Biomedical subjects

M Alonso

Publications and source records attributed to M Alonso.

At least 37 records · Page 2Linked to original sources

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

[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↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

Relationships between bilateral asymmetry and tonic immobility reaction or heterophil to lymphocyte ratio in five breeds of chickens.

Bilateral asymmetry of several morphological traits, tonic immobility reaction, and leucocyte ratio were studied in hens and cocks from four Spanish breeds of chickens (Castellana, Buff Prat, Red Villafranquina, and Barred Red Vasca) and an F2 cross between Castellana and Buff Prat (C x BP - F2). Any two or all three types of bilateral asymmetry (fluctuating asymmetry, directional asymmetry, and antisymmetry) occurred together for the same trait in the different breeds. There was a significant difference in relative asymmetry among breeds (P < 0.05) for feather and spur lengths in males, and considerable negative heterosis for relative asymmetry of leg and wing lengths in C x BP - F2 males (-38 and -12%, respectively). The degree of relative asymmetry varied among traits and was between 3 and 12 times greater for spur length in males and for wing bay area in Villafranquina males. There were significant differences among breeds (P < 0.05) for tonic immobility duration. The duration of tonic immobility was positively associated with the mean relative asymmetry of all traits in females from the Villafranquina breed (r = 0.32; P < 0.05), but this finding was not consistent across the different breeds. No significant difference was found among breeds in terms of heterophil to lymphocyte ratio. Although there was no significant association between mean relative asymmetry of all traits and heterophil to lymphocyte ratio, males from the Villafranquina breed had a positive and significant relationship between relative asymmetry for wing bay area and leucocyte ratio (r = 0.34; P < 0.05). These results suggest that relative asymmetry measures did not provide a general tool to assess fear or stress susceptibility.

Animals↗

PubMed2000

Preferential inactivation of the p53 tumor suppressor pathway and lack of EGFR amplification distinguish de novo high grade pediatric astrocytomas from de novo adult astrocytomas.

Classification of high grade astrocytomas of children into genetic subtypes similar to the adult remains to be defined. Here we report an extensive characterization of 29 high grade pediatric astrocytomas, 7 WHO grade III and 22 WHO grade IV, for genetic alterations frequently observed in high grade adult astrocytomas occurring in either the p53/MDM2/p14ARF or Rb/CDK4/p16INK4a tumor suppressor pathways. In addition, we have assessed the contribution of EGFR overexpression and amplification and LOH for chromosome 10, two genetic alterations commonly associated with the development of de novo adult glioblastoma for their roles in the development of de novo astrocytomas of childhood. Our results suggest two major differences in the genetic pathway(s) leading to the formation of de novo high grade astrocytomas in children compared with those of the adult. Our findings show preferential inactivation of the p53 tumor suppressor pathway in >95% of pediatric astrocytomas versus inactivation of the Rb tumor suppressor pathway in <25% of the same tumors. In addition, de novo high grade pediatric astrocytomas lack amplification of the EGFR gene compared with EGFR amplification in one-third of adult glioblastomas. Since drug treatments and gene therapy strategies exploit specific genetic alterations in tumor cells, our findings have important implications for the future development of treatments for high grade pediatric astrocytomas.

Adolescent↗

PubMed2000

Setting health priorities in a Swiss canton: what do different methods tell us?

STUDY OBJECTIVE: Despite excellent mortality indicators, there is clear evidence that the health status of the population of Geneva could be improved if more attention and resources were devoted to prevention strategies. To identify a set of robust health priorities an original approach was used triangulating results between three methods. METHODS: The study calculated potential years of life lost, disability adjusted years of life lost, and conducted a Delphi survey to gather the opinion of health professionals and the general public. MAIN RESULTS: Several health conditions were unanimously selected by all three methods as top priorities: cardiovascular diseases, AIDS, respiratory cancer, breast cancer for women, suicide and traffic accidents. In addition, two determinants-alcohol abuse and tobacco abuse-for which a clear conceptual link could be established between all methods were chosen. Connections between priorities identified through the DALY and the Delphi method lead to further inclusion of chronic back pain and depression. Some issues solely identified through the Delphi survey were included as they were consistently considered important by professionals and the lay public alike-violence in the family, unemployment, social exclusion. CONCLUSIONS: These results indicate that health priorities, and by extension health care priorities, would benefit from using a mix of quantitative and qualitative research methods. The triangulation of results allows for a broader perspective and makes results more acceptable.

Attitude↗

PubMed2000

High prevalence of the polycystic ovary syndrome and hirsutism in women with type 1 diabetes mellitus.

The current recommendation for strict metabolic control of type 1 diabetes mellitus requires the administration of supraphysiological doses of insulin, which might result in insulin-mediated stimulation of androgen synthesis, as occurs in insulin-resistant states. At present, the prevalence of hyperandrogenic disorders in women with type 1 diabetes mellitus is unknown. Eighty-five women with type 1 diabetes mellitus were evaluated for symptoms and signs of hyperandrogenism. In 68 of the patients, several serum androgen and hormone concentrations were measured. The polycystic ovary syndrome (PCOS) was defined by the presence of menstrual dysfunction, together with clinical and/or biochemical evidence of hyperandrogenism, and exclusion of other etiologies. Eighteen healthy women, menstruating regularly, served as controls for the androgenic profiles. Thirty-three patients (38.8%) presented hyperandrogenic disorders (16 had PCOS, and 17 had hirsutism without menstrual dysfunction). Type 1 diabetic patients with PCOS presented increased serum total and free testosterone concentrations, and serum androstenedione levels, but had normal serum sex hormone-binding globulin and dehydroepiandrosterone-sulfate levels. Hirsute type 1 diabetic women without menstrual dysfunction presented normal serum androgen levels. There were no significant differences between hyperandrogenic and nonhyperandrogenic type 1 diabetes mellitus women in clinical variables such as the duration of diabetes, age at diagnosis of diabetes, conventional or intensive insulin therapy, mean daily insulin dosage, or metabolic control. In conclusion, women with type 1 diabetes mellitus have a high prevalence of hyperandrogenic disorders, including PCOS and hirsutism.

Adult↗