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Biomedical subjects

J Prieto

Publications and source records attributed to J Prieto.

At least 163 records · Page 9Linked to original sources
PubMed1998

Liver transplantation in cirrhotic patients over 60 years of age.

Although life expectancy in Spain is above seventy years, age over sixty is considered a relative contraindication for liver transplantation (LT) in most centers. The aim of this study was to assess the outcome of LT in patients over sixty years of age comparing them to patients under that age. From January 1992 to August 1995, 61 cirrhotic patients underwent LT at our institution; of them, 43 (group I) were younger than 60 years (mean +/- SEM: 51.9 +/- 0.9 years, range: 37-59) and 18 patients (group II) were 60 years or older (64.1 +/- 0.7, range: 60-71). Main pre-transplant variables (sex, etiology of liver disease, presence of hepatocarcinoma, Child-Pugh's score and renal function) were similar in both groups. The follow-up (median and range) for group I was 28 and 3-47 months, and for group II 16.5 and 3-48 months. Actuarial survival rates at one and four years post-LT were respectively 88.3% and 85.6% for group I, and 87.8% and 87.8% for the group II (p = n.s.). There were no differences between both groups regarding the incidence of rejection, major infections, neurologic complications, renal failure, pathological bone fractures, diabetes mellitus or hypertension. Nevertheless, cardiovascular complications were significantly more frequent in group II (p = 0.002) although they were not the cause of death. In conclusion, our results show that the outcome of LT in patients over sixty years old is comparable to that observed in patients under that age. LT should not be contraindicated on the only basis of an age greater than 60 years.

Adult↗
PubMed1998

Prognosis of hepatocellular carcinoma in relation to treatment: a multivariate analysis of 178 patients from a single European institution.

BACKGROUND: Because the prognosis of patients with hepatocellular carcinoma is not fully understood, particularly regarding therapy, we have evaluated it in a series of patients with a homogeneous diagnostic and therapeutic work-up. METHODS: From 1985 to 1996, 42 variables were recorded prospectively in 178 constructive patients who had a diagnosis of hepatocellular carcinoma. Treatment consisted of liver transplantation ( n = 22), partial hepatectomy (n = 11), arterial, chemoembolization ( n = 52), systemic or regional chemotherapy (n = 51), and other therapies (n = 5); 37 patients received no specific therapy. Statistical analysis was performed according to a Cox model. RESULTS: There were no differences between the survival of patients receiving chemotherapy, other therapies, or no treatment (control group n = 93). survival rates a 1,3, and 5 years were 81%, 74%, and 74% for liver transplantation, 72%, 58%, and 58% for hepatectomy, 55%, 26%, and 13% for chemoembolization, and 13%, 3%, and 0% for the control group. Cirrhosis, systemic syndrome, bilobar involvement, Child's stage C disease, and treatment were independent predictors of survival. CONCLUSIONS: This series shows that certain easily accessible parameters may help establish individual prognosis and stratify patients in clinical trials and indicates that chemoembolization, partial resection, and liver transplantation can prolong life expectancy of patients with hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed1998

[The postantibiotic effect of amoxicillin/clavulanic acid on Streptococcus pneumoniae strains of different serotypes and penicillin sensitivity].

Amoxicillin and clavulanic acid, combined in a 4:1 ratio, caused a significant (longer than 0.5 hours) postantibiotic effect (PAE) for the S. pneumoniae stains tested. These strains were from a different serotype (3, 6 and 9) and also had different susceptibility to penicillin. The duration of the PAE depended both on the strain and the amoxicillin/clavulanic acid concentration used. It is significant that for the serotype 9 strain, which was both penicillin and amoxicillin resistant, the duration of the PAE was between 1.5 and 2.2 hours. These results agree with those observed by other authors as to the effectiveness of amoxicillin/clavulanic acid against S.pneumoniae.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed1997

[Antibiotics in Spanish households. Medical and socioeconomic implications. URANO Study Group].

BACKGROUND: To determine the storage of antibiotics in Spanish households and to analyse its source. POPULATION AND METHODS: Quantitative study carried out by telephone interview with housewives or head of the family members in 1,000 households that have been chosen at random and by agreement with a proportion of the territorial distribution of the Spanish population. RESULTS: In 42% of households that have been approached, one (88.1%) or more antibiotic packets were present, being a result of a doctor's prescription in two thirds of cases. In most cases (71.9%) amoxycillin was the antibiotic found. Concerning the pharmaceutical forms, 55% corresponded to solid oral (pills, tablets, capsules), 45% liquid oral forms (syrups, suspensions, sachets), whereas parenteral vials were not identified. Only in the 19% of households with antibiotic packets (8% of the total) there was a member of the family under antibiotic treatment. The economic evaluation of the non administrated antibiotic doses, present in households was about 5,000 millions pesetas. Over 3,000 millions pesetas had been financed by Health Public Administration. CONCLUSIONS: The storage of antibiotics in households is an important factor which increments the cost, reduces the efficiency and decreases the quality of the antibiotic treatment at the community level.

Anti-Bacterial Agents↗
PubMed1997

C-capping and helix stability: the Pro C-capping motif.

Here we have performed a statistical analysis of the protein database to find new putative local C-terminal motifs in alpha-helices. Our analysis shows that certain combinations of X-Pro pairs (Asn, Cys, His, Phe, Tyr, Trp, Ile, Val and Leu), in which residue X is the C-cap and the Pro is at position C', are more abundant than expected. In those pairs, except for the aliphatic residues, the presence of the Pro residue at C' tends to restrict the phi and psi dihedral angles of the residue at position C-cap, around -130 degrees , 70 degrees , respectively. For the aromatic residues as well as for His, the chi1 angle is around -60 degrees and the edge of the His and aromatic rings are close to the carbonyl group of the residue i - 4. In all the pairs having the above dihedral angles for residue C-cap, the main-chain amino group of Pro at C' is close to the last three main-chain carbonyls of the alpha-helix. The above structural arrangements suggests the existence of a stabilising electrostatic interaction of the residues at positions C-cap and C' with the helix macrodipole. We have denominated this putative local motif, the Pro-capping motif. To asses its importance in helix stability we have analysed by nuclear magnetic resonance (NMR) and far-UV circular dichroism (CD) a set of polyalanine-based peptides containing two of the above pairs: His-Pro and Phe-Pro, as well as the corresponding controls. In the case of the His-Pro pair we have found NMR evidence for the formation of the Pro-capping motif in aqueous solution. CD analysis shows that the presence of a Pro residue alters the C-cap properties of the preceding amino acids in the case of His and Phe makes them more favourable. The Pro-capping motif with the appropriate sequence, determines the location of the C terminus of alpha-helices and stabilises the helical conformation having Pro as the C' residue.

Amino Acid Sequence↗
PubMed1997

Non-native local interactions in protein folding and stability: introducing a helical tendency in the all beta-sheet alpha-spectrin SH3 domain.

The relative importance of secondary structure interactions versus tertiary interactions for stabilising and guiding the folding process is a matter for discussion. Phenomenological models of protein folding assign an important role to local contacts in protein folding and stability. On the other hand, simplistic lattice simulations find that secondary structure is mainly the product of protein compaction and that optimisation of folding speed seems to require small contributions of local contacts to the stability of the folded state. To examine the extent to which secondary structure propensities influence protein folding and stability, we have designed mutations that introduce a strong non-native helical propensity in the first 19 residues of the alpha-spectrin SH3 domain. The mutant proteins have the same three-dimensional structure as the wild-type, but they are less stable and have less co-operative folding transitions. There seems to be a relationship between the non-native helical propensity and the compaction of the denatured state. This suggests that in the denatured ensemble under native conditions there is a significant proportion of compact structures with non-native secondary structures. Our results demonstrate that non-local interactions can overcome strong non-native secondary structure propensities and, more important, that optimisation of folding speed and co-operativity requires the latter to be relatively small.

Amino Acid Sequence↗
PubMed1997

Gene transfer and therapy with adenoviral vector in rats with diethylnitrosamine-induced hepatocellular carcinoma.

In rats with diethylnitrosamine (DENA)-induced hepatocellular carcinoma (HCC), we studied in vivo gene transfer efficiency using intraportal injections of recombinant adenovirus carrying the lacZ reporter gene (AdCMVlacZ) and the therapeutic efficacy of adenovirus-mediated transfer of the thymidine kinase gene of the herpes simplex virus (HSV-tk) followed by ganciclovir (GCV) administration. DENA was very effective in inducing HCC but also stimulated nontumor cell replication, as shown by proliferating cell nuclear antigen (PCNA) staining. The study of in vivo gene transfer efficiency in tumor-bearing rats showed that nontumor tissue and small tumor nodules were transduced effectively whereas a poor transduction rate was noted in large tumor nodules. Concerning therapeutic efficacy, three groups of rats with established HCC were studied: group A and B received intraportally recombinant adenovirus carrying HSV-tk (AdCMVtk) or AdCMVlacZ, respectively, and 2 days after GCV was given intraperitoneally for 9 days; group C received only saline. Of the rats from groups B and C, 100% and 93% respectively, exhibited multiple HCC tumor nodules at end of the study. In contrast, a complete regression of tumor was observed in 63% of animals from group A. This group showed significant elevation of serum transaminases and a diffuse hepatotoxic lesion in liver tissue; histological signs of regeneration were observed in surviving animals. Nine out of 19 rats from group A died during the treatment period. We conclude that (i) in the DENA model of HCC, tumoral cells can be destroyed in vivo by the HSV-tk/GCV system despite poor transduction of large tumor nodules, suggesting that toxic metabolites generated by nontumor cells may exert a bystander effect on tumor tissue; (ii) significant hepatoxicity and a high mortality rate occurred in HSV-tk/GCV-treated rats; these side effects appear to be due to the fact that in DENA-treated livers enhanced cell proliferation was present not only in tumor nodules but also in nontumor parenchyma, leading to GCV sensitization of both tissues; (iii) our results have implications concerning the efficacy and potential risks of the HSV-tk/GCV system in the treatment of human HCC.

Adenoviridae↗
PubMed1997

Molecular cloning and characterization of the human AE2 anion exchanger (SLC4A2) gene.

The human AE2 gene (HGMW-approved symbol SLC4A2) encompasses over 17 kb and contains 23 exons intervened by 22 introns. The size range for the exons is 90-255 bp, whereas that for the introns is 80 bp to 2.2 kb. Exon 1 consists solely of 5'-untranslated sequence, and exon 2 encodes the amino-terminal end of the antiport protein. Primer extension experiments suggest that there are multiple transcription initiation sites in leukocytes. The putative promoter region of the human AE2 gene contains no obvious TATA or CCAAT elements in the expected positions but has GC boxes, proposed sites for binding Sp1 transcription factor. These features, as well as the presence of several consensus elements such as GATA, LBP-1, E-box, CACC box, and T-antigen motif, indicate that the human AE2 promoter resembles the erythroid promoter of the human AE1 gene. The human AE2 gene (which has been previously mapped to chromosome 7) has three more introns than the human AE1 gene (mapped to chromosome 17), but downstream of intron 7 in the AE2 gene (corresponding to intron 4 in the AE1 gene), these two genes show a rather similar exon/intron organization.

Amino Acid Sequence↗
PubMed1997

Decreased anion exchanger 2 immunoreactivity in the liver of patients with primary biliary cirrhosis.

Chloride-bicarbonate anion exchanger 2 (AE2) is expressed in a variety of tissues, including the liver and salivary glands, where it may participate in the generation of hydroionic fluxes into secretions. We have previously reported decreased hepatic levels of AE2 messenger RNA in patients with primary biliary cirrhosis (PBC), a cholestatic condition frequently associated with pluriglandular exocrine failure. Here we investigated the expression of AE2 protein in the liver of PBC patients. Using a monoclonal antibody against an AE2 peptide, immunohistochemistry was performed on liver biopsy specimens from subjects with normal liver (n = 7), patients with PBC (n = 13), and patients with cirrhosis or cholestasis other than PBC (n = 17 and 11, respectively). Immunostaining was graded from 0 to 7, according to its intensity and distribution. AE2 immunoreactivity was observed in normal livers, as previously reported, and in many pathological liver biopsy specimens, being mainly restricted to canaliculi and the luminal membrane of terminal and interlobular bile ducts. Canalicular and ductular scores were significantly reduced in the PBC group compared with each control group (normal liver and cirrhosis or cholestasis other than PBC), whereas no differences in immunoreactivity scores were observed among control groups. When four patients with primary sclerosing cholangitis (PSC) were analyzed, they also differed from those with PBC. These results suggest that PBC is characterized by diminished expression of AE2 in the liver. Reduced levels of this transporter protein might be involved in the pathogenesis of cholestasis in PBC.

Adult↗
PubMed1997

Induction of cytotoxic T-cell response against hepatitis C virus structural antigens using a defective recombinant adenovirus.

A replication-defective recombinant adenovirus (RAd), RAdCMV-CE1, containing core and E1 genes of hepatitis C virus (HCV) was constructed. RAdCMV-CE1 was able to express core and E1 proteins both in mice and human cells. Immunization of BALB/c mice with RAdCMV-CE1 induced a specific cytotoxic T-cell response against the two HCV proteins. This response was characterized using a panel of 60 synthetic 14- or 15-mer overlapping peptides (10 amino-acid overlap) spanning the entire sequence of these proteins. Five main epitopes were found in the core protein, four of which had been previously described either in mice or humans. One single novel epitope was found in E1. Fine mapping of this E1 determinant, showed that octamer GHRMAWDM is the minimal epitope recognized by cytotoxic T lymphocytes (CTL). The cytotoxic T-cell response was H-2d restricted, lasted for at least 100 days, and was mediated by T cells with the classic CD4-CD8+ phenotype. This work demonstrates that replication-defective recombinant adenoviruses can efficiently express HCV proteins and are able to induce an in vivo cytotoxic T-cell response against a diversity of epitopes from HCV antigens. These vectors should be taken into consideration in the design of vaccines and also as a means to stimulate specific T-cell responses in chronic HCV carriers.

Amino Acid Sequence↗
PubMed1997

S-adenosyl-L-methionine protects the liver against the cholestatic, cytotoxic, and vasoactive effects of leukotriene D4: a study with isolated and perfused rat liver.

Cysteinyl-leukotrienes can cause cholestasis and liver damage when administered at nanomolar concentrations. Using the isolated and perfused rat liver we analyzed whether S-adenosyl-L-methionine (SAMe) may protect this organ against the noxious effects of leukotriene-D4 (LTD4). We observed that a 2 nmol bolus of this compound decreased bile flow (-12.6% +/- 1.6%, P < .02), and bile salt excretion (-23.5% +/- 2.2%, P < .02; both compared with baseline values), caused the release of glutamic-oxaloacetic transaminase (GOT) and lactic dehydrogenase (LDH) to the hepatic effluent, and increased significantly the perfusion pressure as compared with a control group not receiving LTD4 (6.0 +/- 1.1 vs. 0.2 +/- 0.02 mm hg, respectively; P < .001). The cholestatic effect of LTD4 was attenuated by infusion of SAMe which, at rates of 67 and 100 microg/min, totally prevented the decrease in bile salt excretion. Likewise, in SAMe infused livers, the release to the effluent of GOT and LDH was lower than in the group receiving LTD4 only, and was even lower than in the control group. We also found that the increase in perfusion pressure induced by LTD4 was prevented by SAMe in a dose-dependent manner. Of interest, SAMe increased the biliary excretion of the eicosanoid in a dose-related fashion. We conclude that SAMe reverts the cholestatic, cytotoxic, and hemodynamic effects of LTD4 on the liver, and that these protective effects might be partly because of a stimulation of the biliary excretion of the leukotriene.

Animals↗
PubMed1997

Tumor cell arrest in the microcirculation: lack of evidence for a leukocyte-like rolling adhesive interaction with vascular endothelium in vivo.

Hematogenous spread of tumor cells and metastasis formation in secondary organs are insidious aspects of cancer. In the present intravital microscopic study in the rabbit mesentery, we examined the in vivo flow behavior of six human tumor cell lines of different histological origin. The tumor cells and human neutrophils were injected locally into a side branch of the superior mesenteric artery upstream of the observed microvascular area in the mesentery. None of the tumor cells behaved similar to the leukocytes of which a substantial fraction rolled along the endothelium of small venules. Thus, the tumor cells passed the same venular segments without interacting with the endothelial lining. Yet, three of the tumor cell lines (HT-29, DLD-1, and HCT-8) were strongly positive for the oligosaccharides Lewis(x), sialyl-Lewis(x), and sialyl-Lewis(a) which are recognized by the endothelial selectins that mediate leukocyte rolling. On the other hand, some tumor cells were trapped in the smallest vessels and remained so throughout the experimental period, apparently due to a discrepancy in size between tumor cells and microvessel lumen. Taken together, our in vivo findings suggest that initial microvascular arrest of metastasizing tumor cells is dependent primarily on mechanical factors rather than on receptor-mediated leukocyte-like adhesive interactions.

Animals↗
PubMed1997

Synergistic effect of azithromycin on the phagocytic killing of Staphylococcus aureus by human polymorphonuclear leukocytes.

Many macrolides have been shown to affect the interaction between bacteria and various immune defense mechanisms, such as chemotaxis, accumulation, and bioactivity within phagocytic cells. The interaction of azithromycin with human polymorphonuclear leukocytes (PMNs) was studied in vitro and compared with the interactions between other macrolides and PMNs. The opsonophagocytic killing of Staphylococcus aureus was synergistically enhanced by azithromycin at concentrations below and above the minimal inhibitory concentration, with a reduction of up to 2.82 log10 cfu/ml with 2 mg/ml of azithromycin. Other macrolides were effective only at subinhibitory concentrations. The beneficial azithromycin-leukocyte interaction may explain azithromycin's efficacy against intracellular pathogens.

Anti-Bacterial Agents↗
PubMed1997

Effect of clavulanic acid and/or polymorphonuclear neutrophils on amoxicillin bactericidal activity against Streptococcus pneumoniae.

The effects of polymorphonuclear neutrophils (PMNs) and/or clavulanic acid on the bactericidal activity of amoxicillin (at human serum achievable concentrations) against a serotype 3 penicillin-susceptible Streptococcus pneumoniae strain [minimal inhibitory concentration/minimal bactericidal concentration (MIC/MBC) values of penicillin, amoxicillin, and amoxicillin/clavulanic acid (2:1) = 0.01/0.01 microgram/ml] and a serotype 9 penicillin-resistant strain [MIC/MBC of penicillin, amoxicillin, and amoxicillin/clavulanic acid (2:1) = 1/2 microgram/ml] were studied. Against the penicillin-resistant strain, subinhibitory concentrations of amoxicillin reduced the growth rate; this effect was increased by the addition of clavulanic acid. A reduction of the penicillin-resistant initial inocula (3 x 10(6) cfu/ml) at subinhibitory concentrations was obtained only with amoxicillin plus clavulanic acid and PMNs. At suprainhibitory concentrations, both clavulanic acid and PMNs increased the bactericidal activity of amoxicillin, as evidenced by an increased reduction in the penicillin-resistant initial inocula. The combined effect of these antibiotics and immune defenses may help explain the maintenance of their clinical efficacy in respiratory tract infections, despite the increase in the incidence of penicillin-resistant pneumococci.

Amoxicillin↗
PubMed1997

Repopulation of circulating T, B and NK lymphocytes following bone marrow and blood stem cell transplantation.

A variety of T, B and natural killer (NK) cell subsets defined by surface markers were analyzed by double immunofluorescence flow cytometry in the peripheral blood of patients following autologous bone marrow transplantation (ABMT, n = 14), autologous peripheral blood stem cell transplantation (PBSCT, n = 10) and allogeneic bone marrow transplantation (allo-BMT, n = 6). Patients following ABMT were divided in 2 groups, those who did not received G-CSF post-transplant (ABMT, n = 6) and those who did (ABMT + G, n = 8). All patients following PBSCT or allo BMT received G-CSF. In all the groups prolonged significant decreases with respect to normal numbers were observed for the T CD3+, CD2+ and CD25+ subsets, more profound for the CD4+ subset but less for the CD8+ subset, especially following PBSCT (only decreased at 1 month). A significant expansion of the CD3+CD57+ and CD8+CD57+ phenotypes was noticed between 9 and 12 months following ABMT, the group of longer follow-up. Long-lasting expansion of the NK-like CD3+CD56+ and CD3+CD16+ subsets was also observed. The B CD19+ and CD20+ subsets had a significant overexpression from 4 months after ABMT, showing a normally balanced Igk+:Ig1+ ratio. Concordantly, the HLA-DR+ and HLA-DQ+ subsets showed significant increases. The NK CD56+ and CD16+ subsets had a faster recovery than the T or B subsets in all the groups. However, the CD3-CD56+, CD3-CD16+, CD16+CD56+, CD3-CD8+, and especially the CD3-CD57+, CD16+CD57+, and CD56+CD57+ subsets had a slower recovery than the global CD56+, CD16+, or CD57+ subsets. The biological and clinical implications of these findings are discussed.

B-Lymphocyte Subsets↗