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Biomedical subjects

A M Rodríguez

Publications and source records attributed to A M Rodríguez.

11 recordsLinked to original sources

A second ABC transporter is involved in oleandomycin resistance and its secretion by Streptomyces antibioticus.

A 3.2 kb Sstl-Sphl DNA fragment of Streptomyces antibioticus, an oleandomycin producer, conferring resistance to oleandomycin was sequenced and found to contain an open reading frame of 1710 bp (oleB). Its deduced gene product (OleB) showed a high degree of similarity with other proteins belonging to the ABC-transporter superfamily including the gene product of another oleandomycin-resistance gene (OleC). The OleB protein contains two ATP-binding domains, each of approximately 200 amino acids in length, and no hydrophobic transmembrane regions. Functional analysis of the oleB gene was carried out by deleting specific regions of the gene and assaying for oleandomycin resistance. These experiments showed that either the first or the second half of the gene containing only one ATP-binding domain was sufficient to confer resistance to oleandomycin. The gene oleB was expressed in Escherichia coli fused to a maltose-binding protein (MBP) using the pMal-c2 vector. The MBP-OleB hybrid protein was purified by affinity chromatography on an amylose resin and polyclonal antibodies were raised against the fusion protein. These were used to monitor the biosynthesis and physical location of OleB during growth. By Western analysis, the OleB protein was detected both in the soluble and in the membrane fraction and its synthesis paralleled oleandomycin biosynthesis. It was also shown that a Streptomyces albus strain, containing both a glycosyltransferase (OleD) able to inactivate oleandomycin and the OleB protein, was capable of glycosylating oleandomycin and secreting the inactive glycosylated molecule. It is proposed that OleB constitutes the secretion system by which oleandomycin or its inactive glycosylated form could be secreted by S. antibioticus.

ATP-Binding Cassette Transporters

Comparison between the effects of VIP and the novel peptide PACAP on the exocrine pancreatic secretion of the rat.

The effect of intravenous infusion of pituitary adenylate cyclase-activating peptide (PACAP) 27, a novel regulatory peptide that shows a close structural and chemical similarity to vasoactive intestinal peptide (VIP), on the rat exocrine pancreatic secretion was studied. PACAP and VIP stimulated the flow rate of exocrine pancreatic secretion (p < 0.05). However, protein output and amylase secretion were mainly stimulated by PACAP. Intravenous infusion of VIP increased the plasma levels of secretin (p < 0.05). On the other hand, PACAP released neither secretin nor VIP. Our results show: (a) both PACAP and VIP stimulate exocrine pancreatic secretion, (b) PACAP stimulation of pancreatic amylase and protein secretion is greater than that induced by VIP, and (c) PACAP probably exerts a direct effect on exocrine pancreas whereas some of the actions of VIP might be mediated by secretin.

Amylases

Structure-activity relationship in the gastric cytoprotective effect of several sesquiterpene lactones.

The structural requirements for the gastric cytoprotective activity of several sesquiterpene lactones are reported. A theoretical-experimental study on the potentially active centers is carried out. The biological evaluation of reduced analogues and the simulation of the molecular interactions between these compounds and an endogenous cysteine residue suggest that the presence of a non sterically hindered Michael acceptor seems to be an essential structural requirement for the cytoprotective activity in this family of compounds. This observation suggests that cytoprotection is mediated through a Michael reaction between the sulfhydryl-containing peptides of the mucosa and Michael acceptors present in the molecules under study. This mechanism of action is in addition to and distinct from the one proposed in our previous paper, namely, that these sesquiterpenes stimulate endogenous synthesis of prostaglandins.

Lactones

Structure-activity relationship on excitatory amino acid receptors.

It is generally accepted that the carboxylic amino acids L-Glu and L-Asp play a role as excitatory neurotransmitters at the CNS. In the search of a structure-activity relationship we have made a theoretical conformational analysis with a mechanics molecular model on active compounds on QUIS and NMDA-receptors. We consider the COO-...COO- distance in these compounds as the more important one in order to discuss the different mode of action of this compound at the excitatory amino acid receptors. On QUIS-receptors: We had found that Glu, Asp and QUIS are very flexible molecules that can easily pass from one conformation to another and to get the distance of 3A degrees between the two COO- groups. All these compounds show an important population in conformations with this distance. The antagonist GDEE had 90% of its whole population in folded conformations with a distance of about 3 A degrees between COO-...COO- groups. On NMDA-receptors: IBO is a rigid analogue and the distance COO-...COO- is about 4A degrees at the different conformations found. Asp, Glu, beta-Amglu and NMDA have a considerable flexibility and they can easily adopt the distance required. They leave a considerable population in conformations that present a COO-...COO- distance about 4A degrees. We propose that folded conformations are important for activity on QUIS-receptors, whereas extended conformations are the important on NMDA-receptors.

Central Nervous System

[Hemocultures].

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Bacteriological Techniques

Is leishmaniasis ever cured?

The persistence of parasites in mice cured of Leishmania mexicana infection was investigated by using immunosuppressive drugs and checking for the reappearance of lesions. BALB/c (susceptible) and C57BL/6 (partially resistant) mice infected with 10(4) amastigotes were treated with either thermotherapy or meglumine antimonate and subsequently immunosuppressed with either cyclophosphamide or hydrocortisone. Immunosuppression by either method caused lesions to reappear in both strains of mice regardless of the treatment used to produce clinical cure. In both strains of mice the proportion of animals developing lesions after immunosuppression was greater in the mice cured by the drug. The relevance of these findings to human therapy is discussed.

Animals

[Trypanosoma rangeli Tejera, 1920. VIII. Response to reinfections in 2 mammals].

Under experimental conditions, the course of the infection and the response to the reinfection by Trypanosoma rangeli in mice and Didelphis marsupialis, are studied. During the initial infection the mice show a relatively low parasitaemia and a short patent period. A scanty parasitaemia level of four days length, was observed following the first reinfection, being the mice resistant to new reinfections by T. rangeli. In opossums a lower parasitaemia and a longer patent period than that detected in mice, were observed during the initial infection. The response to reinfections in this mammal, was similar to that observed in mice. After reinfection with T. rangeli, haemagglutinant antibodies in immune-sera of both mice and opossums, were detected. The possible immune-response at the site of deposition against the metacyclic-forms of T. rangeli, and the action of circulating antibodies against the blood forms of the parasite, are speculated to explain the resistance of mice and opossums to the reinfection by T. rangeli.

Animals

[Aortic atresia. Presentation of 7 cases].

The clinical and anatomic findings of 7 patients with aortic atresia were studied. All cases had usual atrial arrangement, atrioventricular and ventriculoarterial concordance. All but one had an intact ventricular septum. All cases presented a hypoplastic left ventricle, and in one, a mitral atresia was found. The clinical diagnosis was made by means of cardiac catheterization and angiocardiography. The presence of a patent ductus arteriosus, the size of the atrial and ventricular septal defects, the diameter of the ascending aorta, pulmonary vascular resistances and right ventricular function are all factors that influence the survival in the patients with aortic atresia.

Abnormalities, Multiple