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Biomedical subjects

C Gauthier

Publications and source records attributed to C Gauthier.

At least 91 records · Page 5Linked to original sources
PubMed1990

Single d(ApG)/cis-diamminedichloroplatinum(II) adduct-induced mutagenesis in Escherichia coli.

The mutation spectrum induced by the widely used antitumor drug cis-diamminedichloroplatinum(II) (cis-DDP) showed that cisDDP[d(ApG)] adducts, although they account for only 25% of the lesions formed, are approximately 5 times more mutagenic than the major GG adduct. We report the construction of vectors bearing a single cisDDP[d(ApG)] lesion and their use in mutagenesis experiments in Escherichia coli. The mutagenic processing of the lesion is found to depend strictly on induction of the SOS system of the bacterial host cells. In SOS-induced cells, mutation frequencies of 1-2% were detected. All these mutations are targeted to the 5' base of the adduct. Single A----T transversions are mainly observed (80%), whereas A----G transitions account for 10% of the total mutations. Tandem base-pair substitutions involving the adenine residue and the thymine residue immediately 5' to the adduct occur at a comparable frequency (10%). No selective loss of the strand bearing the platinum adduct was seen, suggesting that, in vivo, cisDDP[d(ApG)] adducts are not blocking lesions. The high mutation specificity of cisDDP[d(ApG)]-induced mutagenesis is discussed in relation to structural data.

Base Composition↗
PubMed1989

Phlorizin-induced normoglycemia partially restores glucoregulation in diabetic dogs.

The plasma concentration of glucagon (IRG), catecholamines, and hepatic glucose production (Ra) were followed in insulin-induced hypoglycemia in dogs before (normal) and at 14-21 and again at 89-119 days after the injection of alloxan (diabetic). Some diabetic dogs were also tested when euglycemia was restored by phlorizin. In the normal state plasma IRG and epinephrine were raised by a factor of 3 and 15, respectively. Ra increased in two phases, an early peak (350% basal) was followed by a plataeu at about twice basal. In diabetes, irrespective of its duration, plasma IRG was decreased in hypoglycemia, and the rise in plasma epinephrine was significantly reduced. Ra remained unchanged. In phlorizin-treated euglycemic diabetic dogs plasma IRG fell, and the response in plasma epinephrine remained blunted. There was no early rise in Ra, but the same elevated plateau was reached at the same time as in normal animals. In conclusion, the following is observed in diabetic dogs. 1) The sensitivity of alpha-cells to insulin is maintained, but that to hypoglycemia is lost. The concentration of plasma catecholamines is raised less than in normals. With no increase in plasma glucagon this rise is not sufficient to increase Ra. 2) Restoration of euglycemia with phlorizin does not restore normal IRG and epinephrine responses to hypoglycemia but restores the delayed increase of Ra. Thus the restoration of euglycemia in severely diabetic dogs partially restores the responses of the liver, but not of the alpha-cell or sympathetic discharge, to hypoglycemia.

Animals↗
PubMed1988

The binding of beta-2-microglobulin to renal brush-border membrane: affinity measurement, inhibition by serum albumin.

In the kidney, filtered proteins are rapidly reabsorbed so that the final excretion is less than 0.1% of the filtered amount for low molecular weight proteins such as beta 2-microglobulin and a few percent for albumin. In order to investigate the affinity of proteins for luminal membranes, rat renal brush-border membranes were incubated with 125I-labelled human beta 2-microglobulin and the initial binding rate determined by the filtration method. Scatchard plot analysis of binding rate revealed two types of binding sites: one with Km = 0.25.10(-6) M and Vmax = 0.1 nmol/min per mg protein and another with Km = 1.10(-5) M and Vmax = 1.3 nmol/min per mg protein. The lower affinity type is likely to represent non-specific binding the physiological role of which is to be discussed. The higher affinity sites seem to play the major role in binding rate. beta 2-Microglobulin initial binding is reversible, and inhibited by bovine serum albumin. Comparison of the time course of bound beta 2-microglobulin removal by unlabelled beta 2-microglobulin and by albumin suggests that these two proteins have a different internalization mechanism.

Alpha-Globulins↗
PubMed1988

Efficient and easy synthesis of octathymidylate covalently linked to intercalating 9-aminoellipticine.

Reductive amination of 3'-apurinic octathymidylate with 9-aminoellipticine provides octathymidylate covalently linked to intercalating ellipticine through a 3,4-dihydroxypentamethylene linker. Studies of its binding properties to poly(rA) reveals the formation of two different complexes depending of the temperature (Tm 13 degrees C and 38 degrees C) with dT/rA stoichiometry respectively equal to 2/1 and 1/1. When compared to parent octathymidylate, stability of the latter duplex is enhanced by the interaction energy provided by the dye moiety.

Alkaloids↗
PubMed1987

Rapid binding of beta 2-microglobulin to renal brush-border membranes.

125I-labelled human beta 2-microglobulin binding to rat renal brush-border membranes was assessed by an in vitro assay under near physiological incubation conditions (i.e. low content of albumin). Binding rate was 55 pmol/min per mg protein in the presence of 200 nM of beta 2-microglobulin and degradation rate was negligible versus binding rate. The binding rate was in reasonable agreement with the in vivo reabsorption rate, supporting the hypothesis of proteins binding to the luminal membrane during the process of reabsorption. Mild solubilizing treatment (Triton 0.1%) of brush border after beta 2-microglobulin binding yielded the labelled molecule associated with a high-molecular-weight component. Aminopeptidase activity and binding ability were to a certain extent co-purified during the course of the brush-border preparation, suggesting that most of the beta 2-microglobulin binding sites were localized in the brush-border membranes.

Aminopeptidases↗
PubMed1987

[Isotypes of rheumatoid factors and cellular immunity anomalies in rheumatoid polyarthritis. Apropos of 61 cases].

In 61 patients with rheumatoid polyarthritis, we studied the rheumatoid factors isotypes, class IgM, IgG, IgA and the abnormalities of the ratio CD4/CD8 (lymphocytes with membrane phenotype "helper"/lymphocytes with membrane phenotype "suppressor") determined by monoclonal antibodies. We found a statistically significant increase of the rate of IgM rheumatoid factors (p less than 0.0001), IgG (p less than 0.004), IgA (p less than 0.008), in patients with rheumatoid polyarthritis whose ratio exceeded that of the control population. On the other hand, the percentage of rheumatoid factors detected by agglutination was not significantly increased in this group. This increase seemed linked to a specific abnormality of the control of lymphocytes B which synthesize rheumatoid factors.

Adult↗
PubMed1986

Glucoregulatory role of cortisol and epinephrine interactions studied in adrenalectomized dogs.

The importance of basal cortisol (H) and epinephrine (E) levels on glucoregulation, and the effects of E, given to simulate moderate to severe stress (5 times basal rate of infusion), were examined in seven conscious adrenalectomized dogs. Although plasma glucagon (IRG) increased by 47%, insulin (IRI) decreased by 36%, norepinephrine (NE) increased by 103%, and FFA decreased by 26%, glucose concentration and kinetics remained normal after adrenalectomy. A 4-h infusion of H reestablished basal cortisol levels and returned IRG to its basal preadrenalectomy level with no change in IRI, NE, and FFA levels. Glucose production and metabolic clearance decreased concomitantly by 20%, maintaining euglycemia. A 90-min infusion of basal E caused only a transient increase in IRG. The simultaneous infusion of H with E prevented this increase in IRG and returned IRI to preadrenalectomy levels in the absence of any change in NE or glucose. A subsequent infusion of five times basal E, alone, raised circulating E levels and caused a transient decrease in plasma NE, but no change in IRI. There was a similar hyperglycemic response, as seen previously in normal dogs. The simultaneous infusion of H and E prevented the decrease in NE, but did not change the IRI and FFA responses. There was an 80% greater plasma glucose response than seen during infusion of E alone. In conclusion, what E and H lack after adrenalectomy is compensated for by an increase in IRG and a decrease in IRI, and normal glucose concentrations and kinetics are maintained. It appeared that normoglucagonemia required basal H release, whereas normoinsulinemia required both basal H and E secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1985

Glucoregulation in dogs treated with methyl-prednisolone.

In nonanesthetized dogs treated with 3 mg/kg . d methyl-prednisolone (MP) for four days the infusion of phlorizin decreases plasma glucose only transiently. The basal level is restored by an increase in hepatic glucose production. The concentration of plasma glucagon (IRG) is raised only about 26%, compared to the increase of 150% observed previously in untreated dogs. In insulin-induced hypoglycemia, hepatic glucose production increases and both the concentrations of epinephrine and IRG in the plasma are elevated significantly. Recovery from hypoglycemia after the cessation of the infusion is significantly faster than observed previously in normal dogs. The following conclusions were reached: In MP-treated dogs during the infusion of phlorizin (in nonhypoglycemic glucoregulation) normoglycemia is restored faster, and by a much smaller increment in plasma glucagon concentration than previously observed in normal dogs. Regulation in overt hypoglycemia too operates more efficiently. In nonhypoglycemic glucoregulation a small change in plasma glucose concentration appears to be the primary stimulus that releases glucagon to the extent necessary to achieve the appropriate increase in hepatic glucose production in a given endocrine milieu.

Animals↗
PubMed1984

Renal tubular absorption of beta 2 microglobulin.

125Iodinated human beta 2 microglobulin (beta 2m, 5 to 30 mg) was administered to anesthetized rats. Clearance studies showed a low threshold of excretion of injected beta 2m and a high Tm of 400 to 600 micrograms X min-1 X kg-1. A glomerular sieving coefficient of 0.97 was calculated as the slope of the curve: beta 2m excretion rate = F (plasma beta 2m X glomerular filtration rate) for values above saturation. Electrophoresis analysis of proteinuria in agarose gel and sodium dodecyl sulfate polyacrylamide gel showed that injection of saturating doses of beta 2m induced the excretion of proteins of similar size but different charge and that of other proteins of different size. Among the latter, some were excreted transiently in association with beta 2m, whereas others had a delayed excretion suggesting existence of a complex mechanism of reabsorption whose steps remain to be elucidated.

Absorption↗
PubMed1984

Catecholamine responses and their interactions with other glucoregulatory hormones.

We have investigated catecholamine-glucagon-insulin interactions using three stress models: 1) hypoglycemia; 2) exercise; and 3) epinephrine infusion. Phlorizin caused mild hypoglycemia with hypoinsulinemia. Plasma glucagon increased as did hepatic glucose production. Catecholamines did not increase. Insulin caused severe hypoglycemia. Metabolic counterregulation was due mainly to the 40-fold increase in epinephrine. Glucagon played a role only in the recovery from insulin-induced hypoglycemia, which could reflect increased hepatic sensitivity to glucagon with declining plasma insulin. Glucagon suppression during exercise caused transient hypoglycemia due to an inadequate rise in glucose production. Exaggerated epinephrine release during hypoglycemic exercise prevented severe hypoglycemia by inhibiting glucose utilization and stimulating glucose production, with an associated increase in lactate and free fatty acid levels. Hypoglycemic exercise also caused increased cortisol release. Counterregulation was prevented by a euglycemic clamp. We conclude that, during exercise, glucagon is directly responsible for 80% of the increment of glucose production and controls glucose uptake by the muscle indirectly; thus glucagon spares muscle glycogen by increasing hepatic glucose production. Epinephrine infusion in normal dogs caused a transient increase in glucose production and a sustained inhibition of glucose clearance, resulting in hyperglycemia. Insulin rose transiently, followed by a relative inhibition of secretion. Glucagon suppression did not modify the metabolic effects of epinephrine. In alloxan-diabetic dogs, the glucagon response to epinephrine was augmented, whereas in depancreatized dogs, during subbasal insulin infusion, the hepatic response to glucagon was excessive. Glucagon suppression diminished hepatic responsiveness to epinephrine in both models. Stress-induced diabetic instability could relate to exaggerated glucagon release or to increased hepatic sensitivity to glucagon. Thus, during hypoglycemia, exercise, or epinephrine infusion, prevailing plasma insulin levels govern the relative metabolic roles of epinephrine and glucagon.

Adolescent↗