PubMed Health⌕ Search

Biomedical subjects

M Wald

Publications and source records attributed to M Wald.

At least 55 records · Page 3Linked to original sources
PubMed1995

Erythropoietin modified the cardiac action of ouabain in chronically anaemic-uraemic rats.

The results of the studies reported here demonstrate the cardiac non-haematopoietic effect of erythropoietin, providing a new physiological function of the hormone. We demonstrate that myocardium from rat with chronic renal failure (CRF) showed an abnormal response to ouabain associated with an inhibition of cardiac Na+/K+/ATPase activity and with a decrease in the high affinity 3H-ouabain binding sites. The extent to which both actions were improved with the recombinant human erythropoietin (rHuEpo) treatment suggests that the lack of the hormone is responsible for this phenomenon. The fact is that neither contractile nor enzymatic action of rHuEpo was accompanied with the improvement of the functional renal and haematologic parameters, indicating a primary effect on myocardial contractile function of rHuEpo, independent of the anaemic and uraemic state of the animal. The reason why erythropoietin is able to modulate directly the cardiac Na+/K+ pump makes it possible to conclude that the lack of erythropoietin in CRF may be at least in part responsible for the inhibition of cardiac enzymes, altering the contractile behaviour of the heart.

4-Nitrophenylphosphatase↗
PubMed1994

Myocardial mitogenic effect of erythropoietin through the activation of Na(+)-K(+)-ATPase activity.

Erythropoietin is considered unique among the hematopoietic growth factor with a specific action on the differentiation and proliferation of erythroid progenitor cells. We have observed a dose-dependent modulatory action of human recombinant erythropoietin (rHuEpo) stimulated the rate of cell growth but at higher ones (3-10 U/ml) inhibited it. The mitogenic action of the hormone is correlated with cardiac membrane Na(+)-K(+)-ATPase activity since concentrations of rHuEpo that increased cell growth stimulated paranitrophenilphosphatase (pNPPase) activity, while those concentrations that inhibit the enzyme markedly bloqued its mitogenic action. Moreover, ouabain (10(-5) M), concentration that inhibits Na(+)-K(+)-ATPase activity, blunted the stimulatory action of rHuEpo on cell proliferation. We also demonstrated that rHuEpo while activated the cardiac membrane Na(+)-K(+)-ATPase was able to alter the contractile action of ouabain on isolated neonatal rat atria. Indeed rHuEpo (1 U/ml) enhanced the non toxic action of the cardiac glycoside attenuating and delaying the onset of the toxic effect of the drug. These results show that rHuEpo has a non hematopoietic cardiac effect, associated with the cardiac Na(+)-K(+)-ATPase activity, that regulates the myocytes growth and the biological action of cardiac glycosides on isolated rat myocardium.

Animals↗
PubMed1993

The use of an audiotaped analysis in a continuous case seminar.

The use of an audiotaped analysis in a continuous case seminar is evaluated. We compare this case seminar to the traditional one in which an analyst presents process notes, and find that the use of the tape lends itself readily to teaching microanalysis, principles of technique, and observation of affect. Listening to anonymous taped sessions allowed for the possibility of a freer climate for discussion, as none of the seminar participants had a personal relationship with the taped analyst. The disadvantages posed by the absence of the analyst during the seminar also are addressed.

Curriculum↗
PubMed1992

Glycosylated serum protein levels assayed with highly sensitive immunoradiometric assay accurately reflect glycemic control of diabetic patients.

OBJECTIVE: To develop a sensitive and reliable immunoreadiometric assay to measure glycosylated lysine residues on serum proteins (GSP) and to evaluate its efficacy in monitoring glycemic control. RESEARCH DESIGN: The effect of acute and chronic in vitro and in vivo changes in glucose levels on GSP concentration was evaluated. GSP determinations from insulin-dependent diabetic (IDDM) patients, non-insulin-dependent diabetic (NIDDM) patients, and control subjects were correlated with other indices of glycemic control. RESULTS: The GSP levels were unaffected by acute glucose changes after food or intravenous glucose administration but increased during storage at -20 degrees C due to in vitro glycosylation by endogenous glucose. Immediate acidification of the serum prevented this, permitting long-term storage despite high ambient glucose levels. In randomly selected diabetic patients, 96% of GSP values were greater than the mean +3SD of nondiabetic control subjects. In diabetic patients, GSP levels correlated with mean plasma glucose concentrations (Kendall correlation statistics 0.47, P less than 0.001), fasting plasma glucose levels (Kendall statistics 0.42, P less than 0.001), and glycosylated hemoglobin (GHb, Kendall statistics 0.30, P less than 0.005). Induction of near-normal glycemia in poorly controlled NIDDM patients reduced GSP levels with a slope consistent with a half time of disappearance of 4.7 +/- 0.4 days. GSP levels remained elevated in 6 of 10 well-controlled NIDDM patients, despite normal GHb concentrations. Chronic hypoglycemic states, like pregnancy and hyperinsulinemic hypoglycemia, were associated with significantly low GSP levels. CONCLUSION: We describe a reproducible and sensitive immunoradiometric assay for GSP that closely reflects the degree of glycemic control in diabetic patients. Further studies are needed to determine whether this assay may be useful in screening for glucose intolerance or gestational diabetes.

Blood Glucose↗
PubMed1991

Margin analysis of posterior composites in vivo.

One of the major shortcomings of posterior composites is their tendency to shrink during polymerization. Thirty-three class II cavities were filled with Occlusin (OCC) (12), Coltène EX-D2 (CEX) (10), and Dispersalloy (AM) (11). The composites were placed in beveled, enamel-etched cavities by means of an incremental technique. One week and seven mo after placement, replicas were obtained and quantitatively analyzed in the SEM. The composites showed higher percentages of "excellent margin" (EM) (OCC, 70.6%; CEX-D2, 66.6%) than AM (49.2%) at baseline (p less than 0.01) and after seven mo (p less than 0.01). During the experimental period, the percentage of EM decreased by 10% for AM and OCC and by 14% for CEX-D2 (p less than 0.01). With the composites, an increase of "submargination" (SM) was found: OCC, 8.8%, and CEX-D2, 12.7%. An increase (11.2%) in margin fractures occurred for amalgam. Only OCC showed a low but significant increase (6%) in "marginal openings" (MO). This study confirms the inferior micromorphology of AM at the margins. The high amount of MO with the resin composites (16% after seven mo) indicates that, despite the complicated application technique, leakage of the restorations will occur. The margin analysis showed SM (OCC, 18%; CEX-D2, 21%) after seven mo, indicating severe wear. Class II amalgam restorations should not be replaced with the composites used in this study.

Adolescent↗
PubMed1989

Role of thromboxanes in alterations of the diabetic beta-adrenergic system.

The inotropic effects of isoproterenol (ISO), as well as the beta-adrenoceptors population, were measured in cardiac tissues from normal and short-term (3 days) diabetic rats. ISO increased the tension of both normal and diabetic ventricles, but the efficacy (Emax) of the concentration-response curve was greater on ventricles from diabetic rats than in those from the normal control. This phenomenon was accompanied by a decrease in the number of beta-adrenoceptor sites (Bmax) during diabetes. Insulin-treated diabetic hearts partially reversed the phenomenon. Propanolol blocked, in a competitive manner, the positive inotropic action of ISO in both types of ventricles. Inhibition of the synthesis and receptors of thromboxane (TX) reduced the hyperreactivity to ISO and increased the number of beta-adrenoceptors during diabetes, producing Bmax values almost similar to those of the normal heart. Additionally, the diabetic heart generated and released a greater amount of TXB2 than the normal heart, even in the presence or absence of ISO. The stimulatory effect of ISO upon TXB2 release was altered by the specific beta-adrenergic blockade and by verapamil. In addition, the drugs able to induce a sustained increase of endogenous cAMP also inhibited the release of TXB2 by diabetic ventricles. Exogenous TXB2 exerted the same type of hyperreactivity in diabetic ventricles. This phenomenon was accompanied by an inhibition of Na+ + K+-ATPase activity. These results suggest that beta-adrenergic inotropic stimulation is secondary to receptor-mediated hydrolysis of arachidonic acid with subsequent release of thromboxanes, which, in turn, may be responsible for both the superreactivity and the decrease in the number of beta-adrenoceptors during diabetes. The abnormal reactivity to beta-agonists also could be associated with alterations of the diabetic cardiac Na+ + K+-ATPase activity induced by TXB2 whose production is increased during diabetes.

Animals↗
PubMed1988

TXB2: cardiostimulant effect that involves beta-adrenoceptor and Na+ + K+-ATPase activity.

The biological properties of Thromboxane B2 (TXB2) on isolated rat heart were studied. Its actions were compared with U-46619 a Thromboxane A2 mimetic compound and with isoproterenol. TXB2 induced a concentration-dependent increase in contractility, that was non-competitively antagonized by propranolol. In addition TXB2 inhibited Na+ + K+-ATPase activity at the same concentrations that influenced the mechanical activity. Inhibition of beta-adrenoceptors efficiently blocked the inhibitory action of TXB2 upon Na+ + K+-ATPase-activity. Isoproterenol simulated the positive inotropic effect and the inhibitory action of TXB2 on Na+ + K+-ATPase-activity. In contrast, U-46619 did not alter the basal dF/dt, neither the enzyme activity. The foregoing results suggest that TXB2 resembles the biological effect of catecholamines-inducing stimulation of myocardial contractility and inhibition of Na+ + K+-ATPase activity.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1988

Alpha-adrenergic supersensitivity and decreased number of alpha-adrenoceptors in heart from acute diabetic rats.

The inotropic effect of methoxamine, as well as the alpha-adrenoceptor population, were measured in cardiac tissue from normal and short-term (3 days) diabetic rats. Methoxamine increased the tension of both normal and diabetic ventricles, but in diabetic ones, the dose-response curve to methoxamine was shifted to the left and the efficacy of the alpha-agonist was enhanced. This phenomenon was accompanied by an increase in receptor affinity, while the number of alpha-adrenoceptor sites decreased. Inhibitors of alpha 1-adrenoceptors blocked, in a competitive manner, the positive inotropic effect of methoxamine in both types of ventricles. Inhibition of phospholipase C blocked the ventricular response to the methoxamine in nondiabetic as well as in diabetic hearts. Synthetic diacylglyceride (DAG) potentiated the inotropic action of the alpha-agonist in normal ventricles and increased the affinity with a decreased number of alpha-adrenoceptor sites in normal ventricles, producing values of Kd and Bmax similar to those of the acute diabetic heart. Inhibitors of protein kinase C partially reduced the supersensitivity to alpha-agonists in diabetic ventricles and prevented the stimulatory action of DAG upon the positive inotropic effect of methoxamine in normal ventricles. These results suggest that alpha-adrenergic inotropic stimulation is secondary to receptor-mediated hydrolysis of phosphoinositides, generating some oxidative metabolites (DAG) which, in turn, may be responsible for the inotropic effect. In the acute diabetic state, the supersensitivity to alpha-agonist could be due to high activity of phospholipase C (with an increase in DAG production) which induces alteration in the membrane alpha-adrenergic receptors.

Animals↗
PubMed1988

Hypersensitivity to calcium associated with an increased sarcolemmal Ca2+-ATPase activity in diabetic rat heart.

Sarcolemmal Ca2+-dependent ATPase activity and the mechanical response to calcium and verapamil were studied in myocardium from normal rats and those with diabetes induced by streptozotocin. Sarcolemmal Ca2+-ATPase activity was increased in diabetic animals, depending on the duration of the diabetes. Both the maximal velocity and the affinity were greater in hearts of diabetic rats compared with normal controls. In insulin treated diabetic hearts the affinity of the enzyme for calcium decreased but the maximal velocity was not modified. The enzyme activity was stimulated maximally by millimolar concentrations of calcium and inhibited by lanthanum chloride. Calcium induced a concentration dependent increase in dF/dt in normal and diabetic hearts, but in diabetes the dose-response curve to calcium chloride was shifted to the left. Verapamil depressed the dF/dt in a concentration dependent manner in normal and diabetic hearts; but the drug was more effective in diabetic than in normal rats. These results suggest that an increase in sarcolemmal Ca2+-ATPase activity may be of critical importance in the hypersensitivity of diabetic heart in the presence of low extracellular calcium and calcium blockade.

Animals↗
PubMed1988

Antibodies to beta 1 and beta 2 adrenoreceptors in Chagas' disease.

Evidence accumulated over the last decade concerning human and experimental models suggests that an immunopathological mechanism may be involved in the pathogenesis of chronic Chagas' disease. In this paper we demonstrate the existence of two different circulating IgG in chagasic patients which bind with myocardial beta 1 and spleen cell beta 2 adrenoceptors, acting as non-competitive inhibitors. Both chagasic IgG against beta 1 and beta 2 adrenoceptor increased intracellular levels of cAMP that could be blocked by specific beta 1 and beta 2 adrenoceptor antagonists. The specificity for beta 1 and beta 2 adrenoceptors and the independence of other tissue reactive antibodies was demonstrated by IgG absorption with turkey red blood cell (TRBC), human lymphocytes (HL) or guinea pig red blood cells (GPRBC). The F(ab')2 fraction acted similarly. This supports the specificity of beta 1 and beta 2 adrenoceptors to the chagasic IgG and the independence of the other tissue reactive antibodies, such as EVI system. The probable pathogenic role of both beta 1 and beta 2 adrenergic chagasic antibody is discussed.

Antibody Specificity↗
PubMed1988

Dual effects of alpha-adrenoceptor agonist on contractility of mice isolated atria.

Contractility responses of mice atria to alpha-adrenergic agonists (methoxamine and clonidine) were studied. The alpha-adrenergic agonists increased the rate of force development (dF/dt) and decreased contractile frequency. The positive inotropic effect was mediated through cardiac alpha-adrenoceptors, while the negative chronotropic effect involved parasympathetic activation. Blockers of phospholipase C inhibited both the positive inotropic and the negative chronotropic effects of the alpha-adrenergic agonists. Inhibitors of phospholipase A2 and cyclooxygenase activity attenuated the positive inotropic effect of the agonists without modifying the negative chronotropic effect.

Animals↗
PubMed1980

1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU)-induced pulmonary fibrosis.

Clinical data are presented on 14 patients undergoing BCNU therapy for a primary intracranial glioma (11 biopsied, 3 suspected) in whom pulmonary fibrosis developed as a consequence of the therapy. Pulmonary diffusion abnormalities, dry hacking cough, and chest x-ray changes herald the onset of the process. Microscopic evaluation of lung specimens revealed a wide spectrum of change including hyaline membrane formation, alveolar septal thickening, interstitial fibrosis, and granuloma formation. It is concluded that BCNU causes pulmonary fibrosis that is primarily but not necessarily dose-related and may not be reversible.

Adolescent↗