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Biomedical subjects

B Fournier

Publications and source records attributed to B Fournier.

18 recordsLinked to original sources

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

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

Effect of carrageenan-induced inflammation on the binucleate keratinocytes of guinea pig palatal mucosa.

A 1% carrageenan solution was injected into the palatal mucosa of male guinea pigs between the two first molars. Biopsy specimens were taken 1, 3, 6, 12 and 24 hours after the injection. Control specimens with healthy mucosa and tyrode injected mucosa were used in order to evaluate the carrageenan-induced inflammation. An intense inflammatory reaction occurred within hours after the carrageenan solution injection. The palatal epithelium exhibited a considerable increase in the number of binucleate cells (P less than 0.001). As proposed by several authors, the inflammation of the underlying connective tissue might explain this phenomenon. The presence of binucleate cells would be an indication that the migration of epidermal cells from the basal to the horny layer proceeds in a hasty and immature fashion.

Animals

Biochemical values of immigrant groups in north-east France.

Laboratory-test results for a population of immigrants living in north-east France revealed differences between the concentration of the blood constituents of immigrants and native French people. By immigrants we mean persons now living in France but coming from other geographical locations such as Italy, the Iberian Peninsula, northern or central Europe, northern Africa, or the Near or Middle East. Multiple regression analysis confirmed the need to establish reference limits in immigrants for many blood constituents because of a significant shift of the curve relative to that for the French population. We have determined appropriate reference limits, for some ten blood constituents in each group of immigrants.

Adolescent

Comparison between ketanserin and LY 53857 on vascular and cardiac 5-HT2 and alpha 1-adrenergic receptors in the pithed rat.

In normotensive pithed rats, both ketanserin and LY 53857 potently antagonized the increase in blood pressure induced by 5-HT in a noncompetitive manner. However, LY 53857 differs from ketanserin in that it shifts the pressor dose-response curve to 5-HT in a parallel way at low doses but in a noncompetitive way at higher doses. Ketanserin and LY 53857 were weak antagonists of the pressor effects of phenylephrine. LY 53857 was more potent and more selective than ketanserin for 5-HT2 vs alpha 1-adrenergic receptors.

Adrenergic alpha-Antagonists