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Biomedical subjects

L Rodriguez

Publications and source records attributed to L Rodriguez.

At least 73 records · Page 4Linked to original sources

Structural basis for the deoxyribonucleic acid affinity of bleomycins.

The role of the bithiazole moiety of bleomycin in the interaction of the antibiotic with DNA has been studied by the use of synthetic bithiazole derivatives. The DNA affinity of individual C-terminal (bithiazole) analogues of bleomycin was measured in terms of the ability of these species to block the binding of bleomycin to DNA, as judged by diminution of the DNA degradation that attends bleomycin binding. DNA degradation was monitored both by release of [3H]thymine from radiolabeled PM-2 DNA and by alteration of bleomycin-treated DNA oligomers of defined sequence derived from Escherichia coli plasmid pLJ3. It was found that the affinity of the bithiazole derivatives for DNA depended on the presence of the bithiazole moiety itself but more importantly on the number and spacing of positively charged groups; 2'-(2-aminoethyl)-2,4'-bithiazole-4-[3-[(4-aminobutyl) amino]propyl]carboxamide (14), having three positively charged groups at neutral pH, was a reasonably effective inhibitor of DNA degradation by bleomycin. Consistent with the importance of the spacing of the positively charged groups, tetrapeptide S (12) was found to be significantly less inhibitory toward DNA degradation by bleomycin than tripeptide S, in spite of their equal number of positively charged groups and the greater structural similarity of the former to bleomycin A2. Bleomycin is known to cleave DNA perferentially at certain sequences. It was shown that the inhibitors employed in this study diminished DNA cleavage proportionately at each cleavage site; no alteration was observed in the specificity of cleavage. A number of the bithiazole analogues employed as inhibitors of bleomycin-mediated DNA degradation were also utilized in fluorescence quenching experiments with calf thymus DNA. Consistent with the belief that these species inhibit bleomycin degradation by competitive binding to the DNA substrate, the best inhibitors exhibited the greatest fluorescence quenching upon admixture of DNA.

Bacteriophages

Nitrogen bridgehead compounds. 18. New antiallergic 4H-pyrido[1,2-a]pyrimidin-4-ones. 1.

A new type of antiallergic agent, 9-hydrazono-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-ones, was synthesized and evaluated for inhibitory effects in the rat reagenic passive cutaneous anaphylaxis (PCA) screen. Several racemic 6-methyl derivatives were found to be more potent than disodium chromoglycate intravenously and some were also active orally. Structure-activity relationships are discussed. High stereospecificity was observed in the 6-methyl series between the enantiomers with 6S and 6R absolute configuration, the former being more active. Compound 17, (+)-6(S)-methyl-9-(phenylhydrazono)-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid [Chinoin-1045; UCB L140], has an ED50 value of 1.0 mumol/kg po and is now under clinical investigation.

Animals

Rupture of the inferior vena cava during open-heart surgery. Aetiology and surgical management.

Bleeding during open-heart surgery is a not unusual complication. Rupture of the inferior vena cava during dissection of the heart from adhesions from a previous operation for mitral disease or congenital palliative surgery is a serious and sometimes fatal complication. Its treatment is a challenge even to the most experienced heart surgeon. In two of our three patients, vena cava rupture occurred during open-heart surgery for correction of mitral and aortic valvular disease. In one patient, congenital infundibular stricture of the right ventricle, associated with tricuspid valve insufficiency, was present. In this report, some relevant data were presented from each case and the aetiology of the rupture is discussed.

Adult

Successful replacement of the aortic valve, mitral valve and ascending aorta with re-implantation of the coronary arteries.

A 63-year-old man was operated upon with replacement of the aortic valve, mitral valve and ascending aorta with re-implantation of the coronary arteries. A composite graft with a 27 mm Björk-Shiley tilting disc prosthesis was inserted with 3 continuous Prolene sutures in the aortic position. The coronary arteries were thereafter re-implanted in holes made in the graft. A 31 mm Björk-Shiley valve was sutured in the mitral position with about 20 isolated mattress sutures of Ti-Cron. Selective myocardial hypothermia was instituted with Ringer's solution of 4 degrees C. The total perfusion time was 185 min compared with 240 and 275 min in two previously reported, similar cases. We consider that the use of cardioplegia, a composite graft and continuous sutures makes it possible to reduce the operation time in these complex cases. Our patient is in good condition 9 months postoperatively.

Aortic Aneurysm

Regulation of acid phosphatase synthesis in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae-136ts (Hutchison, H.T., Hartwell, L.H. and McLaughlin, C.S. (1969) J. Bacteriol. 99, 807--814) derepressed acid phosphatase was almost exclusively located outside the permeability barrier. Only a minor part of the activity was associated with the protoplasts; about half of it (48%) in the soluble fraction, the rest bound to the internal (45%) and plasma (7%) membranes. The activity found in the membranes of derepressed cells decreased by 30--40% after addition of inorganic phosphate or cycloheximide suggesting that this activity is the precursor of the external enzyme. The alkaline phosphatase activity level could not be modified by changes in the concentration of inorganic phosphate. Acid phosphatase was not synthesized if the cells were transferred to a low phosphate medium at the moment of incubation at 37 degrees C or in the presence of cycloheximide at 23 degrees C. The data suggested that enzyme formation is the result of the transcription and translation of a specific gene(s) and not the activation of a proenzyme. Inorganic phosphate did not inhibit the translation of mRNA though it may act at the level of the transcription.

Acid Phosphatase

Human tumor-lymphocyte interaction in vitro. III. T lymphocytes in autologous tumor stimulation (ATS).

The T-cell nature of the responding cells in autologous tumor stimulation (ATS) was proven by (1) E-rosette formation of lymphocytes attached to tumor cells during the early period of co-cultivation; (2) blast-transformed E-rosetting cells detectable at the end of the test period (day 6) and (3) the reactivity of T-enriched lymphocyte subset and unresponsiveness of T-depleted fractions. Preparation of tumor suspensions devoid of lymphocytes made it possible to carry out cross-tests between patients. Blastogenesis with allogeneic tumors was rare. The restricted autologous nature of the reaction is a strong indication for genuine tumor-relatedness.

Adenocarcinoma

Two-stage replacement of tricuspid valve in active endocarditis.

One month after a 21-year-old female drug addict with tricuspid staphylococcal endocarditis seemed to have been cured by antibiotic therapy she relapsed. Further antibiotic treatment for one month failed to control the infection. Tricuspidectomy was when performed and the infection was eliminated. A valve prosthesis was inserted 3 months later. She recovered and is now fully restored to health. We recommend this two-stage surgical technique in similar cases.

Adult

Left ventricular rupture as a complication of mitral valve replacement.

We are not the first to attempt repair of left ventricular rupture complicating mitral valve replacement, as 18 analogous cases have been reported earlier in the literature. Our series comprises 8 patients, 5 of who, survived. A review of these 26 cases provided several facts of interest to surgeons dealing with this complication. The rupture occurred either as a laceration in the posterior atrioventricular groove (type I, 16 of 26 patients) or as a perforation of the midportion of the left ventricle (type II, 10 of 26 patients). Intraoperative rupture (17 of 26 patients) was usually detected on termination of bypass, whereas delayed rupture (9 of 26 patients) occurred after chest closure or in the recovery room. The morality rate was about 50 per cent for the intraoperative type, and no patient survived a delayed rupture. The prognosis appeared to be most in intraoperative type II lesions. The main factors affecting the prognosis were (1) instant reinstitution of extracorporeal circulations and (2) avoidance of the circumflex coronary artery during repair of type I lesions located close to the anterolateral mitral commissure. Attempts to suture a ventricular rupture on the pressure-loaded, beating heart were always unsuccessful and frequently extended the laceration. Patients with the delayed type of rupture died of hemorrhage before they could again be placed on bypass. It may be preferable to reopen the lefr atrium in order to repair a type I laceration. In type II perforations, direct repair with buttressed sutures should be attempted from the exterior of the heart. The angulated metal cannula for drainage of the left ventricle was identified as a possible, but not previously reported, cause of myocardial perforation. It is hoped that the use of a soft cannula or a metal cannula with an angle of 60 degrees instead of 90 degrees will reduce the incidence of this complication.

Female

Percutaneous fixation of supracondylar fractures of the humerus in children.

Of 1,118 supracondylar fractures of the humerus in children treated over a six-year period, 189 are described with a follow-up of more than two years. These patients were treated with closed reduction and percutaneous fixation of the fragments with two wires. Eighty-five per cent of the final results were satisfactory.

Child

Modification by calcium dobesilate of histamine effects on capillary ultrastructure.

The ultrastructure of blood capillaries and venules are studied in rat skin. After i.v. injection of histamine the luminal surface of the endothelial cells show protrusions of variable size. Numerous gaps have been found in the capillary wall, specially in the venules. These alterations are not observed in the animals that were treated with calcium dobesilate before the administration of histamine. In these cases the capillary structure are indistinguishable of the controls. The possible effects of the histamine and calcium dobesilate on the cell coat and cell junctions of the endothelial capillary cells are discussed.

Animals