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Biomedical subjects

C García

Publications and source records attributed to C García.

At least 91 records · Page 5Linked to original sources
PubMed1999

Orthotopic models of human pancreatic cancer.

Orthotopic transplantation of solid tumor fragments of human tumors in nude mice reproduces their pattern of local growth and distal dissemination. While lymphatic, hepatic or peritoneal dissemination can be reproduced, perineural invasion is absent. Early passages (less than 3) of xenografts show a high degree of stability regarding K-ras, p53 and p16 gene status. On the other hand, advanced passages of tumors acquire additional alterations in the p15 and Smad4 genes. Mutations in K-ras, p53, p15 and Smad4 genes can be acquired, in this model system, in the more advanced stages of pancreatic tumor dissemination. Finally, it is also possible to standardize local growth of these tumors as well as its dissemination pattern giving us a preclinical tool to evaluate the anticancer activity of new drugs.

Adenocarcinoma↗
PubMed1999

Novel arylpyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxides as inhibitors of platelet aggregation. 1. Synthesis and pharmacological evaluation.

A series of N-1-substituted derivatives of pyrazino[2,3-c][1,2, 6]thiadiazine 2,2-dioxides bearing aryl groups at the pyrazino moiety have been prepared. The synthesis involves ring formation between the diaminothiadiazine and suitable dicarbonyl compounds and subsequent introduction of the substituent at N-1. The compounds have been tested in vitro, as inhibitors of rabbit and human platelet aggregation, and ex vivo against rat platelet aggregation induced by arachidonic acid, ADP, collagen, U46619, and I-BOP. The results obtained indicate that some pyrazino[2,3-c][1,2, 6]thiadiazine derivatives show significant platelet aggregation inhibition similar to other antithrombotic agents and that the antiplatelet properties may be mediated by interference with the arachidonic acid pathway.

Animals↗
PubMed1999

Two progesterone-dependent endometrial nuclear factors bind to an E-box in the rabbit uteroglobin gene promoter: involvement in tissue-specific transcription.

We studied the implications of progesterone-dependent transcription factors in the hormonal and tissue-specific induction of the uteroglobin gene (ug) in the rabbit endometrium. Previously, we have observed the interaction of two progesterone-dependent endometrial nuclear proteins (TRBPs) with sequences downstream from the ug TATA box. Using electrophoretic mobility shift assays (EMSA) we show here that TRBPs specifically interacted with an E-box localized almost immediately downstream from the ug TATA box. UV crosslinking of affinity-purified TRBPs to the radiolabeled oligonucleotide probe confirmed that these factors were proteins with molecular mass of about 40-50 kDa. Ferguson's analysis of the Mr of the DNA-TRBP complexes suggested that TRBPs interacted with the E-box either as homo- or heterodimers. This interaction did not result in detectable bending of the DNA. EMSA analysis with nuclear extracts from different rabbit tissues suggested that TRBPs might be endometrium-specific nuclear factors. Involvement of the E-box in the tissue-specific transcription from the ug promoter was assessed by transient expression experiments using different cell lines transfected with a reporter gene driven by the ug promoter which contained either the intact E-box or a mutated version that completely abolished its interaction with TRBPs. These experiments indicated that, in all cell lines of nonendometrial lineage, destruction of the E-box increased transcription from the ug promoter, whereas in two cell lines of endometrial origin this mutation either had no appreciable effect or slightly reduced the transcription from the promoter. Thus, this E-box and endometrial helix-loop-helix proteins might be involved in the hormonal and tissue-specific regulation of ug transcription.

Animals↗
PubMed1999

Uptake, cellular distribution and DNA damage produced by mercuric chloride in a human fetal hepatic cell line.

A human hepatic cell line (WRL-68 cells) was employed to investigate the uptake of the toxic heavy metal mercury. Hg accumulation in WRL-68 cells is a time and concentration dependent process. A rapid initial phase of uptake was followed by a second slower phase. The transport does not require energy and at low HgCl2 concentrations (<50 microM) Hg transport occurs by temperature-insensitive processes. Subcellular distribution of Hg was: 48% in mitochondria, 38% in nucleus and only 8% in cytosolic fraction and 7% in microsomes. Little is known at the molecular level concerning the genotoxic effects following the acute exposure of eucaryotic cells to low concentrations of Hg. Our results showed that Hg induced DNA single-strand breaks or alkali labile sites using the single-cell gel electrophoresis assay (Comet assay). The percentage of damaged nucleus and the average length of DNA migration increased as metal concentration and time exposure increased. Lipid peroxidation, determined as malondialdehyde production in the presence of thiobarbituric acid, followed the same tendency, increased as HgCl2 concentration and time of exposure increased. DNA damage recovery took 8 h after partial metal removed with PBS-EGTA.

Cell Line↗
PubMed1999

[To be ill and a foreigner in health care institutions].

The majority of the people from foreign countries who search for help in the national health system are living in poverty and come from the rural areas near the mediterranean sea. They are here either as refugees for political reasons or because they are looking for work. Thus they have come to meet accultural processes of different sizes. In a subjective way they react to a failed acculturation by showing off a ruined self-confidence and a false motivation. Their situation towards the national health system is defined by various factors: 1. Original culture influence, 2. Ruined self-confidence and they are therefore prone to health defects, 3. Special form of symptom (pathoplastic), 4. Changed department to institutional things. In comparison with that the cultural situation of the institute's staff shows characteristic symptoms of life in a modern capitalistic society--which appears normal to them. If we compared their situation with the one of the migrants--always keeping the theory of cultural relativism in mind--we have to consider this relation as highly problematic. This lecture wants to critically illustrate the global comparison between the two basic positions of the migrants and the staff working for health institutions and draw conclusions.

Acculturation↗
PubMed1999

Oxidative refolding chromatography: folding of the scorpion toxin Cn5.

We have made an immobilized and reusable molecular chaperone system for oxidative refolding chromatography. Its three components-GroEL minichaperone (191-345), which can prevent protein aggregation; DsbA, which catalyzes the shuffling and oxidative formation of disulfide bonds; and peptidyl-prolyl isomerase-were immobilized on an agarose gel. The gel was applied to the refolding of denatured and reduced scorpion toxin Cn5. The 66-residue toxin, which has four disulfide bridges and a cis peptidyl-proline bond, had not previously been refolded in reasonable yield. We recovered an 87% yield of protein with 100% biological activity.

Animals↗
PubMed1999

Ultrastructural and immunocytochemical evidences of core-particle formation in the methylotrophic Pichia pastoris yeast when expressing HCV structural proteins (core-E1).

Particulate antigens of the Hepatitis C virus (HCV) are reported for the first time by transmission electron microscopy in Pichia pastoris. The yeast was cloned to express the first 339 NH2-terminal amino acids of the HCV polyprotein (C-E1.339 polypeptide). The C-E1.339 polypeptide covers the putative 191 aa of the core protein (aa 1-191) and 148 aa of the E1 envelope antigen (aa 192-339). Virus-like particles (VLP) with diameters ranging from 20 nm to 30 nm were specifically observed in those cells expressing the HCV polyprotein. The VLP appeared along the membrane of the endoplasmic reticulum, but were fundamentally localized in vacuoles, either free or inside autophagic bodies. Clustered particles, chains of particles, high-density reticular structures, and crystalloid bodies were also detected, the last one being an orderly arrangement of particles with 20 nm diameters. The crystal-associated particles are well differentiated from the intracellular VLP because of their uniform size and shape. We argue that membrane components are retained in the architecture of the VLP, conferring to this particle certain heterogeneity. Both kinds of particles, the VLP formed after treatment with NP-40 and the crystal-associated particles, were core protein-positives. Whether they reflect mature HCV nucleocapsid or intermediary states in the viral nucleocapsid morphogenesis remains unknown. We conclude that, like mammalian cell lines, the P. pastoris yeast could be an appropriate host for the analysis of HCV polyprotein processing and, eventually, virus assembly.

Gene Expression↗
PubMed1999

Acute and subchronic toxicity studies of the new quinolone antibacterial agent irloxacin in rodents.

Irloxacin (6-fluorine-7-(pyrrol-1-yl)-1-ethyl-1, 4-dihydro-4-oxo-quinolone-3-carboxylic acid, CAS 91524-15-1), a new quinolone antibacterial agent, was administered as a single dose to rats and mice both by oral and intraperitoneal route in oder to study its acute toxicity. Its oral subchronic toxicity was also assessed by treating rats for 4 and 13 weeks. The results obtained showed that irloxacin was well tolerated after single administration in mice and rats, with LD50 values above 2000 and 5000 mg/kg for intraperitoneal and oral administration, respectively. In the oral subchronic toxicity studies, the histopathological examination performed after the 13-week treatment period confirmed the kidney as the target organ for toxicity. Increased presence of lipofuscin in the kidneys was observed in animals receiving 2000 or 450 mg/kg/d, and degeneration and/or dilatation of proximal renal tubules and chronic interstitial nephritis in males receiving these dosages. No histopathological findings were observed in the kidneys of animals receiving 100 mg/kg/d for 13 weeks. Other relevant findings were, presence of dark or cloudy urine with slightly lower pH in animals receiving dosages of 450 mg/kg/d and above, increased urinary protein concentration in animals receiving 2000 or 450 mg/kg/d, and increased plasma urea concentration in those receiving 2000 mg/kg/d. Moreover, increased plasma phospholipids and total cholesterol concentration, and increased liver and kidney weights were observed among treated animals. As a summary, the results have shown that irloxacin has a low acute toxicity in both mice and rats. For repeat oral administration in rats, 100 mg/kg can be considered as the non-toxic effect level after a treatment period of 13 weeks.

Administration, Oral↗
PubMed1999

Barrett's esophagus and chemotherapy, a case report.

There have been few reports of Barrett's esophagus associated with chemotherapy in children. We report the case of a 3-year-old patient diagnosed with acute lymphoblastic leukemia who developed Barrett's esophagus after BMF-90 chemotherapeutic regimen. A stricture appeared as a complication of Barrett's metaplasia and Nissen fundoplication was performed. Symptoms improved shortly after surgery and regression of Barrett's esophagus was observed 2 years later. Children treated with antileukemic chemotherapy may develop Barrett's esophagus without previous clinical apparent gastroesophageal reflux. Endoscopic surveillance has been advised in these patients. Barrett's esophagus may regress after antireflux surgery.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Improving the efficiency of artificial selection: more selection pressure with less inbreeding.

The use of population genetic variability in present-day selection schemes can be improved to reduce inbreeding rate and inbreeding depression without impairing genetic progress. We performed an experiment with Drosophila melanogaster to test mate selection, an optimizing method that uses linear programming to maximize the selection differential applied while at the same time respecting a restriction on the increase in inbreeding expected in the next generation. Previous studies about mate selection used computer simulation on simple additive genetic models, and no experiment with a real character in a real population had been carried out. After six selection generations, the optimized lines showed an increase in cumulated phenotypic selection differential of 10.76%, and at the same time, a reduction of 19.91 and 60.47% in inbreeding coefficient mean and variance, respectively. The increased selection pressure would bring greater selection response, and in fact, the observed change in the selected trait was on average 31.03% greater in the optimized lines. These improvements in the selection scheme were not made at the expense of the long-term expectations of genetic variability in the population, as these expectations were very similar for both mate selection and conventionally selected lines in our experiment.

Animals↗
PubMed1999

Elevated expression of liver gamma-cystathionase is required for the maintenance of lactation in rats.

Liver gamma-cystathionase activity increases in rats during lactation; its inhibition due to propargylglycine is followed by a significant decrease in lactation. This is reversible by N-acetylcysteine administration. To study the role of liver gamma-cystathionase and the intertissue flux of glutathione during lactation, we used lactating and virgin rats fed liquid diets. Virgin rats were divided into two groups as follows: one group was fed daily a diet containing the same amount of protein that was consumed the previous day by lactating rats (high protein diet-fed rats); the other virgin group was fed the normal liquid diet (control). The expression and activity of liver gamma-cystathionase were significantly greater in lactating rats and in high protein diet-fed virgin rats compared with control rats. The total glutathione [reduced glutathione (GSH) + oxidized glutathione (GSSG)] released per gram of liver did not differ in lactating rats or in high protein diet-fed rats, but it was significantly higher in these two groups than in control virgin rats. Liver size and the GSH + GSSG released by total liver were significantly higher in lactating rats than in high protein diet-fed virgin rats, and this difference was similar to the amount of glutathione taken up by the mammary gland (454.2 +/- 36.0 nmol/min). The uptake of total glutathione by the lactating mammary gland was much higher than the uptakes of free L-cysteine and L-cystine, which were negligible. These data suggest that the intertissue flux of glutathione is an important mechanism of L-cysteine delivery to the lactating mammary gland, which lacks gamma-cystathionase activity. This emphasizes the physiologic importance of the increased expression and activity of liver gamma-cystathionase during lactation.

Acetylcysteine↗
PubMed1999

Susceptibility of penicillin-resistant and penicillin-susceptible Streptococcus pneumoniae to newer antimicrobial agents.

Agar dilution minimum inhibitory concentration (MIC) methodology, according to NCCLS guidelines, was used to test the activity of three glycopeptides (LY 333328 [LY], vancomycin [VAN], and teicoplanin [TEI]), four fluoroquinolones (trovafloxacin [TRO], BAY 12-8039 [BAY], ciprofloxacin [CIP], and ofloxacin [OFL]), five macrolide-lincosamide-streptogramin antibiotics (erythromycin [ERY], azithromycin [AZI], miocamycin [MOM], clindamycin CLN], and quinupristin-dalfopristin [SYN] against 126 Streptococcus pneumoniae strains, isolated in Lozano Blesa Hospital of Zaragoza (Spain). MIC50/MIC90 (microg/ml) values for penicillin-susceptible (PS), penicillin-intermediate (PI) and penicillin-resistant (PR) strains show an excellent antipneumococcal activity of LY 333326--a new glycopeptide, for the fluoroquinolones trovafloxacin and moxifloxacin [BAY 12-8039], and for quinupristin/dalfopristin, regardless of the resistance phenotype of the strains.

Anti-Bacterial Agents↗