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Biomedical subjects

M Miranda

Publications and source records attributed to M Miranda.

At least 37 records · Page 2Linked to original sources
PubMed2002

Cattle as biomonitors of soil arsenic, copper, and zinc concentrations in Galicia (NW Spain).

Determination of soil concentrations of trace and pollutant metals over large spatial areas requires laborious and expensive sampling effort. In this study, we examined the feasibility of using calves as biomonitors of soil semimetal and trace metal concentrations in Galicia (NW Spain), a region in which calves are predominantly reared on grass or locally grown forage. We determined the concentrations of arsenic, copper, and zinc in the liver, kidney, muscle, and blood of calves from across Galicia and related them to the metal concentrations in the soil from the areas in which the animals were reared. For each element, liver (but not usually kidney, muscle, or blood) concentrations were significantly elevated in animals from areas with higher soil concentrations. Liver arsenic concentrations were only markedly greater in animals from areas with soil arsenic levels > 20 mg/kg, and calves may not be sensitive enough biomonitors of background variation in soil levels, although they may be useful for monitoring anthropogenic arsenic contamination. Copper and zinc liver levels increased progressively with soil levels, and the pattern was especially marked for copper. The relatively unusual copper metabolism of cattle and other ruminants may make them particularly good biomonitors for environmental concentrations of this metal.

Abattoirs↗
PubMed2002

Contribution of cattle products to dietary intake of trace and toxic elements in Galicia, Spain.

In Galicia, Spain, liver copper concentrations, muscle zinc concentrations and kidney cadmium concentrations (in adult cattle) can exceed acceptable maximum concentrations which have been adopted by some countries. The aim was to calculate the contribution of cattle products to the daily intake of trace and toxic metals by humans in Galicia and to evaluate whether there was any health risk to consumers. This was done by comparing calculated intakes with published acceptable daily intake rates for toxic elements and with the accepted safe ranges for population mean intakes of the essential metals. Typically, the contribution of cattle meat and offal to the daily cadmium, lead and arsenic intake of people in Galicia was minimal because offal is rarely eaten. However, liver from older cattle, especially animals from relatively contaminated areas, could pose a health risk if offal was consumed in substantial quantities. Muscle and liver from Galician cattle that exceeded acceptable maximum concentrations for copper and zinc did not pose a risk to human health.

Animals↗
PubMed2002

Chronic eosinophilic leukaemia presenting with erythroderma, mild eosinophilia and hyper-IgE: clinical, immunological and cytogenetic features and therapeutic approach. A case report.

A 23-year-old, white male metallurgist presented with pruritic erythematous maculo-papules over the trunk and upper limbs and 6 months later developed erythroderma, eosinophilia and multi-organ dysfunction. A diagnosis of chronic eosinophilic leukaemia was made on the basis of myeloproliferative involvement of both peripheral blood and bone marrow, associated with eosinophilic differentiation and a t(5;12)(q33;p13) translocation. The initial therapeutic approach was interferon alfa-2b plus cytosine arabinoside, for 13 months, followed by hydroxyurea plus vincristine. There was improvement of skin lesions, disappearance of eosinophilia and decrease of serum immunoglobulin E, towards normal values.

Adult↗
PubMed2001

Stalk segment 5 of the yeast plasma membrane H+-ATPase: mutational evidence for a role in glucose regulation.

In P(2)-type ATPases, a stalk region connects the cytoplasmic part of the molecule, which binds and hydrolyzes ATP, to the membrane-embedded part through which cations are pumped. The present study has used cysteine scanning mutagenesis to examine structure-function relationships within stalk segment 5 (S5) of the yeast plasma-membrane H(+)-ATPase. Of 29 Cys mutants that were made and examined, two (G670C and R682C) were blocked in biogenesis, presumably due to protein misfolding. In addition, one mutant (S681C) had very low ATPase activity, and another (F685C) displayed a 40-fold decrease in sensitivity to orthovanadate, reflecting a shift in equilibrium from the E(2) conformational state toward E(1). By far the most striking group of mutants (F666C, L671C, I674C, A677C, I684C, R687C, and Y689C) were constitutively activated even in the absence of glucose, with rates of ATP hydrolysis and kinetic properties normally seen only in glucose-metabolizing cells. Previous work has suggested that activation of the wild-type H(+)-ATPase results from kinase-mediated phosphorylation in the auto-inhibitory C-terminal region of the 100-kDa polypeptide. The seven residues identified in the present study are located on one face of the S5 alpha-helix, consistent with the idea that mutations along this face serve to release the auto-inhibition.

Adenosine Triphosphate↗
PubMed2001

Developmental expression and distribution of amphibian glutathione transferases.

This work is aimed at detecting the expression and location of embryonic Bufo bufo GST (bbGSTP1-1) and adult B. bufo GST (bbGSTP2-2) during toad development, in order to assign a putative role to these enzymes also on the basis of their compartmentalization and to verify whether during the premetamorphic liver ontogeny the bbGSTP2-2 form appears. This study was also performed in the adult liver (the primary site of Pi class GST expression) and in the mature ovary, to discern if the embryonic form derives from maternal form. The results show that the embryos and the ovary express only bbGSTP1-1. Moreover, bbGSTP1-1 distribution is the same both in the early embryos and in the ovary: this strongly suggests that bbGSTP1-1 is of maternal origin. As development goes on, a wide distribution of bbGSTP1-1 all over the differentiating organs is observed. The embryonic liver expresses exclusively the bbGSTP1-1 form, while the adult liver is highly positive only towards the bbGSTP2-2 form. This implies that the switch towards the adult bbGSTP2-2 form occurs in metamorphic or postmetamorphic phases and that the detoxication metabolic requirements of the embryo may be completely fulfilled by the bbGSTP1-1 isoenzyme.

Animals↗
PubMed2001

The effect of mussel size, temperature, seston volume, food quality and volume-specific toxin concentration on the uptake rate of PSP toxins by mussels (Mytilus galloprovincialis Lmk).

The accumulation of paralytic shellfish poisoning (PSP) toxins by bivalves is a serious threat to public health all over the world. However, very little is known about the uptake kinetics of these toxins and the environmental factors that may modify this process. We have studied the effect of mussel size, temperature, seston volume, food quality, and volume-specific toxin concentration (VOSTOC), on the uptake rate of paralytic shellfish poisoning (PSP) toxins by mussels (Mytilus galloprovincialis), by means of a second order factorial experiment. Over a 3-day period, the mussels were fed artificial diets containing Alexandrium minutum AL1V (a PSP toxin producer), Tetraselmis suecica, Ensiculifera sp1 and silt, to the levels required by each treatment. Mussel size, seston volume and VOSTOC were found to be statistically significant when the total toxin accumulated per weight of wet tissue was considered. Mussel size affected the uptake negatively and latter two positively. The interactions, mussel size-VOSTOC and mussel size-food quality were also significant. The response was not linear as shown by the significance of the quadratic term of mussel size. Notwithstanding, when the PSP toxins accumulation per mussel was analysed, only one factor, the VOSTOC and the interactions, food quality-mussel size and food quality-seston volume, were found to be significant. VOSTOC was the most important factor in the accumulation of toxins, in our opinion, probably due to toxin assimilation being mainly regulated by the probability of contact between the toxins and the cellular walls of the digestive system. The size of the bivalve is also especially important because toxin concentration is usually calculated per weight of bivalve tissue and because the weight-specific ingestion increases with mussel size. The food quality, which was directly related to the assimilation of organic matter, had an inverse effect on toxin assimilation. In our opinion, this is probably due to the effect of inorganic particles in enhancing the disruption of Alexandrium cells. Temperature had no effect on the uptake rate except for the accumulation of the gonyautoxin GTX1.

Journal Article↗
PubMed2001

Morphofunctional mitochondrial response to methylglyoxal toxicity in Bufo bufo embryos.

Methylglyoxal (2-oxopropanal) is a reactive alpha-oxoaldehyde that can be formed endogenously mainly as a by-product of glycolytic pathway. It is a cytotoxic compound with significant antiproliferative properties as it can bind, under physiological conditions, to nucleic acids and proteins, forming stable adducts. We have recently shown that exogenous methylglyoxal (150-600 microM) is highly toxic for amphibian embryos where it produces, when added to the culture water, inhibition of cell proliferation in the early developmental stages, followed by severe malformations and strongly reduced embryonic viability. In this work we investigate the morphofunctional effect of methylglyoxal on the common toad B. bufo embryo mitochondria in order to verify if its dysmorphogenetic action might be also ascribed to impairment of mitochondrial functions. The mitochondria were isolated from embryos at the developmental stages of morula, neural plate and operculum complete and developing in the presence of 600 microM methylglyoxal. The results show that exogenous methylglyoxal is highly toxic at mitochondrial level, where it produces proliferation, swelling and membrane derangement. As a consequence, mitochondria from treated embryos show decreased oxidative phosphorylation efficiency, as indicated by the significant reduction both of the respiratory control index values and of the embryonic ATP content. On the basis of these data, it is possible that the methylglyoxal-induced embryonic malformations as well as the strongly reduced viability might be also ascribed to energy depletion.

Adenosine Diphosphate↗
PubMed2001

Allogeneic stem cell transplantation for Evans syndrome.

Evans syndrome is a rare disorder characterized by combined autoimmune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Standard treatments consist of transfusions, corticosteroids, splenectomy, IVIG, anabolic steroids, vincristine, alkylating agents, or cyclosporine. In a patient with refractory disease, an allogeneic hematopoietic stem cell transplant (HSCT) resulted in complete clinical and serologic remission for more than 30 months. Allogeneic HSCT may be the only current curative therapy for Evans syndrome but may also be complicated by significant toxicities.

Adrenal Cortex Hormones↗
PubMed2001

Amino acid permeases in developing seeds of Vicia faba L.: expression precedes storage protein synthesis and is regulated by amino acid supply.

Full length cDNAs encoding three amino acid permeases were isolated from seed-specific libraries of Vicia faba. The predicted proteins VfAAP1, VfAAP3 and VfAAP4 share up to 66% identity among themselves. Functional characterization of VfAAP1 and VfAAP3 in a yeast mutant showed that these permeases transport a broad range of amino acids. However, VfAAP1 had a preference for cysteine and VfAAP3 for lysine and arginine. VfAAP1 was highly expressed in cotyledons at early developmental stages and moderately in other sink tissues. Its peak of expression in cotyledons corresponded to the appearance of storage protein transcripts, suggesting that this transporter fulfills an important role in providing amino acids for storage protein biosynthesis. VfAAP3 was expressed most abundantly in maternal tissues, that is in roots, stems, gynoecia, pods and seed coats at different developmental stages. VfAAP4 transcripts could not be detected by northern hybridization. In situ hybridization showed that VfAAP1 mRNA is distributed throughout cotyledon storage parenchyma cells, but could not be detected in the abaxial epidermal cell layer. It also accumulate in the chlorenchyma and thin-walled parenchyma cells of seed coats. VfAAP1 mRNA levels were lower in cotyledons cultured in the presence of glutamine, whereas expression of a vicilin storage protein gene was up-regulated under similar conditions. Cysteine repressed the expression of the GUS reporter gene under control of the VfAAP1 promoter, suggesting that this transporter is modulated at the transcriptional level. Regulation of amino acid transport in relation to storage protein accumulation is discussed.

Amino Acid Transport Systems↗
PubMed2001

[Restless legs syndrome: a clinical study in adult general population and in uremic patients].

BACKGROUND: The restless legs syndrome (RLS) is a movement disorder characterized by an imperative urge to move the legs, associated with paraesthesias, motor restlessness and worsening of symptoms at night with at least partial relief by activity. Its prevalence ranges between 2-15% of general adult population and 20-30% of uremic patients. AIM: To evaluate the frequency and the clinical features of RLS in a sample of general adult population and in uremic patients, in Chile, correlating it with biochemical parameters. METHOD: 100 relatives of outpatients and 166 uremic patients undergoing chronic haemodialysis were interviewed assessing the presence and severity of RLS according to current diagnostic criteria. Biochemical parameters assessed were hematocrit, serum ferritin, phosphate, intact parathyroid hormone (iPTH) levels. RESULTS: 13% of the general population sample was affected, 15% of them were severe. Forty three cases were found among uremic patients (25.9%) (p < 0.01 vs general population), 60% of them were severe and women were affected with higher frequency (p < 0.05) and severity (p < 0.01). Four patients presented RLS even during hemodialysis. No correlation was found with biochemical parameters. Most RLS cases had not been diagnosed previously. CONCLUSIONS: In our population RLS is common and undetected. It is especially prevalent and severe in uremic patients: we found no evidence that anaemia, iron deficiency or iPTH level play a major pathogenic role. Our findings emphasize the need of greater medical awareness of RLS because available therapy may improve the quality of life.

Adolescent↗
PubMed2001

[Chronic hepatic encephalopathy: the role of high serum manganese levels and its relation with basal ganglia lesions in nuclear magnetic resonance of the brain. Clinical case].

Chronic hepatic encephalopathy (CHE) is a disabling complication of chronic liver failure and porto-systemic shunt. The pathogenesis of CHE remains unclear but increased levels of ammonia are a basic feature. Several clinical and experimental observations support a role for manganese (Mn) in the pathogenesis of this disorder. Increased blood levels of Mn have been described in patients with CHE and this could lead to its accumulation on the basal ganglia and characteristic hyperintensities of basal ganglia as seen on magnetic resonance imaging (MRI) of the brain. We report on the clinical features and characteristic radiologic findings of a patient who presented with the neurologic syndrome of CHE and who had very high blood levels of Mn in the absence of an occupational exposure to this metal. Our report supports the hypothesis that Mn has a role in the pathogenesis of CHE and also suggests that brain MRI is a useful marker of the brain metabolic repercussion due to CHE.

Ammonia↗
PubMed2000

Sequence and analysis of chromosome 1 of the plant Arabidopsis thaliana.

The genome of the flowering plant Arabidopsis thaliana has five chromosomes. Here we report the sequence of the largest, chromosome 1, in two contigs of around 14.2 and 14.6 megabases. The contigs extend from the telomeres to the centromeric borders, regions rich in transposons, retrotransposons and repetitive elements such as the 180-base-pair repeat. The chromosome represents 25% of the genome and contains about 6,850 open reading frames, 236 transfer RNAs (tRNAs) and 12 small nuclear RNAs. There are two clusters of tRNA genes at different places on the chromosome. One consists of 27 tRNA(Pro) genes and the other contains 27 tandem repeats of tRNA(Tyr)-tRNA(Tyr)-tRNA(Ser) genes. Chromosome 1 contains about 300 gene families with clustered duplications. There are also many repeat elements, representing 8% of the sequence.

Arabidopsis↗
PubMed2000

Stalk segment 4 of the yeast plasma membrane H+-ATPase. Mutational evidence for a role in the E1-E2 conformational change.

In the P(2)-type ATPases, there is growing evidence that four alpha-helical stalk segments connect the cytoplasmic part of the molecule, responsible for ATP binding and hydrolysis, to the membrane-embedded part that mediates cation transport. The present study has focused on stalk segment 4, which displays a significant degree of sequence conservation among P(2)-ATPases. When site-directed mutants in this region of the yeast plasma membrane H(+)-ATPase were constructed and expressed in secretory vesicles, more than half of the amino acid substitutions led to a severalfold decrease in the rate of ATP hydrolysis, although they had little or no effect on the coupling between hydrolysis and transport. Strikingly, mutant ATPases bearing single substitutions of 13 consecutive residues from Ile-359 through Gly-371 were highly resistant to inorganic orthovanadate, with IC(50) values at least 10-fold above those seen in the wild-type enzyme. Most of the same mutants also displayed a significant reduction in the K(m) for MgATP and an increase in the pH optimum for ATP hydrolysis. Taken together, these changes in kinetic behavior point to a shift in equilibrium from the E(2) conformation of the ATPase toward the E(1) conformation. The residues from Ile-359 through Gly-371 would occupy three full turns of an alpha-helix, suggesting that this portion of stalk segment 4 may provide a conformationally active link between catalytic sites in the cytoplasm and cation-binding sites in the membrane.

Adenosine Triphosphate↗
PubMed2000

Biochemical, electrophoretic and immunohistochemical aspects of malate dehydrogenase in truffles (Ascomycotina).

The malate dehydrogenase (MDH; EC 1.1.1.37; L-malate-NAD(+)-oxidoreductase) activities of truffles of the genus Tuber (Tuber melanosporum Vittad., Tuber brumale Vittad., Tuber aestivum Vittad., Tuber magnatum Pico, Tuber rufum Pico) have been characterized with regard to the K(m) and V(max) values in the direct and reverse reactions. The isoelectrofocusing has revealed bands showing pI values ranging from pH 5.85 to 7.8. The MDH of T. melanosporum has been partially purified by hydroxyapatite treatment, DEAE-cellulose and Sephadex G-75 columns. With the partially purified T. melanosporum MDH activity polyclonal anti-T. melanosporum MDH antibodies have been prepared and used to localize MDH in the mycorrhizae and ascocarps of T. melanosporum. These antibodies inhibit T. melanosporum MDH activity as well as that of T. magnatum but not that of rabbit liver; this supports the specificity of the MDH antibodies used to localize MDH in truffle tissues.

Animals↗
PubMed2000

Arsenic, cadmium, lead, copper and zinc in cattle from Galicia, NW Spain.

Knowledge of trace and toxic metal concentrations in livestock is important for assessing the effects of pollutants on domestic animals and contaminant intakes by humans. Metal levels in cattle have been measured in various countries but not in Spain. In this study, the (wet wt.) concentrations of three toxic elements (arsenic, cadmium, lead) and two trace elements (copper, zinc) were quantified in the liver (Li), kidney (Ki), muscle (M) and blood (Bl) of calves (males and females between 6 and 10 months old) and cows (2-16 years old) from Galicia, NW Spain. For the toxic elements, geometric mean concentrations of arsenic in calves (sexes combined) and cows were 10.8 and 10.2 microg/kg (Li), 11.3 and 15.2 microg/kg (Ki), 3.75 and 4.25 microg/kg (M), 3.23 and 2.92 microg/l (Bl). The corresponding cadmium concentrations were 7.78 and 83.3 microg/kg (Li), 54.3 and 388 microg/kg (Ki), 0.839 and 0.944 microg/kg (M), 0.373 and 0.449 microg/l (Bl). Geometric mean concentrations of lead in calves and cows were similarly low and were 33.0 and 47.5 microg/kg (Li), 38.9 and 58.3 microg/kg (Ki), 6.37 and 12.5 microg/kg (M), 5.47 and 12.2 microg/l (Bl). Sex had almost no effect on the amount of toxic metal accumulated except that kidney cadmium concentrations were significantly higher in females than males. Age did influence accumulation; cadmium and lead (but not arsenic) concentrations in most tissues were significantly greater in cows than female calves. For the trace elements, geometric mean copper levels in calf and cow tissues were 49.9 and 36.6 mg/kg (Li), 4.27 and 3.63 mg/kg (Ki), 0.649 and 1.68 mg/kg (M) and 0.878 and 0.890 mg/l (Bl). The corresponding zinc concentrations were 46.3 and 52.5 mg/kg (Li), 14.2 and 20.7 mg/kg (Ki), 47.3 and 52.5 mg/kg (M) and 2.80 and 2.22 mg/l (Bl). Female calves had significantly higher levels than males of muscle zinc and blood copper and zinc. Female calves accumulated more copper but less zinc in the liver and kidneys compared with cows; this may have been associated with the chronic, low-level cadmium accumulation observed in cows. Overall, the levels of arsenic, cadmium, lead and zinc in cattle in Galicia do not constitute a risk for animal health. However, up to 20% of cattle in some regions in Galicia had levels of copper in the liver that exceeded 150 mg/kg wet wt. These animals may be at risk from copper poisoning.

Abattoirs↗