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C Delgado

Publications and source records attributed to C Delgado.

At least 55 records · Page 3Linked to original sources
PubMed1997

Modulation of electrical heterogeneity by compensated hypertrophy in rat left ventricle.

Modulation of the regional distribution of the action potential by left ventricular hypertrophy and the role of the L-type Ca2+ current (I(Ca)) and transient outward current (I(to)) in the action potential duration (APD) were investigated in normal and hypertrophied rat ventricular myocytes from the apex (A), septum (S) and left ventricular free wall (FW) by using whole cell current- and voltage-clamp techniques. Hypertrophy was induced by abdominal aortic constriction. In control cells, the APD measured at 20% repolarization (APD20) assumed the shortest values in the A and the longest in the S, whereas FW cells showed intermediate values. Hypertrophy significantly prolonged the APD20 and increased APD variability within the A and FW regions but did not modify the APD in S cells. Analysis of the APD, I(Ca), and I(to) at the instant of 20% repolarization in the same cell showed that in control cells the shortest APD20 was associated with a prominent I(to) in the A and FW, whereas the long APD20 was identified with a lower I(to) in S myocytes. Hypertrophy-induced prolongation ofAPD20 was associated with a reduction in the I(to) in the A and FW. Significant correlations could be established between the APD20 and the "net current," defined as the algebraic addition of I(to) and I(Ca) in the A and FW control groups but not in the control S or hypertrophied cells whatever their origin. Our results indicate that interregional APD heterogeneity is lost while intraregional APD variability is increased in the A and FW during the hypertrophic process. These effects are largely due to a change in the balance between the I(Ca) and I(to), which is a major contributing factor to the heterogeneity of the initial phase of repolarization in the normal rat ventricle.

Action Potentials↗
PubMed1997

A chloride current component induced by hypertrophy in rat ventricular myocytes.

The effect of hypertrophy on membrane currents of rat left ventricular myocytes was studied with the whole cell voltage-clamp method. We found that the slope of the total time-independent current density-voltage relationship was increased in hypertrophied cells. No change in the zero-current potential was observed. Surprisingly, the dominant time-independent current, the inward rectifier K+ current (measured as the Ba(2+)-sensitive current density) was unchanged. We therefore investigated the identity of the outwardly rectifying Ba(2+)-resistant current seen in the hypertrophied rat ventricular myocytes but not present in control cells. We found that this current 1) was not carried by monovalent cations, 2) was partially blocked by anthracene-9-carboxylic acid (9-AC), and 3) was sensitive to variations in extracellular Cl concentration. These findings are consistent with the current being carried at least partially by Cl-. The presence of an additional Cl(-)-dependent component in hypertrophied cells is supported by the actions of 9-AC on the measured action potentials (APs). 9-AC had no effect on control cells APs but prolonged hypertrophied cell APs. We conclude that a Cl- current component develops in hypertrophied rat heart cells. This component appears to shorten the AP duration and might thus provide protection from cardiac arrhythmias.

Animals↗
PubMed1996

Enhanced tumour specificity of an anti-carcinoembrionic antigen Fab' fragment by poly(ethylene glycol) (PEG) modification.

Polyethylene glycol (PEG) modification of a chimeric Fab' fragment (F9) of A5B7 (alpha-CEA), using an improved coupling method, increases its specificity for subcutaneous LS174T tumours. PEGylation increased the area under the concentration-time curve (AUC0-144) in all tissues but there were significant differences (variance ratio test, F = 27.95, P < 0.001) between the proportional increases in AUC0-144, with the tumour showing the greatest increase. The increase in AUCtumour from F9 to PEG-F9 was similar to the reported increase from Fab' to F(ab')2 while the increase in AUCblood by PEGylation of F9 was only 21% of the reported increase from Fab' to whole IgG. A two sample t-test showed no significant differences between maximal tumour/tissue ratios for PEG-F9 and F9 while the tumour/tissue ratios for PEG-F9 remained high over a longer period, with tumour levels at least double those for F9. PEG-F9 emerges as a new generation antibody with potential advantages for both radioimmunotherapy and tumour imaging. Since there was a reduction in antigen binding, optimisation of PEGylation might further improve tumour specificity. The latter resulted from complex effects on both the entry into and exit rates from tumour and normal tissues in a tissue-specific fashion.

Adenocarcinoma↗
PubMed1996

Cholesterol oxidase from Rhodococcus equi is likely the major factor involved in the cooperative lytic process (CAMP reaction) with Listeria monocytogenes.

The CAMP reaction between Listeria monocytogenes and Rhodococcus equi was studied by a diffusion assay. Listeria monocytogenes displayed identical cooperative haemolytic effect with supernatant cultures of R. equi or with commercial cholesterol oxidase (COX). This result, even with enzymes of different sources (commercial COX is obtained from Pseudomonas spp.) suggests that this enzyme secreted by R. equi has a crucial role in the synergistic haemolytic (CAMP) reaction with L. monocytogenes. The mechanism of the cooperative lytic process between L. monocytogenes and R. equi may represent a different and novel mechanism reaction, in which the COX may not act as a conventional second-step factor, and a reaction different to the direct interaction with the cholesterol of the erythrocyte membrane may be involved.

Cholesterol Oxidase↗
PubMed1996

Polyethylene glycol modification: relevance of improved methodology to tumour targeting.

Of all the polymers applied to molecule altering structural chemistry, polyethylene glycol (PEG) modification has numerous benefits and relatively few drawbacks. PEG is now increasingly being applied to the problems of tumour targeting, both in the context of the passive targeting of PEG-liposomes and in active targeting strategies using PEGylated anti-tumour antibodies. PEG can also serve as a useful linker molecule between targeting moieties and other agents, including cytotoxic or imaging agents and targeted liposomes. Despite these demonstrated benefits and the level of attention which PEGylation has received, relatively little consideration has been given to two key areas: first, the extent to which the coupling method has an impact on both the functionality of the PEG-adduct and the acquisition of beneficial properties; second, that the impact of PEGylation on biodistribution is complex, thus any attempt to optimise a PEG-peptide or PEG-liposome for a particular task must involve an examination of all the individual facets of the effects of PEGylation. Studies investigating the underlying principles of tumour targeting suggest that current views concerning the optimisation of PEGylated vehicles for tumour localisation need to be re-examined.

Antibody Formation↗
PubMed1996

Use of rhG-CSF in the collection of peripheral blood stem cells for autologous blood stem cell transplantation in acute myeloblastic leukemia.

The use of recombinant granulocyte colony-stimulating factor (rhG-CSF) alone is attractive for the collection of peripheral blood stem cells (PBSC) in several malignancies. In acute myeloblastic leukemia (AML), not enough experience has been gained with rhG-CSF and leukapheresis is more common after recovery from antileukemia chemotherapy. This is the case report of a patient who received rhG-CSF alone to mobilize stem cells where the cells collected in the leukapheresis bag had a blastic immunophenotype.

Granulocyte Colony-Stimulating Factor↗
PubMed1995

Silent giant left atrium. A case report.

A sixty-two-year-old white woman with a 14.5 cm (145 mm) silent giant left atrial enlargement secondary probably to rheumatic heart disease is presented. Aside from mild progressive shortness of breath during the past year, the patient had been asymptomatic all her life. Her clinical picture was manifested for the first time by syncope secondary to slow atrial fibrillation, for which a permanent pacemaker was required. The correct diagnosis of the enlarged chamber was not possible through the routine chest roentgenogram. In this case, the echocardiogram, nuclear angiogram, and computed tomography were the pertinent studies needed to reach the diagnosis.

Cardiomegaly↗
PubMed1995

[Kinetic model of micro-organism growth: the case of Xanthomonas campestris].

Microbial growth is studied and kinetic models to describe the process rate useful in the scale-up are proposed. The growth of Xanthomonas campestris NRRL B-1459, a bacterium producing xanthan, a major industrial gum, is studied. Experimental data are arranged by means of different methods, and linear and non-linear regression techniques are applied in several ways (i.e. fixing or not fixing the values of certain parameters) and they are compared. To obtain parameter values with statistical meaning, two parameters must be calculated (namely, the maximum specific growth rate and the maximum biomass concentration available) by means of a non-linear regression technique employing the logistic equation. The maximum specific growth rate is related to temperature by means of different equations, but that of Ratkowsky et al. is the most suitable for X. campestris growth. Studied variables present no tendency to error and the reproduction of experimental data is very good.

Bacteriological Techniques↗
PubMed1994

Quantitative analysis of polyethylene glycol (PEG) in PEG-modified proteins/cytokines by aqueous two-phase systems.

Covalent attachment of poly(ethylene glycol) (PEG) to proteins produces conjugates with altered/improved physicochemical and biological properties which depend upon the number of PEG chains linked. Quantification of the attached PEG is however not a trivial issue. The partition coefficient, K, of the PEG-protein conjugate in PEG/dextran two-phase systems provides a quantitative measure for the degree of modification. A linear relationship between log K and the number of PEG chains was observed in fractionated PEG-modified-granulocyte-macrophage colony stimulating factor conjugates having 1 to 3 substitutions. Furthermore, in mixtures of PEG-bovine-serum-albumin conjugates with increasing degrees of modification, a linear relationship was found between log K and n, the average substitution. The increment in log K per PEG chain added is protein specific and this suggests that the interactions between the PEG-protein conjugate and the polymers in the phase system are more complex than just a simple affinity of the PEG for the PEG-rich top phase. Increasing the polymer concentration in the phase system produces larger increments in log K per PEG molecule attached and the proportionality between log K and number of PEG molecules is only compromised for conjugates with high degree of substitution when partitioned in biphasic systems of high concentration of polymers.

Chemical Phenomena↗
PubMed1994

Assessment of tricuspid regurgitation by Doppler color flow imaging: angiographic correlation.

The correlation between data obtained by Doppler color flow imaging and angiographic severity has been investigated in mitral and aortic regurgitation. However, similar studies have not been performed for tricuspid regurgitation (TR). This study was performed to establish the correlation between measurements of regurgitant jet area by Doppler color flow imaging and the angiographic severity of TR. Fifty-four patients with rheumatic heart disease who underwent right ventriculography and transthoracic Doppler color flow imaging were studied. The regurgitant jet area was measured as the largest clearly definable flow disturbance in apical four-chamber and right ventricle inflow views, and expressed in both views as the absolute jet area or as the ratio of maximal jet area to right atrial area. Correlation of all Doppler color flow measurements with angiographic grades of TR were comparable, absolute jet area in apical four-chamber view being closest at r = 0.80. A regurgitant jet area in apical four-chamber view < 5 cm2 predicted minimal or mild TR by angiography with a sensitivity of 78% and a specificity of 100%, whereas a regurgitant jet area > 10 cm2 predicted severe TR with a sensitivity of 92% and a specificity of 91%. Values between 5 and 10 cm2 predicted moderate TR with a sensitivity of 89% and a specificity of 89%. Sensitivity and specificity were not improved with use of the ratio of jet area to right atrial area or with use of right ventricle inflow view. Thus, Doppler color flow jet measurements correlate closely with angiographic results in the evaluation of TR.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

Retrosternal goiter associated with chylothorax.

We describe a case of chylothorax in a female patient with a large retrosternal goiter. After subtotal thyroidectomy by means of a Kocher cervicotomy, the chylothorax disappeared in 48 h. At present, 2 years after surgical removal, the patient remains asymptomatic, without recurrent pleural chylous effusion. Until now, to our knowledge, only one such case had been reported.

Aged↗
PubMed1994

[The estimation of the severity of tricuspid insufficiency by Doppler color: the effects of gain, pulse repetition frequency and the echographic view].

INTRODUCTION AND OBJECTIVES: Regurgitant jet area is to date the most widely accepted color Doppler parameter for quantitation of atrium-ventricular regurgitations. In experimental studies, it has been demonstrated that color regurgitant jet area is greatly influenced by technical settings. The present study was aimed to analyze the effect of gain setting, pulse repetition frequency and echocardiographic plane on color jet area in patients with tricuspid regurgitation. METHODS: We studied 64 patients with nontrivial (more than 1 cm2), rheumatic tricuspid regurgitation. Examinations were performed in apical four-chamber and right ventricle inflow-tract views, at two gain settings (subsaturation gain and 1/3 reduced gain) and at two pulse repetition frequencies (3.1 and 3.8 kHz). Therefore, every regurgitant jet was study under 8 different technical conditions. The remaining technical settings were held unchanged included throughout the studies. The traced area induced central varianced and aliased signals, as well as the immediately contiguous nonturbulent velocities that were moving in the same direction as the jet. Measurements were taken from 5 and 3 representative cycles in patients with atrial fibrillation and sinus rythm, respectively. RESULTS: Globally, reduction in gain setting produced a color area decrease by 50%. This reduction was of greater extent for small jets (less than 5 cm2, 45 +/- 17%) with respect to larger jets (more than 5 cm2, 61 +/- 30%, p = 0.0009). Results were similar for both apical four-chamber and right ventricle inflow views and for the two pulse repetition frequencies. At a given color gain level and echocardiographic view, pulse repetition frequency at 3.1 kHz produced greater color areas (by 3-11%) than frequency at 3.8 kHz, but the difference was not significant. Overall, color jet area was significantly greater in right ventricle inflow view than in apical four-chamber view, but substantial individual variability was observed. Difference between both views was greater than 40% in 28% of patients, with the largest color area in right ventricle inflow view in most, especially in those patients with eccentric jets. CONCLUSIONS: Gain setting and echocardiographic view greatly affect regurgitant jet area by color Doppler in patients with tricuspid regurgitation. Therefore, standardization of technical settings is mandatory in order to avoid diagnostic pitfalls.

Aged↗
PubMed1994

Effects of DNA topoisomerase II inhibitors on human bone marrow progenitor cells.

Topoisomerase II (topo II) is a target for many cytotoxic agents. Two observations, however, warrant caution in their therapeutic use: first, these agents can inhibit differentiation and second, perturbations in function render the enzyme error-prone. Illegitimate recombination events occurring at sites where topo II acts in differentiation could be particularly important in the development of secondary malignancies (relatively frequent after therapy with agents that target topo II). Topo II inhibitors are heterogeneous in mechanisms of action; in site-specificity of cleavable complex 'entrapment' (where present) and in the relative potency against the two topo II isoforms, all potentially influencing the site of maximum DNA damage. The object of this study was to examine the effect of topo II inhibitors on human haemopoietic precursor cells, to determine which have most impact on differentiation. We selected two which act via cleavable complex entrapment, but with different site preferences (m-AMSA and VP-16), and two acting via other mechanisms (merbarone and fostriecin). VP-16 and m-AMSA showed similar patterns with low dose stimulation of granulocyte-macrophage colony formation and high dose inhibition of all colony types. The stimulation was accompanied by an increase in colony size and blast content, consistent with a low dose inhibition of differentiation. Forstriecin, in contrast, stimulated predominantly mixed and erythroid colonies. Merbarone failed to increase colony formation. Neither produced substantial inhibition of colony formation. The effects on granulocyte-macrophage progenitors were confirmed using 7-day suspension cultures, using nitroblue tetrazolium (NBT) reduction and 3-4,5,dimethylthiazol 2,5-diphenyl tetrazolium bromide (MTT) assays for differentiated cells and total cell mass, respectively. These results demonstrate that the effects of topo II inhibitors on haemopoietic cell proliferation and differentiation are agent-specific and can involve lineage-restricted partial inhibition of differentiation.

Adult↗
PubMed1993

Functional and molecular characterization of tumor-infiltrating lymphocytes transduced with tumor necrosis factor-alpha cDNA for the gene therapy of cancer in humans.

TNF is effective in causing the regression of selected murine tumors when administered at high concentrations. Therapeutic levels in humans cannot be obtained systemically, however, because of dose-limiting toxicity. The development of immunotherapy with IL-2 and tumor-infiltrating lymphocytes (TIL), which can accumulate at tumor sites in some patients, and of efficient retroviral techniques for gene transfer into eukaryotic cells has allowed new therapeutic approaches using TNF. We have retrovirally transduced human TIL with the gene for TNF in an attempt to deliver high concentrations of TNF to the tumor site without dose-limiting systemic toxicity. Successful gene insertion was confirmed by Southern hybridization in 16 of 16 transduced and selected TIL cultures from 15 different patients, with an estimated 28 to 93% transduced cells within each culture. Transduced selected TIL cultures produced greater amounts of TNF, compared with nontransduced controls, in 11 of 16 cultures evaluated. However, overall production of TNF was > 30-fold lower, compared with a transduced and highly selected tumor cell line control (MEL-TNF). In addition, steady state levels of vector-derived transcript in nine of 10 transduced selected TIL cultures were < 14% of the amount seen in the MEL-TNF control line. In an attempt to increase TNF production, TIL were transduced with a mutated form of TNF containing the IFN-gamma signal peptide in place of the transmembranous region, to enhance secretion into the endoplasmic reticulum. By using this vector, TNF production increased by an average of fivefold. These studies demonstrate that TIL can be genetically modified to express and secrete a protein for use in targeted cancer therapy but that partial expression blockades exist that prevent maximal cytokine production by introduced genes in TIL.

DNA↗
PubMed1993

Effects of propafenone on calcium current in guinea-pig ventricular myocytes.

1. The modulation of L-type voltage-sensitive calcium channels in guinea-pig isolated ventricular myocytes by propafenone was examined by the whole cell voltage-clamp technique. 2. Propafenone, 10(-7) -5 x 10(-5) M, produced a concentration-dependent inhibition of Ca current (ICa) without any significant change in the current-voltage relation. Half-blocking concentration (IC50) of propafenone for the peak ICa at +10 mV was 5 x 10(-6) M. 3. The voltage-dependence of ICa inactivation was shifted in the hyperpolarizing direction in the presence of 5 x 10(-6) M propafenone. 4. A frequency-dependent relative block by propafenone was observed after repetitive depolarizing test pulses at a frequency of 0.5 and 1 Hz. The recovery of ICa from inactivation was prolonged by propafenone and the reactivation exhibited an additional exponential component attributed to the slow release from drug block of Ca channels. 5. These results suggest that propafenone, at therapeutic concentrations exhibits Ca channel blocking properties that may be involved in its antiarrhythmic mechanism.

Animals↗
PubMed1993

Heterogeneity of the early outward current in ventricular cells isolated from normal and hypertrophied rat hearts.

1. The nature, magnitude and kinetics of the 4-aminopyridine-sensitive early outward current (Ito) were analysed in isolated ventricular myocytes from the septum, the apex and the left ventricular free wall of rat ventricles using the whole-cell voltage clamp method. The modulatory effect of pressure overload-induced cardiac hypertrophy on the regional variations of Ito was assessed in each topographical class of cells. 2. Voltage clamp experiments were performed at room temperature (20-25 degrees C) in the absence of Na+ on both sides of the membrane and in the presence of 3 mM CoCl2. Ito was studied from a holding potential of -80 mV and determined by subtraction of total outward currents elicited by the same protocols in the presence of 3 mM 4-aminopyridine (4-AP) from those obtained in its absence. 3. In normal hearts, membrane passive properties were very similar in each topographical class of cells. Our results confirmed that the predominant early outward current in rat ventricular cells was 4-AP-sensitive, time and voltage dependent, and demonstrated that the magnitude of the current varied on a regional basis: current density of Ito in left ventricular free wall cells (30.1 +/- 9.2 pA/pF at +60 mV) was larger than in apex cells (20.2 +/- 1.7 pA/pF) or in septum cells (11.9 +/- 3.3 pA/pF). We noticed a larger variability in data from left ventricular free wall compared with other regions. 4. No shift in steady-state voltage dependence of Ito activation and inactivation was found. However, the maximal computed chord conductances were (in microS/pF): 0.18 +/- 0.07 for left ventricular free wall cells, 0.13 +/- 0.02 for apex cells, and 0.08 +/- 0.02 for septum cells. These findings might reflect a differential distribution in functional channel densities. 5. No difference in voltage-dependent Ito activation kinetics was present with respect to topography. However, inactivation time constants in septum were longer than those of both other groups. 6. Left ventricular hypertrophy was induced by abdominal aortic constriction and its effects compared to the findings from normal rats. Hypertrophied cells had similar resting potentials but higher capacitance values than normal cells. Although Ito magnitude appeared not to be modified, the current density-voltage curves were slightly shifted to more positive potentials and significantly decreased as compared to normal cells (in pA/pF, at +60 mV): 8.4 +/- 5.0 in the left free wall group, 11.6 +/- 2.0 in the apex group, and 3.8 +/- 1.5 in the septum group.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗