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M Campillo

Publications and source records attributed to M Campillo.

At least 19 recordsLinked to original sources
PubMed2006

Crossover frequency and synaptonemal complex length: their variability and effects on human male meiosis.

In this study, immunocytogenetics has been used in combination with the subtelomere-specific multiplex-fluorescent in-situ hybridization (stM-FISH) assay to identify 4681 autosomal synaptonemal complexes (SCs) of two fertile men. Comparisons of crossover maps for each individual SC between two men with extremely different meiotic crossover frequencies show that a low crossover frequency results in (i) a higher frequency of XY pairs and of small SCs without MLH1 foci and (ii) lower frequency of crossovers in the proximity of centromeres. In both cases, the bivalents which most frequently lacked MLH1 foci were the XY pair and the SC21. Analysis of SC length showed that SC arms can be longer or shorter than the corresponding mitotic one. Moreover, for a given SC, the variation in length found in one arm was independent of the variation observed in the other one (e.g. SC1p arms are longer than SC1q arms). The results confirmed that reduction in the crossover frequency may increase the risk of achiasmate small bivalents and that interindividual differences in crossover frequency could explain the variability in the frequencies of aneuploidy in human sperm. How MLH1 foci are positioned within the SC is discussed based on detailed MLH1 foci distributions and interfoci distances. Finally, evidence that the variation of the SC arm length may reflect the abundance of open and of compact chromatin fibers in the arm is shown.

Chromosome Mapping↗
PubMed2005

Dihydro-beta-agarofuran sesquiterpenes: a new class of reversal agents of the multidrug resistance phenotype mediated by P-glycoprotein in the protozoan parasite Leishmania.

Leishmaniasis is the most important emerging and uncontrolled infectious disease and the second cause of death among parasitic diseases, after Malaria. One of the main problems concerning the control of infectious diseases is the increased resistance to usual drugs. Overexpression of P-glycoprotein (Pgp)-like transporters represents a very efficient mechanism to reduce the intracellular accumulation of drugs in cancer cells and parasitic protozoans, thus conferring a multidrug resistance (MDR) phenotype. Pgps are active pumps belonging to the ATP-binding cassette (ABC) superfamily of proteins. The inhibition of the activity of these proteins represents an interesting way to control drug resistance both in cancer and in infectious diseases. Most conventional mammalian Pgp-MDR modulators are ineffective in the modulation of Pgp activity in the protozoan parasite Leishmania. Consequently, there is a necessity to find effective modulators of Pgp-MDR for protozoan parasites. In this review we describe a rational strategy developed to find specific Pgp-MDR modulators in Leishmania, using natural and semisynthetic dihydro-beta-agarofuran sesquiterpenes from Celastraceae plants. A series of these compounds have been tested on a MDR Leishmania tropica line overexpressing a Pgp transporter to determine their ability to revert the resistance phenotype and to modulate intracellular drug accumulation. Almost all of these natural compounds showed potent reversal activity with different degrees of selectivity and a significant low toxicity. The three-dimensional quantitative structure-activity relationship using the comparative molecular similarity indices analysis (CoMSIA), was employed to characterize the requirements of these sesquiterpenes as modulators at Pgp-like transporter in Leishmania.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Weak localization of seismic waves.

We report the observation of weak localization of seismic waves in a natural environment. It emerges as a doubling of the seismic energy around the source within a spot of the width of a wavelength, which is several tens of meters in our case. The characteristic time for its onset is the scattering mean-free time that quantifies the internal heterogeneity.

Journal Article↗
PubMed2004

The use of a cell-cycle phase-marker may decrease the percentage of errors when using FISH in PGD.

Fluorescent DNA probes are used to characterise the chromosome constitution of preimplantation embryos. FISH is used to select normal or balanced embryos in carriers of balanced chromosomal rearrangements, for embryo sexing or for aneuploidy screening in women of advanced age, who have had recurrent abortions or IVF failures. In most cases, FISH is performed on interphase blastomeres which are asynchronously dividing cells, that can be in G1, S or G2. However, a correct interpretation of a double FISH signal, which may correspond to a split signal, to a replicated chromosome region or to the presence of an extra chromosome is essential to establish an accurate diagnosis. To determine if the cell stage could influence the interpretation of FISH results, we compared the signal characteristics of one locus-specific probe, two different subtelomere region probes, and a centromere region probe in non-dividing Sertoli cells and in proliferating lymphocytes. Most cells had two signals per chromosome pair (i.e., a situation corresponding to G0 in Sertoli cells and to G1 or to a prereplication stage in lymphocytes). Nevertheless, in proliferating cells the percentage of nuclei with a number of signals different from the expected (two unreplicated chromosomes per pair) was different from that found in non-dividing cells (P < 0.05). It was estimated that 10.8% of double dots in dividing cells resulted from DNA replication. The sequence of replication was first the locus-specific region, second a telomere region, and third the centromere. In conclusion, the DNA replication process could result in errors of interpretation (misdiagnosis) in 7% of proliferating cells. Thus, the use of a cell cycle phase-specific marker could avoid errors by indicating the cell stage in which the nucleus analysed is found.

Adult↗
PubMed2002

Multiple scattering of seismic waves.

We present theory and numerical simulations to model seismic wave propagation in the Earth crust. We compare them to observations made in Mexico.

Journal Article↗
PubMed2002

5-HT(4) receptor antagonists: structure-affinity relationships and ligand-receptor interactions.

Among serotonin receptors (5-HTRs), the 5-HT(4) subtype is of considerable interest because it is involved in (patho)physiological processes both in peripheral and central nervous systems. In addition to the clinical use of 5-HT(4R) agonists in the treatment of gastrointestinal motility disorders, the potential use of antagonists in the treatment of irritable bowel syndrome, arrhythmias and micturition disturbances are currently under investigation. This article will review the development of the most important classes of 5-HT(4R) antagonists with an emphasis on benzimidazole derivatives, their structure-affinity relationships, ligand-receptor interactions and pharmacological applications.

Animals↗
PubMed2001

3-D-QSAR/CoMFA and recognition models of benzimidazole derivatives at the 5-HT(4) receptor.

3-D-QSAR/CoMFA methodology and computational simulation of ligand recognition have been successfully applied to explain the binding affinities of a series of benzimidazole derivatives 1-24 acting at serotonin 5-HT(4)Rs. Both derived computational models have facilitated the identification of the structural elements of the ligands that are key to high 5-HT(4)R affinity. The results provide the tools for predicting the affinity of related compounds, and for guiding the design and synthesis of new ligands with predetermined affinities and selectivity.

Benzimidazoles↗
PubMed2001

Observation of equipartition of seismic waves.

Equipartition is a first principle in wave transport, based on the tendency of multiple scattering to homogenize phase space. We report observations of this principle for seismic waves created by earthquakes in Mexico. We find qualitative agreement with an equipartition model that accounts for mode conversions at the Earth's surface.

Journal Article↗
PubMed2001

Computational model of the complex between GR113808 and the 5-HT4 receptor guided by site-directed mutagenesis and the crystal structure of rhodopsin.

A computational model of the transmembrane domain of the human 5-HT4 receptorcomplexed with the GR113808 antagonist was constructed from the crystal structure of rhodopsin and the putative residues of the ligand-binding site, experimentally determined by site-directed mutagenesis. The recognition mode of GR113808 consist of: (i) the ionic interaction between the protonated amine and Asp3.32; (ii) the hydrogen bond between the carbonylic oxygen and Ser5.43; (iii) the hydrogen bond between the ether oxygen and Asn6.55; (iv) the hydrogen bond between the C-H groups adjacent to the protonated piperidine nitrogen and the pi electrons of Phe6.51; and (v) the pi-sigma aromatic-aromatic interaction between the indole ring and Phe6.52. This computational model offers structural indications about the role of Asp3.32, Ser5.43, Phe6.51, Phe6.52, and Asn6.55 in the experimental binding affinities. Asp3.32Asn mutation does not affect the binding of GR113808 because the loss of binding affinity from an ion pair to a charged hydrogen bond is compensated by the larger energetical penalty of Asp to disrupt its side chain environment in the ligand-free form, and the larger interaction between Phe6.51 and the piperidine ring of the ligand in the mutant receptor. In the Phe6.52Val mutant the indole ring of the ligand replaces the interaction with Phe6.52 by a similarly intense interaction with Tyr5.38, with no significant effect in the binding of GR113808. The mutation of Asn6.55 to Leu replaces the hydrogen bond of the ether oxygen of the ligand from Asn6.55 to Cys5.42, with a decrease of binding affinity that approximately equals the free energy difference between the SH...O and NH...O hydrogen bonds. Because these residues are also present in the other members of the neurotransmitter family of G protein-coupled receptors, these findings will also serve for our understanding of the binding of related ligands to their cognate receptors.

Amino Acid Sequence↗
PubMed2001

Separation between the digestive and the respiratory lumina during the human embryonic period: morphometric study along the tracheo-oesophageal septum.

An isolated tracheo-oesophageal fistula could be caused by close proximity of the epithelia of both organs (O'Rahilly & Müller, 1984; Kluth et al. 1987) at certain embryonic stages, the most frequent location being the tracheal bifurcation. Thus the relative position and degree of separation between the digestive and the respiratory tubes throughout their development may be relevant to the origin of this anomaly. The aim of this study was to analyse along the different segments of the tracheo-oesophageal septum (TES) where the closest relationship between both lumina occurred and what degree of separation was present at each segment. Computer imaging techniques were applied on cross sections of a graded series of normal human embryos (Carnegie stages (CS) 13-23). In addition, the differentiation of the primitive TES was also studied (from CS 12) by light microscopy. Between CS 13 and 16 both tubes tended to separate (phase of separation), principally at the proximal segments of the laryngopharyngeal and the tracheo-oesophageal portions of the TES. During this phase the separation between the trachea and oesophagus was wider than between the larynx and pharynx. From CS 17 to CS 23 the digestive and respiratory lumina reached their widest separation at different levels of the laryngopharyngeal portion. Below these levels they tended to come closer together, principally at the proximal segment of the tracheo-oesophageal portion, but also at the distal part of the laryngopharyngeal portion. During this phase of approximation they reached their closest relationship at the proximal (CS 17) and the distal (from CS 18) segments of the tracheo-oesophageal portion. When finally the distal segment of the trachea (which includes the bifurcation) comes closest to the oesophagus, the coats of both organs have already undergone an appreciable differentiation. According to these observations, the origin of the most frequent isolated tracheo-oesophageal fistula at the bifurcation region could not be explained from the normal development of the TES.

Embryonic and Fetal Development↗
PubMed2001

Coherent backscattering of elastic waves: specific role of source, polarization, and near field.

Calculation of coherent backscattering of elastic waves in an infinite isotropic random medium is presented. Despite the simplicity of this geometry, this calculation highlights several specific aspects for seismic detection: near field detection, polarization, and the symmetry of the source. Line profiles and enhancement factors are seen to be time independent and are calculated for kinetic, shear, and compressional energy.

Journal Article↗
PubMed2000

Molecular determinants of MAO selectivity in a series of indolylmethylamine derivatives: biological activities, 3D-QSAR/CoMFA analysis, and computational simulation of ligand recognition.

A series of indolylmethylamine derivatives were assayed toward MAO-A and MAO-B inhibition. The K(i) values of these compounds are in the range from 0.8 to >10(6) nM for MAO-A or from 0.75 to 476000 nM for MAO-B. The most selective MAO-A or MAO-B inhibitors elicit a ratio of K(i) in the order of 1500 or 1000, respectively. Comparison of MAO-A and MAO-B CoMFA models showed that both the steric and electrostatic properties at the 5 position of the indole ring are determinant for MAO selectivity. Computational simulations of the complex between this part of the ligand and Phe-208 of MAO-A or Ile-199 of MAO-B, experimentally identified as responsible for substrate selectivity, allowed us to further characterize the nature of these enzyme-inhibitor interactions.

Amines↗
PubMed2000

Increased morbid risk for schizophrenia in families of in-patients with bipolar illness.

BACKGROUND: It has been reported that relatives of probands with severe, psychotic forms of bipolar illness have increased rates of schizophrenia but not the relatives of individuals with milder, non-psychotic forms of disorder. In this study, we examined the prevalence of psychiatric disorders in the first degree relatives of a sample of 103 inpatients with bipolar disorder and in a matched control sample of 84 healthy individuals. METHOD: Relatives of cases and controls were interviewed using the FH-RDC to determine familial morbid risk for schizophrenia and bipolar disorder. Age- and sex-adjusted morbidity risks were calculated in both samples according to the method of Strömgren. RESULTS: The morbid risks for both bipolar disorder (4.9%) and schizophrenia (2.8%) were higher in relatives of patients than in relatives of controls (0.3% and 0.6% respectively). The relative risks were 14.2 [95% confidence interval (CI)=3.1-64.2] for bipolar disorder and 4.9 (95% CI=1.3-18.8) for schizophrenia. Relatives of women with early onset of bipolar illness had the highest morbid risks for both bipolar illness and schizophrenia. The presence of more than one patient with bipolar disorder in a family increased the risk for schizophrenia nearly fourfold (RR=3.5, 95% CI=1.2-10.2). There was no additional effect of presence of psychotic features. CONCLUSION: Our results suggest that the transmission of psychosis is not disorder-specific. Bipolar illness characterised by a high familial loading is associated with increased risk of schizophrenia in the relatives.

Adolescent↗
PubMed2000

Binding mechanisms of TATA box-binding proteins: DNA kinking is stabilized by specific hydrogen bonds.

One of the common mechanisms of DNA bending by minor groove-binding proteins is the insertion of protein side chains between basepair steps, exemplified in TBP (TATA box-binding protein)/DNA complexes. At the central basepair step of the TATA box TBP produces a noticeable decrease in twist and an increase in roll, while engaging in hydrogen bonds with the bases and sugars. This suggests a mechanism for the stabilization of DNA kinks that was explored here with ab initio quantum mechanical calculations and molecular dynamics/potential of mean force calculations. The hydrogen bonds are found to contribute the energy necessary to drive the conformational transition at the central basepair step. The Asn, Thr, and Gly residues involved in hydrogen bonding to the DNA bases and sugar oxygens form a relatively rigid motif in TBP. The interaction of this motif with DNA is found to be responsible for inducing the untwisting and rolling of the central basepair step. Notably, direct readout is shown not to be capable of discriminating between AA and AT steps, as the strength of the hydrogen bonds between TBP and the DNA are the same for both sequences. Rather, the calculated free energy cost for an equivalent conformational transition is found to be sequence-dependent, and is calculated to be higher for AA steps than for AT steps.

Biophysical Phenomena↗
PubMed1999

An epidemiological comparison of pain complaints in the general population of Catalonia (Spain).

Epidemiological studies help to establish the health status in a country and allow a better allocation of economic resources. This survey estimated pain prevalence in Catalonia (Spain), analysed its relationship with demographic variables and evaluated pain-associated disabilities. The study was carried out in 1964 adults via phone interviews asking about any pain complaint they experienced in the last 6 months, regardless of its intensity and duration. Overall pain prevalence was 78.6%, significantly lower in men, with a trend to decrease with age. Back (50.9%), head (42%) and legs (36.8%) were the most affected locations. Less educated people reported, in general, higher prevalences. Pain described to be most annoying was related to musculoskeletal disease (26.2%) and migraines (16.5%). Pain was either very severe or unbearable in 33% of the sample, with women and older people reporting higher intensities. Personal and social activities were affected in 25.4% of cases and in 10.4% they became virtually impossible. Both the limitation of activity and the need for bed rest, which occurred in 19.6% of those who suffered pain, were more common amongst unemployed people, whereas 10.2% of workers had to take days off work due to pain, and 3.3% were fully incapacitated by it. In conclusion, the prevalence of pain was clearly higher among women, with an inverse relationship to age. Back pain and headaches were most prevalent and pain was rated as very severe to unbearable in one third of the patients. Pain-associated disabilities were a frequent finding. The present survey reports that pain is a substantial problem in the Catalonian population and generally reflects the characteristics of data previously reported in Anglo-saxon and Scandinavian countries.

Adult↗
PubMed1998

Congenital dermatoglyphic malformations in severe bipolar disorder.

Dermatoglyphic alterations may be the result of early prenatal disturbances thought to be implicated in the aetiology of psychiatric illness. In order to test this hypothesis in the particular case of bipolar disorder, we assessed two congenital dermatoglyphic malformations (ridge dissociation (RD) and abnormal features (AF)) and two metric dermatoglyphic traits (total finger ridge count (TFRC) and total a-b ridge count (TABRC)) in a sample of 118 patients with chronic DSM-III-R bipolar illness, and 216 healthy controls. Bipolar cases showed a significant excess of RD and AF (OR = 2.80; 95% CI: 2.31-3.38) when compared with controls. In the cases, the presence of anomalies was associated with earlier age of onset. No differences were found for TFRC and TABRC. No associations were found with sex or familial morbid risk of psychiatric disorders. Our findings add further weight to the suggestion that early developmental disruption is a risk factor for later bipolar disorder.

Bipolar Disorder↗
PubMed1997

The effect of the molecular mechanism of G protein-coupled receptor activation on the process of signal transduction.

A thermodynamic model of signal transduction that incorporates the possibility of multiple conformational states between the inactive and the active forms of the receptor was developed. The obtained equilibrium model is equivalent to the extended ternary complex of Samama et al. (J. Biol. Chem. 268 (1993) 4625-4636) if only two states of the receptor exist. These multiple equilibria between receptor states are modeled by two sets of equilibrium constants: K(piAR) and K(sigma piAR), in the presence of the ligand; and K(piR) and K(sigma piR), in the absence of the ligand. The higher the value of these constants, the more efficiently the active form of the receptor is generated. Intrinsic efficacy of the agonist is defined in the present formulation as the molecular processes induced by ligands in the receptor that lead to the active form of the receptor. Both the energetics (associated to K[piAR]) and mechanism of the process of receptor activation (associated to K[sigma piAR]) are important in eliciting the maximum response. Moreover, analytical expressions of basal activity, potency and maximum response were obtained. These definitions were used to classify the extra cellular ligand as agonists (K[sigma piAR] > K[sigma piR]), inverse agonists (K[sigma piR] > K[sigma piAR] > 0), neutral antagonists (K[sigma piAR] = K[sigma piR]), and pure antagonists.

Computer Simulation↗