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Biomedical subjects

A Michaud

Publications and source records attributed to A Michaud.

At least 19 recordsLinked to original sources
PubMed1992

Study of the protein S system in HIV-infected patients: acquired protein S deficiency or unsuitable assays?

The plasma protein S (PS) system was studied in 120 HIV seropositive patients (CDC classification: group II: n = 35; group III: n = 6; groups IVA, IVC2 or IVE, n = 38; groups IVB, IVC1 or IVD, n = 41). Total PS antigen and C4b-binding protein (C4b-BP) values were not significantly different from control values. Free protein S levels assessed by an immunological method in the supernatant of PEG-precipitated plasma samples (PEG-fPS) were below the normal limit in 85 patients, lower values being found in patients with advanced HIV disease. No correlation was found between PEG-fPS levels and C4b-BP or total PS levels. At least 25 patients had a low functional PS value. Low functional levels of PS were found in each clinical group although there was no difference in the distribution of functional PS values among groups. Crossed immuno-electrophoresis showed an abnormal distribution of PS in some patients, but failed to confirm the marked decrease of free PS in patients with very low PEG-fPS. An impairment of the protein S system is observed in HIV-infected patients. However, the discrepancies found in some patients among the results of the various PS-related assays should lead to a cautious interpretation concerning the incidence of PS deficiency in HIV-infected patients.

Adult↗
PubMed1991

Expression and characterization of recombinant human angiotensin I-converting enzyme. Evidence for a C-terminal transmembrane anchor and for a proteolytic processing of the secreted recombinant and plasma enzymes.

Chinese hamster ovary (CHO) cells have been transfected with either a full-length cDNA encoding human angiotensin I-converting enzyme (kininase II; EC 3.4.15.1) (ACE) or a mutated cDNA, in which the last C-terminal 47 amino acids, including the putative transmembrane domain, are not translated. Cell lines expressing high levels of the wild-type ACE or the mutant were established. The cells transfected with the wild-type cDNA (CHO-ACE) express a membrane-bound ectoenzyme with an intracellular C terminus, as shown by indirect immunofluorescence using an antiserum (28A7) raised against a synthetic peptide corresponding to the deduced C terminus of ACE. This enzyme is structurally, immunologically, and enzymatically identical to human kidney ACE. In addition, CHO-ACE cells also produce a secreted form of the enzyme. Neither this secreted form nor the enzyme purified from human plasma is recognized by the antiserum 28A7, indicating that they undergo a truncation in the C-terminal region. On the other hand, the transfected cells expressing the C-terminally truncated mutant (CHO-ACE delta COOH) do not retain ACE in the plasma membrane, but secrete it into the medium. These results indicate that ACE is anchored to the plasma membrane by the predicted C-terminal transmembrane domain, and the secreted form is derived from the membrane-bound form by a post-translational proteolytic cleavage of the C-terminal region.

Amino Acid Sequence↗
PubMed1989

Effect of sex hormones on plasma T-kininogen in the rat.

The influence of sex hormones on rat plasma T-kininogen concentration was examined. The level of T-kininogen in the post-pubertal female rat is about 3-times that of the male animal. Female rats castrated as adults or 15 days after birth, had low T-kininogen concentrations, near those of male rats. In contrast, castration of mature or immature male animals induced no change in T-kininogen. Treatment of castrated female or male rats with 17 alpha-ethinylestradiol significantly increased the T-kininogen level, whereas administration of testosterone or progesterone had no effect. The influence of estrogen was specific for T-kininogen, since plasma HMW kininogen concentration was the same in male and female rats and was not affected by castration or sex hormone treatment. T-kininogen concentration was not significantly changed in pregnant rat between the 12th and the 20th day of pregnancy, but increased after parturition. It was high in the newborn rat at birth and then decreased similarly over the next 3 weeks in males and females. It continued to decrease in the males, reaching the level of the adult rat, but it increased in the female from 3-4 weeks of age and reached the adult level at about 6-8 weeks. These data indicate that natural estrogens have a physiological influence on the plasma level of T-kininogen in female rats whereas testosterone had no effect on either male or castrated female rats. HMW kininogen is not physiologically dependent on sex hormones.

Acute-Phase Proteins↗
PubMed1988

Effect of dexamethasone on kininogen production by a rat hepatoma cell line.

T Kininogen and High Molecular Weight Kininogen were characterized in the cell culture medium of Fao cells, a highly differentiated cell line derived from the Reuber H35 rat hepatoma. Immunoreactive T Kininogen and High Molecular Weight Kininogen identified by direct and specific RIAs were indistinguishable from standard kininogens. Immunoreactive T Kininogen was further identified by HPLC analysis of T kinin released after trypsin hydrolysis of the cell culture medium. The basal release rate of T kininogen was ten-fold higher than that of High Molecular Weight Kininogen. T Kininogen was not stored within the cells contrary to High Molecular Weight Kininogen. The production of the two kininogens in the cell medium was stimulated by dexamethasone up to five times in a dose-dependent manner. The specific antiglucocorticoid compound RU 38486 did not alter the basal rate of kininogen release by Fao cells, but abolished the stimulation by dexamethasone, indicating that dexamethasone exerts a true glucocorticoid type effect.

Animals↗
PubMed1988

Effect of thyroidectomy on rat T-kininogen.

The thyroid state affects the inflammatory reaction; in general, thyroid hormones increase and hypothyroidism decreases the inflammatory response. T-kininogen is an acute phase protein that inhibits cysteine proteases. The influence of thyroidectomy and 3,5,3'-triiodothyronine (T3)-treatment of thyroidectomized animals was examined on rat plasma T-kininogen concentration. Thyroidectomy increased the T-kininogen level three- to fourfold. A single administration of 10 micrograms T3/100 g body wt in 7-wk postthyroidectomy rats decreased it by approximately 50%. Daily treatment with 0.5 micrograms T3/100 g body wt prevented the increases in T-kininogen. The modifications in plasma T-kininogen concentration were confirmed by high-performance liquid chromatography analysis of the plasma kinins released by trypsin. They demonstrated that T-kinin was greatly and bradykinin slightly increased after thyroidectomy and that T-kinin concentration in T3-treated thyroidectomized animals was almost restored to the control level. The ability of thyroidectomized animals to produce a higher plasma T-kininogen compared with euthyroid animals was further documented when T-kininogen production was stimulated by laparotomy. This procedure resulted in a fourfold increase in T-kininogen in thyroidectomized animals compared with controls. The increase of plasma T-kininogen level after thyroidectomy results from a more active synthesis of the protein, since liver slices from thyroidectomized rats synthesized T-kininogen at a rate about two times higher than normal rats. These data may account at least in part for the diminution of the inflammatory response observed after thyroidectomy.

Animals↗
PubMed1987

A new affinity matrix for mineralocorticoid receptors.

The behavior of mineralocorticoid and glucocorticoid receptors of rabbit kidney cytosol was investigated on two affinity gels: a new affinity matrix prepared with a 3-O-derivative of carboxymethyloxime deoxycorticosterone (deoxycorticosterone gel) and a gel linked to a 17 beta-dexamethasone derivative (dexamethasone gel). Deoxycorticosterone gel was highly specific, since it retained mineralocorticoid but not glucocorticoid receptors, and dexamethasone gel exhibited high selectivity for glucocorticoid receptors since it did not bind mineralocorticoid receptors. The use of these two matrices allowed separation of mineralocorticoid and glucocorticoid receptors and further characterization of each type of cytosolic receptors after its isolation. Cytosolic mineralocorticoid and glucocorticoid receptors stabilized by tungstate were found to have a Stokes radius of approximately 6 nm, as determined by high performance size exclusion chromatography and a sedimentation coefficient of approximately 9 S, determined on a glycerol density gradient containing tungstate, under either high or low salt conditions. The hydrodynamic parameters, binding characteristics, and specificity of mineralocorticoid receptors were the same in the untreated and dexamethasone gel-treated cytosol. Similarly glucocorticoid receptor characteristics remained unchanged after deoxycorticosterone gel treatment, indicating biochemical independence of cytosolic mineralocorticoid and glucocorticoid receptors. The [3H]aldosterone receptor complex eluted from deoxycorticosterone gel was recovered with a 30-40% yield and a purification factor of about 1000. Purified mineralocorticoid receptors had the same sedimentation coefficient as cytosolic mineralocorticoid receptors (9 S) but a different Stokes radius (4 versus 6 nm). The decrease in the Stokes radius of the purified mineralocorticoid receptors was probably due to the gel filtration method. These results indicate that the newly synthesized matrix specific for mineralocorticoid receptors constitutes a powerful tool for their extensive purification.

Aldosterone↗
PubMed1986

Affinity of corticosteroids for mineralocorticoid and glucocorticoid receptors of the rabbit kidney: effect of steroid substitution.

Corticosteroid derivatives coupled in the C3, C7 or C17 position with a long aliphatic chain were synthesized in order to select a suitable ligand for the preparation of a biospecific affinity adsorbent for mineralocorticoid receptor purification. The affinity of these derivatives for mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) was explored in rabbit kidney cytosol. In this model, aldosterone bound to a single class of receptors with high affinity (Kd 1 nM) and mineralocorticoid specificity. RU26988, a highly specific ligand for GR, did not compete for these sites. The C7 and C17 positions were found to be of crucial importance in the steroid's interaction with the mineralocorticoid receptors, since the linkage of a long side chain in these positions induced complete loss of affinity. Hence, deoxycorticosterone no longer bound to MR after 17 beta substitution with a 9-carbon aliphatic chain. This loss of affinity was not observed for glucocorticoids. The 17 beta nonylamide derivative of dexamethasone still competed for GR. Increasing the length of the C7 side of the spirolactone SC26304 suppressed its affinity for MR. Finally, C3 was an appropriate position for steroid substitution. The 3-nonylamide of carboxymethyloxime deoxycorticosterone bound to MR but not to GR, and therefore constitutes a suitable ligand for the preparation of a mineralocorticoid adsorbent.

Adrenal Cortex Hormones↗
PubMed1986

Follow-up of renal morphology and growth of 141 children operated for vesicoureteral reflux: a retrospective computerized study.

This study relates the postoperative evolution after ureterovesical reimplantation for vesicoureteral reflux (VUR) in 141 children who were ten years old or younger at the time of surgery. Renal growth and morphology were evaluated 2 and 5 years after surgery. We estimated renal growth by measuring the ratio of the bipolar parenchymal thickness to the total length of the kidney. We noticed that whatever the degree of reflux might have been, most of the kidneys partially or totally compensated for their growth failure. This growth resumption required many years to be completed. Surgical correction of VUR had favorable consequences on the radiologic aspect of pyelonephritic scars only on some of the kidneys: in these cases, the child's age appeared to be the only factor that had a statistical importance affecting the postoperative evolution of pyelonephritic scarring: the younger the children were at the time of surgery, the better the results obtained.

Age Factors↗
PubMed1986

In vitro comparison of ampicillin-chloramphenicol and ampicillin-cefotaxime against 284 Haemophilus isolates.

Since November 1982 at the Sainte-Justine Hospital in Montreal, ampicillin and cefotaxime were used in association as initial treatment (greater than or equal to 48 h) for childhood bacterial meningitis. In this report is described the in vitro interaction of the new regimen in comparison with that of the previous ampicillin-chloramphenicol combination against 284 Haemophilus isolates. Among the 156 ampicillin-susceptible, beta-lactamase-negative isolates, synergy was detected in 13 with ampicillin-cefotaxime, and antagonism was detected in only 1; in contrast, synergy was found in only 2 strains with ampicillin-chloramphenicol, and antagonism was found in 15. These differences were statistically significant (P less than 0.01). Such significant differences were not observed among the 128 ampicillin-resistant, beta-lactamase-positive Haemophilus isolates. The synergy of ampicillin-cefotaxime did not contribute to a decrease of the MIC of cefotaxime for 90% of isolates tested, whereas the antagonism of ampicillin-chloramphenicol did not contribute to increase the MIC of ampicillin for 90% of isolates tested.

Ampicillin↗
PubMed1985

Renal growth retardation in children: sign suggestive of vesicoureteral reflux?

Of 141 children undergoing surgery for vesicoureteral reflux detected by voiding cystourethrography, preoperative excretory urography demonstrated signs suggestive of vesicoureteral reflux in 154 (67.5%) of 228 refluxing ureter. In 48 refluxing ureters (21%) renal growth retardation was the only sign; the latter was appreciated by applying the index described by Hodson, that is, the ratio of bipolar parenchymal thickness to total renal length. It was concluded that it is important to systematically calculate this simple index from every child's excretory urogram.

Child↗
PubMed1979

Are mineralocorticoid receptors present in human renal adenocarcinoma?

1. The presence of high-affinity sites for [3H]-aldosterone was shown in the normal human renal tissue. 2. [3H]Aldosterone and [3H]dexamethasone binding were studied in human renal adenocarcinoma and in uninvolved external cortex, in 22 patients undergoing nephrectomy for renal adenocarcinoma. Tissue incubations were performed with either [3H]aldosterone (5 x 10(-10) mol/l; 5 x 10(-9) mol/l in the presence of unlabelled glucocorticoids) or [3H]dexamethasone (5 x 10(-9) mol/l). 3. Cytosol [3H]aldosterone binding was six- to seven-fold lower (P less than 0.001) in neoplastic than normal tissue. [3H]Dexamethasone binding was about twofold higher in neoplastic than in normal tissue. This difference was not significant. 4. Nuclear uptake experiments showed that, both in cytosol fractions and nuclei, [3H]aldosterone binding was lower in adenocarcinoma than in normal cortex. 5. The very low binding of [3H]aldosterone suggests that mineralocorticoid receptors are absent in renal adenocarcinoma, an hypothesis in line with the proximal origin of these tumours.

Adenocarcinoma↗
PubMed1979

Mechanism of action of a new antialdosterone compound, prorenone.

Two new aldosterone antagonists, K-prorenoate [potassium 3(17 beta-hydroxy-6 beta, 7 beta-methylen-3-oxo-4-androsten-17 alpha-yl)propionate] and prorenone [3(17 beta-hydroxy-6 beta, 7 beta-methylen-3-oxo-4-androsten-17 alpha-yl) propionic acid gamma-lactone], its lactonic form, were studied in rat kidney using in vitro systems. Study of [3H]prorenone binding by a recently developed computer method indicated a high affinity, low capacity class of sites which are, seemingly, mineralocorticoid receptors. In competition experiments performed on [3H]aldosterone- and [3H]dexamethasone-binding sites, prorenone appeared to be a good competitor for mineralocorticoid-binding sites and a poor competitor for glucocorticoid-binding sites. The specificity of this molecule was further confirmed by its poor ability to displace [3H]dihydrotestosterone from rat prostate androgenic receptors compared to spironolactone [3-(3-oxo-7 alpha-acetylthio-17 beta-hydroxy-4-androsten-17 alpha-yl) propionic acid gamma-lactone]. In the same experiments, K-prorenoate demonstrated a very low affinity for the two types of receptors. The behavior of [3H]prorenone cytosolic complex was also studied in kidney mince experiments, which showed that the [3H]prorenone complex was not able to translocate into the nucleus. Prorenone inhibited the binding of [3H]aldosterone to the receptor and, consequently, the nuclear binding of aldosterone was not observed.

Aldosterone↗