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Biomedical subjects

M Santos

Publications and source records attributed to M Santos.

At least 73 records · Page 4Linked to original sources
PubMed2000

Regulation of intracellular iron levels in iron-acceptor and iron-donor cells.

In recent years many new genes and proteins were identified with crucial functions in iron metabolism. This gave an explosion of our knowledge and understanding of iron related disorders. Mutations have been found that are responsible for disturbances in iron transport, leading to either iron overload or iron deficiency. For experts in the field, these new findings clarify the sky and open new routes for exploring hitherto hidden fields of research. For the physician, however, iron metabolism may become even more complicated. In this review, we have tried to assemble all new iron related genes into the context of pathophysiology. Important results from animal experiments, mainly derived from knockout mouse models, are included in this review as they often explain the phenotype of human disease.

Animals↗
PubMed2000

Genetic polymorphism of alcohol dehydrogenase in europeans: the ADH2*2 allele decreases the risk for alcoholism and is associated with ADH3*1.

Polymorphism at the ADH2 and ADH3 loci of alcohol dehydrogenase (ADH) has been shown to have an effect on the predisposition to alcoholism in Asian individuals. However, the results are not conclusive for white individuals. We have analyzed the ADH genotype of 876 white individuals from Spain (n = 251), France (n = 160), Germany (n = 184), Sweden (n = 88), and Poland (n = 193). Peripheral blood samples from healthy controls and groups of patients with viral cirrhosis and alcohol-induced cirrhosis, as well as alcoholics with no liver disease, were collected on filter paper. Genotyping of the ADH2 and ADH3 loci was performed using polymerase chain reaction-restriction fragment length polymorphism methods on white cell DNA. In healthy controls, ADH2*2 frequencies ranged from 0% (France) to 5.4% (Spain), whereas ADH3*1 frequencies ranged from 47. 6% (Germany) to 62.5% (Sweden). Statistically significant differences were not found, however, between controls from different countries, nor between patients with alcoholism and/or liver disease. When all individuals were grouped in nonalcoholics (n = 451) and alcoholics (n = 425), ADH2*2 frequency was higher in nonalcoholics (3.8%) than in alcoholics (1.3%) (P =.0016), whereas the ADH3 alleles did not show differences. Linkage disequilibrium was found between ADH2 and ADH3, resulting in an association of the alleles ADH2*2 and ADH3*1, both coding for the most active enzymatic forms. In conclusion, the ADH2*2 allele decreases the risk for alcoholism, whereas the ADH2*2 and ADH3*1 alleles are found to be associated in the European population.

Adult↗
PubMed2000

Toward a physical map of Drosophila buzzatii. Use of randomly amplified polymorphic dna polymorphisms and sequence-tagged site landmarks.

We present a physical map based on RAPD polymorphic fragments and sequence-tagged sites (STSs) for the repleta group species Drosophila buzzatii. One hundred forty-four RAPD markers have been used as probes for in situ hybridization to the polytene chromosomes, and positive results allowing the precise localization of 108 RAPDs were obtained. Of these, 73 behave as effectively unique markers for physical map construction, and in 9 additional cases the probes gave two hybridization signals, each on a different chromosome. Most markers (68%) are located on chromosomes 2 and 4, which partially agree with previous estimates on the distribution of genetic variation over chromosomes. One RAPD maps close to the proximal breakpoint of inversion 2z(3) but is not included within the inverted fragment. However, it was possible to conclude from this RAPD that the distal breakpoint of 2z(3) had previously been wrongly assigned. A total of 39 cytologically mapped RAPDs were converted to STSs and yielded an aggregate sequence of 28,431 bp. Thirty-six RAPDs (25%) did not produce any detectable hybridization signal, and we obtained the DNA sequence from three of them. Further prospects toward obtaining a more developed genetic map than the one currently available for D. buzzatii are discussed.

Amino Acid Sequence↗
PubMed2000

Short-time critical dynamics for the transverse ising model.

We have analyzed the short-time critical behavior for the one-dimensional quantum transverse Ising model through Monte Carlo simulations at zero temperature. We used the scaling relation for the dynamics at the early time stages in order to obtain the static critical exponents (beta,nu) and the dynamical critical exponent z for this model. While the values found for the static exponents are in agreement with the exact ones, here, the dynamical critical exponent is found for a quantum spin model.

Journal Article↗
PubMed2000

Short-time dynamics of a metamagnetic model

We studied a layered metamagnetic Ising model with competing ferromagnetic and antiferromagnetic interactions on a square lattice. The model is formed of ferromagnetic chains coupled by an antiferromagnetic interaction. Using Monte Carlo simulations we have determined the phase diagram of the model, which exhibits a tricritical point. By exploring the short-time scaling dynamics, we have found the dynamic and static critical exponents along the continuous transition line between the antiferromagnetic and paramagnetic phases.

Journal Article↗
PubMed2000

Left circumflex coronary artery-to-left atrium fistulas detected by transesophageal echocardiography in heart transplant recipients.

Coronary fistulas are uncommon after heart transplantation. We report two cases of fistulas from an atrial branch of the circumflex coronary artery to the left atrium after heart transplantation. This has not been previously reported in the literature. They were detected with transesophageal echocardiography, and images are shown for the first time. Transesophageal echocardiography may be useful in the follow-up of heart transplant recipients.

Coronary Vessels↗
PubMed2000

Effect of oxidative stress on the uptake of GABA and glutamate in synaptosomes isolated from diabetic rat brain.

It has been suggested that increased oxidative stress might be involved in the pathophysiology of diabetic complications. In this study, we investigated the effect of diabetes on the susceptibility of synaptosomes to oxidative stress (induced by the oxidizing pair ascorbate/Fe(2+)) and on the uptake of the amino acid neurotransmitters gamma-aminobutyric acid (GABA) and glutamate. We found a lower susceptibility of synaptosomes isolated from Goto-Kakizaki (GK) rats, a model of non-insulin-dependent diabetes mellitus, to lipid peroxidation as compared with synaptosomes isolated from Wistar control rats (6.40+/-1.05 and 12.14+/-1.46 nmol thiobarbituric acid reactive substance/mg protein, respectively). The lower susceptibility of GK rat synaptosomes to membrane lipid peroxidation correlates with an increase in synaptosomal vitamin E levels (835+/-58.04 and 624.26+/-50.26 pmol/mg protein in diabetic and normal rats, respectively). In the absence of ascorbate/Fe(2+), no significant differences were observed between the levels of lipid peroxidation of synaptosomes isolated from diabetic and normal rats. Studies of neurotransmitter uptake show that the [(3)H]glutamate uptake was decreased by about 30% in diabetic GK rats as compared with control Wistar rats, whereas the [(3)H]GABA uptake was not significantly different from controls. Under oxidizing conditions, the glutamate uptake in diabetic rats was unaffected, and a decreased GABA uptake (41.39+/-4.41 and 60.96+/-6.4% of control in GK and Wistar rats, respectively) was observed. We conclude that the increased resistance to oxidative stress in GK rat synaptosomes may be due to the increased vitamin E content and that diabetic state and oxidative stress conditions differentially affected the uptake of the neurotransmitters GABA and glutamate.

Animals↗
PubMed2000

[Genetic analysis and relationship to pathogenicity in Botrytis cinerea].

Botrytis cinerea is a plant-pathogenic fungus that produces the disease known as grey mould in a wide variety of agriculturally important hosts in many countries. Ten strains from different locations collected on different years have been isolated and characterized by several methods (morphological, biochemical, genetical and molecular). Results showed that clear morphological differences exist between strains, and showing a relationship between the presence of sclerotia and pathogenicity. The conidial size and the nuclear number were highly variable between different strains. Pulsed-field gel electrophoresis showed a unique karyotype for each strain, highly polymorphic between strains and with a number of bands ranging from 4 to 8. An efficient transformation system has been achieved through the plasmid pAMPF21, containing the region AMA1 of Aspergillus nidulans. Lastly, from a genomic library the gdhA gene has been cloned. This gene produces an RNAm of 1.7 Kb and complements the deficiency on glutamate dehydrogenase activity of A. nidulans.

English Abstract↗
PubMed1999

Activation of mitogen-activated protein kinase regulates eotaxin-induced eosinophil migration.

Eotaxin is a potent eosinophil chemoattractant that plays an important role in regulating eosinophil tissue levels both in healthy individuals and in diseases associated with significant eosinophil infiltrates, such as the allergic inflammation observed in asthma. Here, we demonstrate that treatment of eosinophils with eotaxin induces the phosphorylation of the mitogen-activated protein kinases (MAPKs) p42 and p44, leading to kinase activation. Blockade of MAPK activation by the MAPK kinase inhibitor PD98059 leads to a dramatic decrease in eotaxin-induced eosinophil rolling in vivo and chemotaxis in vitro. This blockade in the leukocyte migration process is consistent with the observed inhibition of actin polymerization and rearrangement within the eosinophil following treatment with MAPK inhibitor. It is suggested, therefore, that the intrinsic mechanism of eotaxin-induced eosinophil rolling and migration involves activation of the p42/p44 MAPK, possibly through regulation of the cytoskeletal rearrangements necessary for chemotaxis.

Actins↗
PubMed1999

Immunohistochemical evidence of the presence of aromatase P450 in the rat hypophysis.

In order to analyze whether aromatase is present in the hypophysis of adult rats, we have performed an immunohistochemical study in young adult male and female rats. Our study has revealed that the hypophysis of adult rats contains aromatase, although marked differences are found between the sexes. The hypophyses of male rats have cells immunoreactive for the enzyme, 34.40% of these hypophyseal cells showing reaction. By contrast, cells from female rats show very little reaction, only 0.84% of them being reactive. No significant differences in the percentage of immunoreactive cells between one phase and another are observed during the estrous cycle. Our results point to the immunohistochemical expression of aromatase in the hypophysis of adult rats and at the same time suggest that its expression is sex-dependent. The enzyme may therefore be involved in the regulation of adenohypophyseal cytology by androgens.

Amino Acid Sequence↗
PubMed1999

Early diagnosis of subependymal giant cell astrocytoma in children with tuberous sclerosis.

OBJECTIVES: Intraventricular astrocytomas (subependymal giant cell astrocytomas) of tuberous sclerosis have a poor prognosis due to the obstruction of CSF flow. The aim of this study was to determine whether they could be differentiated during childhood and at an early preclinical stage, from subependymal nodules without any growing potential. METHODS: The first two MRIs of all children referred to this neuropaediatric centre between 1987 and 1996 were retrospectively blindly reviewed. RESULTS: Out of 60 patients, 24 disclosed subependymal nodules localised near the foramen of Monro, and eight of the 24 developed astrocytomas. Subependymal nodules were first detectable on MRI from 1 year of age in all cases and the first MRI evidence of growth occurred between 1 and 9 years (mean 4 years). At an early stage, subependymal nodules had different characteristics in patients who developed subependymal giant cell astrocytomas from those who did not. The nodules over 5 mm in diameter that were incompletely calcified and enhanced by gadolinium were at higher risk of growing, particularly in children with a familial history of tuberous sclerosis. To detect the subependymal giant cell astrocytomas earlier in tuberous sclerosis, it is advisible to systematically perform an MRI examination before 2 years of age and to repeat it every year if the patient has risk factors for developing astrocytomas.

Brain Neoplasms↗
PubMed1999

Seroprevalence of human cysticercosis in Maputo, Mozambique.

We carried out a serosurvey for cysticercosis among people visiting the Central Hospital of Maputo, the capital of Mozambique, between January and June 1993. A standardized questionnaire was designed to obtain information on demographic, socioeconomic, environmental, and behavioral characteristics related to the transmission of the infection. Four hundred eighty-nine individuals were tested for anti-cysticercosis antibodies: 222 blood donors and patients from the Department of Orthopedics, 148 patients from the Department of Neurology, and 119 patients from the Department of Psychiatry. The overall positivity rate was 12.1% (59 of 489). Anti-cysticercus antibodies was detected in 14.9% of the blood donors and patients from the Department of Orthopedics, 11.5% of the patients from the Department of Neurology, and 7.6% of the patients from the Department of Psychiatry. Living in poor sanitary conditions seems to be an important factor related to human cysticercosis in Maputo, Mozambique.

Adolescent↗
PubMed1999

[Comparison between penicillin and amoxicillin-clavulanic acid for the treatment of recurrent tonsillopharyngitis in childhood].

Fifty-one children aged 2-14 years with recurrent tonsillopharyngitis, presenting dysphagia, fever and lymphadenitis, with more than two similar episodes in the last three years and showing a beta-hemolytic group A streptococci in the pharyngeal smear, were studied. They underwent random treatment for ten days with phenoxymethylpenicillin (40-60 mg/kg/day) (n = 28) or amoxicillin-clavulanic acid (20-40 mg/kg/day) (n = 23) taken orally three times a day. Clinical and bacteriological tests were carried out at 10 days and 2, 6 and 12 months post-treatment. The clinical and bacteriological results showed the superiority of the amoxicillin-clavulanic acid treatment both in the short term (disappearance of symptoms) and in the long term (decrease in recurrence). These results support the idea that betalactamases produced by the pharyngeal flora play an important role in the failures of penicillin.

Adolescent↗
PubMed1998

Adaptive response of iron absorption to anemia, increased erythropoiesis, iron deficiency, and iron loading in beta2-microglobulin knockout mice.

Recently, a novel gene of the major histocompatibility complex (MHC) class I family, HFE (HLA-H), has been found to be mutated in a large proportion of hereditary hemochromatosis (HH) patients. Further support for a causative role of HFE in this disease comes from the observation that beta2-microglobulin knockout (beta2m-/-) mice, that fail to express MHC class I products, develop iron overload. We have now used this animal model of HH to examine the capacity to adapt iron absorption in response to altered iron metabolism in the absence of beta2m-dependent molecule(s). Mucosal uptake, mucosal transfer and retention of iron were measured in control and beta2m-/- mice with altered iron metabolism. Mucosal uptake of Fe(III), but not of Fe(II), by the mutant mice was significantly higher when compared with B6 control mice. Mucosal transfer in the beta2m-/- mice was higher, independent of the iron form tested. No significant differences were found in iron absorption between control and beta2m-/- mice when anemia was induced either by repetitive bleeding or by hemolysis through phenylhydrazine treatment. However, iron absorption in mice made anemic by dietary deprivation of iron was significantly higher in the mutant mice. Furthermore, the beta2m-/- mice manifested an impaired capacity to downmodulate iron absorption when dietary or parenterally iron-loaded. The expression of the defect in iron absorption in the beta2m-/- mice is quantitative, with iron absorption being excessively high for the size of body iron stores. The higher iron absorption capacity in the beta2m-/- mice may involve the initial step of ferric mucosal uptake and the subsequent step of mucosal transfer of iron to the plasma.

Adaptation, Physiological↗
PubMed1998

Nitric oxide synthase activity and L-arginine metabolism in the retinas from streptozotocin-induced diabetic rats.

1. Nitric oxide synthase (NOS) activity was studied in the retinas from normal rats and in the retinas from two groups of streptozotocin-induced (8 days and 4 months) diabetic rats. In each animal group, the NOS activity was correlated to the concentration of amino acids related to L-arginine metabolism and to L-arginine uptake. 2. Retinas from both groups of streptozotocin-induced diabetes (8 days and 4 months) showed an increased NOS activity compared with the NOS activity in retinas from normal rats. In retinas lysate from normal rats, the NOS activity was most potently inhibited by NO-Arg (1 mM), whereas, in both groups of streptozotocin-induced diabetes, the NOS activity was most potently inhibited by the NOS inhibitor aminoguanidine (0.5 mM). 3. The basal levels of the amino acids related to L-arginine metabolism-namely, L-arginine, L-citrulline, L-ornithine and L-glutamine-in retinas from both groups of rats with streptozotocin-induced diabetes were decreased compared with the amino acid levels in retinas from normal rats. 4. The uptake of L-[3H]arginine in retinas from both groups of rats with streptozotocin-induced diabetes was increased compared with the uptake of of L-[3H]arginine in retinas from normal rats.

Animals↗