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Biomedical subjects

M Bouvier

Publications and source records attributed to M Bouvier.

At least 181 records · Page 10Linked to original sources

Hypohaptoglobinaemia as an epidemiological and clinical indicator for malaria. Results of two studies in a hyperendemic region in West Africa.

Hypohaptoglobinaemia is a common phenomenon in tropical countries, where it is probably due to malaria-induced haemolysis. Two studies were carried out in a hyperendemic zone of West Africa to test its specificity and usefulness as an epidemiological indicator for measuring malaria endemicity. The first study evaluated the prevalence of hypohaptoglobinaemia before and after courses of antimalarial chemotherapy of varying duration. The second monitored haptoglobin levels in an untreated population during a whole year to compare its seasonal variations with those of several classic indicators of malaria. These studies suggest that in regions where malaria is endemic the prevalence of hypohaptoglobinaemia could be as useful an indicator as the parasitic index but would be much easier to establish and to monitor.

Adolescent↗

Removal of phosphorylation sites from the beta 2-adrenergic receptor delays onset of agonist-promoted desensitization.

Eukaryotic cells have evolved a variety of mechanisms for dampening their responsiveness to hormonal stimulation in the face of sustained activation. The mechanisms for such processes, collectively referred to as desensitization, often involve alterations in the properties and number of cell-surface hormone receptors. It has been speculated that phosphorylation-dephosphorylation reactions, which are known to regulate the catalytic activities of enzymes, also regulate the function of receptors. Highly specific receptor kinases, such as rhodopsin kinase and beta-adrenergic receptor kinase, which show stimulus-dependent phosphorylation of receptors have been described. Direct evidence for a causal relationship between receptor phosphorylation and desensitization has been lacking however. Here we report that prevention of agonist-stimulated beta 2-adrenergic receptor (beta 2AR) phosphorylation by truncation of its serine and threonine-rich phosphate acceptor segment delays the onset of desensitization. We also show that selective replacement of these serine and threonine residues by alanine and glycine delays desensitization even further. These data provide the first direct evidence that one molecular mechanism of desensitization of G-protein-coupled receptors involves their agonist-induced phosphorylation.

Amino Acid Sequence↗

[Serum, synovial and intra-articular pharmacokinetics of naproxen after one-gram oral administration in patients with rheumatoid polyarthritis].

After a reminder of the major points of the pharmacokinetics of non-steroid anti-inflammatory drugs, the authors report the results of a multicentric study of the kinetics of naproxen after oral intake of one single dose of 1 gram in patients with rheumatoid arthritis. The half-life is longer in the synovial fluid than in the serum, 23 hours versus 17 hours. The balance point is obtained at the 24th hour and, at that time, the naproxen level in the synovium and the joint fluid are 32 and 60 p. cent, respectively, of the corresponding maximum concentrations.

Administration, Oral↗

The effect of diet texture on healing following temporomandibular joint discectomy in rabbits.

This study evaluates the healing of the rabbit temporomandibular joint (TMJ) following discectomy in animals fed coarse or ground diets. Twenty New Zealand rabbits were divided into four groups with two unoperated groups serving as controls. A unilateral discectomy was performed and the animals were placed on either a regular (coarse) or a ground diet immediately following surgery. After 3 months, histologic evaluation demonstrated that fibrocartilage thickness was greatest in the discectomy-coarse diet operated joint, less in the discectomy-ground diet operated joint, still less in the discectomy-coarse diet unoperated joint, and unaffected in the control animals. The results of this study demonstrate that diet texture can affect TMJ healing following discectomy. The adverse responses of the coarse diet affected not only the operated joint but also the unoperated contralateral joint.

Animals↗

Phosphorylation of the rev gene product of human immunodeficiency virus type 1.

Replication of human immunodeficiency virus type 1 requires the functional expression in trans of the virally encoded rev gene product (previously called art/trs). Here we demonstrate that this protein can be metabolically labeled with 32Pi. The phosphate receptor in the rev protein is shown to be exclusively serine. Treatment of rev-expressing cells with phorbol ester, a specific activator of protein kinase C, led to significant but transient enhancement of the level of rev phosphorylation. These results indicate that the rev protein is posttranslationally modified in vivo and suggest that the level of this modification is subject to modulation by extracellular stimuli.

Electrophoresis, Polyacrylamide Gel↗

Effects of age on the ability of the rat temporomandibular joint to respond to changing functional demands.

This investigation examined the ability of the tissues of the temporomandibular joint (TMJ) to adapt to changing functional demands in young, growing rats compared with mature rats. Functional demands on the TMJ were varied by feeding diets with different physical consistencies. The first group was fed a soft diet for the experimental period. The second group was fed a hard diet, and the third group was initially fed the soft diet, then switched to the hard diet at the mid-point of the experimental period. Gross dimensions of the condyle, mandible, and maxilla were measured with calipers. Thickness of the articular, proliferative, transitional, and hypertrophic zones of the condylar cartilage, and the amount of bone in the subcondylar region and condylar neck were measured on histological sections. Gross dimensions of the condyle were significantly smaller in the soft-diet group compared with the hard- and soft/hard-diet groups in both growing and mature rats. The individual zones of the condylar cartilage were also significantly narrower in the soft-diet group in both growing and mature rats. However, the soft/hard-diet group of mature rats showed only a significant reduction in the thickness of the articular zone of the condylar cartilage compared with the hard-diet group. There were also narrower proliferative and transitional zones in the mature rats fed a soft/hard diet. In contrast, all of these zones showed full recovery in the young rats fed a soft/hard diet. The data presented here suggest that increasing age may diminish the capacity of the TMJ to adapt to altered function and consequently may play a significant role in the development of degenerative joint disease.

Adaptation, Physiological↗

Expression of a human cDNA encoding the beta 2-adrenergic receptor in Chinese hamster fibroblasts (CHW): functionality and regulation of the expressed receptors.

A human beta-adrenergic receptor cDNA was transfected and expressed in transformed Chinese hamster fibroblasts (CHW). The expressed receptor exhibited a typical beta 2-adrenergic selectivity for agonists and antagonists as assessed by radioligand binding and adenylate cyclase activation. Guanine nucleotide-sensitive high affinity binding of the agonist, isoproterenol, indicated effective coupling of the expressed receptor to a guanine nucleotide-regulatory protein. The level of expression of beta 2-AR in various cell clones varied over 200-fold and was positively correlated with the levels of beta 2-AR mRNA. In cells expressing between 0.04 and 3.0 pmol of beta 2-AR/mg of membrane protein, the efficacy of isoproterenol for stimulating adenylate cyclase increased with increasing numbers of expressed receptors but reached a plateau and started to decrease in clones with higher beta 2-AR density (3.0-8.0 pmol/mg of membrane protein). Preincubation of beta 2-AR-expressing cells with isoproterenol for 15 min led to significant reduction in the level of isoproterenol-sensitive adenylate cyclase activity. This agonist-induced desensitization was also accompanied by phosphorylation of the beta 2-AR. These data indicate that the expressed human beta 2-AR displays typical functional characteristics of adenylate cyclase-coupled receptors including agonist-induced desensitization. Moreover, the availability of this series of cellular clones, which differ markedly in their density of beta 2-AR, provides a unique set of biological reagents for future studies of beta 2-AR function and regulation.

Adenylyl Cyclases↗

[Mucociliary function of 10 patients with ankylosing spondylarthritis with normal lung radiographs].

Bi-apical pulmonary fibrosis particular to ankylosing spondylitis is found in 1 to 10% of cases. The non-specific fibrosis or fibrosis of a more specific character such as iritis or the aortic disease are discussed. The fibrosis may be provoked by repeated infections which would favour an eventual hypoventilation at the apices secondary to the rigidity of the thoracic cage. To test this hypothesis we have studied muco-ciliary clearance in 10 subjects presenting with ankylosing spondylitis without any pulmonary radiological lesion and have compared these to 7 control subjects. No statistical difference was found in the clearance rate between the control subjects and the patients on the one hand (whether or not they had extra articular manifestations) and between the different areas of the lung (notably superior and inferior) in patients on the other hand. Thus this bi-apical fibrosis does not seem to explain the phenomena repeated infections at the apices which might have been favoured by any secondary deficiency in muco-ciliary clearance and hypoventilation of the apices. It seems most likely that the fibrosis has a specific origin related to the nature of the disease.

Adult↗

The multiple membrane spanning topography of the beta 2-adrenergic receptor. Localization of the sites of binding, glycosylation, and regulatory phosphorylation by limited proteolysis.

The beta 2-adrenergic receptor (beta-AR) is an integral membrane glycoprotein of apparent Mr approximately equal to 64,000. The amino acid sequence deduced from the beta-AR gene reveals homology with the visual pigment rhodopsin of retinal rod outer segments. We have proposed a structural model of beta-AR which is similar to that elucidated for rhodopsin. In this paper we identify a number of structural and topographical characteristics of beta-AR consistent with the model through the use of limited proteolysis. Limited trypsinization of beta-AR reconstituted in lipid vesicles yields two insoluble (integral membrane) domains of Mr approximately equal to 38,000 and 26,000. Identical results were obtained in intact cells, indicating that the cleavage site of the receptor is accessible at the extracellular surface of the plasma membrane. The amino-terminal domain (38 kDa) contains the ligand binding site (as revealed by photoaffinity labeling) and the sites of glycosylation (as revealed by its sensitivity to endoglycosidase F), whereas the carboxyl-terminal domain (26 kDa) contains all the sites of in vitro phosphorylation by cAMP-dependent protein kinase and the beta-adrenergic receptor kinase. Of four canonical sites for N-linked glycosylation, two near the amino and two near the carboxyl terminus, only those in the amino-terminal domain (Asn6 and Asn15) are utilized and sensitive to endoglycosidase F. Carboxypeptidase Y treatment of reconstituted native beta-adrenergic receptor generates a truncated (approximately 57 kDa) glycopeptide that has lost most of the sites phosphorylated by beta-AR kinase and one of the sites phosphorylated by protein kinase A. The various features delineated, including the length of the carboxypeptidase Y-sensitive region, the extracellular location of the trypsin-sensitive site, the location of the sites of phosphorylation and glycosylation all constrain the receptor to a rhodopsin-like structure with multiple membrane spanning segments.

Amino Acid Sequence↗

Regulation of adrenergic receptor function by phosphorylation. II. Effects of agonist occupancy on phosphorylation of alpha 1- and beta 2-adrenergic receptors by protein kinase C and the cyclic AMP-dependent protein kinase.

The present study was undertaken to determine the ability of protein kinase C and protein kinase A to directly phosphorylate the purified alpha 1- and beta 2-adrenergic receptors (AR). Both the catalytic subunit of protein kinase A and the protein kinase C, purified from bovine heart and pig brain, respectively, are able to phosphorylate the purified alpha 1-AR from DDT1 MF-2 smooth muscle cells. Occupancy of the receptor by an alpha 1 agonist, norepinephrine (100 microM), increases the rate of phosphorylation by protein kinase C but not by protein kinase A. The maximum stoichiometry of phosphorylation obtained is not affected by the agonist and reached 3 mol of PO4/mol of receptor for protein kinase C and 1 mol of PO4/mol of receptor for protein kinase A. The phosphopeptide maps of the trypsinized alpha 1-AR phosphorylated by each kinase differ drastically. The beta 2-AR purified from hamster lungs can also be phosphorylated by the two kinases. In contrast to the alpha 1-AR, the occupancy of the beta 2-AR by the agonist isoproterenol (20 microM) increases the rate of phosphorylation of the beta 2-AR by protein kinase A but not by protein kinase C. The maximum amount of phosphate incorporated into the receptor is not affected in either case by the agonist and reaches 1 mol of PO4/mol of receptor with protein kinase A and 0.4 mol of PO4/mol of receptor with protein kinase C. The phosphopeptide maps of the trypsinized receptor phosphorylated by either kinase reveal similar profiles. Thus, both alpha 1-AR and beta 2-AR are substrates for protein kinase A and protein kinase C. Agonist occupancy of the two receptors facilitates their phosphorylation only by the protein kinase coupled to their own signal transduction pathway. These observations suggest that "feedback" and "cross-system" phosphorylation may represent distinct and differently regulated mechanisms of modulation of receptor function.

Animals↗

Synovial lipoma arborescens of the hip.

Lipoma arborescens is a rare intra-articular tumor usually found in the knee joint. The reported lesion involved the inferomedial recess of the right hip synovium, in a 29-year-old male. The clinical findings were nonspecific. Both arthrography and computerized tomography (CT) of the hip disclosed the tumor which, on CT examination, showed an inhomogeneous low density, due to its fat content. The final diagnosis was given by histological examination of the resected mass. No recurrence was observed after one year. The long-term prognosis probably depends more on the underlying disorder of the joint than on the lipoma itself.

Adult↗

Deformation of the adult rheumatoid rearfoot. A radiographic study.

Three hundred ninety-seven adult rheumatoid feet were examined. Those in whom pain had been present since the onset of the disease were compared radiographically with the painless feet in standing position: examination of the talar angle and of the internal arch showed flattening on the affected feet. The calcaneal angle, on the other hand, showed no difference between the two groups, but this latter parameter is little affected by the valgus pronation deformity of the hindfoot most often seen in patients who had experienced foot pain.

Adult↗

Variation in alkaline-phosphatase activity with changing load on the mandibular condylar cartilage in the rat.

Biomechanical loads were varied by feeding diets of different consistencies. One group was fed hard diet for eight weeks, a second soft diet for eight weeks, and a third soft diet for four weeks followed by four weeks of hard diet. In all groups, alkaline-phosphatase activity was localized primarily in cells and extracellular matrix of the hypertrophic zone, and in cells lining trabeculae of the subcondylar bone. The staining intensity in the hypertrophic zone was slightly less in the soft-diet and soft/hard-diet groups than in the hard-diet group. The thickness of the cell layer staining positively for alkaline-phosphatase was significantly less in the soft-diet group than in the hard- and soft/hard-diet groups.

Alkaline Phosphatase↗

Effects of morphine on electrical activity of the rectum in man.

1. The effects of morphine on the electrical activity of the human rectum were investigated. 2. In healthy volunteers, morphine (0.04-0.16 mg/kg, i.v.) induced spike activity that could become cyclical. 3. All the effects of morphine were antagonized by naloxone (0.03-0.2 mg/kg, i.v.), but not blocked by atropine (0.007-0.014 mg/kg, i.v.). 4. In patients with spinal cord injury, morphine was observed to have similar excitatory effects. Spinal cord transection was complete in all patients, so that participation of supraspinal nervous structures in these effects could be ruled out. The sacral parasympathetic nervous centres could not have been involved in two patients in whom the medullary cone was also destroyed. The thoracolumbar sympathetic nervous centres were not completely destroyed in any of the patients, however, so that the possibility that these centres may have been involved cannot be entirely ruled out. 5. Morphine failed to activate an aganglionic rectum in a patient with Hirschsprung's disease, indicating that it had no direct effect on smooth muscle cells. It is therefore probable that morphine may have an effect on the intrinsic innervation.

Action Potentials↗