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Biomedical subjects

C Alonso

Publications and source records attributed to C Alonso.

At least 271 records · Page 15Linked to original sources

Characterization and 400-MHz 1H-NMR analysis of urinary fucosyl glycoasparagines in fucosidosis.

Fucosyl glycoasparagines accumulating in the urine of a patient with fucosidosis were isolated using reverse-phase HPLC. Structural analysis of 25 glycoasparagines was carried out by combination of methylation and 400-MHz 1H-NMR spectroscopy analyses. The compounds represent different steps in the incomplete catabolism of N-glycosidically linked glycans, as the result of an alpha-L-fucosidase deficiency. All of the glycoasparagines possess a fucose residue alpha-1,6-linked to the GlcNAc 1 residue attached to asparagine. Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). The present study allows precise assignments of the NMR parameters for most of the fucosyl linkages occurring in N-glycosidically linked glycans of the N-acetyllactosamine type.

Carbohydrate Sequence↗

Inflammatory component: a worsening factor in locally advanced breast cancer treated by radiotherapy and systemic therapy.

Locally advanced and inflammatory carcinomas of the breast are two distinct entities with clear differential clinical criteria. We described a particular type of locally advanced breast cancer which, during its evolution, developed inflammatory characteristics limited to a small area of the skin. It, therefore, did not meet the common diagnostic criteria of inflammatory carcinoma. In our series, studied from December 1977 to January 1987, we treated 59 cases of locally advanced breast cancer and 105 cases of locally advanced breast cancer with an inflammatory component. The actuarial overall survival was 53.3% at 5 years and 38.4% at 7 years. Differences were observed when the two tumor types were compared. Specifically, locally advanced breast cancer with an inflammatory component had a worse prognosis, poorer survival and poorer disease-free rates than locally advanced breast cancer.

Adult↗

A potential Z-DNA-forming sequence is located between two transcription units alternatively expressed during development of Drosophila hydei.

Recent studies have demonstrated that Z-DNA exists in vivo in Escherichia coli as well as in Drosophila and mammalian cells. In the present paper, we show the existence in vivo of Z-DNA epitopes in the developmentally regulated subregion 4-75C of polytene chromosomes in Drosophila hydei. The Z-DNA epitopes were detected in subdivision C2 only during late third instar when the transcriptional activity of the locus was high. Accumulation of nonhistone chromosomal proteins in that locus was also detected during late third instar only at the time of the Z-DNA formation. Northern blot data and nucleotide sequence analysis indicated that the Z-DNA-forming sequence is located between two transcription units whose expression is regulated during the third instar. Our results suggest that in subdivision 4-75C2 a B- to Z-DNA flux occurs at a specific time during late third instar and that this flux may play a negative as well as a positive role in gene expression.

Animals↗

Assessment of anthracycline-induced myocardial damage by quantitative indium 111 myosin-specific monoclonal antibody studies.

To assess chemotherapeutically induced myocardial damage, myosin-specific antibody scans and ejection fraction measurements were performed in 32 patients with breast cancer and in 9 patients with other tumours. All patients had received chemotherapy including anthracyclines. The ejection fraction decreased by less than or equal to 10% in 14 of 41 (34%) patients after chemotherapy. Antimyosin uptake in the myocardium was observed in 38 of 41 (92%) patients after chemotherapy. Antimyosin uptake was quantified by means of a heart-to-lung ratio, revealing a correlation between the degree of antimyosin uptake in the myocardium and the cumulative dose of anthracycline. Patients with a decreased ejection fraction showed more intense antimyosin uptake, indicating more severe myocardial damage. A higher degree of antimyosin uptake was found in 17 breast cancer patients treated with doxorubicin compared with 15 patients treated with mitoxantrone. We conclude that antimyosin studies provide a sensitive, non-invasive method to monitor myocardial damage in patients treated with anthracyclines. Antimyosin uptake in the myocardium precedes ejection fraction deterioration. This technique may be helpful in the early identification of patients at risk of congestive heart failure during chemotherapy including anthracyclines.

Adult↗

DNA binding properties and antileukemic (L1210) activity of a Pt-pentamidine complex.

The DNA thermal stabilizing effect and the antileukemic properties of a Pt-pentamidine complex have been studied. The results indicate that the pentamidine ligands in Pt-pentamidine probably have an interaction with the DNA stronger than that of pentamidine alone because they are bound to the nucleic acid through the cis-PtCl2 residues. However, the cis-PtCl2 residues do not seem to significantly destabilize the helix. Two types of evidences are consistent with this hypothesis: (1) a decrease in the dielectric constant of the medium does not remove the pentamidine ligands from the Pt-pentamidine: DNA complex, and (2) the renaturation of the DNA in Pt-pentamidine:DNA complex is DNA concentration independent. 1H- and 13C-NMR spectroscopic data together with the elemental analysis indicate that the complex is a stoichiometric oligomer of formula [(cis-PtCl2)3(pentamidine)3] [PtCl4]2. This drug exhibits significant antineoplastic activity in BDF1 mice bearing i.p. L1210 leukemia. At a concentration of 50 mg/kg, about 15% of the LD50 for the 1,5 and 9 days schedule, the antitumor activity (T/C = 337%) is considerably superior to that of cis-DDP (T/C = 215%) or carboplatin (T/C = 220%) at doses representing 75% and 50%, respectively, of the LD50 for the same treatment schedule. Moreover, it was found that the nephro-hepatotoxicity of the complex is low.

Animals↗

Calcified constrictive pericarditis. Ultrasonic debridement.

A case of complete debridement of a calcified pericardium in a patient with constrictive pericarditis is reported. The use of an ultrasonic surgical aspirator facilitated disintegration of calcium without damaging the adherent epicardium and myocardium.

Aged↗

In situ right gastroepiploic artery. A conduit for coronary revascularization.

The internal mammary artery is widely recognized as the graft of choice for coronary artery bypass grafting at present. Alternative conduits have been investigated in order to find other adequate long-term grafts. The right gastroepiploic artery has been recently used as a graft to bypass distal coronary vessels. From November 1989 to June 1990, we have implanted this artery in 46 cases. Pedicled grafts were implanted in 20 patients to the main right coronary artery, in 21 patients we grafted the right distal branches, in 3 patients the left anterior descending, and in 2 the circumflex branches. Mean grafts per patient were 3 in this series, with a mean of 2.2 arterial grafts per patient. One patient died in the early postoperative period. The remaining patients had an uncomplicated postoperative evolution. Thirteen patients underwent graft and coronary angiography. Direct or indirect graft patency was confirmed in all cases. The final important issue concerning the long-term patency of this graft will be solved in the future, but short-term patency rates of the right gastroepiploic artery can be anticipated when proper techniques are used.

Adult↗

Distribution of a novel mycolic acid in species of the genus Mycobacterium.

We found that Mycobacterium porcinum ATCC 33776T (T = type strain) contains a new kind of mycolic acid with a methoxy group at the omega-1 position. This mycolic acid was identified by comparing it with the previously described methoxymycolic acids. The patterns of mycolic acid methyl esters from 418 strains belonging to 44 species of mycobacteria were studied by using thin-layer chromatography. In addition to M. procinum ATCC 33776T, representative strains of M. porcinum, Mycobacterium fortuitum, "Mycobacterium peregrinum," Mycobacterium senegalense, and a recently isolated Mycobacterium sp. contained appreciable amounts of the newly described mycolic acid.

Chromatography, Thin Layer↗

Short-term effects of administration of anticonvulsant drugs on free carnitine and acylcarnitine in mouse serum and tissues.

1. The short-term evolution of concentrations of free carnitine and acylcarnitine was studied in the serum, liver, kidney, heart and skeletal muscle of mice after administration of single therapeutic doses of the anticonvulsant drugs, valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHT) and phenobarbitone (PHB). 2. The effects of the drugs were immediate but transitory, control levels of free carnitine and acylcarnitine having been recovered or almost recovered in serum and in all tissues 8 h post administration (p.a.). 3. VPA was the only drug that significantly reduced free carnitine concentration in serum, which recovered control levels by 4 h p.a. 4. All the drugs studied brought about marked deficits of serum acylcarnitine, which had disappeared 2 h p.a. in the case of VPA and not until 8 h p.a. for CBZ, PHT or PHB. 5. The minimum concentrations of free carnitine and acylcarnitine in serum were invariably associated with the maximum concentration of drug in serum. 6. Free carnitine concentration was not affected by VPA in any tissue, PHT and PHB brought about significant deficits in heart and kidney, and CBZ a significant deficit in muscle. 7. Acylcarnitine concentration was significantly reduced in heart, kidney and muscle by CBZ, PHT and PHB, but in liver the effects of all drugs were very small. 8. These results are compatible with the hypothesis that the primary cause of anticonvulsant-induced alteration of carnitine metabolism is interference with renal reabsorption of carnitine.

Animals↗

Alteration of renal carnitine metabolism by anticonvulsant treatment.

We administered therapeutic doses of valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHT), and phenobarbital (PHB) to mice for 7 days, and 8 hours after the final dose we measured the concentrations of carnitine in serum, liver, kidney, skeletal muscle, and heart, and in the 7 days' accumulated urine. The results for serum and urine show that VPA induced a significant increase in renal clearance of acylcarnitine without affecting that of free carnitine, whereas CBZ, PHT, and PHB significant increased clearance of free carnitine but not that of acylcarnitine. Thus, VPA appears to reduce tubular resorption of acylcarnitine, and CBZ, PHT, and PHB appear to reduce tubular resorption of free carnitine.

Ammonia↗

[Physician's legal responsibility].

The professional responsibility of the physician and the concept of malpractice are analyzed. In determining malpractice, the intention and the mode of action are more important than the actual damage that may be caused. Legal sanctions for malpractice must be based on objective evidence of inexcusable negligence in the medical action. A moral attitude stressing the values of Medicine rather than fear from legal sanctions should underlie all medical practice.

Ethics, Medical↗

[Myocardial revascularization with the gastroepiploic artery. The initial experience].

The internal mammary artery is widely recognized as the graft of choice for coronary artery bypass grafting at present. Alternative conduits have been investigated in order to find other adequate long-term grafts. The right gastroepiploic artery has been recently used as a graft to bypass distal coronary vessels. From November 1989 to April 1990 we have implanted this artery in 33 cases (32 in situ and one free grafts). The pedicled grafts were implanted in 17 patients in the main right coronary artery, in 13 we grafted the right distal branches, in one the left anterior descending, and the circumflex branch in one. The free graft was implanted in the first diagonal. Mean grafts per patient was of three in this series, with a mean of 2 arterial grafts per patient. One patient died in the early postoperative period. The remaining patients had an uncomplicated postoperative period. Thirteen patients underwent graft and coronary angiography. Direct or indirect graft patency was confirmed in all cases. The final important issue concerning the long-term patency of this graft will be solved in the future, but short-term patency rates of the right gastroepiploic artery can be anticipated when proper techniques are used.

Adult↗

[Value of studying the extraluminal and intraluminal surfaces in the detection of catheter colonization].

612 catheters have been prospectively investigated. In all of them, both the external and the internal surfaces were cultured, the former with the semiquantitative technique of Maki and the latter with the semiquantitative technique of Liñares. 102 of the 469 central venous catheters (22%), 21 of 70 catheters used for parenteral nutrition (30%), and 19 of the 73 arterial catheters (26%) were positive with one or both techniques. The external surface was positive in 95% of central venous catheters, in 90% of the parenteral nutrition catheters, and in 95% of the arterial catheters, whereas the internal surface was positive in only 59%, 62% and 42%, respectively. The routine study of the internal surface of the catheters does not appear as justified. In our opinion, the microbiological study of catheters should be individualized depending on the relative importance of the skin or the connections in a particular catheter type. The quantitative study of the intraluminal surface should only be carried out in those catheters where connections represent a significant pathogenetical route. These catheters constitute only a small proportion of those that we receive for culture in the Microbiology Laboratory; therefore, this approach represents a considerable simplification of our daily routine.

Bacteria↗

Analysis of the mechanisms involved in NK resistance induced by a new tumor factor NK-RIF.

The mechanisms involved in susceptibility or resistance of neoplasic cells to lysis by NK cells are not well known. We have recently described a 12-kDa factor (NK-RIF), produced and released by different tumor cell lines, making K562 resistant to NK lysis without affecting the cytotoxic function of NK effector cells. In this paper we further study the mechanism involved in NK resistance of K562 mediated by NK-RIF and its biological implications. The results show that NK-RIF does not affect the binding capacity of target and effector cells nor the levels of HLA class I antigen expression on the target cells, as a proof that resistance to NK-mediated lysis is not always associated with a defect in target effector binding or with an increased MHC class I antigen expression. However NK-RIF-treated K562 loses its capacity to induce NK cell activation and the subsequent capacity to release NKCF and makes K562 resistant to lysis by NKCF. Therefore our results show that induction of resistance to NK cytotoxicity can be the result of the modulation of target structures responsible for inducing effector cell activation without affecting target/effector binding molecules. This indicates that the structures involved in adherence and activation of NK cells have a different nature and that molecules other than HLA participate in NK resistance.

Biological Factors↗

Sequence and expression of the Drosophila phenylalanine hydroxylase mRNA.

We report the cloning, nucleotide (nt) sequence and expression of the cDNA (pah) encoding phenylalanine hydroxylase (PAH) of Drosophila melanogaster. The strong hybridization signals observed in genomic blots when D. melanogaster DNA was probed with 32P-labeled human pah cDNA, indicated the existence of a high degree of sequence similarity between the pah genes of both species. The length of the pah genomic fragment is about 30 to 40 kb. The cDNA contains 84 bp of the 5'-untranslated region, 1359 bp of the protein-coding region and 87 bp of the 3' region, with only one polyadenylation signal. The isolated cDNA is probably full-length, since the size of the D. melanogaster PAH mRNA is 1.5 kb. At the nt level, the similarity of the D. melanogaster cDNA with human and rat pah cDNAs is 57.9% and 58.1%, respectively. The highest similarities are restricted to the nt sequence coding for the presumed hydroxylation domain. There is no nt sequence similarity between the first three exons of the human pah gene and an equivalent fraction of the D. melanogaster pah gene. At the amino acid (aa) level, the similarity in the presumed hydroxylation domain is 88.5%, in which two motifs of the structure AGLLSSXXXL are found, where X represents any aa. It was interesting to notice the conservation of aa 408, 311 and 280, where mutations are associated with phenylketonuria in humans. We observed, moreover, that, as it occurs in humans and rats, the expression of the D. melanogaster pah gene is tissue-specific and temporally regulated.

Amino Acid Sequence↗