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Biomedical subjects

G Levesque

Publications and source records attributed to G Levesque.

34 records · Page 2Linked to original sources
PubMed1995

Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease.

Some cases of Alzheimer's disease are inherited as an autosomal dominant trait. Genetic linkage studies have mapped a locus (AD3) associated with susceptibility to a very aggressive form of Alzheimer's disease to chromosome 14q24.3. We have defined a minimal cosegregating region containing the AD3 gene, and isolated at least 19 different transcripts encoded within this region. One of these transcripts (S182) corresponds to a novel gene whose product is predicted to contain multiple transmembrane domains and resembles an integral membrane protein. Five different missense mutations have been found that cosegregate with early-onset familial Alzheimer's disease. Because these changes occurred in conserved domains of this gene, and are not present in normal controls, they are likely to be causative of AD3.

Alzheimer Disease↗
PubMed1995

[Long acting sandostatine (sandostatine LAR) in the treatment of acromegaly].

A long-acting depot formulation of octreotide (Sandostatin LAR, Sandoz LTD) has been recently developed. Preliminary studies indicated that, in acromegalic patients previously controlled by Sandostatin 300-600 micrograms/day in 2-3 sc injections, the intramuscular administration of 20-30 mg of Sandostatin LAR achieved, during one month a similar control of GH hypersecretion. In the present study, the variations of plasma levels of octreotide, GH and IGF1 were followed during 2 months in acromegalic patients receiving a unique injection of 20 mg (n = 4) or 30 mg (n = 4) of Sandostatin LAR. Following Sandostatin LAR 20 mg i.m, the baseline values of GH (8.1 +/- 2.5 micrograms/l) and IGF1 (684 +/- 92 micrograms/l) were normalized after 2 weeks and remained into the normal range during the 28 following days. Similar results were obtained, after a 30 mg i.m administration of Sandostatin LAR. In this later case, the maximal inhibition of GH and IGF1 (1.3 +/- 1.0 micrograms/l and 392 +/- 266 micrograms/l respectively) lasted 2 months. These data showed that a monthly injection of Sandostatin LAR (20-30 mg) allowed a correct control of GH hypersecretion in this series of acromegalic patients.

Acromegaly↗
PubMed1988

Application of the reaction of dithioesters with epsilon-amino groups in lysine to the chemical modification of proteins.

The reaction of lysine with dithioesters was applied to horseradish peroxidase donor: hydrogen-peroxide oxidoreductase, EC 1.11.1.7) using carboxymethyl dithiotridecanoate: three to four lysine residues were modified. The modified enzyme was soluble and active in diethyl ether. Papain (EC 3.4.22.2) was modified with carboxymethyl dithiobenzoate: two lysine residues were modified. The modified enzyme was soluble and active in dimethylsulfoxide. From these results it is concluded that dithioesters are efficient reagents for the modification of peripheral lysine residues of proteins. Aromatic dithioesters, less reactive but more selective, should be recommended for thiol-dependent enzymes such as papain.

Amines↗
PubMed1985

Effects of trichothecenes (T-2 toxin) on protein synthesis in vitro by brain polysomes and messenger RNA.

The effects of T-2 toxin on protein synthesis were tested in two reticulocyte lysate in vitro systems pretreated with micrococcal nuclease. One of the test systems contained purified globin mRNA and was initiation dependent. The other contained rat brain polysomes and incorporated amino acids by an elongation dependent process. T-2 toxin inhibited the translation of globin mRNA at all concentrations tested, from 10(-8) M to 10(-4) M. Rat brain polysomes were much less sensitive to T-2 toxin than globin mRNA. While high concentrations of the toxin (10(-4) M) led to partial inhibition of protein synthesis by polysomes, low concentrations (10(-8) M and 10(-6) M) stimulated protein synthesis. Comparison of the above results with those obtained by other workers suggest that the T-2 toxin may inhibit not only the initiation step of translation, but also elongation and termination, depending upon the concentration of the toxin and the nature of the translation system. A similar mechanism may operate for all the trichothecene toxins that exert their effect through binding to ribosomal peptidyl transferase.

Animals↗
PubMed1982

Possible involvement of the amygdaloid complex in morphine analgesia as studied by electrolytic lesions in rats.

The analgesic effects of morphine (5 mg/kg i.p.) were studied in biamygalectomized rats. (1) Using the tail-flick test neither withdrawal latencies nor morphine time-course and efficacy were affected by the lesions. (2) The threshold for vocalization to electrical stimulation of the tail was greatly increased in lesioned rats; however, statistical analysis revealed no significant change in the analgesic efficacy of morphine.

Amygdala↗
PubMed1981

Low-dose heparin in gynecologic surgery: effect on blood coagulation tests.

The laboratory control of low-dose heparin therapy is generally regarded as unnecessary. A laboratory study of the effects of low-dose heparin was performed using different methods: an amidolytic method and a method involving the inhibition of factor Xa in a coagulation test. Variations in partial thromboplastin time, recalcification clotting time, thrombin time and the plasma antithrombin III levels were also studied. These tests were repeated (days 0, 1, 3, 8) in 27 women between the ages of 27 and 62 years who were undergoing gynecological surgery. They received 5,000 IU of heparin either twice or thrice daily. There was no correlation between heparin levels in the blood and global clotting tests simultaneously performed. The plasma heparin levels varied between 0 and 0.15 IU/ml with both methods. A detectable heparin concentration on days 1, 3 and 8 was present in only half of the cases receiving the twice daily regimen. The plasma antithrombin III activity and concentration were not modified during treatment.

Adult↗
PubMed1979

A simple device for uniform inoculation of nutrient surfaces.

A simple and inexpensive device for uniform surface inoculation is described. Efficiency and uniformity of inoculation were estimated with agar plates exposed to a bacterial suspension, containing 10 different strains, atomized with a spray gun. The fine mist settled, after a fall of 106 cm, upon the agar surfaces at the bottom of a cylindrical chamber. No significant differences were observed with regard to uniformity of inoculation between nine plates.

Agar↗
PubMedDate not supplied

Epileptic discharges induced by intermittent light stimulation in photosensitive baboons: a current source density study.

The current source density (CSD) method was applied to the study of paroxysmal discharges (PDs) induced by intermittent light stimulation (ILS) in Papio papio baboons made photosensitive by a subconvulsant dose of allylglycine. CSD was studied in the motor and premotor areas (4 and 6). Laminar profiles of sinks and sources are similar in both areas. Nevertheless, the motor area seems to become involved first since it shows the earliest and most prominent sink in layer III. Such a sink, correlated with the PD spike, moves progressively upward to the cortical surface. The localization and other experimental arguments obtained by the same method suggest that this sink could be mainly of dendritic origin. The cortico-cortical afferents to the superficial layers of the motor area might thus determine the generation of this sink. A smaller sink, detected at the same latency between layers V and VI could correspond to synaptic activations due to thalamo-cortical afferents probably arriving on the pyramidal cells which project to the spinal cord. Intense sinks correlated with the PD wave in layer V could be passive, due to active sources lying just above and/or below, because in previous studies an inhibition of the cellular discharges was always observed in correlation with the wave. It is suggested that ILS triggered PDs involve visual cortico-cortical afferents directed mainly to the superficial layers of the motor area provoking an intense synaptic activation of the cellular elements situated at this level.

Allylglycine↗
PubMedDate not supplied

Normal brain development in PS1 hypomorphic mice with markedly reduced gamma-secretase cleavage of betaAPP.

Presenilin 1-null mice die at birth from brain and skeletal developmental deformities due to disrupted Notch signaling. Presenilin 1-null mice also have severely reduced gamma-secretase cleavage of betaAPP. The assumption has been that facilitation of Notch signaling and betaAPP processing by presenilin 1 are analogous functions. Here we describe a presenilin 1-targetted mouse model that expresses extremely low levels ( approximately 1% of normal) of mutant PS1-M146L. Homozygous mice have significantly reduced viability due to a Notch-like phenotype. The animals that survive have severe axial skeletal deformities and markedly diminished gamma-secretase activity and accumulation of betaAPP-C100, but no obvious abnormalities in brain development. These results suggest that, in mice, a marked reduction of PS1-facilitated gamma-secretase activity is not detrimental to normal brain development.

Amyloid Precursor Protein Secretases↗
PubMedDate not supplied

Presenilin 1 is actively degraded by the 26S proteasome.

The metabolic pathways governing the turnover of presenilin 1 (PS1) have been incompletely worked out. The PS1 holoprotein has low abundance in many cells and appears to undergo endoproteolytic cleavage near residue 298. We provide evidence that one mechanism by which the PS1 holoprotein is degraded is through the action of the 26S proteasome. We also show that the proteasome does not participate in the endoproteolytic cleavage.

Alzheimer Disease↗