminated rice oil in Japan (yusho) in 1968 and in Taiwan (yu-cheng) in 1979. Sixteen yusho patients were followed from 1982 to 1990 and three yu-cheng individuals from 1980 to 1989. From the three yu-cheng patients, blood lipid values for the two persistent toxic congeners, 2,3,4,7,8-pentachlorodibenzofuran (PnCDF) and 1,2,3,4,7,8-hexachlorodibenzofuran (HxCDF), varied from 50 micrograms/kg at first sampling to about 1 micrograms/kg at last sampling corresponding to half-lives for elimination (t1/2) of 2-21/2 years. The blood lipid values for the same PCDF congeners in yusho patients varied from 5 micrograms/kg down to 0.1 micrograms/kg. The calculated t1/2 were more variable with median values closer to 10 years. Planar PCBs #126 and #169 were present at lower concentrations than the PCDFs. For seven of the other PCB congeners, half-lives for elimination in the yu-cheng individuals varied from 1.2 up to 4.6 yr depending on the degree of chlorination. For the yusho patients, the elimination for the PCBs was longer. These results show that clearance of the toxic PCDFs and PCBs in humans is non-linear with faster elimination at higher exposure followed by slower decreases as background levels are approached. Such a clearance pattern can best be explained by a two compartment liver and fat pharmacokinetic model.

Adolescent↗
PubMed1993

Placental pathology in discordant twins.

OBJECTIVE: The aim of this study was to evaluate placental abnormalities in relation to birth weight discordance in dichorionic and monochorionic twins. STUDY DESIGN: The maternal charts and placental abnormalities of 147 structurally normal twin pairs with cords labeled at delivery were reviewed. The placental weight belonging to each twin was determined by measuring the length, width, and thickness in each of the two placental disks. Placental weight, chorionicity, infarction, abruptio placentae, decidual vascular abnormality, villous fibrosis and hypovascularity, chronic villitis, and intraplacental thrombi were also assessed. Birth weight was discordant if > or = 20%. The data were analyzed with chi 2 and analysis of variance after log transformation of skewed discordancy values. RESULTS: Of the 147 twin pairs, 99 were dichorionic and 48 monochorionic. Placental weights were known for 91 dichorionic and 40 monochorionic twins. Of the lighter cotwins in dichorionic twin pairs 36.3% (33/91) belonged to the heavier placenta, 49.5% (45/91) belonged to the lighter placenta, and 14.3% (13/91) had an equal share of the placental weight with the heavier sibling (p < 0.05). In 42.4% (42/99) the lighter dichorionic twin had more placental lesions than the heavier twin, in 38.4% (38/99) the same number of lesions were present in both placentas, and in 19.2% (19/99) the heavier twin had more placental lesions. There was linear correlation between percent discordance and number of placental lesions in the lighter twin. In dichorionic twins 18 of the 99 (18.1%) were discordant. In 77.8% (14/18) the lighter twin had more placental lesions than the heavier twin, in 16.7% (3/18) the number of lesions was the same in both, and in 5.6% (1/18) the heavier twin had one more lesion than the lighter twin (p < 0.05). In monochorionic twins, regardless of birth weight discordance, no differences in placental abnormalities were observed. CONCLUSIONS: In dichorionic twins significant birth weight discordance was attributable not to differences in placental weight but to a greater number of placental lesions in the lighter twin than in the heavier twin (p < 0.05). This did not hold true for monochorionic twins.

Analysis of Variance↗
PubMed1993

Dopamine D3 receptor: basic and clinical aspects.

The recently discovered dopamine D3 receptor can be considered as a D2-like receptor: it is encoded by a gene comprising several introns; it is both an autoreceptor and a postsynaptic receptor, well recognized by antipsychotics. It differs, however, from the D2 receptor by a much more discrete expression, mostly in few limbic brain areas, e.g. shell of nucleus accumbens, islands of Calleja, and a considerably higher affinity for dopamine. Two association studies preliminarily suggest that the homozygotes for a D3 receptor gene polymorphism display twofold higher risk of schizophrenia, whereas several linkage studies led to inconclusive results.

Amino Acid Sequence↗