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Biomedical subjects

J A Lopez

Publications and source records attributed to J A Lopez.

At least 73 records · Page 4Linked to original sources
PubMed1991

[Contribution to the pharmacodynamic study of a ketosulphoxide derivative (omega-methylsulphinyl alpha-acetothiophene). Activity on the CNS].

In order to establish the pharmacological profile of a series of ketosulphoxide derivatives which have been synthesized in the pharmaceutic and organic chemistry department of the Sevilla Pharmacy Faculty, a study of omega-methylsulphinyl alpha-acetothiophene has been initiated. Experiments were carried out on male Swiss mice, using a dosage of 100 and 200 mg/kg. High toxicity tests have been undertaken, followed by an investigation of activity at CNS levels. The results obtained show that the composite mentioned has a marked depressant activity lacking in any significant toxic effects.

Animals↗
PubMed1990

What causes spasm of atherosclerotic arteries? Is regression of plaques beneficial?

We would like to emphasize three points. First, atherosclerosis produces a profound alteration of vascular responses, which may lead to spasm in several vascular beds. Second, we have proposed that leukocytes as well as platelets may play a critical role in the pathophysiology of vasospasm. Third, there is bad news and good news in relation to regression of atherosclerosis. Maximal vasodilator capacity does not improve consistently during regression of atherosclerosis, but endothelium-dependent relaxation improves, hypersensitivity of blood vessels subsides, and we speculate that susceptibility to vasospasm may be abolished.

Animals↗
PubMed1989

Response of the mesenteric circulation to serotonin in normal and atherosclerotic monkeys: implications for the pathogenesis of non-occlusive intestinal ischaemia.

We tested the hypothesis that atherosclerosis potentiates vasoconstrictor responses in the mesenteric circulation to stimulation of serotonergic and alpha-adrenergic receptors. In normal monkeys, infusion of serotonin had little effect on blood flow to the stomach, duodenum, and colon. In contrast, in atherosclerotic monkeys, serotonin produced a modest decrease in blood flow to the stomach and duodenum, and virtually abolished blood flow to the colon. Vasoconstrictor responses to phenylephrine in the stomach and duodenum were not altered by atherosclerosis, but responses were potentiated in the colon of atherosclerotic monkeys. In summary, atherosclerosis greatly potentiates vasoconstrictor responses to serotonin in the mesenteric circulation, particularly in vessels to the colon. We speculate that release of serotonin during adherence and aggregation of platelets at atherosclerotic lesions, coupled with augmented vasoconstrictor responses to serotonin, may play a role in the pathogenesis of non-occlusive mesenteric ischaemia.

Animals↗
PubMed1989

Effect of early and advanced atherosclerosis on vascular responses to serotonin, thromboxane A2, and ADP.

In monkeys with early and advanced atherosclerosis, we examined responses to the three major vasoactive agonists that are released when platelets aggregate. Measurements were obtained in normal cynomolgus monkeys and in monkeys fed an atherogenic diet for 4 +/- 1, 9 +/- 1, and 19 +/- 1 months (mean +/- SEM). Morphometry of femoral and iliac arteries indicated that 4 months of atherogenic diet produced only slight intimal thickening, 9 months produced early lesions, and 19 months produced approximately 5-10 fold greater intimal proliferation than did 9 months of atherogenic diet. Serotonin and adenosine 5'-diphosphate (ADP), which are endothelium-dependent agonists, and adenosine and phenylephrine, which are endothelium-independent agonists, were injected intra-arterially into the perfused hind limb. Thromboxane A2 analogue U46619 also was studied. Vasoconstrictor responses to serotonin were potentiated, and vasodilator responses to ADP were impaired by early and advanced atherosclerosis. In contrast, vasoconstrictor responses to phenylephrine and vasodilator responses to adenosine were similar in all groups. Vasoconstrictor responses to U46619 were potentiated by advanced atherosclerosis. Thus, vascular responses to serotonin, ADP, and thromboxane A2 are altered by atherosclerosis in a direction that would favor vasoconstriction when platelets aggregate. Furthermore, because responses to endothelium-dependent agonists are altered, these data suggest that endothelium is dysfunctional in early atherosclerosis. These findings may explain, in part, the propensity for exaggerated vasoconstriction even in arteries with minimal atherosclerotic lesions.

Adenosine Diphosphate↗
PubMed1989

Vascular responses to leukocyte products in atherosclerotic primates.

Little is known about the possible role of leukocytes in the pathogenesis of vasospasm. We hypothesized that vasoactive products released by leukocytes might produce constriction of atherosclerotic arteries. To test this hypothesis, we infused fmet-leu-phe (fMLP), a peptide that activates leukocytes to release their vasoactive products, into the perfused hind limb of normal and atherosclerotic cynomolgus monkeys. Infusion of fMLP did not change resistance of large arteries in normal monkeys. In contrast, fMLP produced pronounced constriction of large arteries in atherosclerotic monkeys. To determine whether leukotrienes, platelet-activating factor, or prostaglandin E2 (PGE2), which are released by leukocytes, may contribute to leukocyte-induced vasoconstriction in atherosclerotic monkeys, we injected leukotriene D4, platelet-activating factor, and PGE2 intra-arterially into the perfused hind limb. Leukotriene D4 and platelet-activating factor had minimal effects on large arteries in both normal and atherosclerotic monkeys. PGE2 produced marked constriction of large arteries in atherosclerotic, but not normal, monkeys. Thus, pronounced constriction in atherosclerotic, but not normal, arteries during infusion of fMLP suggests that products released by leukocytes may mediate vasoconstriction in atherosclerotic vessels. Vasoconstrictor responses to PGE2 are profoundly potentiated by atherosclerosis, which suggests that PGE2 may contribute to leukocyte-induced vasoconstriction.

Animals↗
PubMed1988

Analysis of genetic variability and mapping of point mutations in influenza virus by the RNase A mismatch cleavage method.

We have applied the RNase A mismatch cleavage method to analyze genetic variability in RNA viruses by using influenza virus as a model system. Uniformly labeled RNA probes synthesized from a cloned hemagglutinin gene of a given viral strain were hybridized to RNA isolated from other strains of characterized or uncharacterized genetic composition. The RNA.RNA heteroduplexes containing a variable number of base mismatches were digested with RNase A, and the resistant products were analyzed by denaturing polyacrylamide gel electrophoresis. We show that many of these single base mismatches are cleaved by RNase A, generating unique and characteristic patterns of resistant RNA fragments specific for each of the different viral strains. Comparative analysis of the cleavage patterns allows a qualitative estimation of the genetic relatedness and evolution of field strains. We also show that cleavage by RNase A at single base mismatches can readily detect and localize point mutations present in monoclonal antibody-resistant variants. This method should have wide applications in the study of RNA viruses, not only for epidemiological analysis but also in some diagnostic problems, such as characterization of phenotypic mutants.

Animals↗
PubMed1988

The alpha and beta chains of human platelet glycoprotein Ib are both transmembrane proteins containing a leucine-rich amino acid sequence.

The primary structure of the beta chain of human glycoprotein Ib (GPIb), the platelet receptor for von Willebrand factor, has been established by a combination of cDNA cloning and amino acid sequence analysis. A lambda phage cDNA expression library prepared from human erythroleukemia cells (HEL cells) was screened with a radiolabeled affinity-purified rabbit polyclonal antibody to the beta chain of GPIb. Eighteen positive clones were isolated and plaque-purified and the nucleotide sequences of three were determined. The composite sequence spanned 968 nucleotides and included a 5' untranslated region of 22 nucleotides, an open reading frame of 618 nucleotides encoding a signal peptide of 28 amino acids and a mature protein of 181 amino acids, a stop codon, and a 3' noncoding region of 307 nucleotides. The 3' noncoding sequence also contained a polyadenylylation signal (AATAAA) 14 nucleotides upstream from the poly(A) tail of 18 nucleotides. Edman degradation of the intact beta chain and of peptides produced by chemical cleavage yielded amino acid sequences spanning 76 residues that were identical to those predicted from the cDNA. The amino-terminal region of the beta chain contains a leucine-rich sequence of 24 amino acids that is similar to a sequence that occurs as seven tandem repeats in the alpha chain of GPIb and nine tandem repeats in leucine-rich alpha 2-glycoprotein. The leucine-rich sequence in the beta chain of GPIb is flanked on both sides by amino acid sequences that are similar to those flanking the leucine-rich tandem repeats of the alpha chain of GPIb and leucine-rich alpha 2-glycoprotein. The amino-terminal region of the beta chain of GPIb is followed by a transmembrane segment of 25 amino acids and an intracellular segment of 34 amino acids at the carboxyl terminus of the protein. The intracellular segment contains an unpaired cysteine and two potential sites for phosphorylation by cAMP-dependent protein kinase.

Amino Acid Sequence↗
PubMed1988

Inhibitory monoclonal antibody against a (myristylated) small-molecular-weight antigen from Plasmodium falciparum associated with the parasitophorous vacuole membrane.

A small-molecular-weight antigen that occurs in asexual blood stages in synchronized cultures of Plasmodium falciparum was detected by a monoclonal antibody which inhibits parasite growth in vitro. This antigen, QF116, showed a molecular weight of 15,000 in parasite strain FCR-3K+ from The Gambia and 19,000 in strain FCQ-27 from Papua New Guinea. The protein did not show significant glycosylation by galactose or glucosamine labeling but was found to be acylated by myristic acid. By using immunogold labeling and electron microscopy, the location of the antigen could be attributed to the parasitophorous vacuole membrane and to inclusions and vesicles residing within the cytoplasm of the erythrocyte host cell.

Animals↗
PubMed1988

Effect of intracarotid administration of ouabain in dogs.

Recent work has documented both centrally mediated vasoconstriction and, paradoxically, a withdrawal of sympathetic activity in response to cardiac glycosides. In the present study the possibility that these different neurogenic responses might be dose related was investigated by infusing ouabain (5, 10, and 20 micrograms) for 5 min into the right common carotid artery of 51 anesthetized mongrel dogs. Effects on vascular resistance in the isolated, separately perfused but innervated gracilis muscle were measured. A 5-microgram infusion of ouabain (n = 6) produced a prolonged decrease in gracilis vascular resistance (GVR) of 19.4 +/- 5.4% (SE) from 43.4 +/- 6.7 (SE) to 33.7 +/- 4.2 mmHg.ml-1.100 g muscle.min (resistance units, RU). This vasodilatory response was not present in nine additional dogs following denervation of the carotid bifurcation. A 10-microgram infusion had no significant effect on GVR (n = 5), but the 20-microgram infusion of ouabain (n = 8) caused a rapid increase in GVR from 42.1 +/- 5.0 to 47.6 +/- 5.7 RU, an increase of 14.4 +/- 5.6%, which was not influenced by denervation of the carotid bifurcation (n = 8). This vasoconstriction was transient returning toward the control levels by 20 min following the infusion. These data indicate important dose-related differences in vascular responses to ouabain that are directionally opposite and mediated by separate neurogenic mechanisms. At high doses a centrally mediated vasoconstriction dominates, whereas at low doses carotid bifurcation mediated vascular dilatation occurs.

Animals↗
PubMed1988

Responsiveness of iliac collateral vessels to constrictor stimuli in atherosclerotic primates.

This study was performed to examine, first, the protective effects and responses of collateral vessels of the hind limb in normal and atherosclerotic monkeys and, second, the effects of chronic arterial occlusion on the development of atherosclerosis. The iliac artery was ligated on one side in cynomolgus monkeys. Sixteen months later, we recorded the pressure gradient across the limb collaterals and measured blood flow with microspheres. Collateral conductance was fivefold greater after chronic ligation of the iliac artery than after acute ligation. Despite dilatation or growth of collateral vessels after chronic ligation, iliac pressure was reduced distal to the ligation. Blood flow to the limb was normal after chronic ligation in both normal and atherosclerotic monkeys. Collateral vessels constricted in response to infusion of phenylephrine and serotonin in normal and atherosclerotic monkeys. Thus, one conclusion of this study is that collateral vessels restore limb blood flow to normal after chronic vascular occlusion in both normal and atherosclerotic monkeys, but the protective effects of collateral vessels may be compromised by vasoconstrictor stimuli. Morphometric measurements indicated that occlusion of the iliac artery reduced proliferation of atherosclerotic intima distal to the occlusion in the cholesterol-fed monkeys. Thus, a second conclusion of this study is that atherosclerosis is attenuated below an arterial occlusion.

Animals↗