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Biomedical subjects

M A Rubio

Publications and source records attributed to M A Rubio.

At least 19 recordsLinked to original sources

Effects of hTERT on metal ion-induced genomic instability.

There is currently a great interest in delayed chromosomal and other damaging effects of low-dose exposure to a variety of pollutants which appear collectively to act through induction of stress-response pathways related to oxidative stress and ageing. These have been studied mostly in the radiation field but evidence is accumulating that the mechanisms can also be triggered by chemicals, especially heavy metals. Humans are exposed to metals, including chromium (Cr) (VI) and vanadium (V) (V), from the environment, industry and surgical implants. Thus, the impact of low-dose stress responses may be larger than expected from individual toxicity projections. In this study, a short (24 h) exposure of human fibroblasts to low doses of Cr (VI) and V (V) caused both acute chromosome damage and genomic instability in the progeny of exposed cells for at least 30 days after exposure. Acutely, Cr (VI) caused chromatid breaks without aneuploidy while V (V) caused aneuploidy without chromatid breaks. The longer-term genomic instability was similar but depended on hTERT positivity. In telomerase-negative hTERT- cells, Cr (VI) and V (V) caused a long lasting and transmissible induction of dicentric chromosomes, nucleoplasmic bridges, micronuclei and aneuploidy. There was also a long term and transmissible reduction of clonogenic survival, with an increased beta-galactosidase staining and apoptosis. This instability was not present in telomerase-positive hTERT+ cells. In contrast, in hTERT+ cells the metals caused a persistent induction of tetraploidy, which was not noted in hTERT- cells. The growth and survival of both metal-exposed hTERT+ and hTERT- cells differed if they were cultured at subconfluent levels or plated out as colonies. Genomic instability is considered to be a driving force towards cancer. This study suggests that the type of genomic instability in human cells may depend critically on whether they are telomerase-positive or -negative and that their sensitivities to metals could depend on whether they are clustered or diffuse.

Apoptosis↗

Mechanisms for dynamic crack branching in brittle elastic solids: strain field kinematics and reflected surface waves.

We report on a numerical simulation study of dynamic fracture in strip-shaped plates in which we implement a fracture criterion that fully respects mode-I symmetry. The crack dynamics is studied as a function of the length of the initial notch. The cracks show accelerated straight motion until branching appears. We show that branching can be triggered by two different mechanisms: namely, the kinematics of the strain field and back-reflected surface waves traveling on the crack lip. We also propose a qualitative explanation for the kinematic branching mechanism in terms of the effects of the lattice discretization on Yoffe's stress field. The kinematic branching mechanism is understood by analyzing the disconnection times of the nodes ahead and aside of the crack tip.

Journal Article↗

Severe hypocalcemia following total thyroidectomy after biliopancreatic diversion.

Patients undergoing malabsoprtive operations for bariatric surgery are prone to disturbances of bone metabolism, but this does not commonly lead to clinical symptoms. We present a morbidly obese patient who had undergone the biliopancreatic diversion of Larrad, and presented clinical symptoms of severe hypocalcemia and tetany after total thyroidectomy. Very high doses of i.v. calcium and calcitriol and 10 days of hospitalization were required to control the symptoms and correct plasma levels. The physiological aspects that contribute to this situation are discussed.

Adult↗

[Implications of fiber in different pathologies].

Three decades ago, the observations of Trowell and Burkitt gave rise to the "fibre theory", in which it was contended that there was a link between the consumption of a diet rich in fibre and non-processed carbohydrates and the level of protection against many of the "first world diseases" such as constipation, diverticulosis, cancer of the colon, diabetes, obesity and cardiovascular disease. Since that time, numerous studies have been presented to analyze the relationship between fibre and disorders of the gastrointestinal tract and other processes with severe health implications. The present revision looks at the experience accumulated over this period regarding the importance of the consumption of fibre for certain phatologies. It not only deals with the epidemiological relationship existing between fibre intake and the development of diseases such as cancer of the colon or cardiovascular disorders but also reviews the interest of fibre a therapeutic agent, in view of the current information available on its different mechanism of action. Thus the possibility of using soluble fibre has taken on renewed interest for the treatment of inflammatory intestinal disease, for control of diarrhoea, in irritable bowel syndrome or no modulate the concentrations of glycaemia or cholesterol. Three is a discussion of the discrepancies found between the consumption of fibre and diverticular disease, the treatment of constipation and the association with obesity and cardiovascular disease. Despite the accumulated evidence on the consumption of fibre, there is currently no consensus as to recommendations on what type of fibre and the optimal amount that should be consumed. A high fibre intake (> 25-30 g/day) based on a variety of food sources (fruit, vegetable, legumes, cereals) is the only way to avoid many of the disorders mentioned. The consumption of a particular type of fibre (soluble or insoluble) is limited to the treatment of certain processes, because its individual relationship with many disorders is still pending determination.

Cardiovascular Diseases↗

Time scaling regimes in aggregation of magnetic dipolar particles: scattering dichroism results.

We report experimental results on the aggregation kinetics in magnetorheological fluids subject to a constant uniaxial magnetic field using the technique of scattering dichroism. We show that the number of aggregated particles displays a long-time power-law dependence with exponents that correspond to two different aggregation regimes. These regimes coincide with 3D and 1D-like aggregation. We also derive the values of both time exponents for the number of aggregated particles.

Journal Article↗

Eating behavior in morbidly obese patients undergoing gastric surgery: differences between obese people with and without psychiatric disorders.

BACKGROUND: This study analyzes eating behavior in a group of morbidly obese patients who have undergone gastric reduction surgery for weight loss, and evaluates whether the existence of psychiatric comorbidity marks significant differences in their eating behavior. METHODS: The study group was composed of 100 morbidly obese patients (85 females, 15 males) who had received surgical treatment for weight reduction (vertical banded gastroplasty). 40 of these patients (40%) met ICD-10 criteria for the diagnosis of psychiatric disorders and were included in the "Psychiatric Obese group" (PO). The other 60 patients (60%) did not show ICD-10 diagnostic criteria and were included in the "Non-Psychiatric Obese group" (NO). Each patients completed the Binge Eating Scale (BES), the Three Factor Eating Questionnaire, the Bulimia Investigatory Test-Edinburgh (BITE), and the Eating Disorder Inventory (EDI). RESULTS: Significant differences were found between the two groups (PO and NO) in the Binge Eating Scale (p < 0.001), Three Factor Eating Questionnaire subscale Disinhibition (p < 0.001), BITE (p < 0.001), Eating Disorder Inventory subscale Perfectionism (p < 0.002), and Global EDI (p < 0.001). Logistic regression analysis showed correlation between PO group and Global EDI (Odds Ratio OR = 1.43) and BITE (OR = 1.16). No significant gender differences were found for eating behavior, clinical diagnosis, age, percentage of weight loss, time after operation, and BMI before surgery. CONCLUSION: Surgically treated morbidly obese patients with a psychiatric disorder (PO) have a more destructured eating pattern (with a predominance of binge eating and disinhibition) than NO.

Adult↗

End processing precedes mitochondrial importation and editing of tRNAs in Leishmania tarentolae.

All mitochondrial tRNAs in Leishmania tarentolae are encoded in the nuclear genome and imported into the mitochondrion from the cytosol. One imported tRNA (tRNA(Trp)) is edited by a C to U modification at the first position of the anticodon. To determine the in vivo substrates for mitochondrial tRNA importation as well as tRNA editing, we examined the subcellular localization and extent of 5'- and 3'-end maturation of tRNA(Trp)(CCA), tRNA(Ile)(UAU), tRNA(Gln)(CUG), tRNA(Lys)(UUU), and tRNA(Val)(CAC). Nuclear, cytosolic, and mitochondrial fractions were obtained with little cross-contamination, as determined by Northern analysis of specific marker RNAs. tRNA(Gln) was mainly cytosolic in localization; tRNA(Ile) and tRNA(Lys) were mainly mitochondrial; and tRNA(Trp) and tRNA(Val) were shared between the two compartments. 5'- and 3'-extended precursors of all five tRNAs were present only in the nuclear fraction, suggesting that the mature tRNAs represent the in vivo substrates for importation into the mitochondrion. Consistent with this model, T7-transcribed mature tRNA(Ile) underwent importation in vitro into isolated mitochondria more efficiently than 5'-extended precursor tRNA(Ile). 5'-Extended precursor tRNA(Trp) was found to be unedited, which is consistent with a mitochondrial localization of this editing reaction. T7-transcribed unedited tRNA(Trp) was imported in vitro more efficiently than edited tRNA(Trp), suggesting the presence of importation determinants in the anticodon.

Animals↗

Selective importation of RNA into isolated mitochondria from Leishmania tarentolae.

All mitochondrial tRNAs in kinetoplastid protozoa are encoded in the nucleus and imported from the cytosol. Incubation of two in vitro-transcribed tRNAs, tRNA(Ile)(UAU) and tRNA(Gln)(CUG), with isolated mitochondria from Leishmania tarentolae, in the absence of any added cytosolic fraction, resulted in a protease-sensitive, ATP-dependent importation, as measured by nuclease protection. Evidence that nuclease protection represents importation was obtained by the finding that Bacillus subtilis pre-tRNA(Asp) was protected from nuclease digestion and was also cleaved by an intramitochondrial RNase P-like activity to produce the mature tRNA. The presence of a membrane potential is not required for in vitro importation. A variety of small synthetic RNAs were also found to be efficiently imported in vitro. The data suggest that there is a structural requirement for importation of RNAs greater than approximately 17 nt, and that smaller RNAs are apparently nonspecifically imported. The signals for importation of folded RNAs have not been determined, but the specificity of the process was illustrated by the higher saturation level of importation of the mainly mitochondria-localized tRNA(Ile) as compared to the level of importation of the mainly cytosol-localized tRNA(Gln). Furthermore, exchanging the D-arm between the tRNA(Ile) and the tRNA(Gln) resulted in a reversal of the in vitro importation behavior and this could also be interpreted in terms of tertiary structure specificity.

Adenosine Triphosphate↗

C to U editing of the anticodon of imported mitochondrial tRNA(Trp) allows decoding of the UGA stop codon in Leishmania tarentolae.

All mitochondrial tRNAs in kinetoplastid protists are encoded in the nucleus and imported into the organelle. The tRNA(Trp)(CCA) can decode the standard UGG tryptophan codon but can not decode the mitochondrial UGA tryptophan codon. We show that the mitochondrial tRNA(Trp) undergoes a specific C to U nucleotide modification in the first position of the anticodon, which allows decoding of mitochondrial UGA codons as tryptophan. Functional evidence for the absence of a UGA suppressor tRNA in the cytosol, using a reporter gene, was also obtained, which is consistent with a mitochondrial localization of this editing event. Leishmania cells have dealt with the problem of a lack of expression within the organelle of this non-universal tRNA by compartmentalizing an editing activity that modifies the anticodon of the imported tRNA.

Animals↗

[Lipid profile of the Spanish population: the DRECE (diet and risk of cardiovascular disease in Spain) study. DRECE study group].

BACKGROUND: In Spain the mortality rate due to cardiovascular disease (CVD) is relatively low compared to that of other developed countries. Until now few epidemiological studies have been performed among the global Spanish population to evaluate a relation between CVD risk factors and the lipid profile that could justify our privileged situation. For, this reason, the DRECE study was designed to know the situation at present in Spain respect to the risk of suffering from CVD in particular, the lipid profile. POPULATION AND METHODS: This study included 4,787 subjects (2,324 males and 2,463 females) with an age ranging from 5-60 years, representative of the total Spanish population with these characteristics during the period from 1992 to 1994. Medical history was made for all participants, who also underwent a physical examination. The following parameters were determined: total cholesterol (TC), triglycerides, high-density lipoproteins cholesterol HDLc, cholesterol transported by low-density lipoproteins, LDLc (estimated by the Friedewald's formula), apolipoprotein AI and apoliprotein B (immunoturbidimetry). RESULTS: The results obtained and expressed in mean (SD) show that, although the population has total cholesterol concentrations (190.1 [42.4] and 192.8 [44.8] mg/dl for females and males, respectively) and LDLc (113.9 [37.9] and 117.5 [38.1] mg/dl for females and males, respectively) with values as high as those found in developed countries, the HDLc concentrations (58.6 [13.2] and 51.5 [13.4] mg/dl for women and men, respectively) are also increased and this could be the reason why the mortality rate in Spain caused by CVD is lower than in other countries. CONCLUSIONS: The finding of high HDLc levels and their antiatherogenic role could justify that, at best in part, the rate mortality in Spain is lower than in other developed countries.

Adolescent↗

The pur7 gene from the puromycin biosynthetic pur cluster of Streptomyces alboniger encodes a nudix hydrolase.

Pur7 is the product of a gene from the puromycin biosynthetic pur cluster of Streptomyces alboniger. It was expressed in Escherichia coli as a recombinant protein fused to a His tag and then was highly purified through a Ni(2+) column. It showed a 3'-amino-3'-dATP pyrophosphohydrolase (nudix) activity which produced 3'-amino-3'-dAMP and pyrophosphate. This is consistent with the presence of a nudix box in its amino acid sequence. As observed with other nudix hydrolases, Pur7 has an alkaline pH optimum and a requirement for Mg(2+). Among a large variety of other nucleotides tested, only 3'-amino-3'-dTTP was a Pur7 substrate, although at lower reaction rates than 3'-amino-3'-dATP. These findings suggest that Pur7 has a high specificity for the 3' amino group at the ribofuranoside moiety of these two substrates. The K(m) and V(max) values for these dATP and dTTP derivatives were 120 microM and 17 microM/min and 3.45 mM and 12.5 microM/min, respectively. Since it is well known that 3'-amino-3'-dATP is a strong inhibitor of DNA-dependent RNA polymerase, whereas 3'-amino-3'-dAMP is not, Pur7 appears to be similar to other nudix enzymes in terms of being a housecleaning agent that permits puromycin biosynthesis to proceed through nontoxic intermediates. Finally, the identification of this activity has allowed a revision of the previously proposed puromycin biosynthetic pathway.

Acetyltransferases↗

The Pur10 protein encoded in the gene cluster for puromycin biosynthesis of Streptomyces alboniger is an NAD-dependent ATP dehydrogenase.

The pur10 gene of the puromycin (pur) cluster of Streptomyces alboniger is essential for the biosynthesis of this antibiotic. Highly purified Pur10 protein, obtained in Escherichia coli as a recombinant protein fused to a histidine tail, had an NAD-dependent ATP dehydrogenase activity. The Km and Vmax values for ATP were 0.49 mM and 14.5 nmol/min and for NAD 0.53 mM and 15.2 nmol/min, respectively. The ATP-derived product of the reaction apparently decomposed producing a triphosphorylated compound plus an adenine derivative. These and previous results suggested that Pur10 carries out the first step of the puromycin biosynthetic pathway, namely, conversion of ATP into 3'-keto-3'-deoxyATP.

Adenosine Triphosphate↗

[Surgery of mechanical complications of acute myocardial infarct].

Reviewed are the current surgical methods for the treatment of mechanical complications after an acute myocardial infarction, specially the subacute ventricular rupture, the most frequent complication, and in which we have the greatest experience in the world. Mechanical complications constitute the second cause of death after myocardial infarction, following pump failure. The most frequent mechanical complication is ventricular rupture, which is the cause of death in 26% of the cases of acute myocardial infarction. The setting of solid diagnostic tools, with the association of echocardiographic and hemodynamic criteria, has permitted the identification of a large number of patients with subacute ventricular rupture before death, and has allowed them to be treated surgically. The surgical techniques have evolved to more conservative methods and, nowadays, nearly all the patients can be operated on without extracorporeal circulation and using sutureless techniques. The results is greater surgical survival with satisfactory functional status at follow up. The incidence of septal and papillary muscle rupture is considerably less frequent, but of great interest. The surgical results have been improved on the basis of early diagnosis, aggressive surgical attitude, and better reparative and myocardial protection techniques.

Heart Rupture, Post-Infarction↗

Comparative analysis of ribonuclease P RNA using gene sequences from natural microbial populations reveals tertiary structural elements.

PCR amplification of template DNAs extracted from mixed, naturally occurring microbial populations, using oligonucleotide primers complementary to highly conserved sequences, was used to obtain a large collection of diverse RNase P RNA-encoding genes. An alignment of these sequences was used in a comparative analysis of RNase P RNA secondary and tertiary structure. The new sequences confirm the secondary structure model based on sequences from cultivated organisms (with minor alterations in helices P12 and P18), providing additional support for nearly every base pair. Analysis of sequence covariation using the entire RNase P RNA data set reveals elements of tertiary structure in the RNA; the third nucleotides (underlined) of the GNRA tetraloops L14 and L18 are seen to interact with adjacent Watson-Crick base pairs in helix P8, forming A:G/C or G:A/U base triples. These experiments demonstrate one way in which the enormous diversity of natural microbial populations can be used to elucidate molecular structure through comparative analysis.

Bacteria↗

Sod and catalase inactivation by singlet oxygen and peroxyl radicals.

Both superoxide dismutase and catalase are readily deactivated by singlet oxygen and by the radicals produced in the pyrolysis of 2,2'-azo-bis-(2-amidinpropano) under aerobic conditions. The rate constant for the loss of enzymatic activity induced by singlet oxygen are 3.9 x 10(7) and 2.5 x 10(7) M-1 sec-1 for SOD and catalase, respectively. The similarity between these values implies that in systems where SOD and catalase are exposed to similar singlet oxygen concentrations, it can be expected a parallel inactivation of both enzymes. The inactivation of both enzymes by the radicals produced by 2,2'-azo-bis-(2-amidinopropane) pyrolysis under aerobic conditions follows a first-order kinetics at low enzyme concentrations and a zero-order kinetics at higher concentrations. Although at low enzymatic concentrations the rate of inactivation of both enzymes is similar, this results from a compensation of effects because there are wide differences in the reactivity of both enzymes towards peroxyalkyl radicals. Catalase is considerably more reactive, but a large number of protein/radical reactive interactions are needed to inactivate one enzyme. On the other hand, the reactivity of SOD is smaller, but the average enzyme activity decreases by nearly 20% in each SOD/radical reactive interaction.

Animals↗

[Hashimoto toxicosis: diagnostic criteria and a 10-year follow up].

An study was carried out of the association of Basedow disease (B) and Hashimoto toxicosis (H), the response to the usual therapeutic regimens and prognostic factors for the clinical course. Seventy-one patients with the diagnosis of autoimmune hyperthyroidism were included. Sixty-one of them were prospectively followed for 8.4 +/- 2.2 years (range: 5-10 years). All patients were treated following the same criteria with antithyroid drugs and aggressive therapy (radioiodine or surgery). Two groups were differentiated: group H (62%), with titers of antimicrosomal antibodies (AMSA) > or = 1/6,400 and a positive perchlorate discharge test (PDT), and group B, with AMSA titers < 1/6,400 and negative PDT. During follow-up a three-fold number of relapses was observed in group H compared with group B, a higher frequency towards spontaneous hypothyroidism in the evolution (23% in H versus 0% in B), and higher requirements of radioiodine in H than in B. In our experience, H makes up and important percentage of autoimmune hyperthyroidism (62%) with a clinical course characterized by a higher number of relapses, higher requirements of radioiodine and a higher rate towards spontaneous hypothyroidism.

Adolescent↗

Granulocyte-macrophage colony-stimulating factor, phorbol ester, and sodium butyrate induce the CD11c integrin gene promoter activity during myeloid cell differentiation.

To analyze the activity of the CD11c promoter during myeloid differentiation without the limitations of transient expression systems, we have stably transfected the myeloid U937 cell line with the pCD11C361-Luc plasmid, in which the expression of the firefly luciferase cDNA is driven by the CD11c promoter region -361/+43, previously shown to confer myeloid specificity to reporter genes. The stable transfectants (U937-C361) retained the ability to differentiate in response to phorbol-ester (PMA), sodium butyrate (SB), granulocyte-macrophage colony-stimulating factor (GM-CSF), and other differentiating agents. U937-C361 differentiation correlated with increased cellular luciferase levels, showing the inducibility of the CD11c promoter during myeloid differentiation and establishing the U937-C361 cells as a suitable system for studying the myeloid differentiation-inducing capacity of cytokines, growth, factors, and other biological response modifiers. Unexpectedly, the inducibility of the CD11c gene promoter showed distinct kinetics and magnitude on the PMA-, SB-, GM-CSF-triggered differentiation. Moreover, SB synergized with either PMA or GM-CSF in enhancing both the CD11c promoter activity and the cell surface expression of p150,95 on differentiating U937 cells. Furthermore, we showed the existence of a c-Myb-binding site at -85, the importance of the -99/-61 region in the CD11c promoter inducibility during PMA- or SB-triggered differentiation, and the dependency of the GM-CSF and PMA responsiveness of the CD11c promoter on an intact AP-1-binding site located at -60. These results, together with the lack of functional effect of mutations disrupting the Sp1-and Myb-binding sites within the proximal region of the CD11c promoter, indicate that the myeloid differentiation pathways indicated by SB and phorbol esters (or GM-CSF) activate a distinct set of transcription factors and show that the myeloid differentiation-inducibility of the CD11c gene maps to the -99/-53 proximal region of the promoter.

Base Sequence↗