Biomedical subjects

Eduardo López

Publications and source records attributed to Eduardo López.

13 recordsLinked to original sources

PubMed2006

Differential atrial versus ventricular ANKRD1 gene expression is oppositely regulated at diastolic heart failure.

Diastolic heart failure (DHF) was produced in 6-day-old piglets by intravenous administration of Doxorubicin, and ANKRD1 protein and mRNA levels were determined in atrial (A) and ventricular (V) chambers of failing vs control hearts. In controls, ANKRD1 showed a left-right (L-R) asymmetric distribution with protein levels 2-fold higher in the LA as compared to the RA, and 8-fold higher in the LV than the RV. In failing hearts, ANKRD1 levels were augmented about 2-fold in each ventricle but equally reduced in both atria as compared to controls. ANKRD1 downregulation in atria is discussed as a process associated with advanced DHF.

Animals↗

PubMed2006

Universal behavior of optimal paths in weighted networks with general disorder.

We study the statistics of the optimal path in both random and scale-free networks, where weights are taken from a general distribution P(w). We find that different types of disorder lead to the same universal behavior. Specifically, we find that a single parameter (S defined as AL(-1/v) for d-dimensional lattices, and S defined as AN(-1/3) for random networks) determines the distributions of the optimal path length, including both strong and weak disorder regimes. Here v is the percolation connectivity exponent, and A depends on the percolation threshold and P(w). We show that for a uniform P(w), Poisson or Gaussian, the crossover from weak to strong does not occur, and only weak disorder exists.

Journal Article↗

PubMed2005

Possible connection between the optimal path and flow in percolation clusters.

We study the behavior of the optimal path between two sites separated by a distance on a d-dimensional lattice of linear size L with weight assigned to each site. We focus on the strong disorder limit, i.e., when the weight of a single site dominates the sum of the weights along each path. We calculate the probability distribution P(l opt/r,L) of the optimal path length l opt, and find for r <<L a power-law decay with l opt, characterized by exponent g opt. We determine the scaling form of P(l opt/r,L) in two- and three-dimensional lattices. To test the conjecture that the optimal paths in strong disorder and flow in percolation clusters belong to the same universality class, we study the tracer path length l tr of tracers inside percolation through their probability distribution P(l tr/r,L). We find that, because the optimal path is not constrained to belong to a percolation cluster, the two problems are different. However, by constraining the optimal paths to remain inside the percolation clusters in analogy to tracers in percolation, the two problems exhibit similar scaling properties.

Journal Article↗

PubMed2005

Anomalous transport in scale-free networks.

To study transport properties of scale-free and Erdos-Rényi networks, we analyze the conductance G between two arbitrarily chosen nodes of random scale-free networks with degree distribution P(k)-k(-lambda) in which all links have unit resistance. We predict a broad range of values of G, with a power-law tail distribution phi(SF)(G)-G(-g(G)), where g(G)=2lambda-1, and confirm our predictions by simulations. The power-law tail in phi(SF)(G) leads to large values of G, signaling better transport in scale-free networks compared to Erdos-Rényi networks where the tail of the conductivity distribution decays exponentially. Based on a simple physical "transport backbone" picture we show that the conductances of scale-free and Erdos-Rényi networks are well approximated by ck(A)k(B)/(k(A)+k(B)) for any pair of nodes A and B with degrees k(A) and k(B), where c emerges as the main parameter characterizing network transport.

Computer Systems↗

PubMed2005

Current flow in random resistor networks: the role of percolation in weak and strong disorder.

We study the current flow paths between two edges in a random resistor network on a L X L square lattice. Each resistor has resistance e(ax) , where x is a uniformly distributed random variable and a controls the broadness of the distribution. We find that: (a) The scaled variable u identical with u congruent to L/a(nu) , where nu is the percolation connectedness exponent, fully determines the distribution of the current path length l for all values of u . For u >> 1, the behavior corresponds to the weak disorder limit and l scales as l approximately L, while for u << 1 , the behavior corresponds to the strong disorder limit with l approximately L(d(opt) ), where d(opt) =1.22+/-0.01 is the optimal path exponent. (b) In the weak disorder regime, there is a length scale xi approximately a(nu), below which strong disorder and critical percolation characterize the current path.

Journal Article↗

PubMed2005

ANKRD1 specifically binds CASQ2 in heart extracts and both proteins are co-enriched in piglet cardiac Purkinje cells.

It has been suggested that the cardiac ankyrin repeat domain 1 protein (ANKRD1), also known as CARP, can play a pathophysiological role in the contractile responsiveness of myocardium. Here, we study the potential functional roles of ANKRD1 by searching for endogenous cardiac proteins that interact preferentially with ANKRD1 in the heart-tissue extract from neonatal piglets, using non-biased pull-down approaches. These approaches identified, for the first time, a selective interaction between ANKRD1 and endogenous cardiac calsequestrin-2 (CASQ2) that is important for Ca2+ release and excitation-contraction coupling. Blot-overlay and co-immunoprecipitation assays provided further confirmation of the direct and specific interaction between the two proteins. Mapping of the peptides involved in the interaction revealed five non-overlapping binding sequences for CASQ2 on ANKRD1, as well as, three binding peptides for ANKRD1 in CASQ2. For the first time, we show by immunohistochemistry that endogenous ANKRD1 and CASQ2 are co-enriched in piglet cardiac Purkinje cells. Collectively, the results provide the first sing of a possible functional interaction between ANKRD1 and CASQ2 and suggest a potentially novel role for both proteins in cardiac Purkinje fibers.

Aging↗

PubMed2005

Epstein-Barr virus associated with primary CNS lymphoma and disseminated BCG infection in a child with AIDS.

BACKGROUND: AIDS patients are at increased risk of developing concurrent infections with viral, parasitic, fungal or mycobacterial organisms. They can present constitutional symptoms of fever and weight loss, either due to infections or an underlying lymphoma which may coexist. CASE REPORT: A child with HIV-AIDS and mild encephalopathy is reported, who during the course of a confirmed disseminated mycobacterial disease developed neurological impairment. Post-mortem examination revealed disseminated BCG infection and Epstein-Barr associated primary CNS lymphoma. Epstein-Barr virus (EBV) presence was assessed by LMP-1 protein labelling by immunohistochemistry and in situ hybridisation (ISH) for Epstein-Barr virus-encoded RNAs (EBERs) in formalin-fixed and paraffin-embedded sections. CONCLUSIONS: BCG vaccination among HIV-1 infected children leads to the risk of disseminated BCG infection. BCG immunization programmes should be reconsidered for children at risk of HIV infection, because the risk of delayed complications is independent of the immunological status at the time of the vaccination. Only isolated cases of primary CNS lymphoma occurring in HIV-infected children have been reported, and a striking association with EBV infection has been demonstrated.

AIDS-Related Opportunistic Infections↗

PubMed2004

Universality of the optimal path in the strong disorder limit.

We study numerically the optimal paths in two and three dimensions on various disordered lattices in the limit of strong disorder. We find that the length l of the optimal path scales with geometric distance r , as l approximately r (d(opt) ) with d(opt) =1.22+/-0.01 for d=2 and 1.44+/-0.02 for d=3 , independent of whether the optimization is on a path of weighted bonds or sites, and independent of the lattice or its coordination number. Our finding suggests that the exponent d(opt) is universal, depending only on the dimension of the system.

Journal Article↗

PubMed2004

Left-right asymmetric ventricular expression of CARP in the piglet heart: regional response to experimental heart failure.

BACKGROUND AND AIM: Cardiac ankyrin repeat protein (CARP), whose expression is down-regulated in response to doxorubicin (Dox) in vitro, has been proposed to be a marker of experimentally-induced cardiac hypertrophy in rodent models. In piglets, the rapid hypertrophy rate of the left ventricle (LV) as compared to that of the right ventricle (RV) represents a natural model of asymmetric ventricular enlargement. We tested whether CARP expression correlates with postnatal ventricular hypertrophy and to what extent CARP can be sensitive to Dox treatment in vivo. METHODS: CARP mRNA and protein levels were quantified (by Northern blot hybridization, semi-quantitative RT-PCR and Western blot) in the piglet heart, both during early postnatal development and upon Dox-induced cardiomyopathy (Dox-CM). RESULTS: The study revealed: (1) significantly augmented CARP mRNA and protein levels in the LV compared to the RV resulting in left vs. right asymmetry in ventricular CARP expression throughout early postnatal development; (2) dose- and chamber-dependent CARP mRNA and protein enrichment in ventricular myocardium in response to Dox; and (3) abolishment of asymmetric patterns of ventricular CARP expression at heart failure resulting from Dox-CM. CONCLUSIONS: (1) CARP is differentially regulated in the LV and RV during both postnatal development and disease; and (2) monitoring of ventricular CARP expression patterns can be used for further analysis of transition from compensated to overt heart failure.

Animals↗

PubMed2004

FDA/PI flow cytometry assay of complement-mediated cytotoxicity of antibodies generated during xenotransplantation.

BACKGROUND: A flow cytometry complement-mediated cytotoxicity assay (FCCA) using fluorescein diacetate (FDA) and propidium iodide (PI) to measure antibody-dependent toxicity is useful to determine the success of xenotransplant organs. We evaluated the validity of different mathematical models as a measure of cytotoxicity in FCCA. METHODS: Sera from untreated baboons (n = 7) and from immunosuppressed animals (n = 5) undergoing different xenotransplantation protocols with pig organs were tested by endogenous FCCA and a similar assay also using exogenous complement, and the results were compared with those of a complement-dependent hemolytic assay to detect anti-pig antibodies (APHA). The influence of PI/FDA staining and the use of several mathematical models were analyzed. RESULTS: For both groups of animals, we observed high correlations between the endogenous and exogenous FCCA pathways and between calculations based on PI and FDA staining. Of the four mathematical models tested--the Von Krogh equation, two exponential models, and area under the curve--the Von Krogh equation was the most appropriate in terms of goodness of fit and concordance with APHA. CONCLUSIONS: FDA/PI FCCA is useful to measure endogenous and exogenous complement-mediated cytotoxicities, and it has advantages related to identification of potential new xenoantibodies. Although all four mathematical models produced acceptable solutions, the Von Krogh equation was the best option.

Animals↗

PubMed2003

Myocardin mRNA is augmented in the failing myocardium: expression profiling in the porcine model and human dilated cardiomyopathy.

The implication of myocardin and homeodomain only protein (HOP) in combinatorial molecular pathways that guide heart development and cardio-specific gene expression has recently been reported. However, expression of these genes in the failing heart has not yet been investigated. This study was designed to elaborate a molecular profile of myocardin and HOP expression in the failing ventricular myocardium through the use of both explanted human heart samples and heart biopsies from neonatal piglets with doxorubicin-induced cardiomyopathy (Dox-CM). Myocardin and HOP mRNA levels were estimated by both northern blot hybridization and semiquantitative RT-PCR in human ventricular preparations in end-stage failure due to dilated cardiomyopathy (DCM), as well as in nonfailing donor hearts. Similar experiments were performed with ventricular samples from normal and Dox-treated neonatal piglets. The gene expression of brain natriuretic peptide (BNP) was used as a molecular marker of myocardial damage and failure. The study revealed the following novel findings: (1) myocardin transcripts are detected in neonatal human and pig hearts at lower levels than in mature cardiac tissues, (2) the myocardin transcript pool is significantly augmented in the failing human and porcine myocardium as compared to that in nonfailing heart samples, (3) in the failing human myocardium, increased levels of myocardin mRNA are associated with a diminished HOP transcript content, and (4) the inverse proportion in cardiac myocardin/HOP mRNA pools observed in explanted human hearts is also traceable in normal human heart and aorta. A possible dual consequence of increased myocardin and decreased HOP expression levels on serum response factor-dependent cardiac-specific expression in the normal heart and at heart failure is discussed. Therefore, increased abundance of the myocardin mRNA pool is judged to be a novel CM-related feature which, alone or in association with decreased HOP transcript levels, can be responsible for dysregulation of myocardin-mediated gene expression in failing myocardium.

Amino Acid Sequence↗

PubMed2003

Postbreakthrough behavior in flow through porous media.

We numerically simulate the traveling time of a tracer in convective flow between two points (injection and extraction) separated by a distance r in a model of porous media, d=2 percolation. We calculate and analyze the traveling time probability density function for two values of the fraction of connecting bonds p: the homogeneous case p=1 and the inhomogeneous critical threshold case p=p(c). We analyze both constant current and constant pressure conditions at p=p(c). The homogeneous p=1 case serves as a comparison base for the more complicated p=p(c) situation. We find several regions in the probability density of the traveling times for the homogeneous case (p=1) and also for the critical case (p=p(c)) for both constant pressure and constant current conditions. For constant pressure, the first region I(P) corresponds to the short times before the flow breakthrough occurs, when the probability distribution is strictly zero. The second region II(P) corresponds to numerous fast flow lines reaching the extraction point, with the probability distribution reaching its maximum. The third region III(P) corresponds to intermediate times and is characterized by a power-law decay. The fourth region IV(P) corresponds to very long traveling times, and is characterized by a different power-law decaying tail. The power-law characterizing region IV(P) is related to the multifractal properties of flow in percolation, and an expression for its dependence on the system size L is presented. The constant current behavior is different from the constant pressure behavior, and can be related analytically to the constant pressure case. We present theoretical arguments for the values of the exponents characterizing each region and crossover times. Our results are summarized in two scaling assumptions for the traveling time probability density; one for constant pressure and one for constant current. We also present the production curve associated with the probability of traveling times, which is of interest to oil recovery.

Journal Article↗

PubMedDate not supplied

Xeno-implantation of pig chondrocytes into rabbit to treat localized articular cartilage defects: an animal model.

Articular cartilage has only a limited ability to regenerate. The transplantation of autologous chondrocytes is currently used to treat focal defects in human articular cartilage, although use of organs, tissues, or cells from different species is being investigated as an alternative treatment. The object of this study was to use xeno-transplantation of cultured pig chondrocytes for the repair of rabbit chondral defects, and to analyze the significance of tissue rejection in this animal model. Partial chondral defects, including removal of cartilage tissue and a part of the subchondral bone, were created in the lateral femoral condyles of 30 adult New Zealand White rabbits. A periosteal flap was sutured to the native cartilage with the cambium layer facing the defect. As a control, culture medium was injected into the defect void of one group of rabbits while in a treatment group, chondrocytes, isolated from normal femoral pig cartilage, were injected into the defect void. All rabbits were killed by 24 weeks. Macroscopic changes of the cartilage were analyzed using Mankin's score. The distal femoral portion was studied histologically using hematoxylin and eosin, alcian blue, toluidine blue, and Mason's trichrome. Pig cells and pig genetic material were detected in the neo-synthesized tissue by immunohistochemical detection of SLA-II-DQ and polymerase chain reaction analysis of the gene SLA-II-DQB. The synovial membrane was studied histologically by hematoxylin and eosin staining. In the control group, on average, less than 25 percent of the chondral defect was filled. The repair tissue had an irregular surface with few cells similar to chondrocytes or fibroblasts and a minimal formation of extracellular matrix. In the treatment group, the chondral defect was approximately 90 percent filled with good integration between the neo-synthesized cartilage and the native cartilage. The repair tissue had a smooth surface with cells similar to chondrocytes and a hyaline-like extracellular matrix. The neo-synthesized cartilage was morphologically similar to hyaline cartilage. Importantly, there were no signs of graft-vs.-host rejections or infiltration by immune cells. In the neo-synthesized tissue, pig genetic material was detected in 27 +/- 5 percent of all cells. These cells containing pig genetic material were distributed throughout the neo-synthesized cartilage. We conclude that the xeno-transplantation of chondrocytes could be an alternative method for the repair of articular cartilage defects.

Animals↗