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Biomedical subjects

M Gilbert

Publications and source records attributed to M Gilbert.

At least 217 records · Page 12Linked to original sources
PubMed1985

Tissue plasminogen activator release in vivo in response to vasoactive agents.

Release of tissue plasminogen activator into the circulation of rats in response to intravascular injections of vasoactive agents is studied by using a sensitive and specific clot lysis assay. Intra-arterial bradykinin elicits a rapid and transient rise in circulating plasminogen activator, which is maximum within one minute and is cleared within four to eight minutes. The plasminogen activator is fibrin dependent and is neutralized by an antiserum to human tissue-type plasminogen activator. Bradykinin is 1,000-fold more potent than the other agonists tested, which include histamine, norepinephrine, epinephrine, eledoisin-related peptide, arginine-vasopressin, lysine-vasopressin, desmopressin acetate, carbachol, and acetylcholine. Potency of bradykinin is related to its amino acid sequence. Sequential infusions of bradykinin produce a tachyphylactoid response that could be overcome by increasing the dose of the sequential bradykinin challenge. It is concluded that the characteristics of the responses to bradykinin and other agents in vivo differ significantly from those observed in isolated tissue preparations.

Animals↗
PubMed1985

Presence of natural autoantibodies in hyperimmunized mice.

Mice were immunized with various antigens in complete Freund's adjuvant following various injection schedules. Hybridomas were produced from the spleens of these immunized mice and examined for production of antibodies directed against the antigen injected and against a panel of self (tubulin, actin, myosin, DNA) and non-self antigens (myoglobin, spectrin, peroxidase, trinitrobenzene). Two to five percent of the hybrids were found to secrete polyspecific antibodies able to react with two or more antigens of the panel. Several of these hybrids were subcloned and expanded into ascites. The monoclonal immunoglobulins they secreted were isolated and shown to be IgM (kappa) and to possess the polyspecific antibody function. Several hybrids were also found to secrete antibodies reacting with the immunizing antigen as well as one or more antigens of the panel. The antibody secreted by one subclone which reacts with both the immunizing antigen, prolactin and one of the panel antigens, TNP, has been isolated using a DNP-immunoadsorbent. The isolated antibody was found to be a monoclonal IgM (kappa) immunoglobulin and to react both with prolactin and TNP. The hypothesis is advanced that cells carrying polyspecific natural antibodies as receptors after a given antigenic stimulation proliferate into cells producing highly specific antibodies for epitopes of that given antigen; the cells with polyspecific receptors will be continuously replaced by new cells probably on bone-marrow origin.

Animals↗
PubMed1984

The hippocampus, context, and information processing.

Two experiments are described in which groups of rats with bilateral hippocampal lesions, cortical lesions, and operated controls are compared on tests of discrimination learning, retention, and reversal learning. Experiment 1 examined the effects of varying prior training and context on new learning. Experiment 2 used a transfer paradigm to compare extent of original learning by hippocampal and control groups in a discrimination task involving multiple discriminanada . The major findings were that rats with hippocampal damage were less efficient at processing information and were more constrained by contextual influences than control rats.

Animals↗
PubMed1984

High pressure liquid chromatographic assay for mexiletine in serum.

A highly sensitive, rapid, and specific high pressure liquid chromatographic assay for the analysis of the antiarrhythmic agent mexiletine is reported. The method involves extraction of mexiletine with organic solvent followed by analysis using fluorescence detection. The minimum measurable limit is 1 ng and inter- and intra-day coefficients of variation are less than 5.8%. The method is useful for pharmacokinetic studies and routine serum monitoring of mexiletine.

Chromatography, High Pressure Liquid↗
PubMed1984

Uterine blood flow and substrate uptake in conscious rabbit during late gestation.

The aim of this study was the quantitation of the metabolic demands of the uterus in rabbits between days 24 and 30 of gestation, a time at which there is a fourfold increase in fetal weight. Serial measurements of substrate concentrations in maternal artery and uterine vein were performed over this period. Uterine blood flow was measured on days 24 and 30. Uterine substrate uptake was calculated by application of the Fick principle. Over the gestation range studied, the absolute uterine blood flow increased proportionally to the uterine weight gain. The uterine arteriovenous differences for glucose (G), lactate (L), free fatty acids (FFA), ketone bodies (KB), and oxygen (O2) were constant throughout the study. At both gestational ages, the weight-specific uterine substrate consumption (G, FFA, KB, O2) and production (L) were respectively similar. On days 24 and 30 the amount of G directed to the gravid uterus represented approximately 13 and approximately 36% of the maternal glucose turnover rate, respectively. The maximum contributions of G and FFA to the uterine oxygen consumption on day 24 were 80 and 30%, respectively. We have thus confirmed that at term the gravid uterus is a site of high glucose consumption. Finally, we demonstrated that in a nonruminant species, FFA would be a substantial source of carbon.

Animals↗
PubMed1984

Glucose turnover rates in chronically catheterized non-pregnant and pregnant rabbits.

Glucose turnover rates have been measured in conscious, chronically catheterized, non-pregnant and pregnant rabbits. Non-pregnant rabbits were studied weekly for 4 wk. Pregnant animals were studied once while non-pregnant and then weekly for up to 4 wk during pregnancy. Glucose turnover rate was measured using a primed-constant infusion of [U-14C]glucose and [6-3H]glucose. The weight of the rabbits did not vary throughout the 4-5 wk of study in either the non-pregnant or pregnant group. Seven pregnant rabbits delivered pups which weighed an average of 61 g each. In non-pregnant rabbits, blood glucose concentration did not vary with time. In the pregnant rabbits, blood glucose concentration fell by the end of gestation to an average value of 74.6 +/- 2.7 mg/dl, significantly less (P less than 0.01) than the glucose concentration in the same animals before pregnancy, 88.2 +/- 2.4 mg/dl. The weight specific glucose turnover rate did not vary with time in either the non-pregnant (4.38 +/- 0.16 mg X min-1 X kg-1) or pregnant rabbits (3.89 +/- 0.29 mg X min-1 X kg-1). Blood glucose clearance did not change over time in the non-pregnant rabbits but did increase in the pregnant rabbits in late pregnancy. Blood glucose clearance was inversely related to the fall in blood glucose concentration.

Animals↗
PubMed1984

Some aspects of maternal metabolism throughout pregnancy in the conscious rabbit.

Studies of maternal metabolism during pregnancy have focused principally upon the latter half of gestation. However, maternal metabolic adaptations to pregnancy may occur at all stages of pregnancy. To study maternal metabolism throughout pregnancy, we developed a chronically catheterized rabbit model in which animals could be studied under conscious, stress-free conditions when nonpregnant and then serially throughout pregnancy. Anesthesia produced marked hyperglycemia. In contrast, chronic catheterization and daily handling did not affect blood concentrations of glucose, lactate, ketone bodies, or free fatty acids, or food intake. Glucose concentration decreased with pregnancy to a value at term equal to 85% of the prepregnancy value. Lactate concentration rose significantly in the second half of pregnancy but changes in free fatty acids and ketoacid levels were not significant. These results are discussed from a comparative physiologic point of view, emphasizing the unique aspects of rabbit metabolism during pregnancy and the importance of performing such studies under conscious, stress-free conditions.

Anesthesia↗
PubMed1984

Glucagon and insulin secretion and their biological activities in hypothermic rats.

To clarify the impact of hypothermia on the hormonal control of glucose metabolism, rats were rendered hypothermic (25 C) after catheterization of the portal vein. Glucose, insulin, glucagon, and catecholamine concentrations were serially monitored, and the regional blood flows were measured, allowing the estimation of hormone outputs. Hypothermia reduced the portal blood flow by 50% without changing arterial blood pressure, blood gases, or pH. Portal plasma insulin secretion dropped (0.05 +/- 0.01 vs. 0.23 +/- 0.04 mU/min), and glucagon secretion increased (0.81 +/- 0.18 vs. 0.38 +/- 0.10 ng/min). The B cell responses to glucose, arginine, and glucagon were abolished, while the A cell response to arginine was not significantly affected. Glucose intolerance was apparent after iv glucose or arginine loads. Haloperidol and to a lesser extent phentolamine suppressed the cold-induced glucagon rise. Phentolamine and to a lesser extent haloperidol alleviated the cold-induced suppression of insulin release. Propranolol, naloxone, and atropine were relatively inactive. The cold-induced glucose intolerance was not corrected by phentolamine treatment. A marked resistance to iv insulin was apparent in these rats, which is in contrast to a normal sensitivity to iv glucagon.

Animals↗
PubMed1984

Effect of insulin on glucose uptake by the maternal hindlimb and uterus, and by the fetus in conscious pregnant sheep.

Previous studies have demonstrated the presence of insulin receptors on the maternal surface of the placenta in several species and the specific binding of insulin to the placenta in sheep. However, both in-vitro and in-vivo studies have produced conflicting evidence concerning the effect of insulin on placental glucose uptake. To clarify this problem, we measured maternal hindlimb, uterine and fetal glucose and oxygen extractions and glucose/oxygen quotients in chronically catheterized, non-stressed, late-gestation pregnant sheep over 1 h at a constant concentration of arterial plasma glucose, and again during the next 2 h at the same glucose level but at a higher insulin concentration using glucose 'clamp' methodology. Insulin produced a 4.9-fold increase in glucose extraction and a 3.5-fold increase in glucose/oxygen quotient across the hindlimb; in contrast, insulin did not significantly affect uterine or fetal glucose extraction or glucose/oxygen quotient. We conclude that in contrast to other tissues of the pregnant ewe, placental glucose uptake and transfer are insensitive to variations in maternal insulin concentration.

Animals↗
PubMed1983

Primary response to GAT in F344 rats: anti-GAT antibodies, nonspecific immunoglobulins, and expression of the GAT-13 idiotype.

It has been reported that antigen induces differentiation of two populations of Ig-containing cells: the first one to appear, IgCC, synthesizes nonspecific Ig and the second, AbCC, synthesizes antibodies. Along with other arguments, the observation that nonspecific Ig bear idiotypic determinants, which cross-react with those of antibodies, had led to the hypothesis that IgCC are precursors of AbCC. However, the synthesis of such idiotype-positive nonspecific Ig before the appearance of the antibodies has not yet been proven. This problem was investigated by analyzing the primary response to poly(Glu60-Ala30-Tyr10) (GAT) in F344 rats. Kinetics studies of cells synthesizing Ig expressing a major idiotype (GAT-13), and of cells synthesizing Ig not expressing GAT-13 idiotype, revealed that these two cell populations were undetectable before the appearance of the anti-GAT antibodies. This demonstrates that IgCC differentiation is not a necessary condition for the development of all antibody responses.

Animals↗
PubMed1982

Analysis of a major rat idiotype associated with Anti-GAT antibodies.

An anti-idiotypic antiserum was raised in a rabbit against a pool of purified F.344 rat anti-GAT antibodies. GAT-13, the idiotype defined by this serum, is present in all F.344 anti-GAT sera from primary and secondary anti-GAT responses. Anti-GAT sera of 13 inbred rat strains, with different RT1 haplotypes and with different heavy- and light-chain allotypes, all express idiotypic determinants cross-reacting with GAT-13. Thus, like in mice anti-GAT antibodies from rats express public idiotypic determinants. The anti-idiotypic serum also recognizes a highly conserved idiotypic specificity present on mouse and guinea-pig anti-GAT antibodies. The mouse, rat and guinea-pig express a similar highly conserved idiotypic specificity after immunization with GAT. All anti-GAT antibodies from the mouse and guinea-pig bear this idiotypic specificity. These results confirm the existence in the anti-GAT response of interspecies cross-reactive idiotypic determinants.

Animals↗
PubMed1982

Action of salbutamol on carbohydrate metabolism in the rat fetus.

The metabolic action of salbutamol in fetuses was studied after acute (day 21 of pregnancy) and chronic (5 daily infusions from day 16 to day 20 of pregnancy) treatment of pregnant rats. A single injection of salbutamol on day 21 of gestation induced an increase in plasma insulin levels prior to the rise of blood glucose concentration. After the chronic treatment, fetuses from treated mothers showed a decrease in insulin-secreting ability in response to a maternal glucose injection. However, no modifications in fetal liver and placental glycogen contents or in birth weight could be demonstrated. These results suggest that a chronic treatment of pregnant rats with salbutamol could affect the fetal pancreatic responsiveness to glucose.

Albuterol↗
PubMed1982

Glucose turnover rate during pregnancy in the conscious guinea pig.

The glucose turnover rate (GTR) has been determined in conscious pregnant guinea pigs from 33-63 days of gestation. Eighteen animals were studied, using a constant infusion technique of trace amounts of 6-[3H]-glucose and U-[14C]-glucose. The GTR 6-[3H] (mg X min-1) increased progressively with gestation. At term the value is approximately 2-fold higher than in the nonpregnant females. The weight specific GTR 6-[3H] (min X min-1 X kg-1) did not change significantly with gestation. The % of [14C] recycling increased from 0% at 40 days gestation to 20% at term. As with GTR, the metabolic clearance of glucose (ml X min-1) increased with gestational age and exceeded the clearance of nonpregnant animals after 50 days of pregnancy. Expressed per kg of body weight, the metabolic clearance of glucose was not significantly different in pregnant and nonpregnant animals.

Animals↗
PubMed1982

Fetal weight and its relationship to placental blood flow and placental weight in experimental intrauterine growth retardation in the rat.

The effects of experimental intrauterine growth retardation on fetal and placental weight and placental blood flow were studied in rats on day 21.5 of pregnancy. Two experimental approaches were employed. (1) Uterine artery ligation on one side on day 18.5 induced large individual variations in fetal and placental weight as well as in placental blood flow. We showed that fetal weight and placental blood flow were closely related for the values of flow ranging from 0.2 to 1.0 ml.min-1 and the values of fetal weight ranging from 2.5 to 4.5 g. In the opposite horn (control horn), variations of flow ranged from 1.0 to 2.2 ml.min-1 and they occurred without notable change of fetal weight. A relationship between fetal and placental weight was observed as well. In the ligated horn smaller fetuses had smaller placental weight. (2) Maternal fasting, 48 hours before term i.e. between 19 and 21 day of pregnancy decreases both fetal weight and placental blood flow by about 10% and 50% respectively as compared to the control values on day 21. Placental weight is virtually unchanged. The present data allow us to conclude that a marked decrease in maternal placental blood flow might be one of the main causes leading to intrauterine growth retardation.

Animals↗