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Biomedical subjects

R Santamaria

Publications and source records attributed to R Santamaria.

At least 19 recordsLinked to original sources
PubMed2005

Selectivity of a model zeolite ring over hydrocarbons with different symmetry, travelling with different orientations and speeds.

We explore the selectivity of a model zeolite ring over representative hydrocarbons of crude oil. The model ring consists of 7 silicon tetrahedral units and one chemically active aluminum site through which hydrocarbons with symmetries varying from almost spherically symmetric to linear chains (1D), planar (2D), and pyramidal (3D) structures diffuse. The selectivity is further investigated when the hydrocarbons travel with different orientations and speeds. The semiclassical Born-Oppenheimer molecular dynamics approximation is used to characterize the chemical dynamics, as well as to determine the energetics and reaction products. The simulations reveal noticeable differences in energy profiles and charge populations. Our results are important to understand aspects of mass transport and some of the factors that control the catalytic activity in zeolites.

Hydrocarbons↗
PubMed2000

Functional and molecular modelling studies of two hereditary fructose intolerance-causing mutations at arginine 303 in human liver aldolase.

We have identified a novel hereditary fructose intolerance mutation in the aldolase B gene (i.e. liver aldolase) that causes an arginine-to-glutamine substitution at residue 303 (Arg(303)-->Gln). We previously described another mutation (Arg(303)-->Trp) at the same residue. We have expressed the wild-type protein and the two mutated proteins and characterized their kinetic properties. The catalytic efficiency of protein Gln(303) is approx. 1/100 that of the wild-type for substrates fructose 1,6-bisphosphate and fructose 1-phosphate. The Trp(303) enzyme has a catalytic efficiency approx. 1/4800 that of the wild-type for fructose 1,6-bisphosphate; no activity was detected with fructose 1-phosphate. The mutation Arg(303)-->Trp thus substitution impairs enzyme activity more than Arg(303)-->Gln. Three-dimensional models of wild-type, Trp(303) and Gln(303) aldolase B generated by homology-modelling techniques suggest that, because of its larger size, tryptophan exerts a greater deranging effect than glutamine on the enzyme's three-dimensional structure. Our results show that the Arg(303)-->Gln substitution is a novel mutation causing hereditary fructose intolerance and provide a functional demonstration that Arg(303), a conserved residue in all vertebrate aldolases, has a dominant role in substrate binding during enzyme catalysis.

Amino Acid Substitution↗
PubMed1999

Microstructure and properties of pitch-based carbon composites

Pitches prepared in the laboratory by thermal treatment and air-blowing of a commercial coal-tar pitch were used as matrix precursors of carbon composites using granular petroleum coke, foundry coke, amorphous graphite and anthracite. Pitches were characterized by standard procedures (elemental analysis, softening point, solubility tests and carbon yield) and light microscopy (mesophase content). Pitch pyrolysis behaviour was monitored by thermogravimetric analysis and from the optical texture of cokes. Pitch wettability to the different carbons, at different temperatures, was also studied. Experimental conditions selected for the preparation of composites were based on pitch composition and properties. The main microstructural features of composites were determined by light microscopy and scanning electron microscopy. Composite properties were described in terms of their density, porosity and compressive strength, and related to composite microstructure and the characteristics of the precursors. Thermal treatment and air-blowing of pitch improved carbon composite structure and properties. The lowest porosities and best mechanical properties were observed in those composites obtained with the thermally treated pitches combined with foundry coke and anthracite.

Journal Article↗
PubMed1993

The molecular basis of hereditary fructose intolerance in Italian children.

We investigated the molecular defects of the aldolase B gene in five unrelated patients affected by hereditary fructose intolerance. The techniques used were DNA amplification, direct sequencing and allele-specific oligonucleotide (ASO) hybridization. The most frequent substitutions found in the hereditary fructose intolerance alleles analysed were the A174D and the A149P mutations, which account for 50% and 30% of the alleles, respectively. In two unrelated families, we found a rare mutation, the MD delta 4 previously described only in one British family, which may be an important cause of the disease in Italy.

Base Sequence↗
PubMed1991

Extracellular complementation of a developmental mutation implicates a small sporulation protein in aerial mycelium formation by S. coelicolor.

The filamentous bacterium S. coelicolor differentiates by forming aerial hyphae, which protrude into the air and metamorphose into chains of spores. Aerial hyphae formation is associated with the production of a small, abundant protein, SapB, which is present in a zone around colonies of differentiating bacteria. Production of SapB is impaired in bld mutants, which are blocked in aerial hyphae formation, but not in whi mutants in which spore formation is prevented. We report that aerial hyphae formation by a newly identified bld mutant is restored by juxtaposition of the mutant near colonies of SapB-producing bacteria or by the application of the purified protein near mutant colonies. These observations implicate SapB in aerial mycelium formation and suggest that SapB is a morphogenetic protein that enables hyphae on the surface of colonies to grow into the air.

Bacterial Proteins↗
PubMed1989

Assignment of human aldolase C gene to chromosome 17, region cen----q21.1.

The mapping of the gene coding for human aldolase C has been studied using a specific cDNA probe and genomic blots from a panel of human-hamster somatic cell hybrids. The results show that the aldolase C gene is on chromosome 17. In situ experiments have restricted the mapping to the region 17cen----q21.1. Using the same panel of human-hamster somatic cell hybrids, we have confirmed the localization of aldolase A and B on chromosomes 16 and 9, respectively.

Animals↗
PubMed1988

Visualizing gene expression in time and space in the filamentous bacterium Streptomyces coelicolor.

Streptomycetes are prokaryotic microorganisms that exhibit a complex, mycelial fungus-like cycle of morphological differentiation. Development involves at least two spatially separated types of cells: the branching hyphae of the substrate mycelium, which penetrate the stratum upon which the colony feeds, and the upwardly protruding hyphae of the aerial mycelium, which undergo metamorphosis into spores. The luciferase-encoding luxA and luxB operon of the luminescent marine bacterium Vibrio harveyi was used as a promoter probe to visualize gene expression in differentiating colonies of Streptomyces coelicolor. Promoters for developmental genes of several kinds gave distinctive temporal and spatial patterns of light emission.

DNA, Bacterial↗
PubMed1988

Promoter determining the timing and spatial localization of transcription of a cloned Streptomyces coelicolor gene encoding a spore-associated polypeptide.

Streptomyces coelicolor is a filamentous, gram-positive bacterium that exhibits a complex cycle of morphological differentiation involving the formation of an aerial mycelium of multinucleoid hyphae which undergo septation to form long chains of spores. We report the identification of two proteins of 13 and 3 kilodaltons, designated SapA and SapB, respectively, that are produced during formation of the aerial mycelium and are found in assocation with purified, mature spores. We cloned the structural gene (sapA) for one of these spore-associated proteins. Nucleotide sequence analysis suggests that the 13-kilodalton polypeptide is derived from a larger pre- or preproprotein containing a leader sequence of 37 amino acids. Nuclease protection-hybridization analysis and experiments using the Vibrio harveyi, luciferase-encoding luxAB operon as a gene tag demonstrated that expression of sapA is controlled from a promoter contained within a region of less than 110 base pairs in length, whose transcription start site is located approximately 50 base pairs upstream from the initiation codon for the sapA open reading frame. Transcription of sapA was induced at the time of appearance of the aerial mycelium, and the level of sapA transcripts was significantly reduced in certain mutants blocked in aerial mycelium (bld) and or spore (whi) formation. As further evidence of the association of sapA transcription with morphological differentiation, experiments in which we monitored sapA transcription topographically by use of a sapA-luxAB operon fusion demonstrated a close spatial correlation between colony regions undergoing aerial mycelium formation and zones of sapA-promoted light emission.

Amino Acid Sequence↗
PubMed1987

Mapping of a restriction fragment length polymorphism within the human aldolase B gene.

Peripheral blood DNA was hybridized to the full-length cDNA and the cloned structural gene of human aldolase B. With PvuII endonuclease a restriction fragment length polymorphism was detected that was present in the heterozygous state in about 21% of the individuals tested. A map of the human aldolase gene was constructed for the two groups of individuals found to produce different fragments after PvuII digestion. This allowed the localization of the polymorphic site within the gene, which was found to be due to the loss of a PvuII site in the last intron upstream from the 3' end. This polymorphism may be used as a genetic marker to study individuals affected by hereditary fructose intolerance.

Chromosome Mapping↗
PubMed1986

Mapping through somatic cell hybrids and cDNA probes of protein C to chromosome 2, factor X to chromosome 13, and alpha 1-acid glycoprotein to chromosome 9.

The previously unassigned gene coding for the anti-coagulatory protein C has been mapped on chromosome 2 using a cDNA probe and genomic blots from a human-hamster somatic cell hybrid panel. The assignments of the genes coding for the coagulation factor X to chromosome 13, and for alpha 1-acid glycoprotein to chromosome 9 have been confirmed using a similar direct approach.

Animals↗
PubMed1985

Mapping of X-linked Becker muscular dystrophy through crossovers identified by DNA polymorphisms and by haplotype characterization in somatic cell hybrids.

The analysis of 10 X-linked DNA polymorphisms (five mapping on the short arm and five on the long arm) in two Becker muscular dystrophy pedigrees has been used to localize this gene in the known sequence of DNA polymorphic markers on the X chromosome. In the first pedigree, the carrier mother, whose phase for Becker and for five informative polymorphisms is known, has transmitted a double recombinant X chromosome to one of her two affected sons. The discordance between these two affected brothers for four of the five informative polymorphisms indicates that the Becker gene is located between RC8 or D2 on one side and pDP34 on the other. In the second pedigree, where the maternal grandfather is dead and two maternal first cousins are affected, the phase of DNA polymorphic alleles has been identified in somatic cell hybrids resulting from the fusion of hamster fibroblasts with lymphocytes of the mothers and aunt of the patients. The discordance between the two first cousins for two of the four informative DNA polymorphisms is best explained by the occurrence of a single recombination in the X chromosome carried by one of them. This result further restricts the localization of the Becker gene to a region of the short arm delimited by B24 and L 1.28. Regional and fine gene mapping through the approach described in this paper should become useful in the future for X-linked as well as for autosomal genes.

Animals↗
PubMed1985

Calcium blocking properties of piprofurol.

Piprofurol is a benzofuran chalcon derivative. It was studied under various experimental conditions which allow the recognition of calcium antagonistic activity. Piprofurol inhibited in a concentration-dependent manner the calcium-induced contractions in isolated potassium depolarized preparations of rat aorta (pA2: 9.29) and relaxed the K+-induced contraction of the dog coronary artery and the rabbit basilar artery (IC's 50: 2 10(-8) M; 3 10(-9) M). Piprofurol also inhibited noradrenaline-induced vascular smooth muscle contractions but the antagonism was clearly noncompetitive and the contractions induced were altered by concentrations two orders of magnitude higher than the concentration inhibiting calcium-induced contractions. Calcium antagonism was demonstrated in cardiac muscle: calcium mediated slowly rising action potentials were evoked in partially depolarized guinea-pig papillary muscle by electrical stimulation in the presence of isoprenaline. Piprofurol decreased the rate of rise of these slow action potentials. The inhibitory effect was reversed by an elevation of the calcium concentration in the bath fluid. Piprofurol exerts a negative inotropic effect (IC50: 5 10(-6) M) on guinea-pig papillary muscle. The ratio IC50 inotropic action/IC50 relaxant activity was 230, i.e. higher than that obtained with verapamil or diltiazem, and near that observed for cinnarizine. The pharmacological profile from in vivo dog experiments is in agreement with its in vitro properties: coronary sinus blood flow was increased and heart rate decreased. These effects suggested a potentially anti-ischaemic activity. This is confirmed in anaesthetized dogs, where piprofurol reduced the epicardial ST-segment elevation following coronary artery occlusion, and in isolated heart preparations, where it decreased the leakage of LDH during periods of anoxia and reoxygenation.

Action Potentials↗
PubMed1984

Isolation and nucleotide sequence of a full-length cDNA coding for aldolase B from human liver.

Two recombinant clones, pA2 and pA3, containing cDNA sequences for human aldolase B have been isolated from a full length human liver cDNA library. The larger one, pA3, has been subcloned in M13 phage and completely sequenced with the chain terminator method. The sequence covers 1,600 nucleotides including the whole coding region (1,050 nucleotides), 67 nucleotides from the 5' non-coding region and the whole 3' non-coding region, 440 nucleotides long, down to the poly-A tail. Comparison with rabbit aldolase A and with a partial sequence of rat aldolase B, shows a homology of about 76% for aldolase A and of about 94% for aldolase B, which indicates that the sequenced cDNA codes for the liver isoenzyme. This is the first complete sequence reported for human aldolase B. The pA3 clone strongly hybridizes to 18S mRNA from human adult liver as expected from the size of the isolated cDNA.

Amino Acid Sequence↗