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Biomedical subjects

P Leone

Publications and source records attributed to P Leone.

At least 73 records · Page 4Linked to original sources
PubMed1994

Direct measurement of extracellular lactate in the human hippocampus during spontaneous seizures.

The effect of clinical, spontaneous-onset seizures on extracellular fluid lactate was investigated by the method of lactography, the in vivo on-line measurement of lactate levels using microdialysis. Studies of experimental animals have suggested that generation of extracellular lactate as measured by microdialysis is an index of local glucose utilization and is dependent on the activity of neurons under physiological conditions. Patients with medically refractory complex partial epilepsy underwent stereotactic implantation of combination depth electrode/microdialysis probes into both hippocampi for 7-16 days. During spontaneous complex partial seizures with secondary generalization, extracellular lactate levels rose by 91 +/- 32%. Moreover, this increase persisted for 60-90 min. During a unilateral hippocampal seizure that did not propagate to the contralateral hippocampus, the increase in lactate content was restricted to the side of seizure activity. Between seizures, extracellular lactate levels correlated with the frequency of interictal spikes. In summary, these data suggest that brief clinical seizures increase nonoxidative glucose metabolism significantly as measured by the generation of extracellular lactate. Furthermore, the increase in extracellular lactate levels is limited to the site of seizure activity. Lactate is transported extracellularly via a lactate/proton cotransporter, therefore, the rise in extracellular lactate level may mediate the drop in pH0 associated with seizure activity. As acidification of the extracellular compartment has an inhibitory effect on neuronal excitability, the rise in extracellular lactate content may be a mechanism of seizure arrest and postictal refractoriness. Moreover, extracellular lactate may also mediate the decreased seizure susceptibility associated with frequent interictal spikes.

Adolescent↗
PubMed1994

Direct characterization of bovine microsatellites from cosmids: polymorphism and synteny mapping.

A (TG)8 oligonucleotide probe was used to screen 186 cosmids from a commercial bovine cosmid library. Of the 56 positive discovered, 7 were sequenced in the region of the microsatellite and analysed for polymorphism. These microsatellites, IDVGA-2, -3, -7, -8, -9, -10, -11 showed the following number of alleles and polymorphism information content (PIC) values (7/0.616, 8/0.693, 6/0.641, 5/0.643, 2/0.239, 10/0.844, 6/0.720). The microsatellites were also assigned to synteny groups as follows: IDVGA-2/U17, IDVGA-3/U16, IDVGA-7/U7, IDVGA-8/U29, IDVGA-9/U3, IDVGA-10/U19, IDVGA-11/A (probably U18).

Animals↗
PubMed1993

Mesolimbic dopamine neurotransmission is increased by administration of mu-opioid receptor antagonists.

Microdialysis and high pressure liquid chromatography were used to assess the effects of ventral tegmental area microinjections of the mu-opioid receptor antagonists D-Pen-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) and beta-funaltrexamine (beta-FNA) on extracellular ventral striatal dopamine and metabolite concentrations. While CTOP is known to antagonize the increases in extracellular ventral striatal dopamine and dopamine metabolite concentrations induced by ventral tegmental area microinjections of a mu-opioid receptor agonist, it produced dose-orderly increases in ventral striatal dopamine and dopamine metabolite concentrations when administered by itself. beta-FNA also elevated dopamine and metabolite concentrations. These mu-agonist-like effects of the mu-opioid receptor antagonists were unexpected and suggest that a complex local circuitry mediates opioid-dopamine interactions in the ventral tegmental area. Since mu-opioids are known to act on ventral tegmental neurons that contain gamma-aminobutyric acid (GABA), a model of interactions between GABAergic afferents to the ventral tegmental area and ventral tegmental GABAergic interneurons is proposed.

Amino Acid Sequence↗
PubMed1993

Ventral mesencephalic delta opioid receptors are involved in modulation of basal mesolimbic dopamine neurotransmission: an anatomical localization study.

Microdialysis was used to examine the anatomical localization of mesencephalic delta opioid receptors that participate in modulation of mesolimbic dopamine (DA) neurotransmission. Independent groups of rats were injected with DPDPE into the ventral tegmental area (VTA) or interpeduncular nucleus (IPN). Extracellular nucleus accumbens DA and DOPAC concentrations were elevated after DPDPE injections into either site, but injections into the VTA were effective at lower doses than were injections into the IPN. Thus, it appears that the DA-modulating actions of DPDPE are mediated in the VTA rather than the IPN.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Construction of a library of bovine genomic fragments enriched in CpG islands.

A procedure is described to isolate DNA probes from the bovine genome that are enriched in sites for the so-called rare cutter restriction endonucleases. A collection of SacII (CvCGCGG)-Hin-dIII fragments from bovine sperm was established in the plasmid Bluescript. 180 clones were picked at random and analysed for the presence of inserts with sites for the following rare cutters: EagI, BsshII, NarI, MluI, NruI, NaeI: 70% of the clones contained at least 1 site and 5% contained four different such sites. 22.8% had multiple sites for one or more of the rare cutters tested. Sequence analysis for 16 clones confirmed the cloning of DNA with a G+C content and a proportion of CpG vs GpCs indicative of CpG islands.

Animals↗
PubMed1993

Striatal tissue preparation facilitates early sampling in microdialysis and reveals an index of neuronal damage.

Injury-induced efflux of dopamine was compared between two microdialysis preparations. Rats were implanted with guide cannulae 5-10 days prior to microdialysis experiments. In one group, ventral striatal tissue was punctured with stainless steel obturators that remained in place until the day of the experiment. In the other group, the tissue was not punctured until the microdialysis probes were inserted. Rats from each group were dialyzed with calcium-free artificial extracellular fluid or tetrodotoxin 4 h after probe insertion. In the rats with previously punctured tissue, calcium depletion reduced dialysate dopamine concentrations to 8% of baseline. Dialysis with tetrodotoxin reduced dopamine concentrations to less than 1% of baseline. In the rats with freshly punctured tissue, dopamine concentrations were reduced only to 50% of baseline levels by calcium depletion and to 30% during dialysis with tetrodotoxin. Thus, penetration of the tissue prior to testing can significantly reduce the acute injury-induced efflux of dopamine. Further, a significant correlation was found between baseline 3,4-dihydroxyphenylacetic acid/dopamine ratios and the efficacy of tetrodotoxin in reducing dialysate dopamine concentrations. Thus, basal 3,4-dihydroxyphenylacetic acid/dopamine ratios appear to provide an index of the amount of injury-induced dopamine efflux following probe insertion.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Differential involvement of ventral tegmental mu, delta and kappa opioid receptors in modulation of basal mesolimbic dopamine release: in vivo microdialysis studies.

In vivo microdialysis was used to assess the involvement of ventral tegmental area (VTA) mu, delta, and kappa opioid receptors in modulation of basal extracellular ventral striatal dopamine (DA) and DA-metabolite concentrations. Independent groups of chloral hydrate-anesthetized rats were given VTA microinjections of selective opioid agonists, and extracellular ventral striatal DA and DA-metabolite concentrations were assayed using HPLC. VTA microinjections of [D-Ala2, N-Me-Phe4-Gly5-ol]-enkephalin (DAMGO; a mu agonist) and [D-Pen2, D-Pen5]-enkephalin (DDDPE; a delta agonist) each caused dose-orderly increases in ventral striatal DA and DA-metabolite concentrations. The effective concentrations of DPDPE were 100- to 1000-fold higher than the effective concentrations of DAMGO. VTA microinjections of (trans-(dl)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclo-hexyl]- benzeneacetamide) methane sulfonate hydrate (U-50,488H); a kappa agonist) failed to alter ventral striatal DA concentrations at any dose tested, but subsequent systemic injections significantly decreased DA and DA-metabolite concentrations. Pretreatment with VTA microinjections of 17-cyclopropylmethyl-6,7-dehydro-4,5-epoxy-3,14-dihydroxy-6,7,2',3'- indolmorphinan hydrochloride (naltrindole; a delta antagonist) (delta antagonist) antagonized VTA DPDPE-mediated increases in ventral striatal DA and DA-metabolite concentrations but failed to antagonize VTA DAMGO-mediated increases. Pretreatment with D-Pen-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP; a mu antagonist) antagonized VTA DAMGO-mediated increases but failed to antagonize VTA DPDPE-mediated increases. Thus both mu and delta receptor agonist appear capable of increasing ventral striatal DA and DA-metabolite concentrations through selective actions on their preferred class of opioid receptors in the VTA. The increases in ventral striatal DA and DA-metabolite concentrations that are seen after systemic treatment with kappa opioid agonists appear not to involve VTA opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1992

Direct sequencing and bidirectional allele specific polymerase chain reaction of the bovine beta-casein B variant.

We have used the polymerase chain reaction (PCR) to amplify exon VII of the bovine beta-casein gene. The mutations responsible for the B variant were identified by direct sequencing of the amplification products. A bidirectional allele-specific PCR method (BAS-PCR) has been developed using oligonucleotides overlapping the mutation site at their 3' ends. This new procedure allows a rapid and reliable discrimination between the B and non-B alleles of beta-casein.

Alleles↗
PubMed1991

Morphine-dopamine interaction: ventral tegmental morphine increases nucleus accumbens dopamine release.

Microdialysis and high-performance liquid chromatography with electrochemical detection were used to determine extracellular levels of dopamine following ventral tegmental morphine injections into chloral hydrate-anesthetized rats. Morphine (13.2 nanomoles in 0.5 microliter of Ringer's solution) caused 50-150% increases in nucleus accumbens dopamine and metabolites; latency for the effect was on the order of 15 min with peak effects occurring in 30-50 min. Contralateral dopamine levels were influenced only minimally. These data suggest opiate receptors in or near the ventral tegmental area as sites of the opioid action that is responsible for opioid activation of the mesolimbic dopamine system.

Animals↗
PubMed1990

Long range restriction analysis of the bovine casein genes.

Pulsed field gel electrophoresis (PFGE) was used to analyse the organization of the bovine alpha s1, alpha s2, beta and kappa casein genes. High molecular weight DNA was prepared from fibroblasts and lymphocytes embedded in agarose and was digested with the restriction endonucleases Clal, Sall, Smal, Xhol. The digestion products were separated by PFGE, transfered to nitrocellulose filters and hybridized to probes corresponding to the cDNAs of the four bovine casein genes. The casein genes were demonstrated to be physically linked within a region of 300 kb, represented by two adjacent Xhol fragments in fibroblasts and by a single fragment in lymphocytes. A restriction map of the casein locus was derived and the order of the genes was shown to be kappa, alpha s2, beta, alpha s1.

Animals↗
PubMed1990

Genetic variation and distances of five Italian native sheep breeds.

Genetic distances among five of the most important Italian native sheep breeds were estimated by using gene frequencies of four blood group and seven blood protein loci and by three different computing methods. The values of the three distance matrices were highly correlated. Genetic distances were found within the range values reported in the literature for local breeds. Shorter distances fitted the historical evidence of migrations.

Animals↗
PubMed1989

5HT3 receptor antagonists block morphine- and nicotine- but not amphetamine-induced reward.

The effect of two potent and specific antagonists of 5HT3 receptors, ICS 205-930 and MDL 72222, on the reinforcing properties of amphetamine, morphine and nicotine was studied in rats. Drug-induced reinforcement was assessed by measuring drug-conditioned place preference. ICS 205-930 and MDL 72222 dose-dependently reduced the place preference induced by morphine (1.0 mg/kg SC). At doses of 0.030 mg/kg SC the two antagonists completely blocked morphine-induced place preference while doses of 0.015 mg/kg SC significantly reduced it. ICS 205-930 and MDL 72222 at doses of 0.030 mg/kg SC also prevented the place preference induced by nicotine (0.6 mg/kg SC). In contrast, ICS 205-930 and MDL 72222 up to doses of 0.030 mg/kg SC failed to modify the place preference elicited by amphetamine (1.0 mg/kg SC). The results indicate that 5HT3 receptors are specifically involved in the reinforcing properties of morphine and nicotine.

Amphetamine↗
PubMed1989

SCH 23390 blocks drug-conditioned place-preference and place-aversion: anhedonia (lack of reward) or apathy (lack of motivation) after dopamine-receptor blockade?

The influence of the D1 antagonist SCH 23390 on the motivational properties of rewarding (morphine, nicotine and diazepam) and aversive (naloxone, phencyclidine and picrotoxin) drugs was studied in the rat in a two-compartment place-conditioning paradigm, which included a pre-conditioning test for spontaneous place-preference. The specific D1 dopamine-receptor antagonist SCH 23390 (0.05 mg/kg SC), paired with both compartments or, separately, with the preferred or with the non-preferred compartment, failed to affect the spontaneous unconditioned preference of the animal. Pairing of morphine (1.0 mg/kg SC), nicotine (0.6 mg/kg SC) or diazepam (1.0 mg/kg IP) with the less preferred compartment induced significant preference for that compartment. Pairing of SCH 23390 (0.05 mg/kg SC) with both compartments completely blocked the place-preference induced by morphine, nicotine and diazepam. Naloxone (0.8 mg/kg SC), phencyclidine (2.5 mg/kg SC) or picrotoxin (2.0 mg/kg IP) paired with the preferred compartment elicited place-aversion. Pairing of SCH 23390 (0.05 mg/kg SC) with both compartments abolished also the place-aversion induced by naloxone, phencyclidine and picrotoxin. The results indicate that blockade of dopamine transmission blocks the motivational properties of rewarding as well as aversive stimuli. It is suggested that neuroleptics rather than simply blocking the rewarding impact of positive reinforcers (anhedonia, lack of pleasure) exert a more general influence on conditioned behaviour by blocking the affective impact of negative as well as positive reinforcers (apathy, lack of motivation).

Animals↗
PubMed1987

Blockade of D-1 receptors by SCH 23390 antagonizes morphine- and amphetamine-induced place preference conditioning.

Morphine (0.5 mg/kg s.c.) and amphetamine (1 mg/kg s.c.) used in a two-compartment place preference test induced strong place preference when paired to the non-preferred environments. They did not modify preference under basal conditions but completely reversed morphine- and amphetamine-induced place preference. Pairing of haloperidol (0.2 mg/kg s.c.) to both environments also abolished the morphine-induced place preference.

Amphetamine↗
PubMed1978

Verrucous lesion in patients with discoid lupus erythematosus. Clinical, histopathological and immunofluorescence studies.

Seven cases of classical discoid lupus erythematosus of the face associated with hyperkeratotic, papulo-nodular lesions on the arms and hands were studied. Clinically the hyperkeratotic lesions resembled keratoacanthomas or hypertrophic lichen planus. The clinical course was marked by chronicity, an absence regression of the lesions, and resistance to treatment. Histopathologically, a lichenoid cellular reaction seemed to play a key role in the development of the hypertrophic lesions which resembled either keratoacanthomoas or hypertrophic lichen planus. Elastic fibres were prominent in the upper dermis, the lower levels of the epidermis and in the hyperkeratotic horny layer. Immunofluorescence of the papulo-nodular lesions demonstrated the deposition of IgG and IgM in a globular pattern at the dermal-epidermal junction. Discontinuous deposition of these antibodies was also seen at the basement membrane zone. On the basis of the immunofluorescence, histopathological and clinical studies, we suggest that the verrucous, hyperkeratotic lesions on the upper extremities represent an unusual, but distinct, form of discoid lupus erythematosus.

Adult↗