A decade of liver transplantation in primary liver tumors.
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Actuarial Analysis↗
Biomedical subjects
E Moreno
Publications and source records attributed to E Moreno.
Steroid withdrawal is safe and beneficial in stable cyclosporine-treated liver transplant patients.
BACKGROUND: In the immunosuppression of orthotopic liver transplant recipients, steroids are used despite their unspecific action and long-term side effects. Few studies have been carried out on steroid withdrawal and many aspects remain to be elucidated. METHODS: A prospective study was performed to analyse the effect of steroid withdrawal on 86 patients with stable graft function, more than 1 year after orthotopic liver transplant. Thirty patients had chronic hepatitis in the graft. Seventy-two continued with cyclosporine (CsA) and 14 with CsA-azathioprine (AZA) therapy. The follow-up was 23.2 +/- 8.1 months (range 12-52 months). A paired t-test was used for statistical analysis. RESULTS: No acute or chronic rejection occurred, and steroids were not reinstituted. There were no changes in serum transaminase levels, but bilirubin levels decreased (p < 0.01). At the end of the follow-up, we found improvements in blood pressure in hypertensive patients (systolic 156.1 +/- 8.4 mmHg vs. 139.4 +/- 8.7 mmHg, p < 0.001); body weight (72 +/- 13.5 kg vs. 70.8 +/- 13 kg, p < 0.05); serum cholesterol (211.3 +/- 42 mg/dl vs. 191.6 +/- 43.5 mg/dl, p < 0.001) and bone mineral density in lumbar spine (0.823 +/- 0.13 g/cm2 vs. 0.893 +/- 0.135 g/cm2, p < 0.001). Four of ten diabetic patients were no longer insulin-dependent and insulin requirements decreased in the remaining six. No significant biochemical changes were found in patients with hepatitis in the graft, and we found an improvement in inflammatory activity in the nine biopsied patients. CONCLUSIONS: Steroid withdrawal with CsA monotherapy is feasible, safe and beneficial in patients who have stable liver graft function 1 year after orthotopic liver transplant. We consider that AZA therapy is not necessary unless drastic reduction of CsA levels is required because of renal dysfunction.
Adult↗
Multiple hypothalamic factors regulate pyroglutamyl peptidase II in cultures of adenohypophyseal cells: role of the cAMP pathway.
In the adenohypophysis, thyrotrophin-releasing hormone (TRH) is inactivated by pyroglutamyl peptidase II (PPII), a TRH-specific ectoenzyme localized in lactotrophs. TRH slowly downregulates surface PPII activity in adenohypophyseal cell cultures. Protein kinase C (PKC) activation mimics this effect. We tested the hypothesis that other hypothalamic factors controlling prolactin secretion could also regulate PPII activity in adenohypophyseal cell cultures. Incubation for 16 h with pituitary adenylate cyclase activator peptide 38 (PACAP; 10(-6) M) decreased PPII activity. Bromocryptine (10(-8) M), a D2 dopamine receptor agonist, or somatostatin (10(-6) M) stimulated enzyme activity and blocked the inhibitory effect of [3-Me-His2]-TRH, a TRH receptor agonist. Bromocryptine and somatostatin actions were suppressed by preincubation with pertussis toxin (400 ng ml(-1)). Because these hypophysiotropic factors transduce some of their effects using the cAMP pathway, we analysed its role on PPII regulation. Cholera toxin (400 ng ml(-1)) inhibited PPII activity. Forskolin (10(-6) M) caused a time-dependent decrease in PPII activity, with maximal inhibition at 12-16 h treatment; ED50 was 10(-7) M. 3-isobutyl-1-methylxanthine or dibutiryl cAMP, caused a dose-dependent inhibition of PPII activity. These data suggest that increased cAMP down-regulates PPII activity. The effect of PACAP was blocked by preincubation with H89 (10(-6) M), a protein kinase A inhibitor, suggesting that the cAMP pathway mediates some of the effects of PACAP. Maximal effects of forskolin and 12-O-tetradecanoylphorbol 13-acetate were additive. PPII activity, therefore, is independently regulated by the cAMP and PKC pathways. Because most treatments inhibited PPII mRNA levels similarly to PPII activity, an important level of control of PPII activity by these factors may be at the mRNA level. We suggest that PPII is subject to 'homologous' and 'heterologous' regulation by elements of the multifactorial system that controls prolactin secretion.
Aminopeptidases↗
A two-component regulatory system playing a critical role in plant pathogens and endosymbionts is present in Brucella abortus and controls cell invasion and virulence.
Two mutants showing increased sensitivity to polycations and surfactants were obtained by transposon mutagenesis of virulent Brucella abortus 2308 Nalr. These mutants showed no obvious in vitro growth defects and produced smooth-type lipopolysaccharides. However, they hardly multiplied or persisted in mouse spleens, displayed reduced invasiveness in macrophages and HeLa cells, lost the ability to inhibit lysosome fusion and were unable to replicate intracellularly. Subsequent DNA analyses identified a two-component regulatory system [Brucella virulence related (Bvr)] with a regulatory (BvrR) and sensory (BvrS) protein. Cloning of bvrR in the BvrR-deficient mutant restored the resistance to polycations and, in part, the invasiveness and the ability to multiply intracellularly. BvrR and BvrS were highly similar (87-89% and 70-80% respectively) to the regulatory and sensory proteins of the chromosomally encoded Rhizobium meliloti Chvl-ExoS and Agrobacterium tumefaciens Chvl-ChvG systems previously shown to be critical for endosymbiosis and pathogenicity in plants. Divergence among the three sensory proteins was located mostly within a periplasmic domain probably involved in stimulus sensing. As B. abortus, R. meliloti and A. tumefaciens are phylogenetically related, these observations suggest that these systems have a common ancestor that has evolved to sense stimuli in plant and animal microbial environments.
Animals↗
Clinical, virological, and histologic evolution of hepatitis C virus infection in liver transplant recipients.
We designed a prospective study to assess the time course and evolution of hepatitis C virus (HCV) infection in 152 patients who underwent a liver transplantation (LT) in our institution. Forty-four recipients (29%) were infected by HCV after transplantation: 40 who developed recurrent infection after LT and four who acquired infection during or after LT. No differences were found in survival actuarial rates at 1, 2, and 4 years after transplantation for patients infected by HCV vs. noninfected ones. Graft hepatitis occurred in 66% of HCV-infected recipients: 18 developed chronic active hepatitis (10 of them with intense fibrosis) and 2 developed cirrhosis during the follow-up. Infection by the HCV-1b genotype was found in 79% of the infected recipients and in 100% of those in whom histologic evolution was worst. Fourteen grafts were lost in 44 HCV-infected recipients, in comparison with 12 in 108 HCV-negative patients (P = .007), mostly because of chronic rejection. HCV infection did not affect life expectancy in the midterm follow-up for LT patients. However, it was often associated with the occurrence of early and severe graft hepatitis and with a higher incidence of graft loss due to chronic rejection.
Adult↗
Delineation of the epitope recognized by an antibody specific for N-glycolylneuraminic acid-containing gangliosides.
P3 is a mouse monoclonal antibody (mAb) that binds to several NeuGc-containing gangliosides. It also reacts with antigens expressed in human breast tumors (Vázquez et al. (1995) Hybridoma , 14, 551-556). In this work, the binding specificity of P3 has been characterized in more detail using a panel of glycolipids that included several disialylated gangliosides and several chemical derivatives of NeuGc-GM3. The carboxyl group and the nitrogen function of sialic acid were found to play important roles in the antibody binding, whereas the glycerol tail appears to be nonrelevant. Molecular modeling was used to analyze the binding data, including the finding that P3 selectively recognizes the internal NeuGc in GD3. For this purpose, conformational studies of GD3 were performed using molecular dynamics. It was concluded that sialic acid binds the P3 antibody through its upper face (the one on which the carboxyl group is exposed) and the C4-C5 side of the sugar ring, whereas none or very little contact between the galactose residue and the protein is evident. Conformational analysis of GD3 revealed that, despite the large flexibility of the NeuGcalpha8NeuGc linkage, the P3 binding epitope on the external sialic acid is not well exposed for any of the possible conformations this linkage can adopt, whereas the internal sialic acid presents the epitope in a proper way for several of these conformations. As a final result, a coherent picture of the epitope that fits the wide binding data was obtained.
Animals↗
Genome evolution within the alpha Proteobacteria: why do some bacteria not possess plasmids and others exhibit more than one different chromosome?
Animal intracellular Proteobacteria of the alpha subclass without plasmids and containing one or more chromosomes are phylogenetically entwined with opportunistic, plant-associated, chemoautotrophic and photosynthetic alpha Proteobacteria possessing one or more chromosomes and plasmids. Local variations in open environments, such as soil, water, manure, gut systems and the external surfaces of plants and animals, may have selected alpha Proteobacteria with extensive metabolic alternatives, broad genetic diversity, and more flexible and larger genomes with ability for horizontal gene flux. On the contrary, the constant and isolated animal cellular milieu selected heterotrophic alpha Proteobacteria with smaller genomes without plasmids and reduced genetic diversity as compared to their plant-associated and phototrophic relatives. The characteristics and genome sizes in the extant species suggest that a second chromosome could have evolved from megaplasmids which acquired housekeeping genes. Consequently, the genomes of the animal cell-associated Proteobacteria evolved through reductions of the larger genomes of chemoautotrophic ancestors and became rich in adenosine and thymidine, as compared to the genomes of their ancestors. Genome organisation and phylogenetic ancestor-descendent relationships between extant bacteria of closely related genera and within the same monophyletic genus and species suggest that some strains have undergone transition from two chromosomes to a single replicon. It is proposed that as long as the essential information is correctly expressed, the presence of one or more chromosomes within the same genus or species is the result of contingency. Genetic drift in clonal bacteria, such as animal cell-associated alpha Proteobacteria, would depend almost exclusively on mutation and internal genetic rearrangement processes. Alternatively, genomic variations in reticulate bacteria, such as many intestinal and plant cell-associated Proteobacteria, will depend not only on these processes, but also on their genetic interactions with other bacterial strains. Common pathogenic domains necessary for the invasion and survival in association with cells have been preserved in the chromosomes of the animal and plant-associated alpha Proteobacteria. These pathogenic domains have been maintained by vertical inherence, extensively ameliorated to match the chromosome G + C content and evolved within chromosomes of alpha Proteobacteria.
Animals↗
Comparison of ceftriaxone, amikacin, and ciprofloxacin in treatment of experimental Yersinia enterocolitica O9 infection in mice.
Ceftriaxone and ciprofloxacin were effective in the treatment of Yersinia enterocolitica O9 intestinal infection in mice. Amikacin was less effective. The impact of these drugs on indigenous bacteria from the intestinal microbiota was studied.
Amikacin↗
Enzyme immunoassays for serological diagnosis of bovine brucellosis: A trial in Latin America.
The results of a field trial conducted in Latin America with two indirect enzyme-linked immunosorbent assays (ELISAs) and two competitive ELISAs (CELISAs) for the detection of bovine antibody to Brucella abortus are reported. One of the CELISA formats performed most accurately. The percentage of positive reactions in the CELISA relative to the selected positive rose bengal agglutination test (RBT) and complement fixation test (CFT) results was 97.47%, the percentage of negatives relative to the selected negative RBT and CFT results for unexposed cattle was 98.32%, and the percentage of negatives in cattle vaccinated with B. abortus 19 was 96.51%. The same assay format under Canadian conditions had an actual sensitivity of 100%, a specificity of 99.90% in nonvaccinates, and a specificity of 97.7% in a strain 19-vaccinated population. Overall, the CELISA performed as expected and the results were not dissimilar from the results obtained in the Canadian study. This provided further evidence that this CELISA can in many instances differentiate infected cattle from those that are vaccinated or infected with a cross-reacting organism while still giving very few false-positive or false-negative results.
Agglutination Tests↗
Brucella abortus transits through the autophagic pathway and replicates in the endoplasmic reticulum of nonprofessional phagocytes.
Brucella abortus is an intracellular pathogen that replicates within a membrane-bounded compartment. In this study, we have examined the intracellular pathway of the virulent B. abortus strain 2308 (S2308) and the attenuated strain 19 (S19) in HeLa cells. At 10 min after inoculation, both bacterial strains are transiently detected in phagosomes characterized by the presence of early endosomal markers such as the early endosomal antigen 1. At approximately 1 h postinoculation, bacteria are located within a compartment positive for the lysosome-associated membrane proteins (LAMPs) and the endoplasmic reticulum (ER) marker sec61beta but negative for the mannose 6-phosphate receptors and cathepsin D. Interestingly, this compartment is also positive for the autophagosomal marker monodansylcadaverin, suggesting that S2308 and S19 are located in autophagic vacuoles. At 24 h after inoculation, attenuated S19 is degraded in lysosomes, while virulent S2308 multiplies within a LAMP- and cathepsin D-negative but sec61beta- and protein disulfide isomerase-positive compartment. Furthermore, treatment of infected cells with the pore-forming toxin aerolysin from Aeromonas hydrophila causes vacuolation of the bacterial replication compartment. These results are compatible with the hypothesis that pathogenic B. abortus exploits the autophagic machinery of HeLa cells to establish an intracellular niche favorable for its replication within the ER.
Antigens, CD↗
Virulent Brucella abortus prevents lysosome fusion and is distributed within autophagosome-like compartments.
Virulent and attenuated Brucella abortus strains attach to and penetrate nonprofessional phagocytic HeLa cells. Compared to pathogenic Brucella, the attenuated strain 19 hardly replicates within cells. The majority of the strain 19 bacteria colocalized with the lysosome marker cathepsin D, suggesting that Brucella-containing phagosomes had fused with lysosomes, in which they may have degraded. The virulent bacteria prevented lysosome-phagosome fusion and were found distributed in the perinuclear region within compartments resembling autophagosomes.
Bacterial Adhesion↗
Monochromatic aberrations and point-spread functions of the human eye across the visual field.
The monochromatic aberrations of the human eye along the temporal meridian are studied by a novel laser ray-tracing method. It consists of delivering a narrow laser pencil into the eye through a given point on the pupil and recording the aerial image of the retinal spot with a CCD camera. The relative displacement of this image is proportional to the geometrical aberration of the ray (laser pencil) at the retina. We scanned the pupils of four observers in steps of 1 mm (effective diameter, 6.7 mm) and for five field angles (0 degree, 5 degrees, 10 degrees, 20 degrees, and 40 degrees). In addition, the aerial image for each chief ray is a low-pass-filtered version of the retinal point-spread function corresponding to a fully dilated pupil. The resulting spot diagrams, displaying the distribution of ray aberrations, are highly correlated with these point-spread functions. We have estimated the wave-front error by fitting Zernike polynomials (up to the fifth order). Despite the large variation found among observers, the overall rms wave-front error is relatively homogeneous. At the fovea, the average rms value was 1.49 microns when the second-order terms (defocus and astigmatism) were considered; this was reduced to 0.45 micron when the second-order terms were ignored. The rms values increase slowly, in a roughly linear fashion with eccentricity, such that at 40 degrees they are approximately double. These results are consistent with previous findings on the off-axis optical quality of the eye.
Adult↗
Lipoprotein abnormalities in long-term stable liver and renal transplanted patients. A comparative study.
Hyperlipidemia is a common feature after organ transplantation. Most studies have evaluated the lipid profile in recipients of a particular graft, usually renal. In the present work, we studied the lipid profiles of 30 long-term stable liver transplant patients (LTP) and compared their pattern with 40 long-term stable renal transplant patients (RTP) matched for gender, age, and time from transplantation. There were no significant differences between both groups in body mass index, serum glucose, serum creatinine, or urinary protein excretion. In contrast, RTP had higher pre-transplant total cholesterol and triglycerides, received higher doses of steroids (both average and cumulative) and had higher cycosplorine blood levels. After a mean time of 60 months after transplantation, RTP exhibited higher levels of total serum cholesterol (226 +/- 26 vs. 180 +/- 39 mg/dl; p = 0.000 002) and low-density lipoprotein (LDL) cholesterol (152 +/- 22 vs. 112 +/- 37 mg/dl; p = 0.00001). In contrast, there were no differences between RTP and LTP in high density lipoprotein (HDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, total triglycerides, VLDL triglycerides, or lipoprotein (a) [Lp(a)]. By univariate analysis in the whole group, renal graft, prednisone daily dose, cyclosporine blood levels, pre-transplant cholesterol, and triglycerides were associated with increased post-transplant cholesterol levels. By multivariate analysis, prednisone daily dose was the only independent variable predicting increased post-transplant serum cholesterol levels. The present data show that hypercholesterolemia is more frequent among RTP than among LTP. In addition, our data suggest that corticosteroid therapy, rather than the transplanted organ, may be the major contributor to this difference.
Adult↗
Laparoscopic surgery without pneumoperitoneum.
The results of 43 laparoscopic surgeries performed with an abdominal wall retractor designed in the 3rd Surgical Service at "San Roque" Hospital are analyzed. Of them, 42 underwent cholecistectomy and one an endometrosic focus resection, placed in the Douglas sac. The results obtained have been good. There was almost no postoperatory pain due parietal wall traction. The hospital stay was less than 24 hours in 41 cases and less than 48 hours in two. We also point out the absence of complications and the advantages of the parietal traction compared with pneumoperitoneum.
Adult↗
[Congenital dilatation of extrahepatic bile ducts].
The authors present 3 cases of congenital dilatation of extrahepatic bile ducts and performed a review of the bibliography of this frequent pathology. They concluded that the diagnosis could be difficult in the pre-operatory and the cholangeographic methods are the beds. The treatment of choice in the actuality is the ++quistectomy with hepaticojejunostomy in "Y of Roux".
Adult↗
[Caroli disease: a case report and review of literature].
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Caroli Disease↗
Redefinition of the carbohydrate specificity of Erythrina corallodendron lectin based on solid-phase binding assays and molecular modeling of native and recombinant forms obtained by site-directed mutagenesis.
Binding of the N-acetyllactosamine-specific lectin from Erythrina corallodendron (ECorL) to four glycosphingolipids has been tested using the microtiter well assay. The role of several amino acids in the binding site region was studied by combining binding assays and molecular modeling for native and recombinant forms of the lectin. Seven single-point mutants at positions 106 (Y106A), 108 (Y108A, T), 218 (A218G), and 219 (Q219A, N or E) were investigated. A comparison with more than 30 known sequences of legume lectins showed that ECorL is unique in displaying a tyrosine residue or a structural equivalent at position 106. Analyses of the binding results obtained for mutants at positions 106 and 108 using molecular modeling point to complex conformational dependencies between these and several other residues around the binding site. Gln 219 was found to have a large conformational flexibility, which, paradoxically, favors the binding of N-acetyllactosamine-containing glycosphingolipids. Particularly significant is the fact that ECorL exhibits a higher affinity for Fuc alpha2Gal beta4GlcNAc beta-terminated glycosphingolipids than N-acetyllactosamine-terminated ones, in accordance with molecular modeling revealing a perfect fit of the alpha2-linked fucose in a cavity extending from the Gal beta4 binding pocket. These findings lead to a redefinition of the specificity of this lectin, where the affinity for the terminal Fuc alpha2Gal beta4GlcNAc beta trisaccharide should be considered in the first place. The possible biological significance of this specificity remains to be investigated.
Adsorption↗
Role of the cytoskeleton in endocytosis of the yeast maltose transporter.
Certain components of the cytoskeleton play a role in yeast fluid-phase endocytosis as well as in endocytosis of the alpha-factor when this pheromone is bound to its 7-transmembrane segment receptor. The yeast maltose transporter is a 12-transmembrane segment protein that, under certain physiological conditions, is degraded in the vacuole after internalization by endocytosis. In this work, the possible role of the cytoskeleton in endocytosis of this transporter has been investigated. Using mutants defective in beta-tubulin, actin and the actin-binding proteins Sac6 and Abp85. as well as nocodazole, which inhibits formation of microtubules, we have shown that actin microfilaments are involved in endocytosis of the maltose transporter whereas microtubules are not.
Actins↗