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Biomedical subjects

P Hamet

Publications and source records attributed to P Hamet.

At least 235 records · Page 13Linked to original sources
PubMed1984

Precision and costs of techniques for self-monitoring of serum glucose levels.

The poor correlation between serum and urine glucose measurements has led to the development of new techniques for monitoring the blood glucose level in diabetic patients. Either a nurse or the patient can perform these tests, which involve spreading a single drop of blood onto a reagent strip. A colour change that is proportional to the serum glucose level can be read visually or with a reflectance meter. Evaluated against simultaneous serum glucose levels determined by the hospital biochemistry laboratory, those of the new techniques employing reflectance meters all showed excellent correlation (r2 = 0.85 to 0.96). Reagent strips used without meters showed poorer correlation (r2 = 0.69 to 0.90). The instruction given to the patients and one nurse enabled them to obtain more accurate results with one of the meters than nurses not specially trained (r2 = 0.94 and 0.92 v. 0.85 respectively). The mean cost per glucose determination with the new techniques was 75, compared with +1.45 for the laboratory determinations done with automated equipment. It was concluded that the new techniques compared well with the reference method, particularly when reflectance meters were used, and that they were easily applied by the patient, as well as the medical staff, at a reasonable cost.

Blood Glucose↗
PubMed1984

An increase in adenylate cyclase activity precedes DNA synthesis in cultured vascular smooth muscle cells.

Adenylate cyclase activity in cultured rat aortic vascular smooth muscle cells showed a linear correlation with the rate of DNA synthesis. When smooth muscle cells were rendered quiescent by shifting them from a serum-supplemented medium to a medium containing low concentrations of plasma, the cells could be stimulated to proliferate by the addition of serum or by addition of a crude preparation of platelet-derived growth factor. DNA synthesis began at 16 hours and was maximal at 24 hours. Prior to synthesis of DNA there was an increase in adenylate cyclase activity with a peak at 12 hours. Adenylate cyclase activity returned to basal level before DNA synthesis began. The increase in adenylate cyclase activity was not blocked by cycloheximide. Adenylate cyclase activity could also be increased by incubating vascular smooth muscle cells with cholera toxin; however, the time course and magnitude of this increase was different from that caused by growth stimulants. Cholera toxin caused a slight increase in DNA synthesis at 16 hours, but was also cytotoxic to smooth muscle cells. An increase in adenylate cyclase activity may be a prerequisite for the progression from G1 to S.

Adenylyl Cyclases↗
PubMed1984

Immunocytochemical localization of atrial natriuretic factor in the heart and salivary glands.

Antibodies produced in the mouse by repeated intraperitoneal injections of partly purified atrial natriuretic factor (low molecular weight peptide (LMWP) and high molecular weight peptide (HMWP)) have been used to localize these factors by immunohistochemistry (immunofluorescence and immunoperoxidase method) and by immunocytochemistry (protein A-gold technique) in the heart of rats and of a variety of animal species including man and in the rat salivary glands. Immunofluorescence and the immunoperoxidase method gave identical results; in the rat, atrial cardiocytes gave a positive reaction at both nuclear poles while ventricular cardiocytes were consistently negative. The cardiocytes of the right atrial appendage were more intensely reactive than those localized in the left appendage. A decreasing gradient of intensity was observed from the subpericardial to the subendocardial cardiocytes. The cardiocytes of the interatrial septum were only lightly granulated. Sodium deficiency and thirst (deprivation of drinking water for 5 days) produced, as already shown at the ultrastructural level, a marked increase in the reactivity of all cardiocytes from both atria with the same gradient of intensity as in control animals. Cross-reactivity of intragranular peptides with the rat antibodies allowed visualization of specific granules in a variety of animal species (mouse, guinea pig, rabbit, rat, dog) and in human atrial appendages. No reaction could be elicited in the frog atrium and ventricle although, in this species, specific granules have been shown to be present by electron microscopy in all cardiac chambers. With the protein A-gold technique, at the ultrastructural level, single labeling (use of one antibody on one face of a fine section) or double labeling (use of two antibodies on the two faces of a fine section) showed that the two peptides are localized simultaneously in all three types (A, B and D) of specific granules. In the rat salivary glands, immunofluorescence and the immunoperoxidase method showed reactivity exclusively in the acinar cells. The reaction was most intense in the acinar cells of the parotid gland. In the sublingual gland, only the serous cells, sometimes forming abortive "demi-lunes", were reactive. In the submaxillary gland, the reaction was weaker and distributed seemingly haphazardly in the gland. The most constantly reactive cells were localized near the capsule while many cells did not contain visible reaction product.

Adult↗
PubMed1984

Calcium-dependent proteolytic stimulation of adenylate cyclase in platelets from spontaneously hypertensive rats.

Abnormalities of platelet aggregation and cyclic nucleotide metabolism are present in hypertension. We observed a greater increase in the level of cyclic adenosine monophosphate (AMP) after prostaglandin E1 (PGE1) stimulation and a lack of decrease of this cyclic nucleotide by epinephrine in platelets from spontaneously hypertensive rats (SHR) as compared to normotensive rats. The difference in cyclic AMP production between SHR and control rats in response to PGE1 is dependent upon platelet exposure to calcium. Since calcium and cyclic AMP are closely related and are both abnormally regulated in hypertension, we have studied the effect of calcium on adenylate cyclase activity. We show here that two forms of endogenous calcium-dependent proteases (membrane-bound and soluble) stimulate the basal activity and the hormonal responsiveness of adenylate cyclase. The sensitivity of calcium-dependent proteolytic control of adenylate cyclase to very-low concentrations of calcium indicates that the regulation may be physiologically important. Furthermore, calcium exerts a greater influence on platelet adenylate cyclase from SHR than on that from normotensive rats. The adenylate cyclase defect seems to be located in the membrane fraction and may, therefore, result from an increase in the activity of the membrane-bound calcium-protease or may be intrinsic to adenylate cyclase itself. The exact site that is sensitive to proteolysis remains to be established.

Adenylyl Cyclases↗
PubMed1984

The heart as an endocrine gland.

The evidence presented here indicates that atrial cardiocytes, apart from their contractile function, are bona fide endocrine cells which synthesize a peptide of known composition (152AA) through identified pathways [6,7]. Part of the peptide is released into the circulation where it can be measured by radio-immunoassay. A synthetic fragment (8-33AA) of the peptide is endowed with potent and variegated effects on several target tissues: massive diuresis and natriuresis of rapid onset and short duration, inhibition of the secretion of aldosterone from beef and rat zona glomerulosa and, to a lesser extent, of cortisol from beef zona fasciculata, vasodilatation and inhibition of the arterial contraction induced by catecholamines or angiotensin II. This peptide is a potent antihypertensive agent. The presence of receptors in the anterior and posterior pituitary, as well as the significant decrease of adenylate cyclase activity observed in both portions of the gland, indicate that the hormone may act at these levels as well. Thus, the heart is raised from the status of a pump to that of a putative endocrine integrator of cardiovascular homeostasis.

Adenylyl Cyclase Inhibitors↗
PubMed1984

Catecholamine sulfates and platelet phenolsulfotransferase activity in essential hypertension.

Because of high plasma concentrations of conjugated catecholamines and their unknown relationship to hypertension, we determined those conjugates more specifically as catecholamine sulfates together with the sulfoconjugating enzyme-phenolsulfotransferase activity in platelets of 62 patients with essential hypertension and 32 normal controls. Our results indicated: (1) that the pool of total (free and sulfated) catecholamines (dopamine, norepinephrine, and epinephrine) is higher (because of an increase in dopamine sulfate levels) but the degree of epinephrine conjugation is lower in patients with essential hypertension compared with controls; (2) that norepinephrine sulfate levels rise with age in both groups, but the increase in free norepinephrine with age observed in controls was not observed in patients with essential hypertension; and (3) that catecholamine conjugates were found to be exclusively sulfates and platelet phenolsulfotransferase activity was not different in both groups. Platelet phenolsulfotransferase activity was, however, positively correlated with plasma norepinephrine sulfate levels, and the degree of sulfoconjugation of norepinephrine was positively correlated with that of dopamine in controls but not in patients with essential hypertension. These abnormalities occurring in essential hypertension in the absence of intergroup differences in platelet phenolsulfotransferase activity suggest that the enzyme is either not a good marker of the overall activity or that other factors account for the observed differences. Thus, additional determinants of the process of generation and degradation of sulfoconjugated catecholamines, some of which may be more stable markers of sympathetic activity than free catecholamines, need to be explored.

Adult↗
PubMed1983

Platelets and vascular smooth muscle: abnormalities of phosphodiesterase, aggregation, and cell growth in experimental and human diabetes.

Platelets appear to be involved in both the maintenance of homeostasis and the regulation of proliferation of vascular smooth muscle cells. Anomalies of platelet function may be responsible in part for the pathogenesis of vascular disease in experimental and human diabetes. In a search for an appropriate animal model, we have studied platelet function and the properties of platelet cyclic NCL-PDE in rats with streptozocin-induced diabetes, spontaneous diabetes, and human insulin-dependent diabetes mellitus (IDDM). It appears that opposite abnormalities in both aggregation and phosphodiesterase activity exist in the two animal models. In human IDDM, similar abnormalities to those seen in the BB model were observed. Vascular smooth muscle cells in culture can be used as a model for studies of the effect of circulating growth factors in animals and humans. A growth inhibitory factor was found in plasma and serum from STZ and human IDDM but not BB. In humans we observed increased growth-promoting activity of diabetic platelets, but this phenomenon was absent in both animal models. It remains to be evaluated whether these differences may account for the fact that diabetic rats appear resistant to development of vascular complications. It also remains to be established which animal model is the best choice for studying growth abnormalities in diabetes.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Rapid activation of cAMP phosphodiesterase in rat platelets.

Incubation of intact platelets with prostaglandins (PGE1 and PGI2) and phosphodiesterase inhibitors (1-methyl-3-isobutylxanthine, indomethacin, dipyridamol) lead to activation of cAMP phosphodiesterase. The activation was rapid (maximal within 30 s) and stable after removal of agents and homogenization of platelets. The activation remained after DEAE-Sepharose chromatography. The effect of the two types of agents on phosphodiesterase activity was more than additive and activation did not alter the nonlinear kinetic behavior of phosphodiesterase. The mechanism of the ex vivo stimulation is unknown at the present time, however, it does not seem to be due to cellular redistribution of the enzyme. The results suggest that activation of a cAMP-dependent protein kinase is an intermediate step. The ex vivo stimulation is regulated by a calcium-dependent process, since addition of Ca2+ ions and ionophore A23187 to Ca2+ depleted platelets abolished the ex vivo stimulation by PGE1 and MIX.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Extrarenal angiotensin-forming enzymes.

There are two types of enzymes in tissues leading to angiotensin formation: a) those resulting in the formation of angiotensin I, such as renin and cathepsin D, the presence of which is now well established for brain tissue and b) Those leading to the direct formation of angiotensin II without the angiotensin I step, such as cathepsin G and tonin. Recent findings concerning tonin, a serine protease, are described: a) 80% of its amino acid sequence, b) its different characteristics from other serine proteases, from renin, cathepsin D and the angiotensin I converting enzyme, c) the activation of inactive renin, d) its involvement in the 1K-1C hypertensive rats, e) the demonstration of its presence in the distal tubular cells of the rat kidney, and finally, f) its presence in urine and the influence of age and of sodium intake on its urinary excretion.

Amino Acids↗
PubMed1983

Calcium-induced release from platelet membranes of fatty acids that modulate soluble guanylate cyclase.

Incubation of rat or rabbit platelet membranes with Ca++ induced the release of modulators of soluble guanylate cyclase. These modulators increased basal activity and inhibited sodium nitroprusside-stimulated activity in the absence or presence of dithiothreitol. The release, but not the effects, of the modulators was inhibited by trifluoperazine and by mepacrine. Indomethacin and oxyphenbutazone did not influence the release or effects of the modulators. The factors were identified as arachidonic and linoleic acids. These fatty acids produced comparable effects on crude soluble guanylate cyclase from platelets and on the homogeneously purified enzyme from bovine lung. In the presence of MgCl2, the maximal increase in basal activity was observed at 10 to 30 microM arachidonic or linoleic acid with the crude enzyme and at 3 to 6 microM with the purified enzyme. Inhibition of basal activity was observed at higher concentrations. Half-maximal inhibition of Mg++-supported, sodium nitroprusside-augmented activity was observed at 3 to 10 microM fatty acid. The effects of arachidonic acid occurred without a lag period and were quickly reversible. These data demonstrate that unsaturated fatty acids can be released from platelet membranes by a Ca++-dependent process in amounts that are high enough to alter soluble guanylate cyclase activity. The data also indicate that unsaturated fatty acids exert their effects on soluble guanylate cyclase without having to be converted to peroxides by other enzymes.

Animals↗