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Biomedical subjects

S Alvarez

Publications and source records attributed to S Alvarez.

At least 37 records · Page 2Linked to original sources
PubMed2001

C282Y and H63D mutation frequencies in a population from central Spain.

OBJECTIVES: To determine the frequency of hereditary hemochromatosis gene mutations, C282Y and H63D, from 125 autochthonous blood donors originating from a Central region of Spain, to provide epidemiological data about HFE gene in the Iberian Peninsula. METHODS: DNA extracted from blood samples was analyzed by PCR-RFLP. Restriction enzymes were Snab I and Bcl I for C282Y and H63D, respectively. Results were visualized with Ethidium Bromide staining after gel electrophoresis. RESULTS AND DISCUSSION: C282Y frequency was 0.02 and that of H63D was 0.16. Result for C282Y mutation falls within the range of variation of the Mediterranean populations. H63D frequency agrees with those reported for other European populations. In both cases frequencies obtained are the lowest of compared Spanish data. CONCLUSIONS: This study is useful to compare expected versus presented C282Y and H63D frequencies in Spanish populations and to contribute to the knowledge of Spanish variability, rarely analyzed until now for HFE gene mutations.

Europe↗
PubMed2001

Effect of Lactobacillus casei and yogurt administration on prevention of Pseudomonas aeruginosa infection in young mice.

Pseudomonas aeruginosa is an opportunistic pathogen that rarely causes pulmonary disease in normal hosts but one that is an important cause of acute pneumonia in immunocompromised patients, including neonates, and of chronic pneumonia in patients with cystic fibrosis. The aim of this work was to study the effect of oral administration of Lactobacillus casei and yogurt on prevention of P. aeruginosa lung infection in young mice (3 weeks old). This study demonstrates that oral administration of L. casei or yogurt to young mice enhanced lung clearance of P. aeruginosa and phagocytic activity of alveolar macrophages through a dose-dependent effect. There were, however, no significant differences in white blood cell (WBC) differential counts. Furthermore, it was observed that previous administration of L. casei or yogurt induced a significant increase in IgA and IgM levels in bronchoalveolar lavages (BALs) after a P. aeruginosa infection, although there was no relationship with the serum values.

Administration, Oral↗
PubMed2000

Ligand macrocycle structural effects on copper-dioxygen reactivity.

With the goal of understanding how the nature of the tridentate macrocyclic supporting ligand influences the relative stability of isomeric mu-eta 2:eta 2-peroxo- and bis(mu-oxo)dicopper complexes, a comparative study was undertaken of the O2 reactivity of Cu(I) compounds supported by the 10- and 12-membered macrocycles, 1,4,7-R3-1,4,7-triazacyclodecane (R3TACD; R = Me, Bn, iPr) and 1,5,9-triisopropyl-1,5,9-triazacyclododecane (iPr3TACDD). While the 3-coordinate complex [(iPr3TACDD)Cu]SbF6 was unreactive with O2, oxygenation of [(R3TACD)Cu(CH3CN)]X (R = Me or Bn; X = ClO4- or SbF6-) at -80 degrees C yielded bis(mu-oxo) species [(R3TACD)2Cu2(mu O)2]X2 as revealed by UV-vis and resonance Raman spectroscopy. Interestingly, unlike the previously reported system supported by 1,4,7-triisopropyl-1,4,7-triazacyclononane (iPr3TACN), which yielded interconverting mixtures of peroxo and bis(mu-oxo) compounds (Cahoy, J.; Holland, P. L.; Tolman, W. B. Inorg. Chem. 1999, 38, 2161), low-temperature oxygenation of [(iPr3TACD)Cu(CH3CN)]SbF6 in a variety of solvents cleanly yielded a mu-eta 2:eta 2-peroxo product, with no trace of the bis(mu-oxo) isomer. The peroxo complex was characterized by UV-vis and resonance Raman spectroscopy, as well as an X-ray crystal structure (albeit of marginal quality due to disorder problems). Intramolecular attack at the alpha C-H bonds of the substituents was indicated as the primary decomposition pathway of the oxygenated compounds through examination of the decay kinetics and the reaction products, which included bis(mu-hydroxo)- and mu-carbonato-dicopper complexes that were characterized by X-ray diffraction. A rationale for the varying results of the oxygenation reactions was provided by analysis of (a) the X-ray crystal structures and electrochemical behavior of the Cu(I) precursors and (b) the results of theoretical calculations of the complete oxygenated complexes, including all ligand atoms, using combined quantum chemical/molecular mechanics (integrated molecular orbital molecular mechanics, IMOMM) methods. The size of the ligand substituents was shown to be a key factor in controlling the relative stabilities of the peroxo and bis(mu-oxo) forms, and the nature of this influence was shown by both theory and experiment to depend on the ligand macrocycle ring size.

Copper↗
PubMed2000

Magnetic coupling in end-to-end azido-bridged copper and nickel binuclear complexes: a theoretical study.

The influence of structural parameters on the exchange coupling J between metal atoms in end-to-end azido-bridged binuclear complexes of Cu(II) and Ni(II) has been studied by means of density functional calculations. For the case of double-bridged Cu(II) compounds, four ideal pentacoordinate models have been employed in which the coordination spheres of the two metal atoms are either a trigonal bipyramid or a square pyramid, connected through equatorial or axial bridges. The distortion from those ideal geometries along a Berry pathway has also been analyzed. For the hexacoordinate Ni(II) compounds, models with two or one bridging ligands have been studied. The effect of the bridging M-N-N bond angles on the exchange coupling has been analyzed for both the Cu(II) and Ni(II) complexes.

Journal Article↗
PubMed2000

Through-ring bonding in edge sharing dimers of octahedral complexes.

A study of the preferred structures for the M2X2 rings in the binuclear complexes of types [M2(mu-XR2)2L8] and [M2(mu-XR3)2L8] is presented, based on qualitative orbital arguments supported by extended Hückel calculations on Cr compounds. The main conclusions are confirmed by DFT calculations on key compounds of Cr and Mn and agree well with the results of a structural database analysis. With the simplified electron counting scheme deduced, complexes with six or four electrons available for bonding of the M2X2 framework are predicted to have two possible minimum energy structures, with either a short M-M or X-X distance, whereas compounds with eight framework electrons are expected to present no short through-ring distance. Such a behavior is consistent with the framework electron rules reported earlier for compounds with different coordination spheres and provides a general description of the structure and bonding in a variety of compounds with M2X2 diamonds. Metal-metal bonding across the ring can be equally predicted taking into account only the bonding characteristics of the t2g-like orbitals for the XR2- but not for the XR3-bridged complexes. In addition, the framework electron counting scheme has the advantage of being independent of the formal oxidation state assigned to the metal atom.

Journal Article↗
PubMed2000

Structural correlations and conformational preference in edge-sharing binuclear d8 complexes with XR2 bridges. A theoretical study.

The binuclear complexes of d8 transition metal ions of the type [M2(mu-XR2)2L4] (where M = RhI, IrI, NiII, PdII, PtII, or AuIII; X = S, N, P, or As) appear in a variety of molecular conformations in which the coordination planes around the two metal atoms are sometimes coplanar, sometimes bent. For the bent compounds with asymmetric bridges, XR1R2, the substituents adopt different orientations relative to the metal framework and to each other. Ab initio theoretical studies on the different conformers of 30 representative complexes, complemented with a structural database analysis, have allowed the establishment of structural correlations in this family of compounds. The conformational choice results from a delicate balance of different interactions which are qualitatively analyzed, such as the changes in bond angles around the bridging atoms, the existence of weak metal...metal bonding in the bent structures, and steric interactions involving the terminal ligands and the substituents at the bridging atoms.

Journal Article↗
PubMed2000

Human MT6-matrix metalloproteinase: identification, progelatinase A activation, and expression in brain tumors.

The localization of proteolytic enzymes at the cell surface is a widely used strategy for facilitating tumor invasion. In this study, we have cloned a new member of the membrane-type subfamily of matrix metalloproteinases (MT-MMPs), a group of enzymes associated with tumor progression. The cloned cDNA encodes a protein of 562 amino acids with a domain organization similar to that of other MT-MMPs, including a prodomain with a cysteine switch, a catalytic domain with the zinc-binding site, a hemopexin-like domain, and a COOH-terminal extension rich in hydrophobic residues. The predicted protein sequence also contains a short insertion of basic residues located between the propeptide and the catalytic domain and involved in the proteolytic activation of MT-MMPs by furin-like enzymes. Furthermore, immunofluorescence and Western blot analysis of COS-7 cells transfected with the isolated cDNA revealed that the encoded protein is localized at the cell surface. Based on these properties, this novel human matrix metalloproteinase has been called MT6-MMP because it is the sixth identified member of this subfamily of matrix metalloproteinase. Cotransfection of expression plasmids encoding MT6-MMP and progelatinase A resulted in activation of COS-7-secreted progelatinase A, as demonstrated by gelatin zymography. In contrast, transfection of progelatinase A cDNA alone did not lead to the activation of the proenzyme. Northern blot analysis of polyadenylated RNAs isolated from human tissues demonstrated that MT6-MMP is predominantly expressed in leukocytes, lung, and spleen. MT6-MMP was also detected at high levels in SW480 colon carcinoma cells as well as in some anaplastic astrocytomas and glioblastomas, but not in normal colon or brain or in meningiomas. On the basis of these results, we propose that MT6-MMP may facilitate tumor progression through its ability to activate progelatinase A at the membrane of cells from colon carcinomas or brain tumors.

Amino Acid Sequence↗
PubMed2000

Asymmetry and magnetism in bis(oximato)-bridged heterobimetallic compounds: a computational approach.

A density functional study of exchange coupling was carried out for a series of heterobinuclear oximato-bridged transition metal complexes. Model calculations were used to examine the influence of the electronic configuration of the metal atoms on the coupling constants. This analysis was complemented by a study of the variation of the coupling constant with the most usual structural distortions within this family of compounds. The influence of the nature of the terminal ligands as well as that of the symmetry on the bridge were also investigated.

Journal Article↗
PubMed2000

Molecular biology of leukemia.

Identification and characterization of leukemia-related chromosomal translocations have had significant impact on all aspects of the management of acute leukemia, including its diagnosis, assignment of prognosis, and development of an appropriate treatment plan. Several genes are recurrent targets of chromosomal abnormalities, suggesting that they play a key role in leukemogenesis. Significant progress has been made to define potentially unifying molecular mechanisms of leukemic transformation. Hopefully, these findings will provide the basis for molecularly targeted therapies for leukemia.

Female↗
PubMed2000

Prospective, randomized, controlled study of in vitro fertilization-embryo transfer with a single dose of a luteinizing hormone-releasing hormone (LH-RH) antagonist (cetrorelix) or a depot formula of an LH-RH agonist (triptorelin).

OBJECTIVE: To confirm the value of a single dose of 3 mg of cetrorelix in preventing the occurrence of premature LH surges. DESIGN: Multicenter randomized, prospective study. SETTING: Reproductive medicine units. PATIENT(S): Infertile patients undergoing ovarian stimulation for IVF-ET. INTERVENTION(S): A single dose of 3 mg of cetrorelix (Cetrotide; ASTA Medica, Frankfurt, Germany) (115 patients) was administered in the late follicular phase. A depot preparation of triptorelin (Decapeptyl; Ipsen-Biotech, Paris, France) was chosen as a control agent (39 patients). Ovarian stimulation was conducted with hMG (Menogon; Ferring, Kiel, Germany). MAIN OUTCOME MEASURE(S): Premature LH surges (LH level >10 IU/L), progesterone level greater than 1 ng/L, and IVF results. RESULT(S): No LH surge occurred after cetrorelix administration. The patients in the cetrorelix group had a lower number of oocytes and embryos. The percentage of mature oocytes and fertilization rates were similar in both groups, and the pregnancy rates were not statistically different. The length of stimulation, number of hMG ampules administered, and occurrence of the ovarian hyperstimulation syndrome were lower in the cetrorelix group. Tolerance of cetrorelix was excellent. CONCLUSION(S): A cetrorelix single-dose protocol prevented LH surges in all patients studied. It compares favorably to the "long protocol" and could be a protocol of choice in IVF-ET.

Adult↗
PubMed2000

Reactions of peroxynitrite in the mitochondrial matrix.

Superoxide radical (O2-) and nitric oxide (NO) produced at the mitochondrial inner membrane react to form peroxynitrite (ONOO-) in the mitochondrial matrix. Intramitochondrial ONOO- effectively reacts with a few biomolecules according to reaction constants and intramitochondrial concentrations. The second-order reaction constants (in M(-1) s(-1)) of ONOO- with NADH (233 +/- 27), ubiquinol-0 (485 +/- 54) and GSH (183 +/- 12) were determined fluorometrically by a simple competition assay of product formation. The oxidation of the components of the mitochondrial matrix by ONOO- was also followed in the presence of CO2, to assess the reactivity of the nitrosoperoxocarboxylate adduct (ONOOCO2-) towards the same reductants. The ratio of product formation was about similar both in the presence of 2.5 mM CO2 and in air-equilibrated conditions. Liver submitochondrial particles supplemented with 0.25-2 microM ONOO- showed a O2- production that indicated ubisemiquinone formation and autooxidation. The nitration of mitochondrial proteins produced after addition of 200 microM ONOO- was observed by Western blot analysis. Protein nitration was prevented by the addition of 50-200 microM ubiquinol-0 or GSH. An intramitochondrial steady state concentration of about 2 nM ONOO- was calculated, taking into account the rate constants and concentrations of ONOO- coreactants.

Animals↗
PubMed2000

The content and accessibility of sex education information on the Internet.

The objective of this study was to describe Web sites with sex education material and assess the accessibility of specific information on the Internet. First, the authors conducted a review of Web sites using specific sex education keywords. Second, 27 undergraduate students were asked to locate information on proper condom use and sexually transmitted disease (STD) symptoms. The time, number of search attempts, and number of clicks needed to identify each piece of information were recorded. The authors identified 41 sites with sex education material from almost 6 million pages yielded by the keywords. Sixty-three percent of the 1,556 most compatible pages were categorized as pornography. The students found the information on condom use and STD symptoms in an average of 4 minutes, using fewer then six clicks and two searches. The authors concluded that general information on sex education is difficult to locate on the Internet and often lacks essential elements, but accurate and useful information on specific topics can be more easily obtained.

Adolescent↗
PubMed2000

Multiple lung abscesses due to Ochroconis gallopavum, a dematiaceous fungus, in a nonimmunocompromised wood pulp worker.

An occurrence of multiple chronic lung abscesses managed by lobectomy is described. These abscesses were present for 13 years in the patient, a nonimmunocompromised wood pulp worker. The patient had hemoptysis at presentation. The organism isolated was Ochroconis gallopavum, a dematiaceous fungus known to cause disease in immunocompromised patients and epidemic encephalitis in poultry. The fungus is typically found in warm environments and in decaying compost; for this reason, we postulate that his illness was occupationally acquired.

Adult↗
PubMed2000

Free radical chemistry in biological systems.

Mitochondria are an active source of the free radical superoxide (O2-) and nitric oxide (NO), whose production accounts for about 2% and 0.5% respectively, of mitochondrial O2 uptake under physiological conditions. Superoxide is produced by the auto-oxidation of the semiquinones of ubiquinol and the NADH dehydrogenase flavin and NO by the enzymatic action of the nitric oxide synthase of the inner mitochondrial membrane (mtNOS). Nitric oxide reversibly inhibits cytochrome oxidase activity in competition with O2. The balance between NO production and its utilization results in a NO intramitochondrial steady-state concentration of 20-50 nM, which regulates mitochondrial O2 uptake and energy supply. The regulation of cellular respiration and energy production by NO and its ability to switch the pathway of cell death from apoptosis to necrosis in physiological and pathological conditions could take place primarily through the inhibition of mitochondrial ATP production. Nitric oxide reacts with O2- in a termination reaction in the mitochondrial matrix, yielding peroxynitrite (ONOO-), which is a strong oxidizing and nitrating species. This reaction accounts for approximately 85% of the rate of mitochondrial NO utilization in aerobic conditions. Mitochondrial aging by oxyradical- and peroxynitrite-induced damage would occur through selective mtDNA damage and protein inactivation, leading to dysfunctional mitochondria unable to keep membrane potential and ATP synthesis.

Aging↗
PubMed2000

Gut mucosal immunostimulation by lactic acid bacteria.

The beneficial properties of lactic acid bacteria (LAB) on human health have been frequently demonstrated. The interaction of LAB with the lymphoid cells associated to the gut to activate the mucosal immune system and the mechanisms by which they can exert an adjuvant effect is still unclear, as well as if this property is common for all the LAB. We studied the influence of the oral administration of different geneous of LAB such as Lactobacillus casei, L. acidophilus, L. rhamnosus, L. delbrueckii subsp. bulgaricus, L. plantarum, Lactococcus lactis and Streptococcus thermophilus. We determined if the LAB assayed were able to stimulate the specific, the non-specific immune response (inflammatory response), or both. We demonstrated that all the bacteria assayed were able to increase the number of IgA producing cells associated to the lamina propria of small intestine. This effect was dose dependent. The increase in IgA+ producing cells was not always correlated with an increase in the CD4+ T cell number, indicating that some LAB assayed only induced clonal expansion of B cells triggered to produce IgA. Most of them, induced an increase in the number of cells involved in the inflammatory immune response. CD8+ T cell were diminished or not affected, with exception of L. plantarum that induced an increase at low dose. This fact would mean that LAB are unable to induce cytotoxicity mechanisms. We demonstrated the importance in the selection of LAB to be used as gut mucosal adjuvant. The different behaviours observed among them on the gut mucosal immune response, specially those that induce inflammatory immune response, show that not all the LAB can be used as oral adjuvant and that the beneficial effect of them can not generalized to genous or specie. The immunoadjuvant capacity would be a property of the strain assayed.

Adjuvants, Immunologic↗
PubMed1999

Study of the possible mechanisms involved in the mucosal immune system activation by lactic acid bacteria.

The induction of a mucosal immune response is not easy due to the development of oral tolerance, but under some conditions, bacteria can activate this immune system. Antigens administered orally can interact with M cells of Peyer's patches or bind to the epithelial cells. We have demonstrated that certain lactic acid bacteria are able to induce specific secretory immunity, and others will enhance the gut inflammatory immune response. The aim of this work was to establish the reason for these different behaviors and to define possible mechanisms involved in the interaction of lactic acid bacteria at the intestinal level. We studied IgA+ and IgM+ B cells comparatively in bronchus and intestine and CD4+ T cells and IgA anti-lactic acid bacteria antibodies in the intestinal fluid, induced by oral administration of Lactobacillus casei, Lb. delbrueckii ssp. bulgaricus, Lb. acidophilus, Lb. plantarum, Lb. rhamnosus, Lactococcus lactis, and Streptococcus salivarius ssp. thermophilus. The increase in the IgA+ B cells in the bronchus means that these lactic acid bacteria were able to induce the IgA cycle by interaction with M cells from Peyer's patches or intestinal epithelial cells. The IgM+ cells increased when the stimulus did not induce the switch from IgM+ to IgA+. The increase in the CD4+ cells suggests interaction of Peyer's patches and enhancement of the B- and T-cell migration. The anti-lactic acid bacteria antibody is related to the processing and presentation of the microorganisms to the immune cells. We demonstrated that Lb. casei and Lb. plantarum were able to interact with Peyer's patch cells and showed an increase in IgA-, CD4+ cells, and antibodies specific for the stimulating strain. Lactobacillus acidophilus induced gut mucosal activation by interaction with the epithelial cells without increase in the immune cells associated with the bronchus. Although Lb. rhamnosus and Strep. salivarius ssp. thermophilus interact with epithelial cells, they also induced an immune response against their epitopes. Lactococcus lactis and Lb. delbrueckii ssp. bulgaricus induced an increase of IgA+ cells entering the IgA cycle but not CD4+ cells; thus, these bacteria would have been bound to epithelial cells that activated B lymphocytes without processing and presenting of their epitopes. We did not determine specific antibodies against Lc. lactis or Lb. bulgaricus.

Animals↗