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C Dominguez

Publications and source records attributed to C Dominguez.

At least 19 recordsLinked to original sources
PubMed2006

Light coupling into an optical microcantilever by an embedded diffraction grating.

By measuring the excitation efficiency of an optical waveguide on a diffraction grating one can accurately register the changes in the incidence angle of the exciting light beam. This phenomenon was applied to detect ultrasmall deflections of silicon dioxide cantilevers of submicrometer thickness that were fabricated with corrugation on top to act as diffraction grating couplers. The power of light coupled into the cantilevers was monitored with a conventional photodetector and modulated using mechanical vibration of the cantilever, thus changing the spatial orientation of the coupler with respect to the incident light beam. The technique can be considered as an alternative to the methods known for detection of cantilever deflection.

Journal Article↗
PubMed2005

Data-driven docking: HADDOCK's adventures in CAPRI.

We have shown previously that given high-resolution structures of the unbound molecules, structure determination of protein complexes is possible by including biochemical and/or biophysical data as highly ambiguous distance restraints in a docking approach. We applied this method, implemented in the HADDOCK (High Ambiguity Driven DOCKing) package (Dominguez et al., J Am Chem Soc 2003;125:1731-1737), to the targets in the fourth and fifth rounds of CAPRI. Here we describe our results and analyze them in detail. Special attention is given to the role of flexibility in our docking method and the way in which this improves the docking results. We describe extensions to our approach that were developed as a direct result of our participation in CAPRI. In addition to experimental information, we also included interface residue predictions from PPISP (Protein-Protein Interaction Site Predictor; Zhou and Shan, Proteins 2001;44:336-343), a neural network method. Using HADDOCK we were able to generate acceptable structures for 6 of the 8 targets, and to submit at least 1 acceptable structure for 5 of them. Of these 5 submissions, 3 were of medium quality (Targets 10, 11, and 15) and 2 of high quality (Targets 13 and 14). In all cases, predictions were obtained containing at least 40% of the correct epitope at the interface for both ligand and receptor simultaneously.

Algorithms↗
PubMed2005

Halothane and propofol differentially affect electroencephalographic responses to noxious stimulation.

BACKGROUND: Anaesthetics blunt neuronal responses to noxious stimulation, including effects on electroencephalographic (EEG) responses. It is unclear how anaesthetics differ in their ability to modulate noxious stimulation-evoked EEG activation. We investigated the actions of propofol and halothane on EEG responses to noxious stimuli, including repetitive electrical C-fibre stimulation, which normally evokes neuronal wind-up. METHODS: Rats were anaesthetized with halothane (n=8) or propofol (n=8), at 0.8x or 1.2x the amount required to produce immobility in response to tail clamping [minimum alveolar concentration (MAC) for halothane and median effective dose (ED(50)) for propofol]. We recorded EEG responses to repetitive electrical stimulus trains (delivered to the tail at 0.1, 1 and 3 Hz) as well as supramaximal noxious tail stimulation (clamp; 50 Hz electrical stimulus, each for 30 s). RESULTS: Under halothane anaesthesia, noxious stimuli evoked an EEG activation response manifested by increased spectral edge frequency (SEF) and median edge frequency (MEF). At 0.8 MAC halothane, the tail clamp increased the MEF from approximately 6 to approximately 8.5 Hz, and the SEF from approximately 25.5 to approximately 27 Hz. At both 0.8 and 1.2 MAC halothane, similar patterns of EEG activation were observed with the 1 Hz, 3 Hz and tetanic stimulus trains, but not with 0.1 Hz stimulation, which does not evoke wind-up. Under propofol anaesthesia, noxious stimuli were generally ineffective in causing EEG activation. At 0.8 ED(50) propofol, only the tail clamp and 1 Hz stimuli increased MEF ( approximately 8 to approximately 10-10.5 Hz). At the higher propofol infusion rate (1.2 ED(50)) the repetitive electrical stimuli did not evoke an EEG response, but the tetanic stimulus and the tail clamp paradoxically decreased SEF (from approximately 23 to approximately 21.5 Hz). CONCLUSIONS: Propofol has a more significant blunting effect on EEG responses to noxious stimulation compared with halothane.

Anesthetics, Inhalation↗
PubMed2003

Role of cytokines (interleukin-1beta, 6, 8, tumour necrosis factor-alpha, and soluble receptor of interleukin-2) and C-reactive protein in the diagnosis of neonatal sepsis.

AIM: To investigate whether the serum levels of interleukin-1beta, 6, 8, tumour necrosis factor-alpha and the soluble receptor of IL-2 are useful in the diagnosis of neonatal sepsis, and whether their diagnostic power is increased when in combination with classical markers such as C-reactive protein and white blood cell count. METHODS: Blood samples were collected at admission from 40 neonates with suspected infection. Patients were included in different groups according to the bacteriological and laboratory results: Group I consisted of 20 newborns with positive blood cultures and other biological tests suggestive of infection. Group II included 20 neonates with negative blood cultures and biological tests not suggestive of infection. The control group included 20 healthy neonates with no clinical or biological data of infection. RESULTS: Mean values of C-reactive protein were significantly higher in Group I. No differences were found between the groups for white blood cell count, with the exception of the presence of leucocytosis in Group II. Levels of interleukin-1beta, 6, 8, tumour necrosis factor-alpha, soluble receptor of interleukin-2, and C-reactive protein were significantly higher in infected neonates than in the control groups. Detection sensitivity and specificity were 80 and 92% for C-reactive protein, 60 and 87% for interleukin-1beta, 61 and 80% for interleukin-6, 62 and 96% for interleukin-8, 54 and 92% for tumour necrosis factor-alpha and 63 and 94% for soluble receptor of interleukin-2. The discriminant analysis showed that the best combination for sepsis diagnosis was C-reactive protein + interleukin-8 + soluble receptor of interleukin-2, with a sensitivity of 85% and a specificity of 97.1%. CONCLUSION: Our study suggests that no individual test can on its own identify infected neonates, and that although the combination of C-reactive protein, interleukin-8 and the soluble receptor of interleukin-2 exhibits a high specificity, its sensitivity is limited.

Antineoplastic Agents↗
PubMed2002

Electrochemical platinum coatings for improving performance of implantable microelectrode arrays.

The formation and properties of electrochemical platinum films grown on platinum contacts contained in implantable flexible microelectrodes were investigated. The resulting platinum deposits were obtained by applying cyclic voltammetry to baths containing concentrations around 70 mM of chloroplatinic acid. A pre-activation step was necessary before the platinum-electroplating step in order to achieve good adhesive properties. The benefits of this process were ascribed to higher corrosion resistance, lower impedance and improved adhesion to the sputtered platinum. These improvements can make the application of this electrochemical technique highly useful for increasing the lifetime of implantable microelectrode arrays, such as cuff structures (IEEE Trans. Biomed. Eng. 40 (1993) 640). These medical devices, obtained by semiconductor technology could be used for selective stimulation of nerve fascicles, although, poor long-term performance has been achieved with them. The dissolution rate for platinum thin-film microelectrodes under fixed corrosion test conditions was 38.8 ng/C. Lower rates were observed for electroplated microelectrodes, obtaining a dissolution rate of 7.8 ng/C under analogous experimental ageing conditions. The corrosion behaviour of the electroplated platinum during stimulation experimental conditions was estimated by electrochemical impedance spectroscopy.

Biocompatible Materials↗
PubMed2001

Evolutionary relationships and biogeography of Biomphalaria (Gastropoda: Planorbidae) with implications regarding its role as host of the human bloodfluke, Schistosoma mansoni.

The wide geographic distribution of Schistosoma mansoni, a digenetic trematode and parasite of humans, is determined by the occurrence of its intermediate hosts, freshwater snails of the genus Biomphalaria (Preston 1910). We present phylogenetic analyses of 23 species of Biomphalaria, 16 Neotropical and seven African, including the most important schistosome hosts, using partial mitochondrial ribosomal 16S and complete nuclear ribosomal ITS1 and ITS2 nucleotide sequences. A dramatically better resolution was obtained by combining the data sets as opposed to analyzing each separately, indicating that there is additive congruent signal in each data set. Neotropical species are basal, and all African species are derived, suggesting an American origin for the genus. We confirm that a proto-Biomphalaria glabrata gave rise to all African species through a trans-Atlantic colonization of Africa. In addition, genetic distances among African species are smaller compared with those among Neotropical species, indicating a more recent origin. There are two species-rich clades, one African with B. glabrata as its base, and the other Neotropical. Within the African clade, a wide-ranging tropical savannah species, B. pfeifferi, and a Nilotic species complex, have both colonized Rift Valley lakes and produced endemic lacustrine forms. Within the Neotropical clade, two newly acquired natural hosts for S. mansoni (B. straminea and B. tenagophila) are not the closest relatives of each other, suggesting two separate acquisition events. Basal to these two species-rich clades are several Neotropical lineages with large genetic distances between them, indicating multiple lineages within the genus. Interesting patterns occur regarding schistosome susceptibility: (1) the most susceptible hosts belong to a single clade, comprising B. glabrata and the African species, (2) several susceptible Neotropical species are sister groups to apparently refractory species, and (3) some basal lineages are susceptible. These patterns suggest the existence of both inherent susceptibility and resistance, but also underscore the ability of S. mansoni to adapt to and acquire previously unsusceptible species as hosts. Biomphalaria schrammi appears to be distantly related to other Biomphalaria as well as to Helisoma, and may represent a separate or intermediate lineage.

Animals↗
PubMed2001

Prevalence and contamination levels of Listeria monocytogenes in smoked fish and pâté sold in Spain.

From March to November 2000, 170 samples of smoked fish and 182 samples of pâté for sale in retail outlets and supermarkets in the nine provinces of Castilla and León (Spain) were analyzed for the prevalence of Listeria monocytogenes and other Listeria spp. L. monocytogenes was isolated from 38 (22.3%) of the 170 samples of smoked fish analyzed. Twenty of these positive samples contained L. monocytogenes at >100 CFU/g. Other Listeria spp., such as Listeria innocua (26 isolates), Listeria grayi (9), Listeria welshimeri (3), Listeria seeligeri (3), and Listeria ivanovii (2), were also detected. L. monocytogenes was isolated from 5.4% of the 182 samples of pâté. Only 1 of the 10 positive samples harbored >100 L. monocytogenes CFU/g. Two other species of Listeria were observed in pâté: L. innocua (12 isolates) and L. grayi (2).

Animals↗
PubMed2000

Design, synthesis, and biological evaluation of potent and selective amidino bicyclic factor Xa inhibitors.

Thrombotic diseases are a major cause of death and morbidity. Factor Xa (fXa) plays a vital role in the regulation of normal homeostasis and abnormal intravascular thrombus development in the blood coagulation cascade. A novel series of fXa inhibitors incorporating an amidino 6,5-fused bicyclic moiety at the P1 position has been designed and synthesized based on molecular modeling studies. Structure-activity relationship (SAR) studies have led to selective subnanomolar fXa inhibitors. The most potent fXa inhibitor in this series (72, SE170) has a potent inhibition constant (K(i) = 0.3 nM), is 350-fold selective for fXa over trypsin, and also shows good in vivo efficacy in a rabbit arterio-venous thrombosis model (ID(50) = 0.14 micromol/kg/h). An X-ray crystal structure of 72 complexed to bovine trypsin was completed, and a binding mode of 72 with fXa has been proposed based on modeling with human des-Gla-fXa.

Amidines↗
PubMed2000

Interactions of bile salt micelles and colipase studied through intermolecular nOes.

Colipase is a small protein (10 kDa), which acts as a protein cofactor for the pancreatic lipase. Various models of the activated ternary complex (lipase-colipase-bile salt micelles) have been proposed using detergent micelles, but no structural information has been established with bile salt micelles. We have investigated the organization of sodium taurodeoxycholate (NaTDC) micelles and their interactions with pig and horse colipases by homonuclear nuclear magnetic resonance (NMR) spectroscopy. The NMR data supply evidence that the folding of horse colipase is similar to that already described for pig colipase. Intermolecular nuclear Overhauser effects have shown that two conserved aromatic residues interact with NaTDC micelles.

Amino Acid Sequence↗
PubMed2000

Growth-altering effects of sodium hypochlorite in cultured human dermal fibroblasts.

Sodium hypochlorite, the most widely used antimicrobial active chlorine compound in chemical disinfection, is little used as an antiseptic in clinical practice. This study aimed to assess the capacity of hypochlorite to alter human dermal fibroblast growth in vitro in relation to the concentration and exposure time. Effects of decreasing concentrations of hypochlorite (0.5%-0.00025%) on fibroblast adherence capacity and proliferation, according to varying exposure times and fetal calf serum (FCS) concentrations were investigated combining XTT assay, which provides cytochemical quantification of metabolically-active cell number, and total cell protein content, an indirect method for assessing substrate-adhered cell number. Initial cytotoxicity was produced at 0.0075% hypochlorite within contact time of two hours, provoking concentration-dependent cell detachment. From 0.1% upwards, NaOCl exerted a profound cytotoxic effect on fibroblasts. At later stages (4 h) and concentrations > or = 0.01% hypochlorite produced dose-dependent mitochondrial dysfunction: cell survival progressively diminished from 71% to 10%. Cytotoxic effects were not significantly affected by exposure-time periods, probably because maximum chlorine is released within the first four hours. Hypochlorite concentrations from 0.005% to 0.00025% were found to have no inhibitory effects on cell growth; in fact, they appear to exhibit the opposite effect. Increments in protein content found after 24 h exposure ranged from 30% to 120% above control values. Hypochlorite is highly cytotoxic for fibroblasts at concentrations > or = 0.01% provoking concentration-dependent loss of cell adherence capacity and mitochondrial dysfunction. In contrast, a mitogenic effect was observed with concentrations < or = 0.005% which supports NaOCl as a source growth-promoting activity in cultured human fibroblasts. Hypochlorite proved to be a highly reactive molecule which inhibits or stimulates cell division according to the concentration.

Cell Division↗
PubMed1999

Increased sensitivity to complement and a decreased red blood cell life span in mice mosaic for a nonfunctional Piga gene.

The gene PIGA encodes one of the protein subunits of the alpha1-6-N acetylglucosaminyltransferase complex, which catalyses an early step in the biosynthesis of glycosyl phosphatidylinositol (GPI) anchors. PIGA is somatically mutated in blood cells from patients with paroxysmal nocturnal hemoglobinuria (PNH), leading to deficiency of GPI-linked proteins on the cell surface. To investigate in detail how inactivating mutations of the PIGA gene affect hematopoiesis, we generated a mouse line, in which loxP-mediated excision of part of exon 2 occurs on the expression of Cre. After crossbreeding with EIIa-cre transgenic mice, recombination occurs early in embryonic life. Mice that are mosaics for the recombined Piga gene are viable and lack GPI-linked proteins on a proportion of circulating blood cells. This resembles the coexistence of normal cells and PNH cells in patients with an established PNH clone. PIGA(-) blood cells in mosaic mice have biologic features characteristic of those classically seen in patients with PNH, including an increased sensitivity toward complement mediated lysis and a decreased life span in circulation. However, during the 12-month follow-up, the PIGA(-) cell population did not increase, clearly showing that a Piga gene mutation is not sufficient to cause the human disease, PNH.

Animals↗
PubMed1999

Design and synthesis of potent and selective 5,6-fused heterocyclic thrombin inhibitors.

Thrombin, a serine protease, plays a central role in the initiation of thrombotic events. We report the design, synthesis, and antithrombotic efficacy of XU817 (7), a nonpeptide 5-(amidino) indole thrombin inhibitor. Utilizing the co-crystal structure of XU817 bound in the active site of thrombin we were able to synthesize analogs with enhanced thrombin affinity.

Amidines↗
PubMed1999

Elevated non-transferrin bound iron in the lungs of patients with Pneumocystis carinii pneumonia.

OBJECTIVE: The aim of the present work was to determine the concentrations of iron and iron-binding proteins in the lungs of patients suffering from Pneumocystis carinii (PCP), which is crucial for justifying the treatment with iron-chelating agents in this disease. PATIENTS AND METHODS: Bronchoalveolar lavage was performed in 10 HIV patients with PCP and five healthy controls. Total iron and iron-binding proteins (transferrin, ferritin and lactoferrin) were measured in acellular bronchoalveolar lavage fluid (BALF) in both groups. Iron was determined by atomic absorption spectrometry; transferrin and lactoferrin were measured using specific enzyme-linked immunosorbent assays (ELISA); and ferritin concentration was quantified by automated immunonephelometry. RESULTS: Our findings in patients with PCP demonstrated a six- to seven-fold increase of total iron levels and an eight-fold increase of ferritin in bronchoalveolar lavage fluid when compared with controls. No significant differences were found in transferrin or lactoferrin levels. Moreover, our results suggest that this iron is non-transferrin bound. CONCLUSION: Non-transferrin bound iron is increased in the lower respiratory tracts of PCP patients. This finding would lend experiment support to the use of iron-chelating agents in this disease.

AIDS-Related Opportunistic Infections↗
PubMed1999

In vivo radiosensitizing effect of the adenovirus E1A gene in murine and human malignant tumors.

The adenovirus E1A gene is a potent inducer of chemosensitivity and radiosensitivity through p53-dependent and independent mechanisms. We have studied the sensitivity of murine (MSC11A5, a sarcomatoid epidermoid carcinoma) and human (HeLa, human cervix carcinoma) E1A-expressing tumors, in vivo, after treatment with cisplatin or gamma-irradiation. In athymic mice, half-body irradiation was performed in an AECL Cobalt unit, at an SSD of 80 cm. Daily fractions of 300 cGy over 3 days, up to a total dose of 9 Gy. Cisplatin was injected intraperitoneally at a dose of 9 mg per kg of body weight. After gamma-irradiation or intraperitoneal injection of cisplatin, about 30% of the E1A-expressing tumors regressed completely or were associated with a marked decrease in tumorigenicity over the following weeks. We conclude that malignant tumors, when expressing adenovirus E1A, are very sensitive to treatment with DNA-damaging agents, in vivo, regardless of the p53 status of the tumors.

Adenovirus E1A Proteins↗
PubMed1998

Lead exposure in the general population of the Metropolitan Area of Barcelona: blood levels and related factors.

A cross-sectional study was conducted on 254 individuals not occupationally exposed to lead to determine the degree of lead exposure in the general population of the Metropolitan Area of Barcelona. Blood lead levels (BPb) were analysed by atomic absorption spectrophotometry and zinc protoporphyrin (ZPP) by haemofluorimetry. Blood lead levels were analysed with respect to individuals' age, sex, area of residence, the season of the year the blood was drawn and ZPP. Mean blood lead in our series was 0.22 +/- 0.011 mumol/l (mean +/- S.E.); no significant differences were found with respect to area of residence, sex or season. A linear relationship was observed between BPb and individuals' age (BPb = 0.08 + 0.05 x age; r = 0.37). The prevalence of lead intoxication (BPb > 0.48 mumol/l) was 7.1%. No linear relationship was observed between BPb and ZPP. ZPP determination does not appear to be a good screening method for lead intoxication since it presents low specificity and sensitivity values with an area below the ROC curve similar to the null value line (area below the curve = 0.5052, IC 95% = 0.443-0.568). We conclude that lead exposure does not constitute a serious health problem in the area studied, since BPb levels found are far below the toxic limit and the prevalence of intoxication is similar to that reported in other studies conducted in other developed countries.

Adolescent↗