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Biomedical subjects

M Alonso

Publications and source records attributed to M Alonso.

At least 55 records · Page 3Linked to original sources

Effect of induced triploidy on fin regeneration of juvenile rainbow trout, Oncorhynchus mykiss.

Triploidy was induced in the rainbow trout in order to evaluate whether the altered numbers and sizes of triploid cells could modify fin regeneration. Amputation of one lobe of the tail fin of diploid and triploid juveniles resulted in regeneration for experimentals and controls. Nevertheless, both rate and frequency of regeneration in triploids were significantly increased as compared with diploids, a fact that can be attributed to the increased nuclear and cellular volume in a wide range of tissues, whereas the cell numbers were reduced. These data suggest that a great deal of interesting and important research could be done using triploid animals as experimental models for studying the regeneration of appendages.

Animals↗

Phosphorylated cAMP response element-binding protein as a molecular marker of memory processing in rat hippocampus: effect of novelty.

From mollusks to mammals the activation of cAMP response element-binding protein (CREB) appears to be an important step in the formation of long-term memory (LTM). Here we show that a 5 min exposure to a novel environment (open field) 1 hr after acquisition of a one-trial inhibitory avoidance training hinders both the formation of LTM for the avoidance task and the increase in the phosphorylation state of hippocampal Ser 133 CREB [phosphorylated CREB (pCREB)] associated with the avoidance training. To determine whether this LTM deficit is attributable to the reduced pCREB level, rats were bilaterally cannulated to deliver Sp-adenosine 3', 5'-cyclic monophosphothioate (Sp-cAMPS), an activator of PKA. Infusion of Sp-Adenosine 3',5'-cyclic monophosphothioate Sp-cAMPS to CA1 region increased hippocampal pCREB levels and restored normal LTM of avoidance learning in rats exposed to novelty. Moreover, a 5 min exposure to the open field 10 min before the avoidance training interferes with the amnesic effect of a second 5 min exposure to the open field 1 hr after avoidance training and restores the hippocampal levels of pCREB. In contrast, the avoidance training-associated activation of extracellular signal-regulated kinases (p42 and p44 mitogen-activated protein kinases) in the hippocampus is not altered by novelty. Together, these findings suggest that novelty regulates LTM formation by modulating the phosphorylation state of CREB in the hippocampus.

Amnesia, Retrograde↗

Simple Model of Aerosol Particle Formation by the Evaporation-Condensation Method.

From an engineering point of view the present authors have proposed the simple model of a homogeneous nucleation relationship in the liquid phase that can predict the number concentration of nucleated particles in various operating conditions. Experiments of liquid-phase nucleation in which the precursor monomers were generated by several methods have successfully confirmed the predictions of the model. In the present paper, our previous model of homogeneous nucleation is extended to the case in which the precursor monomers are generated in a gas-phase system. First, a relationship between number concentration and mean volume diameter of nucleated aerosol particles and operating conditions is obtained considering the free molecular regime around the critical nuclei, which is the main difference with the liquid phase. Second, the validity of the relation lies in experimental use of dioctyl sebacate particles generated by evaporation-condensation. As a result, the predictions are in excellent agreement with the experimental results after considering substantial losses of monomers and particles to the walls of the experimental system because in the gasphase the diffusion velocity and the critical supersaturation ratio of monomer are higher than those in the liquid phase. Copyright 2000 Academic Press.

Journal Article↗

Structural comparison of dimeric Eg5, Neurospora kinesin (Nkin) and Ncd head-Nkin neck chimera with conventional kinesin.

Cryo-electron microscopy and 3D image reconstruction of microtubules saturated with kinesin dimers has shown one head bound to tubulin, the other free. The free head of rat kinesin sits on the top right of the bound head (with the microtubule oriented plus-end upwards) in the presence of 5'-adenylylimido-diphosphate (AMPPNP) and on the top left in nucleotide-free solutions. To understand the relevance of this movement, we investigated other dimeric plus-end-directed motors: Neurospora kinesin (Nkin); Eg5, a slow non-processive kinesin; and a chimera of Ncd heads attached to Nkin necks. In the AMPPNP (ATP-like) state, all dimers have the free head to the top right. In the absence of nucleotide, the free head of an Nkin dimer appears to occupy alternative positions to either side of the bound head. Despite having the Nkin neck, the free head of the chimera was only seen to the top right of the bound head. Eg5 also has the free head mostly to the top right. We suggest that processive movement may require kinesins to move their heads in alternative ways.

Adenosine Triphosphate↗

Differential scanning calorimetry study of the hydrophobic hydration of the elastin-based polypentapeptide, poly(VPGVG), from deficiency to excess of water.

The polypentapeptide of elastin, poly(VPGVG), has become an interesting model polypeptide in understanding the mechanism of protein folding and assembly. Due to its simple amino acid composition and the predominance of apolar side chains, this polymer shows strong hydrophobic-hydration phenomena. This paper explores, by calorimetric methods, the nature and structure of the clathrate-like arrangements that take place, surrounding the apolar side chains of the polymer. The performance of these methods, especially differential scanning calorimetry, has a well-gained reputation. In this work, the development of the clathrate-like structures around this model polymer has been followed from water deficiency to water-excess states. Two main conclusions have been obtained from the data obtained. First, there is an upper limit of about 170 water molecules per pentamer as the number of water molecules required to form all the possible clathrate-like structures. Second, these structures exist as an inhomogeneous population with energies spreading in a significantly broad range, which is likely related to differences in geometrical parameters (bond lengths and angles) of the clathrate structure.

Amino Acid Sequence↗

Poliovirus induces apoptosis in the human U937 promonocytic cell line.

The human promonocytic U937 cell line, which is moderately susceptible to poliovirus infection, has been used to investigate the induction of apoptosis by this virus. Infection of U937 cells with poliovirus induces morphological changes typical of apoptosis. Poliovirus-resistant U937 cells (PRU) have been isolated that are resistant to apoptosis induced by poliovirus, but that undergo apoptosis after treatment with TNF plus cycloheximide. Despite the fact that poliovirus triggers nitric oxide production in U937 cells, the inhibitor of inducible nitric oxide (NO) synthase, N(omega)-monomethyl-l-arginine, did not hinder apoptosis after infection, suggesting that NO does not play a direct role in this process. Finally, poliovirus infection of U937 cells led to the cleavage of pro-caspase-3 and poly(ADP-ribose)polymerase, indicating the activation of the CPP32 ICE-like cysteine protease in the induction of apoptosis. Our findings suggest that cellular death takes place in U937 cells productively infected by poliovirus as a result of apoptosis and involves caspase activation.

Apoptosis↗

[Orthostatic hypotension in the aged and its association with antihypertensive treatment].

BACKGROUND: To assess the prevalence of orthostatic hypotension (OH) in an elderly population and to evaluate the influence of hypertension control and of the type of antihypertensive drug used. METHODS: 2,700 elderly patients (> 65 years) from the EPICARDIAN study were included. Blood pressure (BP) was measured twice with the patient seated and once again 1 to 3 minutes afterwards with the patient standing. Hypertension is defined as BP > or = 140/90 mmHg or if the patient received antihypertensive treatment. Orthostatic hypotension was defined as a fall of SBP > or = 20 mmHg and/or DBP > or = 10 mmHg 1 to 3 minutes after the postural change. RESULTS: 71.6% of the patients were classified as hypertensive and 57.1% were receiving pharmacological treatment. The overall prevalence of OH was 6.8% among hypertensive patients, 8.1% and 3.4% in normotensives patients (p < 0.05). No significant difference was found in the prevalence of OH between those receiving (7.7%) or not (8.6%) antihypertensive medication. No association was found either between the prevalence of OH and the type or number of antihypertensive drugs used. 17.6% of the patients reached hypertension optimal control (SBP < 140 and DBP < 90 mmHg), the prevalence of OH in these patients was 5.3%, among the uncontrolled the prevalence was 8.9% (p < 0.05). The adjusted OR was 1.91 (1.1-3.3) for the prevalence of OH in the uncontrolled patients versus the controlled. CONCLUSIONS: The prevalence of OH in the elderly is not very high, being greater among hypertensive than normotensive patients. No association was found between the prevalence of OH and the number of drugs received. Reaching hypertension control reduces the prevalence of OH.

Adrenergic alpha-Antagonists↗

Precipitation of Zinc Sulfide Particles from Homogeneous Solutions.

Zinc sulfide particles were homogeneously precipitated by thermal decomposition of thioacetamide in acidic aqueous solutions in a one-step process. The influence of the operating conditions (initial concentration of zinc ion and TAA) on the nucleation time and number concentration of the generated particles was investigated. The experimental results show that the model of homogeneous nucleation previously developed and successfully tested for silver particle generation by a chemical reduction method can also be applied to the formation of zinc sulfide particles by homogeneous precipitation. Furthermore, in the particle formation method in which the nucleation time t* can be measured, the particle number concentration n* can be predicted by the simple relation n*=1/(4pir*Dt*) (r* is the critical nucleus radius, and D the monomer diffusion coefficient). Thus the particle number concentration can be easily predicted even if the rate expression and the critical supersaturation concentration are unknown. Copyright 2000 Academic Press.

Journal Article↗

A Model for Simultaneous Homogeneous and Heterogeneous Nucleation in the Case of Slow Reaction Rate.

Our previous model for simultaneous homogeneous and heterogeneous nucleation, which was successfully tested for silver particle generation by a chemical reduction method, is extended to the case of slow reaction rate. Nucleation in a system containing seed particles in the case where the reaction rate is slow occurs according to the following rule: homogeneous nucleation is predominant when n(p)/n(0)(*),>1 (n(p) is the seed number concentration, and n(0)(*) the number concentration of homogeneously nucleated particles without seed particles), and heterogeneous nucleation is predominant when n(p)/n(0)(*)<1. This theoretical prediction is in good agreement with the experimental results obtained for zinc sulfide particles generated by homogeneous precipitation. Copyright 2000 Academic Press.

Journal Article↗

High-efficiency passive elution of bacterial lipopolysaccharides from polyacrylamide gels.

We recently described a method for recovering polyacrylamide-gel-separated bacterial lipopolysaccharides (LPS) based on the sensitive on-gel LPS detection (1-10 ng/band) with zinc-imidazole followed by passive elution from 32 microm average size gel microparticles into water. With this procedure, the recovery of rough- or semismooth-type LPS after 3 h elution is about 70-80%, while that of smooth LPS is only about 10%. Here we evaluated whether a simple replacement of water with other eluents would enhance the passive diffusion of LPS. We found that solutions of the detergents sodium dodecyl sulfate (SDS), sodium deoxycholate (DOC) and Triton X-100, or mixtures of the organic solvents acetonitrile and triethylamine and water, increased the recovery of a smooth LPS band from Vibrio cholerae O1 in a concentration-dependent manner. Furthermore, a quantitative recovery of rough or smooth LPS from V. cholerae O1, Escherichia coli O111:B4, E. coli K-235, or Serratia marcescens was feasible in 1% SDS or DOC after 3 h or in 5% triethylamine after only 2 min. A simple dilution of SDS or DOC or evaporation of triethylamine rendered the eluted LPS preparations compatible with biochemical activity determination, as tested by Limulus amebocyte lysate assay. Thus, this improved micropurification method may be a suitable interface between analytical gel electrophoresis and further characterization or use of LPS.

Detergents↗

Retinoid X receptor mRNA expression in human pituitary gland.

Retinoic acid is involved in important physiological processes such as the regulation of growth and differentiation of several tissues, including the pituitary gland. These biological effects are mediated by their binding to two specific intracellular receptors termed retinoic acid and retinoid X receptors, RARs, RXR, respectively). RAR or RXR mRNA expression has been demonstrated in several tissues, but little information is available about its presence in the human pituitary gland. In this report, we demonstrate alphaRXR mRNA expression using the reverse transcription coupled to polymerase chain reaction (RT-PCR) in the human pituitary gland. These results suggest the possibility that RXR may regulate the human pituitary gene expression and hormone secretion.

Adult↗

Nonoperative management of newborn splenic injury: a case report.

Traumatic injury of the spleen is rare in newborns. Nonoperative management of pediatric splenic injuries is now recognized as the treatment of choice, but there is scant experience with the problem in neonates. The authors report their experience with a neonatal splenic rupture, managed nonoperatively.

Birth Injuries↗

Incidence of p14ARF gene deletion in high-grade adult and pediatric astrocytomas.

The INK4a-ARF locus encodes 2 separate proteins through differential splicing of alternative first exons to produce p16INK4a (exon 1alpha) and p14ARF (exon 1beta) products in human cells. The p16INK4a protein inhibits the cyclin D-dependent kinases (CDK) that control the phosphorylation of the Rb protein and cell proliferation. The p14ARF gene product can complex with and sequester the MDM2 protein within the nucleus, thus modulating the activity of the p53 protein. Loss of p16INK4a expression would disrupt the retinoblastoma (Rb)/p16INK4a/cyclin D-dependent kinase (CDK4) pathway, whereas loss of p14ARF expression would inactivate both the Rb and p53/ MDM2/p14ARF pathways through MDM2, which can complex with either Rb or p53. Loss of the p16INK4a gene on 9p21 has been documented in a wide range of human tumors, including one third of glioblastomas. However, in tumors showing homozygous loss of exon 2 of the p16INK4a gene, loss of exon 1beta of the p14ARF gene has not been established. In this study, we have assessed deletion of the p14ARF gene in 29 pediatric and 107 adult high-grade astrocytomas and 9 glioma cell lines, using multiplex PCR analysis for exon 1beta. We found homozygous deletions for exon 1alpha and exon 1beta in 3 of 29 (10%) of the pediatric cases (2 grade III, 1 grade IV), 25 of 107 (23%) of the adult cases (6 grade III and 19 grade IV), and 8 of 9 (89%) of the glioma cell lines. Therefore, loss of the INK4a-ARF locus in high-grade astrocytomas may contribute to the highly malignant behavior and treatment resistance of these tumors through elimination of multiple checkpoint cell cycle control proteins.

Adult↗

Participation of hippocampal metabotropic glutamate receptors, protein kinase A and mitogen-activated protein kinases in memory retrieval.

The ability to recall past events is a major determinant of survival strategies in all species and is of paramount importance in determining our uniqueness as individuals. In contrast to memory formation, the information about the molecular mechanisms of memory retrieval is surprisingly scarce and fragmentary. Here we show that pretest inhibition of the specific upstream activator of mitogen-activated protein kinase kinase, or of protein kinase A in the hippocampus, blocked retrieval of long-term memory for an inhibitory avoidance task, a hippocampal-dependent learning task. An activator of protein kinase A enhanced retrieval. Mitogen-activated protein kinase activation increased in the hippocampus during retrieval, while protein kinase A activity remained unchanged. Pretest intrahippocampal blockade of metabotropic glutamate receptors or alpha-amino-3-hydroxy-5-methyl-4-isoxazolone propionic acid/kainate receptors, but not N-methyl-D-aspartate receptors or calcium/calmodulin dependent-protein kinase II, impaired retrieval. Thus, recall of inhibitory avoidance activates mitogen-activated protein kinase, which is necessary, along with metabotropic glutamate receptors, alpha-amino-3-hydroxy-5-methyl-4-isoxazolone propionic acid/kainate receptors, and protein kinase A, for long-term memory expression. Our results indicate that memory formation and retrieval may share some molecular mechanisms in the hippocampus.

Animals↗

Hepatocyte transplantation. Advancing biology and treating children.

Key advances over the past three decades have allowed the evolution of hepatocyte transplantation from its use as an experimental tool to study liver cell biology to the initial application as a potential treatment modality for patients with liver disease. Although little is known about the cellular and molecular mechanisms regulating the fate of transplanted cells, studies in animal models of liver disease clearly suggest that transplanted hepatocytes have the potential to repopulate diseased livers and correct metabolic defects. Based on these experiments, human hepatocytes have been used in the treatment of children and adults with metabolic disease and liver failure. In initial trials, the improved clinical course following hepatocyte transplantation points to a potential role of the technique as an adjunct to liver transplantation.

Adolescent↗

Seroprevalence of HIV and HTLV in a representative sample of the Spanish population.

HIV and HTLV seroprevalence was determined by means of unlinked anonymous testing of 2144 sera, originally obtained from primary care patients by representative sampling of the Spanish population aged 15-39 years in 1996. HIV-1 seroprevalence was 4.3 per 1000 population in the 15-39 years age group [95% confidence interval (CI), 1.5-10.7] and 5.6 per 1000 (95% CI, 1.8-15.3) in the 20-39 years age group. Seroprevalence proved higher in males and urban residents. No antibodies to HIV-2 and HTLV-I were detected in any of the sera studied. However, presence of antibodies to HTLV-II was confirmed in one serum sample, while HTLV seroreactivity, though detected in another, could not be typed. The two HTLV-positive results equated to a seroprevalence of 1.9 per 1000 in the 20-39 years age group (95% CI, 0.3-8.6). HIV-I seroprevalence was consistent with previous estimates yielded by back-calculation. The level of HTLV seroprevalence found suggests endemicity.

Adolescent↗

Estimating the burden of disease in one Swiss canton: what do disability adjusted life years (DALY) tell us?

BACKGROUND: Examining life expectancy and general mortality rates, the health of the population of Geneva can be described as one of the best in the world. However, in some areas Geneva fares worse than the rest of Switzerland or Europe. To re-appraise the current health priorities of the Genevan population, we analysed the relative importance of specific diseases and injuries calculating DALYs. METHODS: We followed the procedures developed for the Global Burden of Disease (GBD) study to ensure comparability. Some adaptations were made for mortality coding. Disability was estimated based on data for countries classified as Established Market Economies (EME) in the GBD study. RESULTS: Non-communicable diseases accounted for 79% of the disability adjusted life years (DALY), injuries represented 12%, and communicable diseases and other disorders 9%. Ischaemic heart disease was the largest single contributor to DALY, followed by unipolar major depression. Neuropsychiatric disorders and mental health accounted for more than 23% of DALY. CONCLUSIONS: Some of the most important problems identified-depression, osteoarthritis and alcohol abuse-would have been overlooked in an analysis based solely on mortality data. The most striking finding is the importance of mental health problems. The main limitation is the lack of morbidity data for Geneva.

Adolescent↗