[Residual ischemia, angina and re-infarct].
Explore the source record for details and available documents.
Angina Pectoris↗
Biomedical subjects
C Delgado
Publications and source records attributed to C Delgado.
Coupling of poly(ethylene glycol) to albumin under very mild conditions by activation with tresyl chloride: characterization of the conjugate by partitioning in aqueous two-phase systems.
Poly(ethylene glycol) activated with tresyl chloride has been covalently linked to albumin as a result of a 2-h incubation in 0.05 M sodium phosphate buffer, pH 7.5, containing 0.125 M sodium chloride (0.344 OSM). The coupling of poly(ethylene glycol) to albumin was demonstrated by the increase in the partition coefficient of the protein in poly(ethylene glycol)-dextran aqueous two-phase systems. A linear relationship between the log of the partition coefficient of the poly(ethylene glycol)-albumin conjugate and the degree of modification (measured as the amino groups consumed during the coupling step) has been demonstrated. Countercurrent distribution in the two-phase system showed that poly(ethylene glycol)-albumin was heterogeneous with respect to its partitioning behavior, indicating that the albumin was not uniformly modified with poly(ethylene glycol).
Chemical Phenomena↗
Heterogeneity of rat ovarian lactogen receptor species.
Three distinct ovarian lactogen receptor species with unique and highly reproducible HPLC retention times gave corresponding peaks of binding activity and migrated as single bands of 80, 40, and 34 kDa on SDS-PAGE. Reduction of the 80 kDa protein failed to reveal any conversion to the lower molecular weight proteins by either SDS-PAGE analysis or reverse phase HPLC, suggesting that the three binding proteins are not related by disulfide bond formation. Immunological studies indicate an amino acid homology at a C terminal region among the 3 receptor forms and with the rat liver receptor. However, the 80 kDa ovarian receptor also contains a unique sequence derived from microsequencing that is not immunologically apparent in the ovarian lower molecular weight forms of the rat liver receptor. These findings substantiate the existence of at least two populations of ovarian lactogen receptors perhaps originating within the same gene, a high Mr form potentially capable of signal transduction, and truncated forms that could be involved in transport and/or clearance.
Animals↗
Androgen sulfate and glucuronide conjugates in nonhirsute and hirsute women with polycystic ovarian syndrome.
Peripheral androgen action largely determines the occurrence of hirsutism in women. Although serum 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) glucuronide signifies skin 5 alpha-reductase activity and has been used as a marker of hirsutism and peripheral androgen metabolism, other C19 androgen conjugates have recently been measured and may also be useful markers of hirsutism in women. In addition to normal controls we studied both hirsute and nonhirsute patients with polycystic ovarian syndrome who had similar levels of circulating androgen precursors. In these three groups we measured various C19 sulfates and glucuronides including serum 3 alpha-diol glucuronide. Serum androgen precursors were elevated, but were equal in the hirsute and nonhirsute patients. Serum androsterone sulfate and glucuronide, and 3 alpha-diol sulfate and glucuronide clearly differentiated the hirsute from the nonhirsute group. Among the conjugates, androsterone glucuronide was most reflective of the difference between the two groups (100.3 +/- 28.0 versus 42.9 +/- 4.0 ng/ml, p less than 0.05). In hirsute compared with nonhirsute patients with polycystic ovarian syndrome, serum 3 alpha-diol glucuronide was increased by the smallest amount (32%), followed by androsterone sulfate (38%), 3 alpha-diol sulfate (59%), and androsterone glucuronide with the largest increase (134%). Serum androsterone glucuronide and 3 alpha-diol glucuronide both correlated with androstenedione and dehydroepiandrosterone sulfate in hirsute women but not in nonhirsute women. These data suggest that besides serum 3 alpha-diol glucuronide, other C19 sulfate and glucuronide conjugates may reflect peripheral androgen action.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
Phosphorylation and glycosylation of the luteinizing hormone receptor.
Purified testicular and ovarian luteinizing hormone/human chorionic gonadotropin (hCG) receptors are phosphorylated at serine and threonine residues by the catalytic subunit of the cAMP-dependent protein kinase (protein kinase A). Occupancy of the receptors by hCG significantly increased the rate but not the extent of phosphorylation. However, prolonged preincubation of receptors with hCG reduced the subsequent rate of receptor phosphorylation. Identical phosphopeptide maps were obtained for the phosphorylated ovarian and testicular receptors. The phosphorylated receptor, like the native receptor, bound to wheat germ lectin and hCG-Sepharose and migrated as a single band of Mr 90,000 (testis) and Mr 85,000 (ovary) on NaDodSO4/PAGE. Neuraminidase treatment of receptors caused reductions of molecular weight to 82,000 (testis) and 77,000 (ovary), and further treatment with O-Glycanase had minimal effect on molecular size. However, deglycosylation with N-Glycosidase and endoglycosidase F produced a single labeled polypeptide of Mr 59,000 for both gonadal receptors. Treatment of native receptors with neuraminidase caused no apparent change in binding of gonadotropin to blotted receptors, whereas deglycosylated receptors showed a major reduction in hormone binding. These results indicate that luteinizing hormone/hCG receptors are sialoglycoproteins with predominantly N-linked glycosyl residues that account for the size difference between testicular and ovarian receptors and that may participate in the interaction with gonadotropin. Receptor occupancy by agonist leads to a conformational change that facilitates its phosphorylation during initial binding and reduces the rate of phosphorylation after more prolonged exposure to hCG.
Amino Acids↗
Lactogen and LH receptors. Rat P-450 17 alpha, structural analysis and hormonal regulation of mRNA levels in the Leydig cell.
A complete amino acid sequence for rat testis P-450 17 alpha was deduced from nucleotide analysis of a cDNA clone isolated from a rat Leydig cell library. This cDNA expressed in COS-1 cells both 17 alpha-hydroxylase and 17,20 lyase activities. Rat P-450 17 alpha exhibited significant similarity to the nucleotide and deduced amino acid sequences of the bovine and human P-450 17 alpha, particularly with the highly conserved regions and secondary structure. The rat P-450 17 alpha is anchored to the ER by two transmembrane regions: the N-terminal insertion peptide and the stop-transfer sequence. The C-terminal is associated with the ER by four hydrophobic clefts including the steroid-binding site. We have demonstrated a dual effect of hCG, causing early increases of Leydig cell P-450 17 alpha mRNA levels at low doses, while higher desensitizing doses caused marked subsequent reduction of mRNA levels. Our studies demonstrate that gonadotropin stimulation and desensitization of P-450 17 alpha dependent enzymes (17 alpha-hydroxylase/17,20 desmolase) in the adult rat testis and E2 induced desensitization in fetal Leydig cells are related to levels of P-450 17 alpha mRNA.
Animals↗
H-2 antigens and tumour-associated transplantation antigens in clones derived from a methylcholanthrene-induced BALB/c tumour: their influence on the generation in vitro and in vivo of the specific anti-tumour immune response.
The methylcholanthrene GR9 tumour is a fibrosarcoma, originated in a BALB/c (H-2d) mouse, composed of different clones (A7, G2, D8, D6, B11, B3, B7, C11, B10, B9) with different class I (Kd Dd Ld) expression. We present data indicating that MHC class I differences observed between the different clones correlated with RNA levels and can be modified with recombinant interferon-gamma. We also studied the presence of tumour-associated antigens in GR9 and their different clones using the monoclonal antibody (MoAb) technology. We produced two syngeneic MoAbs, A7.2 and A7.6, which reacted to GR9 clones. These MoAbs precipitated a 70-kilodalton molecule and did not react with cells positive for the classical Gp70 antigen such as YC-8, LSTRA (H-2d) and RBL-5 (H-2b) lymphomas. A7.2 and A7.6 MoAbs were also negative with normal cells. In this well-characterized tumour model, we analysed the influence of the expression of class I molecules and tumour-associated antigens upon the generation, in vitro and in vivo, of the specific anti-tumour immune response. We produced syngeneic anti-GR9 A7 cytotoxic T lymphocytes (CTLs) which showed significant cytotoxicity against most of the GR9 clones including clones with low or no H-2 class I expression. These CTLs showed no cytotoxic activity against other tumour cells and concanavalin A blasts, neither could the CTL-specific response be inhibited with A7.2 and A7.6 syngeneic MoAbs nor with a panel of anti-class I MoAbs. In vivo experiments have shown that pre-immunization with the immunogenic clone GR9 A7 protects against a challenge of the different GR9 clones, independently of their class I expression and their in vitro susceptibility to lysis by anti-GR9 A7 CTLs. These results demonstrate the existence of cross-reactive tumor-associated transplantation antigens between different clones of the same tumour and the absence of correlation between in vitro susceptibility to lysis and in vivo tumour rejection. Finally, we discuss these results in the context of anti-tumour effector mechanisms generated in chemically induced tumours.
Animals↗
[Surgical treatment of variant angina. Apropos of a clinical case].
A case of a male 66 years-old patient who presented with a clinical picture of Prinzmetal's variant angina early in the evolution of an acute myocardial infarction is reported. Transient elevation of ST-segment was documented on Holter monitoring in association with angina at rest as well as asymptomatic episodes of ST-segment changes. Significant two-vessels obstructive lesions (left anterior descending and circumflex arteries) was present. As variant angina had several recurrences in spite of medical therapy with nitrates and calcium antagonists, the patient was submitted to coronary by-pass surgery associated to plexectomy. A Thallium myocardial scintigraphy suggests that a peroperative infarction had occurred. The patient was asymptomatic at six months follow-up.
Aged↗
Effect of milrinone on contractility and 45Ca movements in the isolated rabbit aorta.
The effects of milrinone on 45Ca movements and on contractile responses were studied in rabbit aortic smooth muscle. Milrinone, 10(-7)-5 x 10(-4) M, inhibited the responses induced by high K and noradrenaline (NA). These effects were observed when milrinone was added before or after the induced contractions and were similar in aortas with or without endothelium. The Ca-induced contractions of K-depolarized aortas as well as the contractions induced by caffeine in normal and in Ca-free solution were also inhibited dose dependently by milrinone. Milrinone reduced the 45Ca influx in resting or non-stimulated aortic rings as well as in aortic rings stimulated by NA. On the other hand, neither the 45Ca influx stimulated by high K or the 45Ca efflux stimulated by NA were altered by pretreatment with milrinone. It is concluded that milrinone inhibits vascular smooth muscle contractility by probably acting at multiple sites to decrease the availability of intracellular free Ca required for activation.
Animals↗
Solubility behavior of enzymes after addition of polyethylene glycol to erythrocyte hemolysates.
The addition of polyethylene glycol to a hemolysate of rat erythrocytes reduces the solubility of phosphofructokinase and glucose-6-phosphate and 6-phosphogluconate dehydrogenases in an exponential manner with respect to polymer concentration. Analyses of the solubility curves (log solubility versus polymer concentration) obtained at different pH values suggest that the solubility can be related to both the aggregation state and the intrinsic solubility of the proteins promoted by solution conditions. These findings suggest the possibility of using polyethylene glycol in a rational way for the fractional precipitation of a mixture.
Animals↗
Comparison of six new antidepressants on isolated rat atria.
The effects of six new antidepressants were studied and compared as to their electromechanical properties on isolated rat atria. All of the compounds reduced rate and amplitude of contractions, depressed atrial excitability and prolonged the sinus node recovery time. They also inhibited the amplitude of the slow contractions elicited by isoprenaline in K-depolarized atria. In decreasing order, the relative order of potency found was: mianserin approximately equal to maprotiline approximately equal to lofepramine greater than nomifensine approximately equal to trazodone greater than viloxazine. On atrial transmembrane action potentials mianserin, maprotiline and viloxazine decreased amplitude and maximum rate of depolarization and shortened the duration and depolarized the resting membrane potential. All these effects are similar to those previously reported with imipramine and amoxapine. Thus, differences between the cardiodepressant effects of the newer and older antidepressants are only quantitative but not qualitative. Possible explanations of the lower incidence of cardiovascular complications with the newer compounds are discussed.
Action Potentials↗
Electrophysiological effects of 5-hydroxypropafenone on guinea pig ventricular muscle fibers.
The effects of 5-hydroxypropafenone (5-OH-P), the main metabolite of propafenone, were studied in guinea pig papillary muscles obtained from untreated animals and from animals pretreated with 5-OH-P, 3 mg/kg for 24 days. In untreated muscles perfused with 2.7 and 5.4 mM K+, 5-OH-P depressed action potential amplitude and Vmax, reduced the resting membrane potential, and prolonged the effective refractory period (ERP), but had no effect on the duration of the action potential (APD), recovery time (RT), or ERP/RT ratio. 5-OH-P also shifted the membrane responsiveness curve downward and to the left (i.e., in hyperpolarizing direction), prolonged the ERP/APD ratio, depressed the amplitude and Vmax, and shortened the duration of the slow action potentials induced by isoproterenol in K+-depolarized muscles. Pretreatment with 5-OH-P had no effect on phase 0 characteristics or resting membrane potential, but it shortened the APD, ERP, and RT and decreased the ERP/APD ratio. Further addition of 5-OH-P produced similar but more marked changes than in untreated muscles. In papillary muscles perfused with 10 mM K+, the depressant effects of 5-OH-P on phase 0 characteristics and ERP/APD ratio were potentiated. A slight lengthening of the APD was also observed. Because all these effects are similar to those previously described with propafenone, it is concluded that 5-OH-P is an active metabolite which exhibits class 1 antiarrhythmic effects and which may be responsible for some of the cardiodepressant and antiarrhythmic effects previously described for propafenone.
Action Potentials↗
Effects of 5-hydroxy-propafenone in guinea-pig atrial fibres.
The effects of 5-hydroxy-propafenone (5-OH-P), an active metabolite of propafenone, were studied on isolated atrial muscle fibres obtained from non-treated guinea-pigs and from animals pretreated with 5-OH-P, 3 mg kg-1, for 28 days. In untreated atria 5-OH-P, 10(-8) M-10(-4) M, produced a dose-dependent decrease in amplitude and df/dtmax and reduced the amplitude of the slow contractions induced by isoprenaline and histamine in high K+ media. 5-OH-P also produced a dose-dependent decrease in atrial rate, prolonged the sinus node recovery time and reduced the maximum chronotropic responses to isoprenaline. In untreated atrial muscle fibres 5-OH-P depressed action potential amplitude and Vmax, reduced the resting membrane potential and prolonged the action potential duration (ADP) and the effective refractory period, lengthening the effective refractory period relative to APD. Pretreatment with 5-OH-P reduced atrial rate and increased contractile force, but did not modify the action potential characteristics from the values obtained in untreated atria. Further addition of 5-OH-P produced similar but more marked changes than in untreated atria. It is concluded that in guinea-pig isolated atrial muscle fibres 5-OH-P, like propafenone, exhibits class I (membrane stabilizing), class II (antisympathetic) and class IV (Ca antagonistic) antiarrhythmic actions. Therefore, this metabolite could be responsible, at least in part, for some of the antiarrhythmic effects previously attributed to propafenone.
Adrenergic beta-Antagonists↗
Comparative effects of oxodipine and nifedipine in the isolated guinea-pig heart.
The electromechanical effects of 2 dihydropyridines, oxodipine (OXD) and nifedipine, were compared on isolated guinea-pig atrial and ventricular muscle fibres. Intracardiac conduction times were measured in the Langendorff-perfused guinea-pig heart. On isolated atria OXD and nifedipine produced a dose-dependent decrease in rate and amplitude of contractions, the negative inotropic effect being accompanied by a shortening of the time to peak tension and time for total contraction. In both atrial and ventricular muscle fibres OXD and nifedipine shortened the duration of the action potential without altering the resting membrane potential and the Vmax and amplitude of phase 0. OXD also decreased the amplitude and Vmax and shortened the duration of the slow action potentials and decreased the amplitude of the slow contractions elicited by isoprenaline in K-depolarized papillary muscle fibres. In the Langendorff-perfused heart OXD and nifedipine slowed the conduction through the A-V node at concentrations at which it had no effect on intraatrial and intraventricular conduction times. The depression on A-V conduction was more marked with nifedipine than with OXD. All these results indicate that in the guinea-pig heart OXD, a new dihydropyridine, exhibit a potent and selective inhibition of Ca influx via the slow inward current.
Action Potentials↗
Selective precipitation of phosphofructokinase, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase from rat erythrocyte hemolysates by polyethylene glycol.
Precipitation profiles of phosphofructokinase, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase have been established in the range of 0-16% PEG at different pH values. Precipitation generally occurred between narrow limits of polyethylene glycol. The polymer concentration needed to reach any level of enzyme precipitation is dependent on pH. Particular conditions (% PEG and pH) for the selective enzyme enrichment have been determined.
Animals↗
Electrophysiological effects of amoxapine in untreated and in amoxapine-pretreated rat atria.
The effects of amoxapine (10(-7)-10(-4) M) have been studied in rat atrial fibres obtained from untreated animals and animals pretreated for 28 days with amoxapine (10 mg kg-1, i.p.). In untreated atria amoxapine reduced atrial rate, contractile force and df/dtmax, prolonged the sinus node recovery time and decreased atrial excitability. Amoxapine also decreased amplitude and Vmax of the upstroke, prolonged the duration of the action potential (APD) and effective refractory period (ERP) and reduced the resting membrane potential. During the treatment with amoxapine behavioural and cardiovascular adverse effects, including hypotension, tachycardia and prolongation of the Q-Tc, were observed. However, with the exception of the ERP which was significantly prolonged in pretreated atria, pretreatment with amoxapine did not modify the control values of the measured parameters compared to those obtained in untreated atria. Further addition of amoxapine produced similar changes in both pretreated and untreated atria. However, in contrast to untreated atria, in pretreated atria the prolongation of the ERP produced by amoxapine exceeded the prolongation of the APD and thus, the ERP/APD ratio increased. The decrease in atrial excitability was also more marked in pretreated than in untreated atria. Amoxapine inhibited the slow action potentials and contractions induced by isoprenaline in K-depolarized atria. It is concluded that the electrophysiological effects of amoxapine on rat atrial fibres are similar to those described for other tricyclic antidepressants. Possible explanations for the lower cardiodepressant activity of amoxapine are discussed.
Action Potentials↗
Influence of class I H-2 gene expression on local tumor growth. Description of a model obtained from clones derived from a solid BALB/c tumor.
A BALB/c methylcholanthrene-induced tumor was studied for class I and II H-2 expression. GR9 was adapted to tissue culture without any passage in vivo to avoid immunoselection mechanisms. Forty-three clones were obtained and typed for H-2 antigens. A variety of techniques were used for typing, for example, 51Cr release assay, radiobinding assay; absorption with anti H-2 monoclonal antibodies or H-2 allo-antisera and alloreacting cytotoxic T lymphocytes. A heterogeneity of H-2 expression was detected in these clones with clones H-2 K+/D+, to clones H-2K-D-. This heterogeneity was also evident when several GR9 clones were tested for in vivo growth in syngeneic BALB/c mice. Two clones, A7 and B9, were selected for further studies and injected into syngeneic animals to measure local tumor growth. A7 (K+/D+) was rather immunogenic while B9 (K-/D-) was not. These differences were probably due to an immunoresponse, since both clones grow similarly in irradiated syngeneic BALB/c mice. Immunoprecipitations of H-2 antigens and SDS-PAGE analysis confirmed the results obtained in serology. Three isoenzymes were also determined in GR9 clones and their electrophoretic mobility was always identical to that obtained in normal BALB/c tissues. These results suggest that K and D molecules are important structures for an immunoresponse against tumor-associated antigens.
Animals↗
Electrophysiological effects of propafenone on isolated guinea-pig ventricular muscle and sheep Purkinje fibres.
The electrophysiological effects of propafenone on transmembrane potentials were studied in sheep Purkinje fibres and guinea-pig ventricular muscle. In both preparations propafenone decreased the amplitude and Vmax of the action potential and shifted the resting membrane potential to less negative values. In Purkinje fibres, propafenone also slowed the conduction velocity and shortened the action potential duration whereas in ventricular muscle it had no effect on action potential duration. Propafenone also suppressed: the normal automatic mechanism in Purkinje fibres as well as the automaticity induced by BaCl2 and isoprenaline in ventricular muscle fibres with high resting membrane potential (between -75 mV and -85 mV), the abnormal automatic mechanisms, including the slow action potentials induced by BaCl2 and isoprenaline in ventricular muscle and Purkinje fibres depolarized above -55 mV, respectively, and the delayed after-depolarizations induced by ouabain in Purkinje fibres and ventricular muscle. The possible mechanisms responsible for the cardiac effects of propafenone and the therapeutic implications of these electrophysiological effects are discussed.
Action Potentials↗