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M Pons

Publications and source records attributed to M Pons.

At least 37 records · Page 2Linked to original sources
PubMed2001

A graphical method for the analysis of anisotropic rotational diffusion in proteins.

A graphical method for the analysis of relaxation data is presented. It allows a fast estimation of the range of values of the components of the axially symmetric rotational diffusion tensor that are compatible with the experimental relaxation data. The graphical method clearly shows the contribution of different experimental relaxation parameters to the measured anisotropy. In particular, for proteins with moderate anisotropy, data from at least two N-H bonds forming angles close to 0 degrees and 90 degrees with respect to the principal axis of the rotational diffusional tensor are needed. For very anisotropic systems, combination of different relaxation parameters from a single residue is enough to characterize the local anisotropy.

Anisotropy↗
PubMed2001

Use of the Pediatric Risk of Mortality Score as predictor of death and serious neurologic damage in children after submersion.

OBJECTIVE: To evaluate the Pediatric Risk of Mortality score (PRISM score) as a tool to evaluate the vital and neurologic prognosis of patients after submersion. METHODS: We conducted a retrospective analysis of the clinical histories of patients admitted to a tertiary pediatric hospital, Hospital Sant Joan de Déu, Barcelona, Spain from December 1977 to December 1999 as a consequence of near-drowning. PRISM score was calculated for each patient with data obtained upon arrival at the hospital. The probability of death was calculated using this score. RESULTS: There were 60 patients, divided into two groups as they were admitted to the Pediatric Intensive Care Unit (PICU group, n = 41) or to the Short Stay Unit (SSU group, n = 19). All patients in the SSU group survived without impairments, with PRISM scores or=24 or with probability of death >or=42% either died or had serious neurologic impairment. One third of patients with PRISM scores between 17 and 23 and/or probability of death between 16 and 42% either presented serious neurologic impairment or died. CONCLUSIONS: PRISM score enables the determination of either absence or presence of serious impairment or death in pediatric patients after submersion, if they present extreme values on this scale. However, in patients with intermediate PRISM scores, it is not possible to establish a reliable prognosis.

Adolescent↗
PubMed2000

Epidermal growth factor-mediated caveolin recruitment to early endosomes and MAPK activation. Role of cholesterol and actin cytoskeleton.

The endocytic compartment of eukaryotic cells is a complex intracellular structure involved in sorting, processing, and degradation of a great variety of internalized molecules. Recently, the uptake through caveolae has emerged as an alternative internalization pathway, which seems to be directly related with some signal transduction pathways. However, the mechanisms, molecules, and structures regulating the transport of caveolin from the cell surface into the endocytic compartment are largely unknown. In this study, normal quiescent fibroblasts (normal rat kidney (NRK)) were used to demonstrate that epidermal growth factor causes partial redistribution of caveolin from the cell surface into a cellubrevin early endocytic compartment. Treatment of NRK cells with cytochalasin D or latrunculin A inhibits this pathway and the concomitant activation of Mek and mitotic-activated protein (MAP) kinase; however, if cells were pre-treated with filipin, cytochalasin D does not inhibit the phosphorylation of MAP kinase induced by epidermal growth factor. From these results we conclude that in NRK cells the intact actin cytoskeleton is necessary for the EGF-mediated transport of caveolin from the cell surface into the early endocytic compartment and the activation of MAP kinase pathway.

Actins↗
PubMed2000

Long-term hydroxytamoxifen treatment of an MCF-7-derived breast cancer cell line irreversibly inhibits the expression of estrogenic genes through chromatin remodeling.

Antiestrogen resistance is frequently observed in patients after longterm treatment with tamoxifen, a nonsteroidal antiestrogen widely used for endocrine therapy of breast cancer. In vitro studies in resistant cells showed that the expression of natural estrogen-responsive genes is frequently altered. Using MVLN cells, an MCF-7-derived cell model, we previously demonstrated that 4-hydroxytamoxifen (OHT) treatment irreversibly inactivated an estrogen-regulated chimeric luciferase response by a direct effect of the drug and not through a cell selection process (E. Badia et al., Cancer Res., 54: 5860-5866, 1994). In the present study, we present tamoxifen-resistant but still estrogen-dependent clones isolated after long-term treatment of MVLN cells with OHT and show that progesterone receptor (PR) expression was irreversibly decreased in some of these clones, whereas the PRA:PRB ratio of residual PR remained unchanged. The irreversible inactivation of both chimeric luciferase gene and PR gene expression was associated with the disappearance of DNase 1-hypersensitive sites. In the case of the chimeric gene, at least one of these sites was close to the estrogen responsive element. Genomic sequencing analysis of a clone with very low PR content did not reveal any methylation on CpG dinucleotides or any mutation in the PR gene promoter region. In all of the resistant clones tested and independently of their PR content, estrogen receptor expression was only lowered by half and remained functional, whereas pS2 expression was not modified. We also observed that the residual luciferase activity level (1-2%) of the MVLN clones, the luciferase expression of which had been irreversibly inactivated, was raised 4-fold by trichostatin A treatment. We conclude that long-term OHT treatment may modify the chromatin structure and thus could contribute to differentially silencing natural target genes.

Animals↗
PubMed2000

Late endocytic compartments are major sites of annexin VI localization in NRK fibroblasts and polarized WIF-B hepatoma cells.

Annexin VI is an abundant calcium- and phospholipid-binding protein whose intracellular distribution and function are still controversial. Using a highly specific antibody, we have studied the distribution of annexin VI in NRK fibroblasts and the polarized hepatic cell line WIF-B by confocal microscopy. In NRK cells, annexin VI was almost exclusively found associated with endocytic compartments, which were defined by their ability to receive fluid-phase marker internalized from the cell surface. However, extensive colocalization of annexin VI and the endocytic marker was only observed after about 45 min, indicating that annexin VI was primarily in late endocytic compartments or (pre)lysosomes. Consistent with this, annexin VI was predominantly seen on structures that contained the lysosomal protein lgp120, although not on dense core lysosomes by electron microscopy. Two major populations of annexin VI-containing structures were present in polarized WIF-B hepatocytes. One correlated to lgp120-positive (pre)lysosomes and was still observed after treatment with brefeldin A (BFA), while the other appeared to be partially associated with Golgi membranes and was BFA-sensitive. The striking association with prelysosomal compartments in NRK and WIF-B cells suggests that annexin VI could play a role in fusion events in the late endocytic pathway, possibly by acting as a tether between membranes.

Animals↗
PubMed2000

Cellubrevin is present in the basolateral endocytic compartment of hepatocytes and follows the transcytotic pathway after IgA internalization.

The endocytic compartment of polarized cells is organized in basolateral and apical endosomes plus those endocytic structures specialized in recycling and transcytosis, which are still poorly characterized. The complexity of the various populations of endosomes has been demonstrated by the exquisite repertoire of endogenous proteins. In this study we examined the distribution of cellubrevin in the endocytic compartment of hepatocytes, since its intracellular location and function in polarized cells are largely unknown. Highly purified rat liver endosomes were isolated from estradiol-treated rats, and the early/sorting endosomal fraction was further subfractionated in a multistep sucrose density gradient, and studied. Analysis of dissected endosomal fractions showed that cellubrevin was located in early/sorting endosomes, with Rab4, annexins II and VI, and transferrin receptor, but in a specific subpopulation of these early endosomes with the same density range as pIgA and Raf-1. Interestingly, only in those isolated endosomal fractions, endosomes enriched in transcytotic structures (of livers loaded with IgA), the polymeric immunoglobulin receptor specifically co-immunoprecipitated with cellubrevin. In addition, confocal and immuno-electron microscopy identification of cellubrevin in tubular structures underneath the sinusoidal plasma membrane together with the re-organization of cellubrevin, in the endocytic compartment, after the IgA loading, strongly suggest the involvement of cellubrevin in the transcytosis of pIgA.

Animals↗
PubMed2000

Identification and quantification of geosmin, an earthy odorant contaminating wines.

Musty, earthy odors are highly detrimental to the aromatic quality of wines. A characteristic aroma of freshly tilled earth, damp cellar was studied in some red and white wines of different origins. The extraction and purification of the wines marked by this odor have shown after analysis by gas chromatography-olfactometry a unique strong odorous zone having the same odor as the one perceived at tasting. The compound responsible for this odorous zone was identified by gas chromatography-mass spectrometry as geosmin (trans-1,10-dimethyl-trans-9-decalol), which possesses a distinctive earthy odor. Geosmin may be present in wines at levels higher than the racemic geosmin olfactory perception threshold, thus suggesting its contribution to their off-aroma. Moreover, the presence of this compound in juice taken from freshly crushed grapes suggests that microorganisms that develop on the grapes may contribute to the presence of this compound in wines.

Food Contamination↗
PubMed2000

[Electrophysiologic and anatomic atrial remodeling: an atrial rhythmic cardiomyopathy].

In 1995, Wijffels and Alessie, using a curious goat model of atrial fibrillation, introduced the concept of atrial remodelling. The classical atrial substrate (anatomopathological-dilatation and hypokinesis-, and electrophysiological-short refractory periods and decreased conduction-), appeared not only to be one of the causes of atrial fibrillation but also the consequence of atrial fibrillation itself, the mechanism being a vicious circle. In addition to ventricular rhythmic cardiomyopathy, responsible for cardiac failure, the concept of atrial rhythmic cardiomyopathy with the same mechanical and electrophysiological consequences, has developed. These changes, characterised mainly by calcium overload associated with cellular hibernation and differentiation, have not been totally elucidated but have already renewed the physiopathology of atrial fibrillation.

Anti-Arrhythmia Agents↗
PubMed1999

Reporter cell lines to study the estrogenic effects of xenoestrogens.

In order to characterize the estrogenic activity of chemicals, we established complementary in vitro recombinant receptor-reporter gene assays in stably transfected MCF-7 and HeLa cells. MCF-7 cells which express the endogenous estrogen receptor alpha (ER alpha) were stably transfected with only an estrogen-regulated luciferase gene. These cells enable the detection of compounds which bind to ER alpha or interfere with the induction of ER alpha mediated gene expression. Furthermore, HeLa cells, which do not express endogenous ERs, were transfected with an ER alpha or an ER beta construct together with an estrogen-regulated luciferase gene, or a chimeric GAL4-ER alpha receptor and the corresponding luciferase reporter gene. Finally, we tested these four cellular models as tools to check the estrogenic activities of several potential xenoestrogens and to detect estrogenic activity in wastewater sewage treatment effluents. In all of the models, nonylphenol mixture (NPm), 4n-nonylphenol (4nNP), 2,4'-DDE, 4,4'-DDE and wastewater sewage treatment effluent were active, while PCB mixture (Aroclor 1254), PCB 77, atrazine and lindane (gamma hexachlorocyclohexane) were inactive. Dioxin partially activates the estrogen receptor in MCF-7 cells while in HeLa-derived cell lines, it decreased the estrogenic-induced expression of luciferase.

Cell Line↗
PubMed1999

Measurement of relaxation rates of N(H) and H(alpha) backbone protons in proteins with tailored initial conditions.

Several methods are presented for the selective determination of spin-lattice and spin-spin relaxation rates of backbone protons in labeled proteins. The relaxation rates of amide protons in (15)N labeled proteins can be measured by using two-way selective cross-polarization (SCP). The measurement of H(alpha) relaxation rates can be achieved by combining this method with homonuclear Hartmann-Hahn transfer using doubly selective irradiation. Various schemes for selective or nonselective inversion of the longitudinal proton magnetization lead to different initial recovery rates. The methods have been applied to lysine K6 in (15)N-labeled human ubiquitin and to leucine L5 in (15)N- and (13)C-labeled octapeptide YG*G*F*LRRI (GFL) in which the marked residues are (15)N- and (13)C-labeled.

Carbon Isotopes↗
PubMed1999

Molecular dynamics study of kaliotoxin in water.

Kaliotoxin (KTX), a potassium channel blocker found in the venom of the scorpion Androctonous Mauretanicus is a 38 residue polypeptide with a well defined structure consisting of a alpha-helix and a three strand antiparallel beta-sheet interconnected by three disulfide bonds. Although the 3D structure has been determined by NMR, there is a number of features, mainly concerning the conformation and flexibility of the side chains, but also the long range order in the peptide and its fluctuations, that may have escaped the experimental study. These questions are now being addressed using molecular dynamics (MD) simulations. Accordingly, the present work reports the analysis of a 430 ps molecular dynamics trajectory of the polypeptide soaked with 4700 TIP3 water molecules inside a 56 A box. MD calculations were performed with periodic boundary conditions. Analysis of the conformational space sampled by each of the residues along the trajectory, suggests a special behavior of Pro17 and Lys19 both located on the helix. Furthermore, analysis of the relative movements of the secondary structure elements indicates that the alpha-helix and beta-sheets fluctuate in a correlated motion, preserving the tertiary structure of the polypeptide along the trajectory. Finally, analysis of the charge distribution was also examined. The direction of the dipole moment, computed from the center of masses appears to be an interesting feature of the structure probably related to the biological function of the molecule.

Computer Simulation↗
PubMed1999

Monitoring toasting intensity of barrels by chromatographic analysis of volatile compounds from toasted oak wood.

Toasting changes both the quantity and the quality of the extractable substances in the oak wood of barrels used for the aging of fine wines and spirits. Mastery and repeatability of toasting are vital in the production of quality barrels to be used for the aging of wines and spirits. In this study, we show that it is possible for a given cooperage to differentiate barrel toasting levels by analyzing a certain number of volatile and semivolatile compounds resulting from the thermal degradation of oak. Toasted wood components, which can be extracted by the wines or spirits during the aging process, are normally analyzed after the wood has soaked in standard alcoholic solutions and can be used to control the intensity of the wood toasting. The results of the comparative analysis presented in this work show that headspace analysis with a microextractive method using a stationary polydimethylsiloxane type phase is a promising technique for analyzing toasted oak wood from barrels. It is easier to use than the traditional maceration and extraction method and provides similar information.

Chromatography, Gas↗
PubMed1999

Efficacy and tolerance of interferon-alpha(2b) in the treatment of chronic hepatitis C virus infection in haemodialysis patients. Pre- and post-renal transplantation assessment.

BACKGROUND: Hepatitis C virus (HCV) infection represents an important problem for the dialysis population due to its high prevalence and the long-term development of chronic liver disease, particularly following renal transplantation. METHODS: In order to assess the efficacy and tolerance of interferon (IFN) in the treatment of chronic hepatitis C in haemodialysis (HD) patients and their clinical course following renal transplantation, a multicentre, randomized, open-label study was conducted to compare IFN therapy vs a control group. RESULTS: Nineteen HCV RNA-positive patients received 3 x 10(6) U of IFN s.c., three times a week (post-HD), and 17 HCV RNA-positive patients were assigned to the control group. Tolerance to IFN therapy was good in nine patients, while treatment was discontinued in the other 10 due to the occurrence of side effects. HCV RNA was negative at the end of treatment in 14 out of 19 patients (74%) receiving IFN and in one patient (5%) in the control group. Six out of the 14 patients who initially responded to IFN therapy had a virological relapse (43%). Eight patients (42%) remained HCV RNA-negative, three of them until the day that renal transplantation (RT) was performed (7, 12 and 27 months, respectively), as did five patients on HD during the follow-up (27+/-5 months). Eight out of the nine patients (89%) who completed therapy were HCV RNA-negative at the end of treatment, and seven of them (78%) remained HCV RNA-negative during the follow-up on dialysis (21+/-8 months). Mean transaminase (ALT) values were significantly decreased following IFN therapy, while no changes were observed during the follow-up period in the control group. Fifteen patients (10 in the treatment group and five in the control group) underwent RT. Three patients in the treatment group were HCV RNA-negative at RT, and one of them had a virological relapse 20 months after RT, while the other two remained HCV RNA-negative at 3 months and 24 months after RT, respectively. In contrast to the control group, transaminase (ALT) remained within normal limits in all patients in the treatment group. Finally, during the post-RT follow-up, the transaminase mean values were significantly lower in treated patients vs patients in the control group (P<0.05). CONCLUSIONS: It is concluded that the biochemical and virological response to IFN therapy is good in HD patients. In addition, IFN therapy appears to exert a beneficial effect on the course of liver disease following RT, regardless of the virological response. Despite the fact that IFN therapy was discontinued in 10 out of the 19 patients due to the occurrence of side effects, these disappeared following discontinuation of therapy. Therefore, IFN therapy is advisable for HCV-infected dialysis patients who are candidates for RT.

Adult↗
PubMed1999

A "dysautonomic" head-up tilt test pattern in elderly patients with neurocardiogenic syncope.

The characteristics of neurocardiogenic syncope (NCS) in elderly patients remain unclear. We compared the hemodynamic profiles of young and older patients with consecutive and positive head-up tilt tests (HUT). Continuous, noninvasive, and reliable monitoring of arterial pressure (AP) and heart rate (HR) was done throughout 46 consecutive positive HUTs of symptomatic patients. The population (12-82 years old) was divided into two groups: younger patients, Y (n = 25, < or = 65 years), and older patients, O (n = 21). Changes in AP and HR after the first minute of tilting, during the stable orthostatic phase and during syncope were compared. Except for systolic pressure, baseline hemodynamic parameters were similar in Y and O. No difference appeared in the mean time elapsed before syncope (19+/-9 vs 22+/-2 min). Asymptomatic hypotension was observed, only in O, 1 minute after tilting, followed by a progressive fall in the mean AP before syncope (0+/-0.9 vs -1+/-0.7 mmHg/min) without HR increase (0.7+/-1 vs 0+/-0.6 beats/min). This pressure slope was strongly related to age (r = 0.54, P < 0.001). Hemodynamic recording during HUT identifies a dysautonomic pattern in elderly patients with NCS and the abnormal AP/HR responses to orthostasis may be a feature specific to this population. Although the central mechanism of NCS is common to all ages, the age-related characteristics of the trigger event may indicate the need for specific management at different ages.

Adolescent↗
PubMed1999

Chronic constrictive pericarditis induced by long-term bromocriptine therapy: report of two cases.

OBJECTIVE: To report two cases of chronic constrictive pericarditis that appear to be related to the intake of bromocriptine for Parkinson's disease. CASE SUMMARY: Two white men (aged 63 and 69 y) were treated with bromocriptine for four (40 mg/d) and two years (30 mg/d), respectively, with a cumulative dose intake of 58.4 and 21.9 g, respectively. The patients experienced dyspnea with bilateral lower-limb edema and pleural effusion, suggesting right cardiac dysfunction. Echocardiography, computed tomography, and cardiac catheterization results were compatible with a diagnosis of constrictive pericarditis, so pericardectomy was performed on both patients. The anatomic pathology examination showed a fibrous pericardium; cultures were sterile. In the first case, pleural effusion recurred seven months after the pericarditis; bromocriptine was suspected and treatment was discontinued. In the second case, just prior to the pericardectomy, an episode of mental confusion occurred and prompted the cessation of bromocriptine therapy. DISCUSSION: To the best of our knowledge, only one case of constrictive pericarditis induced by bromocriptine therapy has previously been described in the literature. CONCLUSIONS: Our cases call attention to a possible association between bromocriptine use in patients who have Parkinson's disease and constrictive pericarditis.

Aged↗
PubMed1999

[Electrocardiographic aspects of the pathology of the bundle of His].

The ECG appearances of His bundle pathology are very variable and endocavitory recordings are often required to confirm the diagnosis which may be suspected by close analysis of the surface ECG. Truncular AVB is a serious condition as the block is infranodal but with a supraventricular and therefore a narrow QRS complex: it may be median with a double His potential or proximal and distal, which are more difficult to diagnose. Hisian extrasystoles are particularly polymorphic, either overtly, suggesting successively atrial and ventricular extrasystoles, or masked with deceptive pseudo-1st or 2nd degree atrioventricular block. More rarely, hisian tachycardias complicating congenital heart disease in children are observed, particularly in the postoperative period.

Bundle of His↗