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Biomedical subjects

B Fournier

Publications and source records attributed to B Fournier.

At least 109 records · Page 6Linked to original sources

Effects of intestinal insulin-like peptide on glucose catabolism in mealworm larval fat body in vitro: dependence on extracellular Ca2+ for its stimulatory action.

In vitro hormonally induced variations of glucose catabolism in mealworm fat body tissue were examined by a microradiorespirometric method. An insulin-like peptide (ILP) extracted from the midgut of last larval instar mealworm larvae significantly modified glucose catabolism and was dependent on energy metabolism and on the Ca2+ concentration in the culture medium. Using two different labelled substrate molecules, the stimulatory effects of ILP (compared with those of mammalian insulin) on the relative use of the pentose cycle as opposed to the glycolytic-citric acid cycle by the mealworm fat body were measured in vitro. Metabolic variations were evaluated using either [1-14C]glucose or [6-14C]glucose as substrates. Time course and dose-response curves of ILP and the hormonally induced variations in total CO2 and 14CO2 kinetics were determined. Modification in the specific radioactivity kinetics of 14CO2 derived from [1-14C] glucose and [6-14C]glucose molecules under hormonal effects were observed. As demonstrated in in vivo studies, ILP stimulated the relative utilization of the pentose cycle. However, this effect was observed much more rapidly, but for a shorter time, with fat body in vitro. Mammalian insulin produced similar, but not identical effects. Variations in transmembranous Ca2+ cellular exchanges, induced by either EGTA, nifedipine, or calcium ionophore ionomycin included in the culture medium, indicated that the stimulatory effects of ILP depends on this cation.

Animals↗

Comparison of the effects of insulin-like growth factors-I and -II on the human osteosarcoma cell line OHS-4.

The effects of insulin-like growth factor-I (IGF-I) and IGF-II on the human osteoblast cell-line OHS-4 were investigated. Both IGF-I and IGF-II stimulated cell proliferation at nanomolar concentrations and alkaline phosphatase activity was decreased in a dose-dependent manner with either IGF-I or IGF-II. The production of the bone-specific protein osteocalcin was not influenced by either IGF-I or IGF-II. However, they acted synergistically with 1,25-dihydroxy-vitamin D3 at concentrations ranging from 10 to 100 nmol/l. Neither IGF-I nor IGF-II had an effect on either the basal or the parathyroid hormone-stimulated level of adenylate cyclase activity, and likewise they had no effect on phosphodiesterase activity. Binding and cross-linking experiments confirmed the presence of both type-I and type-II IGF receptors on the OHS-4 cells. The present study shows that IGF-I and IGF-II have similar effects on the parameters studied in these osteoblastic cells. They influenced both proliferation and differentiation markers.

Adenylyl Cyclases↗

[Peripheral and central participation in hemodynamic effects of serotonin2 receptor stimulation].

The systemic and regional haemodynamic effects of DOI were investigated in the anaesthetized rat. DOI (1-300 micrograms/kg i.v.) increased mean arterial pressure (MAP), total peripheral resistance (TPR) and all regional vascular resistances studied (hindquarters, mesenteric and renal). DOI was more effective on renal vascular bed. Cardiac output (CO) and heart rate (HR) did not change. The effects of DOI were antagonized by LY 53857 (10 micrograms/kg i.v.) and spiperone (10 or 100 micrograms/kg i.v.), selective 5-HT2 receptor antagonists. Intracerebroventricular administration of DOI (100 micrograms/kg) increased MAP, TPR, regional vascular resistances and did not change HR and CO. Pretreatment with xylamidine (10 micrograms/kg i.v.), a selective peripheral 5-HT2 receptor antagonist, blocked i.v. and i.c.v. effects of DOI. These results suggest that: 1) the increase in MAP induced by the stimulation of 5-HT2 receptors is due to an increase in TPR. All regional vascular resistances participate in the increase of TPR. 2) Peripheral and central 5-HT2 receptors seem to be implicated in the control of regional vascular resistances.

Amphetamines↗

[Variations in blood lipid levels in adolescents: relation to changes in lifestyle. A longitudinal approach].

In order to assess the relationship between changes in life style (taking up smoking, giving up sporting activity) and plasma lipids, 3,650 young subjects aged 14 to 18 years, from the Lorraine region, were examined on two occasions separated by a 5 year interval. At the second examination, 39% of the boys and 33.8% of the girls had taken up smoking, and 52% of the boys and 68% of the girls had given up strenuous physical activity. These changes in life style were associated with a significant change in total cholesterol in boys and also of triglycerides after adjustment of values for age and variation in body mass: starting smoking or the giving up of sporting activities was associated with a greater increase in cholesterol and triglyceride levels. These results underline need for increasing efforts in the prevention of cardiovascular disease in young subjects, and emphasise the importance of maintaining physical activity and of not smoking.

Adolescent↗

Neurotransmitters and stimulation of fluid reabsorption in migratory locust rectal cells.

Several biogenic amines enhance fluid reabsorption and the accumulation of cyclic adenosine-monophosphate (cAMP) in the rectum of the migratory locust but only 5-hydroxytryptamine (5-HT) acts in a dose-dependent manner at low concentrations (between 10(-8) and 5.10(-7) M). Cyclic AMP is a second messenger of 5-HT, and its actions on fluid reabsorption are calcium-dependent. Polymyxin B (a protein kinase C inhibitor) mimics the actions of 5-HT on fluid reabsorption and on calcium-dependent cAMP accumulation. This suggests the presence of other sources of calcium and a possible relationship between several transduction systems within different rectal cells. The second messenger system mediating the 5-HT antidiuretic message differs from those involved in the transduction of the known locust antidiuretic hormones.

1-Methyl-3-isobutylxanthine↗

Pharmacological analysis of the cardiac effects of 5-HT and some 5-HT receptor agonists in the pithed rat.

A pharmacological analysis of the effects of 5-HT on heart rate has been performed in the pithed rat. 5-HT induced a dose-dependent increase in heart rate whereas 5-HT1 receptor agonists--8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 5-methoxy-N,N-dimethyl-tryptamine (5-MeODMT), 5-methoxy 3-(1,2,3,6-tetrahydro-4-piridinyl) 1H indole (RU 24969) and 1-(m-trifluoromethylphenyl)-piperazine (TFMPP)--failed to increase heart rate. The increase in heart rate induced by the selective 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodo-phenyl)-2-aminopropane (DOI) was not significant. The dose-response curve to 5-HT for its tachycardic effects was shifted two-fold to the right by ketanserin and LY 53857 and nine-fold to the right by methiothepin. The effects of high doses of 5-HT (higher than 100 micrograms/kg iv) were antagonized by methiothepin, (-)propranolol, 2-(2-[4(O-methoxyphenyl)-piperazine-1-yl]-ethyl)4,4-dimethyl-1,3 (2H-4H) isoquinoline-dione (AR-C 239) and by pretreatment with reserpine. The 5-HT1 receptor antagonists, pindolol and spiroxatrine, the 5-HT3 receptor antagonist MDL 72222 and the alpha 2-adrenoceptor blocking agent idazoxan failed to antagonize the tachycardia induced by 5-HT. It is concluded that in the pithed rat, the tachycardia induced by 5-HT remained unexplained (implication of 5-HT2 receptors probably different from the classical vascular 5-HT2 receptor, or implication of 5-HT1C receptors?). Moreover, at high doses (higher than 100 micrograms/kg iv), 5-HT may increase heart rate by releasing catecholamines.

Animals↗

Characterization of a new human osteosarcoma cell line OHS-4.

We present a new human osteosarcoma cell line designated OHS-4. These cells showed a high alkaline phosphatase activity that is not regulated by 1,25 dihydroxyvitamin D3. They exhibited a sensitive adenylate cyclase response to parathyroid hormone but not to prostaglandin E2 or human calcitonin. By Northern blot analysis we could detect type I collagen mRNA but none for type III collagen. The cells were able to produce human osteocalcin at a maximum level of 35 ng per million cells when exposed to 2.4 nM 1,25-dihydroxyvitamin D3 for 96 h. We purified this protein from conditioned media using successive chromatography and assessed its identity by partial amino acid sequencing. When injected into nude mice, the cells retained their osteogenic activity and developed calcified tumors. After Von Kossa staining, we observed nonmineralized osteoid deposits and mineralized deposits with a structure similar to that of trabecular bone by light microscopy. On the basis of its osteoblastic characteristics, this new osteosarcoma cell line may represent the human counterpart of the ROS 17/2 cell line. This cell line represents a valuable model for the isolation and characterization of human bone specific proteins.

Adenylyl Cyclases↗

[The early diagnosis of cancer of the breast remains insufficient. A study of breast monitoring in women over 50 years of age in Lorraine-Champagne].

Although breast cancer in women over 50 years of age can be detected by physical examination and mammography, in our region many women of that age do not benefit from a satisfactory breast surveillance: 52.4% of women who had a general check-up between February and May 1989 have their breast examined by a physician once a year or more often; only 30% had a mammography less than three years ago; 34.2% examine themselves at least once a month. Overall, only one out of four women aged over 50 is under satisfactory breast surveillance; this small group of women is characterized by a personal history of breast disease or a family history of breast cancer. Women aged between 50 and 59 years tend to have more regular breast examination than older women. Social or geographical particularities do not seem to provide a significant explanation.

Age Factors↗

Relation between debrisoquine oxidation phenotype and morphological, biological, and pathological variables in a large population.

Factors affecting biological variations in debrisoquine-oxidation polymorphism were investigated in a population of 3065 unrelated supposedly healthy Caucasian subjects, ages 35 to 50 years. This population, including 1526 men and 1539 women, was used to determine whether the debrisoquine-oxidation phenotype can be related with environmental factors such as alcohol intake, smoking habits or medication; with morphological variables; or with 22 blood constituents and some pathological states. A single dose of 10 mg of debrisoquine sulfate was administered to determine the oxidation phenotype. A metabolic ratio (debrisoquine/4-hydroxydebrisoquine) of 10.0 defined a poor metabolizer [frequency of 8.2% (SD 1.0%)] in this sample. Dose recoveries of debrisoquine excretion (mean and SD) were 8.9% (11.9%) and 45.1% (32.2%) in extensive and poor metabolizers, respectively. The mean (SD) amount of debrisoquine administered that was excreted in urine as 4-hydroxydebrisoquine was 17.4% (17.3%) in extensive metabolizers and 0.5% (0.9%) in poor metabolizers. The main factors differing significantly between poor and extensive metabolizers were mean cell volume, mean corpuscular hemoglobin concentration, albumin, and ponderal index. No other blood constituents (e.g., cholesterol, glucose) differed between poor and extensive metabolizers. The lack of correlation with most of the variables tested is of interest in clinical trials, because our findings indicate that no subgroups will be required, making selection of subjects easier.

Administration, Oral↗

Purification and characterization of methylenetetrahydrofolate reductase from human cadaver liver.

Methylenetetrahydrofolate reductase from human cadaver liver was purified to homogeneity. The purified enzyme had a molecular mass of 150 kDa. On SDS-polyacrylamide gel electrophoresis it was dissociated into a single fragment with a molecular mass of 39 kDa. In contrast, fresh lymphocyte enzyme extract showed a major band with a molecular mass of 75 kDa and a minor band of 39 kDa. Fresh liver enzyme was inhibited by S-adenosylmethionine while the purified enzyme from human cadaver liver was not inhibited. These observations suggest that human methylenetetrahydrofolate reductase is composed of two identical subunits of 75 kDa each but is cleaved into a major single band due to autolysis in cadaver liver. The purified cadaver enzyme was a FAD-specific protein. The pH optimum was 6.6 for methylenetetrahydrofolate-NADPH oxidoreductase, 6.5 for methyltetrahydrofolate-menadione oxidoreductase, and 7.2 for NADP-menadione oxidoreductase. The Km values of human liver methylenetetrahydrofolate reductase were 17 microns for NADPH and 38 microns for methyltetrahydrofolate in the reduction of menadione, and 12 microns for NADPH in the reduction of methylenetetrahydrofolate.

Cadaver↗

Plasma osteocalcin: biological variations and reference limits.

Osteocalcin, the most abundant non-collagenous protein in the bone matrix, is partly released in blood. We have measured its concentration by a radio-immunoassay procedure in 1096 apparently healthy subjects from both sexes who came for a health screening examination. Their ages varied from 4 years to over 65 years. Venous blood was drawn in the morning from fasting subjects. Plasma osteocalcin was higher in men than in women. Its level increased significantly with age, body weight, height and bone age until age 12-13 years in girls and 14-15 years in boys. In women, osteocalcin level increased after the age of 50 years and was higher than in men. It remained constant over age 60 years in both sexes, but was higher in women. There was no effect of menstrual cycle in girls at puberty. Plasma osteocalcin did not vary with follicular and luteal phases or with the use of oral contraceptive drugs in women. The usual nonsteroid anti-inflammatory drugs had no effect on blood osteocalcin level. Reference limits according to age and sex are provided.

Adolescent↗

DOI is a mixed agonist-antagonist at postjunctional 5-HT2 receptors in the pithed rat.

The maximal pressor effect induced by DOI in the pithed rat was smaller than that induced by 5-HT, suggesting partial agonistic properties of DOI. DOI shifted the dose-pressor response curve of 5-HT to the right. It is concluded that, in addition to its 5-HT2 agonistic properties, DOI also possesses 5-HT2 antagonistic properties in the pithed rat.

Amphetamines↗

Characterization of DOI, a putative 5-HT2 receptor agonist in the rat.

DOI (1-100 micrograms/kg i.v.) induced an increase in mean blood pressure in the anaesthetized rat. Similarly, in the pithed rat, DOI (1-100 micrograms/kg i.v.) induced a dose-dependent increase in mean blood pressure, as did 5-HT. However, in contrast to 5-HT, DOI did not change the heart rate in either intact or pithed rats. In the pithed rat, the dose-pressor response curves to both 5-HT and DOI were unaffected by MDL 72222 (5-HT3 receptor antagonist), spiroxatrine or (+/-)-pindolol (5-HT1A receptor antagonists), idazoxan (alpha 2-adrenoceptor blocking agent) and AR-C 239 (alpha 1-adrenoceptor blocking agent). Only the selective 5-HT2 receptor antagonist. LY 53857, significantly and dose dependently shifted to the right the dose-response curves to both 5-HT and DOI. These results indicated that DOI possesses 5-HT2 agonistic properties and that the pressor response induced by DOI in the pithed rat is mediated via 5-HT2 receptors.

Amphetamines↗

Evidence that free gamma carboxyglutamic acid circulates in serum.

We report a rapid, sensitive and reproducible method to measure free gamma-carboxyglutamic acid (GLA) in serum using precolumn derivatization with O-phthalaldehyde, reversed-phase chromatography and deproteinization of serum by ultrafiltration. Serum free GLA level in 62 healthy adults was 167 +/- 46 pmol/ml and was increased (302 +/- 195 pmol/ml) in 14 patients with primary hyper-parathyroidism, a disease characterized by an increased bone turnover. Peptide bound GLA averaged 413 pmol/ml. In rabbits receiving massive doses of warfarin during 6 days there was a time- and dose-dependent decrease of serum free GLA but a significant fraction was still measurable. These data indicate that free GLA circulates and originates both from the metabolism of the vitamin K-dependent clotting factors and from bone metabolism.

1-Carboxyglutamic Acid↗

[Multiple primary lung cancers. The importance of early diagnosis and survival after a new surgical excision].

In a series of 1.025 consecutive resections for bronchogenic carcinoma, 68 patients developed a second primary lung cancer identified as the first site of recurrence (median interval of 38 months). Thirty-nine patients (57%) were asymptomatic (detection by chest-X-Ray (N: 28] or sputum cytology (N: 11) and 22 had one or more symptoms. A reoperation was possible in 50% (N: 34) of all patients with an operative (30 day) mortality of 14.7% (5/34) as compared to 3.5% (26/1.025) for the first procedure. Cumulative survival following the second resection was 33% at 5 years while no inoperable patient survived longer than three years. Clinical presentation of the second carcinoma is a significant prognostic variable since no symptomatic patient survived more than two years while 30% of the asymptomatic group survived 5 years (p less than 0.021).

Actuarial Analysis↗