Biomedical subjects

J Castro

Publications and source records attributed to J Castro.

At least 19 recordsLinked to original sources

PubMed2003

Combination of low-dose cisplatin and gemcitabine for treatment of elderly patients with advanced non-small-cell lung cancer.

PURPOSE: To evaluate the feasibility, toxicity and efficacy of the combination of low-dose cisplatin (CDDP) and gemcitabine (GEM) in elderly patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: This phase II trial included 46 patients aged 70 years or older with previously untreated advanced NSCLC. All patients were evaluable for response and toxicity. Treatment consisted of CDDP 50 mg/m(2) on day 1 plus GEM 1000 mg/m(2) on days 1 and 8. The regimen was repeated every 21 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: A total of 190 GEM-CDDP courses were administered (median 4.1 courses per patient). The chemotherapy regimen was well tolerated. No patients developed grade 4 toxicity. Grade 3 toxicities were as follows: neutropenia in six patients (13%), and anemia, thrombopenia and nausea/vomiting in one (2%) each. Two patients (4%) had mild nephrotoxicity. Of the 46 patients, 16 had a partial response (35%, 95% confidence interval, CI, 28-52%), 17 (37%) remained stable and 13 (28%) had disease progression. Eastern Cooperative Oncology Group performance status improved in 17 patients (37%), whereas 25 (54%, 95% CI 44-74%) showed a clinical benefit. Median time to progression was 20 weeks. Overall median survival was 44 weeks, with a 1-year actuarial survival rate of 35%. CONCLUSIONS: The combination of low-dose CDDP and GEM for elderly patients with advanced NSCLC is an effective and well-tolerated chemotherapeutic approach.

Aged↗

PubMed2003

Diode laser modifications for treatment of choroidal neovascularisation.

The aim of this paper is to describe various diode laser modifications and their use in treating choroidal neovascularisation in age-related macular degeneration. Diode lasers are used to treat selected choroidal neovascular membranes. Alterations in microprocessor connectivity, and parameters such as maximum spot size, light delivery time and coupled Joule meter, were made so that ophthalmic surgeons could specify treatment possibilities. A trimodal (photocoagulation, transpupillary thermotherapy and photodynamic therapy) application laser device coupled to a single light source has been developed. The new diode laser modifications were technically successful. Microprocessor connectivity was obtained, larger spot sizes were achieved, light delivery time could be extended and energy parameters were available at the display.

Choroid↗

PubMed2003

Phobic anxiety in 11 nations. Part I: Dimensional constancy of the five-factor model.

The Fear Survey Schedule-III (FSS-III) was administered to a total of 5491 students in Australia, East Germany, Great Britain, Greece, Guatemala, Hungary, Italy, Japan, Spain, Sweden, and Venezuela, and submitted to the multiple group method of confirmatory analysis (MGM) in order to determine the cross-national dimensional constancy of the five-factor model of self-assessed fears originally established in Dutch, British, and Canadian samples. The model comprises fears of bodily injury-illness-death, agoraphobic fears, social fears, fears of sexual and aggressive scenes, and harmless animals fears. Close correspondence between the factors was demonstrated across national samples. In each country, the corresponding scales were internally consistent, were intercorrelated at magnitudes comparable to those yielded in the original samples, and yielded (in 93% of the total number of 55 comparisons) sex differences in line with the usual finding (higher scores for females). In each country, the relatively largest sex differences were obtained on harmless animals fears. The organization of self-assessed fears is sufficiently similar across nations to warrant the use of the same weight matrix (scoring key) for the FSS-III in the different countries and to make cross-national comparisons feasible. This opens the way to further studies that attempt to predict (on an a priori basis) cross-national variations in fear levels with dimensions of national cultures.

Adolescent↗

PubMed2003

Apoptotic and necrotic blebs in epithelial cells display similar neck diameters but different kinase dependency.

Apoptotic and necrotic blebs elicited by H(2)O(2) were compared in terms of dynamics, structure and underlying biochemistry in HeLa cells and Clone 9 cells. Apoptotic blebs appeared in a few minutes and required micromolar peroxide concentrations. Necrotic blebs appeared much later, prior to cell permeabilization, and required millimolar peroxide concentrations. Strikingly, necrotic blebs grew at a constant rate, which was unaffected throughout successive cycles of budding and detachment. At 1 microm diameter, the necks of necrotic and apoptotic blebs were almost identical. ATP depletion was discarded as a major factor for both types of bleb. Inhibition of ROCK-I, MLCK and p38MAPK strongly decreased apoptotic blebbing but had no effect on necrotic blebbing. Taken together, these data suggest the existence of a novel structure of fixed dimensions at the neck of both types of plasma membrane blebs in epithelial cells. However, necrotic blebs can be distinguished from apoptotic blebs in their susceptibility to actomyosin kinase inhibition.

Actomyosin↗

PubMed2003

Association between parasitic intestinal infections and acute or chronic diarrhoea in HIV-infected patients in Caracas, Venezuela.

A cross sectional survey was conducted to determine the association between enteric parasites and diarrhoea in HIV-infected adults in Caracas. Three hundred and four patients were evaluated: 104 had acute diarrhoea, 113 chronic diarrhoea and 87 were controls. Isopora belli infection was associated with acute (P = 0.022) and chronic diarrhoea (P = 0.003), Entamoeba histolytica/dispar infection was also associated with both acute (P = 0.015) and chronic diarrhoea (P = 0.017). Strongyloides stercoralis (P = 0.003), and Cryptosporidium parvum (P = 0.017) infections were associated mainly with chronic episodes. Weight loss (P < 0.001), a non-infectious factor investigated, was significantly associated with diarrhoea. Eosinophilia, a laboratory parameter studied, was found to be associated with strongyloidiasis (P = 0.001), giardiasis (P = 0.001) and isoporiasis (P = 0.003). In summary, the presence of enteric parasites in HIV-infected patients from tropical urban areas with diarrhoea, with or without significant weight loss, must be considered. Similarly, eosinophilia might suggest parasitic infection in these patients.

AIDS-Related Opportunistic Infections↗

PubMed2002

Analysis of endosulfan isomers and endosulfan sulfate in air and tomato leaves by gas chromatography with electron-capture detection and confirmation by gas chromatography-mass spectrometry.

Rapid analytical methods for the determination of endosulfan isomers and endosulfan-sulfate in air and plant samples were developed. The insecticides were trapped from air using a column containing Florisil and extracted with a low volume of ethyl acetate, assisted by sonication. Pesticide residues were determined by gas chromatography with electron-capture detection using a nonpolar capillary column. Residue identities were confirmed by gas chromatography coupled with mass spectrometry. Recoveries of these compounds from air samples were always higher than 78% with an RSD lower than 11% and the detection limits obtained were at least 0.3 ng/l air. Leaf samples were homogenised with ethyl acetate and extracts cleaned-up on an aluminium oxide column. Pesticides were eluted with a hexane-ethyl acetate (80:20, v/v) mixture. Recoveries obtained from plant samples were higher than 78% with an RSD lower than 14% and detection limits in leaves were 0.02 microg/g for each pesticide. These methods were applied to study the volatilisation of endosulfan from tomato leaves under laboratory conditions. A volatilisation rate near 1% of the initial amount of endosulfan per hour was obtained during the first 24 h at room temperature.

Air↗

PubMed2002

Phase II study of a fixed dose-rate infusion of gemcitabine associated with uracil/tegafur in advanced carcinoma of the pancreas.

BACKGROUND: The objectives of this study were to evaluate the efficacy and toxicity of a fixed dose-rate infusion of gemcitabine associated with uracil/tegafur (UFT) in patients with advanced adenocarcinoma of the pancreas. PATIENTS AND METHODS: Forty-three chemotherapy-naïve patients with adenocarcinoma of the pancreas were included in this phase II study. All of whom had a Karnofsky performance status >or=50 and bi-dimensionally measurable disease (either advanced non-resectable or metastatic); median age 59 years (range 39-77); male:female ratio 29:14. Eight patients (19%) had locally advanced disease and 35 (81%) distant metastases. Treatment consisted of gemcitabine 1200 mg/m(2) given as a 120-min infusion weekly for 3 consecutive weeks, plus oral UFT 400 mg/m(2)/day (in 2-3 doses per day) on days 1-21, cycles were given every 28 days. Measurements of efficacy included response rate, clinical benefit response, time to disease progression and overall survival. RESULTS: A total of 192 cycles of chemotherapy were delivered with a median of four per patient. There were two complete responses (5%) and 12 partial responses (28%), producing an overall response rate of 33% [95% confidence interval (CI) 16% to 49%]. Thirteen patients (30%) had stable disease, whereas 16 (37%) had a progression. The median time to progression was 6 months and the median overall survival was 11 months. Twenty-five patients (64%, 95% CI 47% to 78%) experienced a clinical benefit response. Grade 3-4 WHO toxicities were: neutropenia in nine patients (21%); thrombocytopenia in four (9%); anaemia in five (12%); diarrhoea in four (9%); and asthenia in one (2%). CONCLUSIONS: A fixed dose-rate infusion of gemcitabine associated with UFT was well tolerated and showed promising activity in patients with locally advanced or metastatic carcinoma of the pancreas. This is an appropriate palliative treatment in this setting.

Adenocarcinoma↗

PubMed2001

Effects of HsRad51 overexpression on cell proliferation, cell cycle progression, and apoptosis.

Expression of the DNA repair and recombination protein human Rad51 (HsRad51) is increased in transformed cells and in cancer cell lines. In order to study the effects of acute HsRad51 ectopic overexpression on cell proliferation, cell cycle progression, and apoptosis, we generated clones of the human fibrosarcoma cell line HT1080 carrying a HsRad51 transgene under a repressible promoter. The HsRad51-overexpressing cells showed decreased plating efficiency and growth rate in a dose-dependent manner with regard to the degree of overexpression. An accumulation of HsRad51-overexpressing cells in G(2) was observed following release of cells after synchronization with double thymidine block. Moreover, the fraction of apoptotic cells measured by annexin V-FACS increased with the time of HsRad51 overexpression. In the light of these observations, sustained increased levels of HsRad51 may contribute to tumor progression by causing a selection for cells tolerant to the growth-suppressive and apoptosis-inducing effects of acute HsRad51 overexpression.

Annexin A5↗

PubMed2001

Multiresidue analysis of insecticides in soil by gas chromatography with electron-capture detection and confirmation by gas chromatography-mass spectrometry.

A rapid multiresidue method has been developed for the analysis of nine insecticides (organochlorines, pyrethroids and organophosphorus) in soil. The method is based on the sonication extraction of residues from a certain amount of soil placed in a small column, using ethyl acetate. The effect of the residence time of insecticides in soil, the material of the columns used (glass or plastic columns) and the soil moisture content on the recovery of these compounds was also studied. Residues were determined by gas chromatography with electron-capture detection. The average recovery through the method obtained for these compounds varied from 90 to 108% with a relative standard deviation between 1 and 11%. The results of this study pointed out that the recoveries of insecticide residues obtained with plastic or glass columns at different soil moisture content were similar and that the residence of these compounds in soil during several days did not affect their recovery from soil. Confirmation of residue identity was performed by gas chromatography coupled with mass spectrometry.

Chromatography, Gas↗

PubMed2001

Hyperosmotic shock induces both activation and translocation of glucose transporters in mammalian cells.

The effect of osmotic stress on sugar transport was investigated in Clone 9 epithelial cells, which express the glucose uniporter GLUT1, and in 3T3-L1 adipocytes, which express both GLUT1 and GLUT4. An acute hyperosmotic shock increased the uptake of sugars in both cell types. In Clone 9 cells, this was followed by a regulatory volume increase (RVI) response. Stimulation of transport was rapid and reversible, with half-lives (t 1/2) for stimulation of 2-deoxy-D-glucose uptake of 5.6 +/- 0.9 (n=6) and 22.7 +/- 1.5 (n=4) min for Clone 9 cells and adipocytes respectively. The effect was dose dependent, reaching a maximum at 1.1 osM of 2.9 +/- 0.1-fold (n=3) for Clone 9 cells and 8.2 +/- 0.8-fold (n=3) for adipocytes. In the latter, this stimulation correlated with translocation of the glucose transporter isoform GLUT4 to the cell surface and was not significantly different from that elicited by 160 nM insulin (7.6 +/- 1.2-fold, n=3). The effect of osmotic shock was not, however, influenced by inhibitors of either phosphoinositide 3-kinase (PI 3-kinase) (wortmannin, 250 nM) or of p38 mitogen-activated protein kinase (p38 MAP kinase) (SB203580, 20 microM), which reportedly prevent GLUT4 translocation and/or activation by insulin respectively. These inhibitors also had no effect on the stimulation of transport by osmotic shock in Clone 9 cells. However, in contrast to adipocytes, the effect of osmotic shock on glucose transport in Clone 9 cells reflected primarily a change in the intrinsic activity of cell surface transporters and there was only a minor change in their subcellular distribution as assessed by cell immunostaining or no change as assessed by surface biotinylation. These results indicate that the response of cells to osmotic shock can involve changes both in transporter activity and location. The signal transduction pathways involved include neither PI 3-kinase nor the classical, osmotically-activated component, p38 MAP kinase.

3T3 Cells↗

PubMed2001

Necrotic volume increase and the early physiology of necrosis.

Whether a lethally injured mammalian cell undergoes necrosis or apoptosis may be determined by the early activation of specific ion channels at the cell surface. Apoptosis requires K+ and Cl- efflux, which leads to cell shrinking, an active phenomenon termed apoptotic volume decrease (AVD). In contrast, necrosis has been shown to require Na+ influx through membrane carriers and more recently through stress-activated non-selective cation channels (NSCCs). These ubiquitous channels are kept dormant in viable cells but become activated upon exposure to free-radicals. The ensuing Na+ influx leads to cell swelling, an active response that may be termed necrotic volume increase (NVI). This review focuses on how AVD and NVI become conflicting forces at the beginning of cell injury, on the events that determine irreversibility and in particular, on the ion fluxes that decide whether a cell is to die by necrosis or by apoptosis.

Animals↗

PubMed2001

Localization of ribosomal genes in Pleuronectiformes using Ag-, CMA3-banding and in situ hybridization.

In this paper we present the analysis of nucleolar organizer regions (NORs) in five species of the order Pleuronectiformes (Scophthalmus maximus, Scophthalmus rhombus, Platichthys flesus, Solea solea and Solea lascaris), a group of fish poorly studied cytogenetically. In spite of the small chromosome sizes, which characterize the karyotypes of this group, we implement both classical (Ag- and CMA3-staining) and molecular (in situ hybridization with a major rDNA probe) techniques for NOR location. NORs were localized in a single chromosome pair in all species studied and showed size variation within each species. Evidence of a NOR-site polymorphism was detected in Platichthys flesus and Scophthalmus maximus. NOR location was apparently the same within families (S. rhombus vs. S maximus, and S. solea vs. S. lascaris) but clearly differed among families, and supports the phylogenetic relationships proposed for the order Pleuronectiformes.

Animals↗

PubMed2001

Population analysis of an unusual NOR-site polymorphism in brown trout (Salmo trutta L.).

A population analysis of an unusual NOR-site polymorphism previously detected in brown trout (Salmo trutta L.) from North-western Spain was carried out in 225 individuals from 20 native populations from this area. The analysis performed has permitted us to reveal: (i) the ubiquity of this phenomenon in most river basins from NW Spain, 13 extra-NORs not observed in standard trout being detected; (ii) the rDNA constitution of all extra-NORs, as confirmed by CMA3-staining and rDNA-FISH, and their capability to constitute their own nucleolus; (iii) the constant location of extra-NORs within individuals and their stable transmission across generations; and (iv) the telomeric location of Ag-NORs, which were randomly distributed in the karyotype of S. trutta, mostly in the heterozygous condition. Repetitive sequences in the IGS or scattered along rDNA units, rather than chromosome rearrangements, could play an important role in the dispersion of NORs. The polymorphism described seems to have a single geographical origin, since a positive correlation was demonstrated between the degree of polymorphism and geographical distance to a central point of the river basin where the phenomenon showed a higher intensity. The distribution of NOR-site variation as compared with allozyme variation in the populations studied, showed significant statistical differences. Selection against high copy number, or mutation due to changes in NOR location, could be acting on this polymorphism to explain the observed distribution. The high dispersion of NOR-site variants within and among populations suggests the transposition phenomenon responsible for NOR jumping could be still active.

Animals↗

PubMed2001

Allozymic evidence of parapatric differentiation of brown trout (Salmo trutta L.) within an Atlantic river basin of the Iberian Peninsula.

The genetic variation of brown trout from Duero, one of the main Atlantic Iberian river basins, was assessed at 34 enzymatic loci in 62 native populations. A strong intrabasin differentiation was detected (G(ST) = 0.46; range D: 0-0.066), mainly attributable to the existence of two divergent groups of populations within Duero: southern and northern groups. This divergence was mainly a consequence of the unequal distribution of *75 and *100 alleles at sMDH-B1,2* isoloci, which were correlated with substantial differences in genetic diversity among regions. The Lower Course region (nearly fixed for the *100 allele) and Pisuerga River (nearly fixed for the *75 allele) showed lower heterozygosities (H approximately 0.8%) in contrast with adjacent areas, which evidenced intermediate frequencies for both alleles and higher heterozygosities (H: 2.2-3.1%). Vicariance appeared as the more probable explanation for the significant positive correlation detected between genetic and geographical distances in Duero Basin. Genetic relationships with adjacent Iberian drainages indicate a close similarity between the southern group and Cantabric trout, whereas the northern group constitutes an ancient form from this basin. This study confirmed complex genetic relationships in brown trout from northwest Iberia, reasserting the existence of clines at several loci and for genetic diversity. The interaction between Cantabric and Duero trout, as well as the location of the limit of the anadromous form around the 42 degrees N parallel, are both required to understand the genetic characteristics of brown trout from this area.

Alleles↗

PubMed2001

Nonselective cation channels as effectors of free radical-induced rat liver cell necrosis.

Necrosis, as opposed to apoptosis, is recognized as a nonspecific cell death that induces tissue inflammation and is preceded by cell edema. In non-neuronal cells, the latter has been explained by defective outward pumping of Na(+) caused by metabolic depletion or by increased Na(+) influx via membrane transporters. Here we describe a novel mechanism of swelling and necrosis; namely the influx of Na(+) through oxidative stress-activated nonselective cation channels. Exposure of liver epithelial Clone 9 cells to the free-radical donors calphostin C or menadione induced the rapid activation of an approximately 16-pS nonselective cation channel (NSCC). Blockage of this conductance with flufenamic acid protected the cells against swelling, calcium overload, and necrosis. Protection was also achieved by Gd(3+), an inhibitor of stretch-activated cation channels, or by isosmotic replacement of extracellular Na(+) with N-methyl-D-glucamine. It is proposed that NSCCs, which are ubiquitous although largely inactive in healthy cells, become activated under severe oxidative stress. The ensuing influx of Na(+) initiates a positive feedback of metabolic and electrolytic disturbances leading cells to their necrotic demise.

Animals↗

PubMed2001

Enhanced magnification endoscopy: a new technique to identify specialized intestinal metaplasia in Barrett's esophagus.

BACKGROUND: Specialized intestinal metaplasia (SIM) in Barrett's esophagus (BE) is not identifiable by standard endoscopy. Acetic acid instillation enhances the ability to detect columnar epithelium at the squamocolumnar union. Enhanced magnification endoscopy involves the combined use of magnification endoscopy with acetic acid. This study assessed the value of enhanced magnification endoscopy in detecting SIM in patients with BE. METHODS: Patients undergoing endoscopic surveillance because of short segment BE without dysplasia underwent enhanced magnification endoscopy with 1.5% acetic acid instillation. Standard endoscopy was followed by magnification endoscopy and repeated after acetic acid spraying. Surface patterns were characterized prior to and after acetic acid spraying. The observed surface patterns were compared with histology results. RESULTS: Forty-nine patients, 9 women and 39 men, with a mean age of 50.5 years were studied. One was excluded because of unclear definition of the surface pattern. Enhanced magnification endoscopy detected 4 different mucosal surface patterns: I, round pits; II, reticular; III, villous; and IV, ridged. A total of 129 areas were examined. Standard endoscopy identified an endoscopic pattern in 1.5% of the areas, standard endoscopy and acetic acid in 8.5%, magnification endoscopy alone in 38%, and enhanced magnification endoscopy in all 129 endoscopic areas. The yields for detecting SIM according to endoscopic patterns were as follows: pattern I, 0%; II, 11% (odds ratio 0.5, p = 0.54); III, 87% (odds ratio 36, p = 0.001); and IV, 100% (odds ratio 14, p = 0.015). CONCLUSIONS: Enhanced magnification endoscopy is an accurate method of predicting SIM in BE. The simplicity of the technique and its ability to identify characteristic endoscopic patterns with outstanding clarity and resolution that correlate with histologic identification of specialized intestinal metaplasia make enhanced magnification endoscopy an excellent method for the evaluation of patients with BE.

Acetic Acid↗

PubMed2001

High-LET radiation induces apoptosis in lymphoblastoid cell lines derived from atazia-telangiectasia patients.

PURPOSE: To investigate and compare the propensity of Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL), derived from ataxia-telangiectasia (A-T) patients and from unaffected healthy individuals (controls), to undergo apoptosis after exposure to high-linear energy transfer (LET) radiation. MATERIALS AND METHODS: Four A-T (ARO, BMA, CSA and RJO) and two control (JAC and KKB3) LCL were exposed to doses of up to 4Gy of accelerated nitrogen ions (32-45 MeV/u, 8-12Gy/min). For comparative purposes X-ray irradiation (1.36 Gy/min) was also performed. The induction of apoptosis was studied 0-48 h after irradiation with the use of two methods: (1) monitoring of high molecular weight (HMW) DNA fragments by field inversion pulse gel electrophoresis (FIGE); and (2) morphological characterization ofapoptotic cells after fluorescent staining. In parallel, cell-cycle distribution, monitored by DNA flow cytometry, as well as measurements of p53/p21(WAF1) protein levels by Western blots, were investigated in these cells. RESULTS: High-LET radiation-induced apoptosis and G2/M-arrest in both A-T and control LCL. No significant increase in the amount of p53/p21(WAF1) proteins preceded apoptosis in control or in A-T LCL after high-LET irradiation. However, low-LET radiation did induce significant enhanced levels of p53 proteins in control but not in A-T LCL. CONCLUSIONS: LCL from both A-T homozygous and unaffected healthy individuals undergo apoptosis without accumulation of p53/p21(WAF1) proteins after exposure to high-LET radiation. In contrast, low-LET radiation induces apoptosis and significantly increases levels of p53 protein in control but not in A-T LCL.

Apoptosis↗

PubMed2001

Adolescent anorexia nervosa: the catch-up effect in bone mineral density after recovery.

OBJECTIVE: To determine whether bone mineral density (BMD) loss can be reversed in adolescent anorexic patients. METHOD: A prospective study with 108 anorexia nervosa patients (DSM-IV) from 12 to 17 years of age at the Eating Disorders Unit in the Hospital Clinic of Barcelona (Spain). They were first evaluated by dual-energy x-ray absorptiometry in lumbar spine and femoral neck consecutively from 1997 until 1999 and reexamined after 6 to 30 months. Results were compared with normative values of bone mass. RESULTS: Patients with poor outcome (n = 44) had a bone mass loss. Patients with good short-term outcome were divided in two groups. The group with normal BMD at first evaluation (n = 41) had a bone mass gain per year of 3.0% at lumbar spine and 0.5% at femoral neck. The group with low BMD at first evaluation (n = 23) had an increase per year of 9.1% at lumbar spine and 4.5% at femoral neck. In a multiple linear regression analysis with the variables body mass index, age, months with menstruation, and BMD zscore at first evaluation, the only predictor of BMD increase was the first z score both at the lumbar spine (coefficient R = 0.64; p < .001) and at the femoral neck (coefficient R = 0.5; p < .001). CONCLUSIONS: There is a catch-up effect in adolescent patients with low BMD but good short-term outcome.

Adolescent↗