Biomedical subjects

Ana Gonzalez

Publications and source records attributed to Ana Gonzalez.

10 recordsLinked to original sources

PubMed2006

Temperature curve complexity predicts survival in critically ill patients.

RATIONALE: Temperature curve complexity is inversely related to clinical status in critically ill patients. OBJECTIVE: To study if temperature curve complexity analysis predicts clinical outcome and how this test compares to other well-established conventional measures. METHODS: Temperature was continuously recorded in 50 patients with multiple organ failure. Time-series complexity was analyzed using hourly approximate entropy (ApEn) and detrended fluctuation analysis (DFA) values. Sequential Organ Failure Assessment (SOFA) score was obtained every other day, and correlation between complexity and SOFA values was evaluated. Differences in complexity between nonsurviving and surviving patients were likewise analyzed. Logistic regression models were calculated to predict outcome, and receiver operating characteristic (ROC) curves were plotted to compare the predictive power of complexity values versus SOFA. MEASUREMENTS AND RESULTS: There was good correlation between complexity results and clinical scores for each patient. Nonsurvivors exhibited lower complexity values than survivors (minimum ApEn = 0.230 vs. 0.378; maximum DFA = 1.636 vs. 1.507; mean ApEn = 0.459 vs. 0.596; mean DFA = 1.376 vs. 1.288; p < 0.001 for all comparisons). In the logistic regression model, a change of 0.1 in the minimum complexity resulted in severe increases in the odds ratio of dying (7.6-fold for ApEn, 5.4-fold for DFA). In terms of predicting outcome, there were no significant differences in the areas under the ROC curves for complexity values versus SOFA scores. CONCLUSIONS: Low levels of complexity in the temperature curve are indicators of poor prognosis in patients with multiple organ failure. The predictive ability of temperature curve complexity is similar to that of the SOFA score.

APACHE↗

PubMed2006

Evolving technology in bipolar perfused radiofrequency ablation: assessment of efficacy, predictability and safety in a pig liver model.

Bipolar radiofrequency (RF) ablation, especially with perfusion of saline, has been shown to increase volume over monopolar conventional methods. The aims of this study are to study whether this method is linked to too flattened thermal lesions and premature rise of impedance and to elucidate some safety concerns. Eighteen RF ablations were performed using a 1.8-mm-diameter bipolar applicator in the liver of nine healthy pigs through laparotomy with or without temporary vascular occlusion [the Pringle maneuver (PGM)]: group A (n=9), without PGM; group B (n=9), with PGM. Hypertonic saline solutions (3% and 20 %) were injected through the applicator at a rate of 400 ml/h during the procedure. The pigs were followed up and they were euthanased on the 15th day. Impedance, current, power output, energy output, temperatures, diameters of thermal lesion, volume, sphericity ratio of thermal lesion were correlated among groups. Impedance at the end of the procedure (50.00 Omega+/-28.39 and 52.88 Omega+/-26.77, for groups A and B, respectively) was very similar to the starting impedance (50 Omega). In a median of 1 (range, 0-6) time per RF ablation procedure a reduction of 30 W from the selected power supply was observed during the RF ablation procedure linked to a slight increase of impedance. Volume and short diameter of thermal lesion were 21.28 cm3+/-11.78 and 2.85 cm+/-0.87 for group A, 87.51 cm3+/-25.20 and 4.31 cm+/-0.65 for group B. Continuous thermal between both electrodes were described with a global sphericity ratio of 1.91. One major complication (thermal injury to the stomach) was encountered in a case of cross-sectional necrosis of the targeted liver and attributed to heat diffusion after the procedure. This method has been shown to determine: (1) the relative control of impedance during the procedure; (2) ovoid and relatively large thermal lesions with less dependence upon closest vessels.

Analysis of Variance↗

PubMed2005

Homology modelling and active-site-mutagenesis study of the catalytic domain of the pneumococcal phosphorylcholine esterase.

Streptococcus pneumoniae is among the major human pathogens. Several interactions of this bacterium with its host appear to have been mediated by bacterial cell wall components. Specifically, phosphorylcholine residues covalently attached to teichoic and lipoteichoic acids serve as anchors for many surface-located proteins (choline-binding proteins CBPs), including cell-adhesion and virulence factors, and are also recognized by host response components through choline-binding receptors. In this study, we have performed modelling of the catalytic domain of pneumococcal phosphorylcholine esterase (Pce), a modular enzyme that is capable of removing phosphorycholine residues from teichoic and lipoteichoic acids, remodelling their distribution on the bacterial envelope. We wish to contribute to the structural knowledge of Pce. In this pursuit, 3D models of Pce have been established by homology modelling, using the X-ray structure of enzymes from the alpha/beta metallo-lactamase family fold as templates. Theoretical models of pneumococcal phosphorylcholine esterase (Pce) catalytic modules obtained by homology modelling, and corresponding docking studies employed to find out the residues involved in the binding of Zn ions, are discussed according to mutational studies and ab initio calculations. The presence of a binuclear Zn cluster in the catalytic domain of Pce and a likely coordination model are proposed.

Amino Acid Sequence↗

PubMed2005

Intolerance syndrome in failed renal allografts: incidence and efficacy of percutaneous embolization.

BACKGROUND: Immunologic intolerance to a failed renal allograft left in situ is referred to as graft intolerance syndrome, the incidence and predictors of which are unknown. Treatment by transcatheter vascular embolization has been reported to be less invasive than transplantectomy. The incidence of graft intolerance syndrome and results of transcatheter vascular embolization as a first therapeutic approach were studied. METHODS: A retrospective study of 149 transplant recipients who returned to dialysis therapy between June 1989 and December 2001 was performed. After immunosuppression withdrawal, a diagnosis of graft intolerance syndrome was made based on clinical criteria and confirmed by the persistence of renal perfusion under imaging procedures. Potential immunologic predictors were analyzed. RESULTS: Of 149 patients with failed renal allografts, 55 patients (37%) developed graft intolerance syndrome during follow-up (27.5 +/- 34.5 months; range, 1 to 173 months). Manifestations of graft intolerance syndrome were fever (88%), flu-like symptoms (33%), hematuria (39%), local pain (53%), and increased graft size (51%). Most episodes of graft intolerance syndrome appeared within 6 months (virtually all presented within 24 months after graft failure). None of the immunologic variables studied showed an influence on graft intolerance syndrome. Transcatheter vascular embolization was performed in 48 patients and was successful in 31 patients (65%). A second embolization was necessary in 8 patients. No deaths or severe complications were observed. Eleven patients (22%) underwent transplantectomy because of persistent graft intolerance syndrome (n = 8) or graft infection (n = 3). CONCLUSION: Graft intolerance syndrome is common in patients with failed renal allografts left in situ, especially within the first year of returning to dialysis therapy. Our data support transcatheter vascular embolization as first-line therapy for patients with symptomatic failed renal allografts, although 1 in 4 patients will require transplantectomy.

Catheterization↗

PubMed2004

Risk factors for aortic complications in adults with coarctation of the aorta.

OBJECTIVES: We sought to determine the prevalence and predisposing condition for aortic wall complications in adults with either repaired or non-repaired coarctation of the aorta. BACKGROUND: Aortic wall complications may develop in adults with coarctation of the aorta, despite successful surgical repair in childhood. METHODS: A total of 235 adults with coarctation (mean age 27 +/- 13 years) were retrospectively reviewed. Treatment had been performed by surgery in 181 patients (group I) or by balloon angioplasty or stenting in 28 patients (group II). No previous intervention had been carried out in 26 patients with mild coarctation at diagnosis (group III). RESULTS: Forty-four aortic wall complications were found in 37 patients (16%). There were no differences among the three groups with respect to total complications (15%, 18%, and 15%, respectively), ascending aortic aneurysms (9%, 11%, and 12%), or descending aortic aneurysms (4% in all three groups). Multivariate analysis did not show a significant relationship between previous repair, type of repair, age at repair, residual Doppler pressure gradient, or systemic hypertension and the occurrence of aortic complications. Only aging (risk ratio [RR] 1.4 per decade of age, 95% confidence interval [CI] 1.1 to 1.8, p = 0.002) and bicuspid aortic valve (RR 3.2, 95% CI 1.3 to 7.5, p = 0.005) were significantly related to these complications. CONCLUSIONS: Aortic wall complications are frequent in adults with coarctation of the aorta beyond that attributable to associated hemodynamic derangement or previous repair. The only independent risk factors appear to be advanced age and bicuspid aortic valve.

Adolescent↗

PubMed2004

The structural basis of the thermostability of SP1, a novel plant (Populus tremula) boiling stable protein.

We previously reported on a new boiling stable protein isolated from aspen plants (Populus tremula), which we named SP1. SP1 is a stress-related protein with no significant sequence homology to other stress-related proteins. It is a 108-amino-acid hydrophilic polypeptide with a molecular mass of 12.4 kDa (Wang, W. X., Pelah, D., Alergand, T., Shoseyov, O., and Altman, A. (2002) Plant Physiol. 130, 865-875) and is found in an oligomeric form. Preliminary electron microscopy studies and matrix-assisted laser desorption ionization time-of-flight mass spectrometry experiments showed that SP1 is a dodecamer composed of two stacking hexamers. We performed a SDS-PAGE analysis, a differential scanning calorimetric study, and crystal structure determination to further characterize SP1. SDS-PAGE indicated a spontaneous assembly of SP1 to one stable oligomeric form, a dodecamer. Differential scanning calorimetric showed that SP1 has high thermostability i.e. Tm of 107 degrees C (at pH 7.8). The crystal structure of SP1 was initially determined to 2.4 A resolution by multi-wavelength anomalous dispersion method from a crystal belonging to the space group I422. The phases were extended to 1.8 A resolution using data from a different crystal form (P21). The final refined molecule includes 106 of the 108 residues and 132 water molecules (on average for each chain). The R-free is 20.1%. The crystal structure indicated that the SP1 molecule has a ferredoxin-like fold. Strong interactions between each two molecules create a stable dimer. Six dimers associate to form a ring-like-shaped dodecamer strongly resembling the particle visualized in the electron microscopy studies. No structural similarity was found between the crystal structure of SP1 and the crystal structure of other stress-related proteins such as small heat shock proteins, whose structure has been already determined. This structural study further supports our previous report that SP1 may represent a new family of stress-related proteins with high thermostability and oligomerization.

Amino Acid Sequence↗

PubMed2002

Blu-Ice and the Distributed Control System: software for data acquisition and instrument control at macromolecular crystallography beamlines.

The Blu-Ice and Distributed Control System (DCS) software packages were developed to provide unified control over the disparate hardware resources available at a macromolecular crystallography beamline. Blu-Ice is a user interface that provides scientific experimenters and beamline support staff with intuitive graphical tools for collecting diffraction data and configuring beamlines for experiments. Blu-Ice communicates with the hardware at a beamline via DCS, an instrument-control and data-acquisition package designed to integrate hardware resources in a highly heterogeneous networked computing environment. Together, Blu-Ice and DCS provide a flexible platform for increasing the ease of use, the level of automation and the remote accessibility of beamlines. Blu-Ice and DCS are currently installed on four Stanford Synchrotron Radiation Laboratory crystallographic beamlines and are being implemented at sister light sources.

Crystallography, X-Ray↗

PubMed2002

Advantages of high-resolution phasing: MAD to atomic resolution.

The structure of the endoglucanase A from Clostridium thermocellum CelA was re-solved by three-wavelength MAD. Experimental phases were obtained in the resolution range 25-1.0 A. Various structure-solution approaches were tested in order to quantify the contribution of each wavelength. Two-wavelength MAD phasing was sufficient to obtain excellent experimental phases. SAD at the remote wavelength also resulted in interpretable maps. The three-wavelength MAD electron-density map was of excellent quality: for parts of the structure, atom types and bond types could be easily assigned. Double bonds in peptide links and side chains could be located owing to their increased electron density indicating their pi character. Comparison with a previously determined structure of CelA at 1.65 A showed that, apart from a few additional multiple conformers and differently oriented side chains, major differences occur at the protein-solvent interface. A complete additional solvent shell could be observed and the inner shells have been completed. The high accuracy of the structure allowed unambiguous assignment of the protonation state for the active-site catalytic carboxylates.

Cellulase↗

PubMed2002

Ketopremithramycins and ketomithramycins, four new aureolic acid-type compounds obtained upon inactivation of two genes involved in the biosynthesis of the deoxysugar moieties of the antitumor drug mithramycin by Streptomyces argillaceus, reveal novel insights into post-PKS tailoring steps of the mithramycin biosynthetic pathway.

Mithramycin is an aureolic acid-type antimicrobial and antitumor agent produced by Streptomyces argillaceus. Modifying post-polyketide synthase (PKS) tailoring enzymes involved in the production of mithramycin is an effective way of gaining further information regarding the late steps of its biosynthetic pathway. In addition, new "unnatural" natural products of the aureolic acid-type class are likely to be produced. The role of two such post-PKS tailoring enzymes, encoded by mtmC and mtmTIII, was investigated, and four novel aureolic acid class drugs, two premithramycin-type molecules and two mithramycin derivatives, were isolated from mutant strains constructed by insertional gene inactivation of either of these two genes. From data bank comparisons, the corresponding proteins MtmC and MtmTIII were believed to act as a C-methyltransferase involved in the production of the D-mycarose (sugar E) of mithramycin and as a ketoreductase seemingly involved in the biosynthesis of the mithramycin aglycon, respectively. However, gene inactivation and analysis of the accumulated products revealed that both genes encode enzymes participating in the biosynthesis of the D-mycarose building block. Furthermore, the inactivation of MtmC seems to affect the ketoreductase responsible for 4-ketoreduction of sugar C, a D-olivose. Instead of obtaining premithramycin and mithramycin derivatives with a modified E-sugar upon inactivation of mtmC, compounds were obtained that completely lack the E-sugar moiety and that possess an unexpected 4-ketosugar moiety instead of the D-olivose at the beginning of the lower deoxysaccharide chain. The inactivation of mtmTIII led to the accumulation of 4E-ketomithramycin, showing that this ketoreductase is responsible for the 4-ketoreduction of the D-mycarose moiety. The new compounds of the mutant strains, 4A-ketopremithramycin A2, 4A-keto-9-demethylpremithramycin A2, 4C-keto-demycarosylmithramycin, and 4E-ketomithramycin, indicate surprising substrate flexibility of post-PKS enzymes of the mithramycin biosynthetic pathway. Although the glycosyltransferase responsible for the attachment of D-mycarose cannot transfer the unmethylated sugar to the existing lower disaccharide chain, it can transfer the 4-ketoform of sugar E. In addition, the glycosyltransferase MtmGIV, which is responsible for the linkage of sugar C, is also able to transfer an activated 4-ketosugar. The oxygenase MtmOIV, normally responsible for the oxidative cleavage of the tetracyclic premithramycin B into the tricyclic immediate precursor of mithramycin, can act on a substrate analogue with a modified or even incomplete trisaccharide chain. The same is true for glycosyltransferases MtmGI and MtmGII, both of which partake in the formation and attachment of the A-B disaccharide in mithramycin.

Antibiotics, Antineoplastic↗

PubMed2002

Determination of aliphatic hydrocarbons in urban runoff samples from the "Le Marais" experimental catchment in Paris centre.

Aliphatic hydrocarbons were assessed in runoff and waste waters from an urban catchment located in Paris. Runoff were sampled from different types of urban surfaces (11 roofs representing four different covering materials, two courtyards and six streets). Waste water samples were collected at the catchment outlet during dry and wet weather periods as well. This paper gives an overview of the results on the concentration and distribution points of view for both the particulate and the dissolved phases. Results were discussed on the basis of the median. Accordingly, the temporal variability was taken into account. Thus, the concentration medians ranged from 345 to 827, from 297 to 790, and from 393 to 1,359 microg L(-1) in the roof, courtyard and street samples, respectively. The levels found at the catchment outlet during dry and wet weather periods were of the same order of magnitude, i.e. 700 microgL(-1). The particulate phase represented 85% of the total aliphatic hydrocarbon content whatever the sample.

Environmental Monitoring↗