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Biomedical subjects

F Lopez

Publications and source records attributed to F Lopez.

At least 19 recordsLinked to original sources

AGScan: a pluggable microarray image quantification software based on the ImageJ library.

UNLABELLED: Many different programs are available to analyze microarray images. Most programs are commercial packages, some are free. In the latter group only few propose automatic grid alignment and batch mode. More often than not a program implements only one quantification algorithm. AGScan is an open source program that works on all major platforms. It is based on the ImageJ library [Rasband (1997-2006)] and offers a plug-in extension system to add new functions to manipulate images, align grid and quantify spots. It is appropriate for daily laboratory use and also as a framework for new algorithms. AVAILABILITY: The program is freely distributed under X11 Licence. The install instructions can be found in the user manual. The software can be downloaded from http://mulcyber.toulouse.inra.fr/projects/agscan/. The questions and plug-ins can be sent to the contact listed below.

Algorithms↗

Search for the lepton-number-violating decay Xi(-)-->pmu(-)mu(-).

A sensitive search for the lepton-number-violating decay Xi(-)-->pmu(-)mu(-) has been performed using a sample of approximately 10(9) Xi(-) hyperons produced in 800 GeV/c p-Cu collisions. We obtain B(Xi(-)-->pmu(-)mu(-))<4.0x10(-8) at 90% confidence, improving on the best previous limit by 4 orders of magnitude.

Journal Article↗

Search for DeltaS = 2 nonleptonic hyperon decays.

A sensitive search for the rare decays Omega(-)--> Lambdapi(-) and Xi(0)--> ppi(-) has been performed using data from the 1997 run of the HyperCP (Fermilab E871) experiment. Limits on other such processes do not exclude the possibility of observable rates for |DeltaS| = 2 nonleptonic hyperon decays, provided the decays occur through parity-odd operators. We obtain the branching-fraction limits B(Omega(-)-->Lambdapi(-)) < 2.9 x 10(-6) and B(Xi(0)--> ppi(-)) < 8.2 x 10(-6), both at 90% confidence level.

Journal Article↗

Evidence for the decay sigma+ --> pmu+ mu-.

We report the first evidence for the decay Sigma(+)-->pmu(+)mu(-) from data taken by the HyperCP (E871) experiment at Fermilab. Based on three observed events, the branching ratio is B(Sigma(+)-->pmu(+)mu(-))=[8.6(+6.6)(-5.4)(stat)+/-5.5(syst)]x10(-8). The narrow range of dimuon masses may indicate that the decay proceeds via a neutral intermediate state, Sigma(+)-->pP(0),P0-->mu(+)mu(-) with a P0 mass of 214.3+/-0.5 MeV/c(2) and branching ratio B(Sigma(+)-->pP(0),P0-->mu(+)mu(-))=[3.1(+2.4)(-1.9)(stat)+/-1.5(syst)]x10(-8).

Journal Article↗

Heterogeneous airway versus tissue mechanics and their relation to gas exchange function during mechanical ventilation.

We have advanced a commercially available ventilator (NPB840, Puritan Bennett/Tyco Healthcare, Pleasanton, CA) to deliver an Enhanced Ventilation Waveform (EVW). This EVW delivers a broadband waveform that contains discrete frequencies blended to provide a tidal breath, followed by passive exhalation. The EVW allows breath-by-breath estimates of frequency dependence of lung and total respiratory resistance (R) and elastance (E) from 0.2 to 8 Hz. We hypothesized that the EVW approach could provide continuous ventilation simultaneously with an advanced evaluation of mechanical heterogeneities under heterogeneous airway and tissue disease conditions. We applied the EVW in five sheep before and after a bronchial challenge and an oleic acid (OA) acute lung injury model. In all sheep, the EVW maintained gas exchange during and after bronchoconstriction, as well as during OA injury. Data revealed a range of disease conditions from mild to severe with heterogeneities and airway closures. Correlations were found between the arterial partial pressure of oxygen (PaO2) and the levels and frequency-dependent features of R and E that are indicative of mechanical heterogeneity and tissue disease. Lumped parameter models provided additional insight on heterogeneous airway and tissue disease. In summary, information obtained from EVW analysis can provide enhanced guidance on the efficiency of ventilator settings and on patient status during mechanical ventilation.

Animals↗

Search for CP violation in charged-Xi and Lambda hyperon decays.

We have compared the p and p angular distributions in 117 x 10(6) Xi- -->Lambdapi- -->ppi-pi- and 41 x 10(6) Xi+ -->Lambda pi+ -->p pi+pi+ decays using a subset of the data from the HyperCP experiment (E871) at Fermilab. We find no evidence of CP violation, with the direct-CP-violating parameter AXiLambda identical with (alphaXialphaLambda-alpha Xialpha Lambda)/(alphaXialphaLambda+alphaXialphaLambda)=[0.0+/-5.1(stat)+/-4.4(syst)] x 10(-4).

Journal Article↗

Therapeutic immunization with an inactivated HIV-1 Immunogen plus antiretrovirals versus antiretroviral therapy alone in asymptomatic HIV-infected subjects.

To determine whether the addition of an inactivated-gp120-depleted HIV-1 Immunogen to antiretrovirals (ARTs) conferred a beneficial effect on delaying time to virologic failure relative to that obtained by ARTs alone, a phase II clinical trial was performed in 243 asymptomatic, ART naïve, HIV-1 seropositive adults. The Cox model showed that HIV-1 Immunogen treatment was associated with a 34% decrease in the risk of virologic failure (P = 0.056). When the analysis incorporated baseline HIV-RNA stratification the risk of virologic failure in the HIV-1 Immunogen Arm was significantly reduced a 37% compared to the IFA placebo Arm (P = 0.034). The data suggest that therapeutic immunization plus ARTs could influence virologic control.

AIDS Vaccines↗

Feature extraction and signal processing for nylon DNA microarrays.

BACKGROUND: High-density DNA microarrays require automatic feature extraction methodologies and softwares. These can be a potential source of non-reproducibility of gene expression measurements. Variation in feature location or in signal integration methodology may be a significant contribution to the observed variance in gene expression levels. RESULTS: We explore sources of variability in feature extraction from DNA microarrays on Nylon membrane with radioactive detection. We introduce a mathematical model of the signal emission and derive methods for correcting biases such as overshining, saturation or variation in probe amount. We also provide a quality metric which can be used qualitatively to flag weak or untrusted signals or quantitatively to modulate the weight of each experiment or gene in higher level analyses (clustering or discriminant analysis). CONCLUSIONS: Our novel feature extraction methodology, based on a mathematical model of the radioactive emission, reduces variability due to saturation, neighbourhood effects and variable probe amount. Furthermore, we provide a fully automatic feature extraction software, BZScan, which implements the algorithms described in this paper.

Algorithms↗

Amniotic fluid embolism during caesarean section.

Amniotic fluid embolism occurs rarely but is a leading cause of maternal mortality. A high index of clinical suspicion is necessary to make an early diagnosis to reduce morbidity and mortality. We report a non-fatal case of amniotic fluid embolism occurring during a caesarean section, with special emphasis on the mode of development and diagnosis. The initial presentation of this syndrome was a coagulopathy, followed by the usual complications of massive bleeding. Although non-specific, the diagnosis of amniotic fluid embolism was supported by the observation of amniotic fluid in the central venous blood as well as in the broncho-alveolar fluid.

Adult↗

Characteristics of sensitometric curves of radiographic films.

A new type of radiographic film, EDR (extended dose range) film, has been recently become available for film dosimetry. It is particularly attractive for composite isodose verification of intensity modulated radiation therapy because of its low sensitivity relative to the more common Kodak XV film. For XV film, the relationship between optical density and dose, commonly known as the sensitometric curve, depends linearly on the dose at low densities. Unlike XV film, the sensitometric curve of EDR film irradiated by megavoltage x rays is not linearly dependent on the dose at low densities. In this work, to understand the mechanisms governing the shape of the sensitometric curves, EDR film was studied with kilovoltage x rays, 60Co gamma rays, megavoltage x rays, and electron beams. As a comparison, XV film was also studied with the same beams mentioned above. The model originally developed by Silberstein [J. Opt. Soc. Am. 35, 93-107, 1945)] is used to fit experimental data. It is found that the single hit model can be used to predict the sensitometric curve for XV films irradiated by all beams used in this work and for EDR films exposed to kilovoltage x rays. For EDR film irradiated by 60Co gamma rays, megavoltage x rays, and electron beams, the double hit model is used to fit the sensitometric curves. For doses less than 100 cGy, a systematic difference between measured densities and that predicted by the double hit model is observed. Possible causes of the observed differences are discussed. The results of this work provide a theoretical explanation of the sensitometric behavior of EDR film.

Dose-Response Relationship, Radiation↗

Observation of the decay K- --> pi(-)mu(+)mu(-) and measurements of the branching ratios for K+/- --> pi(+/-)mu(+)mu(-).

Using data collected with the HyperCP (E871) spectrometer during the 1997 fixed-target run at Fermilab, we report the first observation of the decay K--->pi(-)mu(+)mu(-) and new measurements of the branching ratios for K+/--->pi(+/-)mu(+)mu(-). By combining the branching ratios for the decays K+-->pi(+)mu(+)mu(-) and K--->pi(-)mu(+)mu(-), we measure Gamma(K+/--->pi(+/-)mu(+)mu(-))/Gamma(K+/--->all) = (9.8+/-1.0+/-0.5)x10(-8). The CP asymmetry between the rates of the two decay modes is [Gamma(K+-->pi(+)mu(+)mu(-))-Gamma(K--->pi(-)mu(+)mu(-))]/[Gamma(K+-->pi(+)mu(+)mu(-))+Gamma(K--->pi(-)mu(+)mu(-))] = -0.02+/-0.11+/-0.04.

Journal Article↗

Epidural analgesia with 0.15% ropivacaine plus sufentanil 0.5 microgram ml-1 versus 0.10% bupivacaine plus sufentanil 0.5 microgram ml-1: a double-blind comparison during labour.

BACKGROUND: Ropivacaine has been claimed to produce less motor block than bupivacaine during epidural analgesia. However, this advantage has not been clearly confirmed in obstetric studies using low analgesic concentrations in a ratio close to that suggested to be equianalgesic. METHODS: This double-blind, randomized, prospective study was performed in 140 parturients who requested epidural analgesia. After a lumbar epidural catheter had been placed, patients received either 0.10% bupivacaine plus sufentanil 0.5 microgram ml-1 or 0.15% ropivacaine plus sufentanil 0.5 microgram ml-1 followed by a continuous infusion. Additional boluses were used for inadequate levels of analgesia. Visual analogue pain scores, motor block, level of sensory block, supplementary boluses and main characteristics of labour were recorded. RESULTS: No differences were observed between the two groups for pain scores, total volume of anaesthetic solution used [59 (23) and 57 (24) ml in the bupivacaine and ropivacaine groups respectively], duration of labour, mode of delivery, side-effects or satisfaction score. The incidence of motor block was not statistically different between the groups (54 and 69% in the bupivacaine and ropivacaine groups respectively, P = 0.07). However, when motor block occurred, survival analysis showed that it occurred sooner in the course of labour with ropivacaine compared with bupivacaine (log rank test, P = 0.012). CONCLUSION: Combined with sufentanil 0.5 microgram ml-1, 0.10% bupivacaine and 0.15% ropivacaine produce effective and equivalent analgesia during labour, with similar incidences of motor block.

Adult↗

Evaluation of Kodak EDR2 film for dose verification of intensity modulated radiation therapy delivered by a static multileaf collimator.

A new type of radiographic film, Kodak EDR2 film, was evaluated for dose verification of intensity modulated radiation therapy (IMRT) delivered by a static multileaf collimator (SMLC). A sensitometric curve of EDR2 film irradiated by a 6 MV x-ray beam was compared with that of Kodak X-OMAT V (XV) film. The effects of field size, depth and dose rate on the sensitometric curve were also studied. It is found that EDR2 film is much less sensitive than XV film. In high-energy x-ray beams, the double hit process is the dominant mechanism that renders the grains on EDR2 films developable. As a result, in the dose range that is commonly used for film dosimetry for IMRT and conventional external beam therapy, the sensitometric curves of EDR2 films cannot be approximated as a linear function, OD = c * D. Within experimental uncertainty, the film sensitivity does not depend on the dose rate (50 vs 300 MU/min) or dose per pulse (from 1.0 x 10(-4) to 4.21 x 10(-4) Gy/pulse). Field sizes and depths (up to field size of 10 x 10 cm2 and depth = 10 cm) have little effect on the sensitometric curves. Percent depth doses (PDDs) for both 6 and 23 MV x rays were measured with both EDR2 and XV films and compared with ion chamber data. Film data are within 2.5% of the ion chamber results. Dose profiles measured with EDR2 film are consistent with those measured with an ion chamber. Examples of measured IMRT isodose distributions versus calculated isodoses are presented. We have used EDR2 films for verification of all IMRT patients treated by SMLC in our clinic. In most cases, with EDR2 film, actual clinical daily fraction doses can be used for verification of composite isodose distributions of SMLC-based IMRT.

Adult↗

Neuronal nitric oxide synthase: a substrate for SHP-1 involved in sst2 somatostatin receptor growth inhibitory signaling.

Somatostatin receptor sst2 is an inhibitory G protein-coupled receptor, which inhibits normal and tumor cell growth by a mechanism involving the tyrosine phosphatase SHP-1. We reported previously that SHP-1 associates transiently with and is activated by sst2 and is a critical component for sst2 growth inhibitory signaling. Here, we demonstrate that in Chinese hamster ovary cells expressing sst2, SHP-1 is associated at the basal level with the neuronal nitric oxide synthase (nNOS). Following sst2 activation by the somatostatin analog RC-160, SHP-1 rapidly recruits nNOS tyrosine dephosphorylates and activates it. The resulting NO activates guanylate cyclase and inhibits cell proliferation. Coexpression of a catalytically inactive SHP-1 mutant with sst2 blocks RC-160-induced nNOS dephosphorylation and activation, as well as guanylate cyclase activation. In mouse pancreatic acini, RC-160 treatment reduces nNOS tyrosine phosphorylation accompanied by an increase of its activity. By opposition, in acini from viable motheaten (mev/mev) mice, which express a markedly inactive SHP-1, RC-160 has no effect on nNOS activity. Finally, expression of a dominant-negative form of nNOS prevents both RC-160-induced p27 up-regulation and cell proliferation inhibition. We therefore identified nNOS as a novel SHP-1 substrate critical for sst2-induced cell-growth arrest.

Animals↗

Multinodular polymyositis in a patient with human immunodeficiency and hepatitis C virus coinfection.

We report a patient who developed multiple inflammatory muscle masses and generalized polymyositis in the setting of combined human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. Magnetic resonance imaging (MRI) of muscles showed patchy edema which was particularly intense within the nodular masses. Polymerase chain reaction (PCR) showed no evidence of either virus within muscle. This report reviews earlier literature on muscle nodules associated with myositis and discusses the differential diagnosis of muscle masses in HIV infection.

Adult↗

Somatostatin inhibits stem cell factor messenger RNA expression by Sertoli cells and stem cell factor-induced DNA synthesis in isolated seminiferous tubules.

Immature porcine Sertoli cells have been reported to be targets for the regulatory peptide somatostatin (SRIF), which inhibits the basal and FSH-induced proliferation of Sertoli cells through a decrease of cAMP production. In the present study, we show that SRIF inhibits both basal and FSH-stimulated expression of the stem cell factor (SCF), a Sertoli cell-specific gene. The SRIF-mediated inhibition of forskolin-triggered, but not of 8-bromoadenosine-cAMP-triggered, SCF mRNA expression demonstrates the involvement of adenylyl cyclase in underlying peptide actions. Moreover, these effects require functional coupling of specific plasma membrane receptors to adenylyl cyclase via inhibitory G proteins, because pertussis toxin prevents SRIF-mediated inhibition of SCF mRNA expression. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assays suggest the involvement of sst2 receptors in SRIF actions on Sertoli cells. The biological relevance of these data is supported by an SRIF-mediated decrease in SCF-induced incorporation of [(3)H]thymidine in isolated seminiferous tubules. In situ hybridization and confocal microscopy show that, in seminiferous tubules only, spermatogonia display both c-kit and sst2 receptors. Taken together, these results suggest that SCF-stimulated DNA synthesis can be inhibited by SRIF in spermatogonia, but not in Sertoli and peritubular cells. Combined RT-PCR and immunohistochemical approaches point toward spermatogonia and Leydig cells as the source of testicular SRIF. These data argue in favor of paracrine/autocrine SRIF actions in testis.

8-Bromo Cyclic Adenosine Monophosphate↗

Dependence of virtual wedge factor on dose calibration and monitor units.

One of the important features of the Siemens Virtual Wedge (VW) is that the VW factor (VWF) is approximately equal to unity for all beams with a total deviation for a given wedge no greater than 0.05, as specified by Siemens. In this note we report the observed dependence of VWF on dose calibration (cGy/MU), monitor units (MU), and beam tuning for a Primus, a linear accelerator with two dose-rate ranges available for VW operation. The VWF is defined as the ratio of doses measured on the beam central axis for the wedge field to the open field; the open field dose is always measured with the nominal high dose-rate beam. When VW operates in the high dose-rate range, the VWF is independent of calibration (cGy/MU). When VW works in the low dose-rate range, the VWF varies linearly with the calibration of the low dose-rate mode. For a linear accelerator that has only one dose-rate range for VW, there is no observable dependence of VWF on the calibration. We also studied the monitor unit dependence of VWF. A discontinuity in VWF was observed at the switching point between the high and low dose-rate ranges. Working with Siemens, we have investigated causes of this discontinuity. As a result of this investigation, the discontinuity in VWF as a function monitor unit is practically removed.

Biophysical Phenomena↗