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Biomedical subjects

J E González

Publications and source records attributed to J E González.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of the genotoxic potential of Mangifera indica L. extract (Vimang), a new natural product with antioxidant activity.

Mangifera indica L. extract (Vimang) consists of a defined mixture of components (polyphenols, terpenoids, steroids, fatty acids and microelements). It contains a variety of polyphenols, phenolic esters, flavan-3-ols and a xanthone (mangiferin), as main component. This extract has antioxidant action, antitumor and immunemodulatory effects proved in experimental models in both in vitro and in vivo assays. The present study was performed to investigate the genotoxicity potential activity of Vimang assessed through different tests: Ames, Comet and micronucleus assays. Positive and negative controls were included in each experimental series. Histidine requiring mutants of Salmonella typhimurium TA1535, TA1537, TA1538, TA98, TA100 and TA102 strains for point-mutation tests and in vitro micronucleus assay in primary human lymphocytes with and without metabolic activation were performed. In addition, genotoxic effects were evaluated on blood peripheral lymphocytes of NMRI mice of both sexes, which were treated during 2 days with intraperitoneal doses of M. indica L. extract (50-150 mg/kg). The observed results permitted to affirm that Vimang (200-5,000 microg/plate) did not increase the frequency of reverse mutations in the Ames test in presence or not of metabolic activation. Results of Comet assay showed that the extract did not induce single strand breaks or alkali-labile sites on blood peripheral lymphocytes of treated animals compared with controls. On the other hand, the results of the micronucleus studies (in vitro and in vivo) showed Vimang induces cytotoxic activity, determined as cell viability or PCE/NCE ratio, but neither increased the frequency of micronucleated binucleate cells in culture of human lymphocytes nor in mice bone marrow cells under our experimental conditions. The positive control chemicals included in each experiment induced the expected changes. The present results indicate that M. indica L. extract showed evidences of light cytotoxic activity but did not induce a mutagenic or genotoxic effects in the battery of assays used.

Animals↗
PubMed2006

Perinatal/postnatal study of D-003, a mixture of long-chain fatty acids, in rats.

D-003 is a mixture of long-chain fatty acids isolated and purified from sugar cane wax with cholesterol-lowering and antiplatelet effects. In order to further characterize the developmental toxicity during the treatment period from late gestation up to weaning of the offspring, pregnant females received 0 (control), 500, and 1,000 mg/kg/day D-003 daily by oral gavage beginning at day 15 of pregnancy and through gestation until day 21 postpartum. Maternal clinical signs, body weight, and food intake were measured at regular intervals during gestation and lactation. Live pups were weighed, sexed, and examined for developmental signs. One female and male of each litter were randomly selected to evaluate the reproductive potential. There were no spontaneous or dose-related maternal deaths during the course of this study. The general health and behavioral condition of offspring was good in all groups. No significant differences among groups were found in comparisons of litter size, survival through the weaning period, sex ratio, and male and female weights. This peri- and postnatal study conducted with D-003 in rats indicated that treatment of the dam during late gestation and lactation did not show adversely effects on reproductive performance or fetal development over two generations.

Animals↗
PubMed2004

Evaluation of the reproductive and developmental toxicity of the D-003, a mixture of long-chain fatty acids, in rats and rabbits.

D-003 is a mixture of long-chain fatty acids isolated and purified from sugar cane wax with cholesterol-lowering properties. D-003 given orally (500 and 1000 mg/kg/day) to female rats for 15 days prior to mating, through mating and gestation to day 21 of lactation and male rats for 4 weeks prior and during mating did not induce toxic effects on reproduction. There were no significant reductions in the number of animals that conceived, in the numbers of pups born to those that did conceive, in the numbers of pups that survived until weaning, and in their body weights at weaning. Drug-treated and control groups' offspring were comparable in growth, physical and behavioral development, spontaneous activity and reproductive performance. Pregnant New Zealand rabbits were given D-003 as oral doses of 500 and 1000 mg/kg/day on days 6 through 18 of gestation without any evidence of embryotoxicity or teratogenicity. The no-observed-effect dose in these two experimental studies was 1000 mg/kg/day. After assessment of the potential of high doses of D-003 to act on developing embryo and reproduction process, no evidence supports the conclusion that D-003 is a reproductive and developmental toxicant/teratogen.

Animals↗
PubMed2003

Lack of developmental toxicity of D-003: a mixture of long-chain fatty acids in rats.

D-003 is a mixture of long-chain fatty acids isolated and purified from sugar cane wax, the major component of which is 1-octacosanoic acid and which possesses effective antiplatelet, antithrombotic and cholesterol-lowering effects. D-003 was suspended in 1% acacia gum solution, and given daily by gavage to rats at dose levels of 5, 100 and 1000 mg/kg/day on days 6 through 15 of gestation. Cyclophosphamide, serving as a positive control, was given at the dose of 50 mg/kg/day on day 15 of gestation. Evidence of maternal or developmental toxicity was not observed in the groups treated with D-003. Maternal clinical signs of toxicity were not observed and the analysis of initial body weight and the body weight gain during the treatment period was comparable among the groups treated with D-003 and control. As expected, cyclophosphamide caused both embryotoxic and teratogenic effects in rats. Meanwhile, no adverse effects on reproductive performance, or on embryonic or fetal development, including visceral and skeletal examination, were seen in any of the groups administered D-003. It is concluded that D-003 administered up to 1000 mg/kg/day did not induce any evidence of developmental toxicity.

Abnormalities, Drug-Induced↗
PubMed2002

'Hbe minus' mutants of hepatitis B virus. Molecular characterization and its relation to viral genotypes.

The precore-core and S genes of HBV were directly sequenced from serum samples of 42 patients with chronic hepatitis B (16 hepatitis Be antigen [HBeAg]+and 26 anti-HBe+). Viral genotype A was identified in 12 cases, genotype D in 11 and genotype F in 19 cases. Precore mutations, mainly M1 (G1896A, stop at codon 28) were similarly found among viral genotypes A and D: seven cases (58%) and six cases (55%), respectively. The selection of M1 mutants from genotype D resulted in a more stable encapsidation signal but was less stable for genotype A precore mutants. Oddly enough, the encapsidation signal of M1 precore mutants from genotype F sequences were evenly distributed among less stable (genotype A M1 mutants) and more stable encapsidation signal (genotype D M1 mutants). This study shows that the selection of precore mutants that preclude the HBeAg expression, including the M1 mutation, does not necessarily depend on the stabilization of the encapsidation signal or the viral genotype In addition, the particular behavior of genotype F genomes at precore region is described.

Adolescent↗
PubMed2000

Ovarian ependymoma. A case report.

We present the case of a 30-year-old woman who was referred to our institution with an erroneous diagnosis of poorly differentiated carcinoma of the ovary. The patient presented pelvic pain for one year prior to surgery. A second laparotomy revealed a bilateral pure ovarian ependymoma that infiltrated the uterus and presented implants on the omentum. Differential diagnosis included mainly endometrioid and small cell carcinoma of the ovary. Presence of typical ependymal rosettes and positivity to GFAP confirmed the diagnosis of ependymoma. Other teratomatous elements were not observed. Ovarian ependymomas are rare tumors; only eight cases, to our knowledge, have been reported in the literature. They have a favorable prognosis; patients with advanced stage disease are reported alive and well after treatment with surgery and chemotherapy.

Adult↗
PubMed2000

Environmental regulation of exopolysaccharide production in Sinorhizobium meliloti.

Exopolysaccharide production by Sinorhizobium meliloti is required for invasion of root nodules on alfalfa and successful establishment of a nitrogen-fixing symbiosis between the two partners. S. meliloti wild-type strain Rm1021 requires production of either succinoglycan, a polymer of repeating octasaccharide subunits, or EPS II, an exopolysaccharide of repeating dimer subunits. The reason for the production of two functional exopolysaccharides is not clear. Earlier reports suggested that low-phosphate conditions stimulate the production of EPS II in Rm1021. We found that phosphate concentrations determine which exopolysaccharide is produced by S. meliloti. The low-phosphate conditions normally found in the soil (1 to 10 microM) stimulate EPS II production, while the high-phosphate conditions inside the nodule (20 to 100 mM) block EPS II synthesis and induce the production of succinoglycan. Interestingly, the EPS II produced by S. meliloti in low-phosphate conditions does not allow the invasion of alfalfa nodules. We propose that this invasion phenotype is due to the lack of the active molecular weight fraction of EPS II required for nodule invasion. An analysis of the function of PhoB in this differential exopolysaccharide production is presented.

Bacterial Proteins↗
PubMed1998

Biosynthetic control of molecular weight in the polymerization of the octasaccharide subunits of succinoglycan, a symbiotically important exopolysaccharide of Rhizobium meliloti.

Succinoglycan, a symbiotically important exopolysaccharide of Rhizobium meliloti, is composed of polymerized octasaccharide subunits, each of which consists of one galactose and seven glucoses with succinyl, acetyl, and pyruvyl modifications. Production of specific low molecular weight forms of R. meliloti exported and surface polysaccharides, including succinoglycan, appears to be important for nodule invasion. In a previous study of the roles of the various exo gene products in succinoglycan biosynthesis, exoP, exoQ, and exoT mutants were found to synthesize undecaprenol-linked fully modified succinoglycan octasaccharide subunits, suggesting possible roles for their gene products in polymerization or transport. Using improved techniques for analyzing succinoglycan biosynthesis by these mutants, we have obtained evidence indicating that R. meliloti has genetically separable systems for the synthesis of high molecular weight succinoglycan and the synthesis of a specific class of low molecular weight oligosaccharides consisting of dimers and trimers of the octasaccharide subunit. Models to account for our unexpected findings are discussed. Possible roles for the ExoP, ExoQ, and ExoT proteins are compared and contrasted with roles that have been suggested on the basis of homologies to key proteins involved in the biosynthesis of O-antigens and of certain exported or capsular cell surface polysaccharides.

Dimerization↗
PubMed1998

Intracellular detection assays for high-throughput screening.

New optical assay methods promise to accelerate the use of living cells in screens for drug discovery. Most of these methods employ either fluorescent or luminescent read-outs and allow cell-based assays for most targets, including receptors, ion channels and intracellular enzymes. Furthermore, genetically encoded probes offer the possibility of custom-engineered biosensors for intracellular biochemistry, specifically localized targets, and protein-protein interactions.

Animals↗
PubMed1998

A novel screening method for isolating exopolysaccharide-deficient mutants.

A screening method based on differential staining of the wild type and exopolysaccharide-deficient mutants of Rhizobium (Sinorhizobium) meliloti by the lipophilic dye Sudan Black B is described. Mutants defective in the production of either succinoglycan or EPS II (galactoglucan) were isolated by using this method, which might also prove useful for isolating exopolysaccharide-defective derivatives of other bacteria.

Azo Compounds↗
PubMed1997

Improved indicators of cell membrane potential that use fluorescence resonance energy transfer.

BACKGROUND: Fluorescence detection of cell membrane potentials is an important technique in neurobiology, cell physiology and pharmaceutical screening, but traditional one-fluorophore indicators either respond too slowly or have limited sensitivity. Recently, we introduced two-component sensors based on the transfer of fluorescence resonance energy from fluorescent lectins bound on one side of the plasma membrane to highly fluorescent oxonol acceptors that electrophorese from one face of the membrane to the other in response to membrane potential. RESULTS: We have found that fluorescent lectins can often be advantageously replaced in such sensors by fluorescently labeled phospholipids. A coumarinlabeled phosphatidylethanolamine donor and a bis(1,3-dihexyl-2-thiobarbiturate)trimethineoxonol acceptor gave the largest sensitivity of fluorescence ratio (>50% per 100 mV) ever reported. The response was also speeded several-fold by lengthening the mobile dye to the pentamethineoxonol analog, the <0.4 ms time constant of which was shorter than action potential durations. Photodynamic damage due to singlet oxygen was reduced by administering a natural carotenoid, astaxanthin. CONCLUSIONS: Voltage-sensitive fluorescence resonance energy transfer already gives record-setting performance on single cells and will continue to be rationally improvable.

Animals↗
PubMed1996

Rhizobium meliloti exopolysaccharides: synthesis and symbiotic function.

Bacterial exopolysaccharide (EPS) is required for establishment of the nitrogen-fixing symbiosis between Rhizobium meliloti and its host plant, Medicago sativa (alfalfa), but the precise role of EPS in this interaction is not well defined. Bacterial mutants which fail to produce EPS induce nodules on the roots of the host plant, but fail to invade these root nodules. Research conducted in our lab and others suggests that EPS plays a specific role in the R. meliloti-M. sativa symbiosis. A common theme emerging from these studies is that small quantities of low-molecular-weight (LMW) EPS are sufficient to mediate successful invasion by R. meliloti mutants which fail to produce EPS, implying that LMW EPS may act as a signaling molecule during this process.

Carbohydrate Sequence↗
PubMed1996

Low molecular weight EPS II of Rhizobium meliloti allows nodule invasion in Medicago sativa.

Effective invasion of alfalfa by Rhizobium meliloti Rm1021 normally requires the presence of succinoglycan, an exopolysaccharide (EPS) produced by the bacterium. However, Rm1021 has the ability to produce a second EPS (EPS II) that can suppress the symbiotic defects of succinoglycan-deficient strains. EPS II is a polymer of modified glucose-(beta-1,3)-galactose subunits and is produced by Rm1021 derivatives carrying either an expR101 or mucR mutation. If the ability to synthesize succinoglycan is blocked genetically, expR101 derivatives of Rm1021 are nodulation-proficient, whereas mucR derivatives of Rm1021 are not. The difference in nodulation proficiency between these two classes of EPS II-producing strains is due to the specific production of a low molecular weight form of EPS II by expR101 strains. A low molecular weight EPS II fraction consisting of 15-20 EPS II disaccharide subunits efficiently allows nodule invasion by noninfective strains when present in amounts as low as 7 pmol per plant, suggesting that low molecular weight EPS II may act as a symbiotic signal during infection.

Genetic Complementation Test↗
PubMed1995

Voltage sensing by fluorescence resonance energy transfer in single cells.

A new mechanism has been developed for achieving fast ratiometric voltage-sensitive fluorescence changes in single cells using fluorescence resonance energy transfer. The mechanism is based on hydrophobic fluorescent anions that rapidly redistribute from one face of the plasma membrane to the other according to the Nernst equation. A voltage-sensitive fluorescent readout is created by labeling the extracellular surface of the cell with a second fluorophore, here a fluorescently labeled lectin, that can undergo energy transfer with the membrane-bound sensor. Fluorescence resonance energy transfer between the two fluorophores is disrupted when the membrane potential is depolarized, because the anion is pulled to the intracellular surface of the plasma membrane far from the lectin. Bis-(1,3-dialkyl-2-thiobarbiturate)-trimethineoxonols, where alkyl is n-hexyl and n-decyl (DiSBA-C6-(3) and DiSBA-C10-(3), respectively) can function as donors to Texas Red labeled wheat germ agglutinin (TR-WGA) and acceptors from fluorescein-labeled lectin (FI-WGA). In voltage-clamped fibroblasts, the translocation of these oxonols is measured as a displacement current with a time constant of approximately 2 ms for 100 mV depolarization at 20 degrees C, which equals the speed of the fluorescence changes. Fluorescence ratio changes of between 4% and 34% were observed for a 100-mV depolarization in fibroblasts, astrocytoma cells, beating cardiac myocytes, and B104 neuroblastoma cells. The large fluorescence changes allow high-speed confocal imaging.

Animals↗
PubMed1988

Analysis of the promoters and transcripts involved in IS10 anti-sense RNA control.

Genetic analysis of eleven mutations affecting the IS10 promoters, pIN and pOUT, involved in anti-sense RNA control of transposase gene expression, and characterization of the transcripts, reveal that: (i) The transposase message (RNA-IN) and the anti-sense RNA (RNA-OUT) have been unambiguously identified in vivo. (ii) Five mutations affect pIN activity, and establish that pIN is the only IS10 promoter transcribing the tnp gene, and the only such IS10 promoter that responds to DNA-adenine methylation. (iii) Six mutations alter pOUT activity, and establish that pOUT is the only IS10 promoter specifying the anti-sense RNA-OUT. (iv) The latter, however, need not be so: heterologous promoters, if properly positioned, can also specify active anti-sense RNAs. (v) These heterologously promoted anti-sense RNAs are processed to species closely resembling native RNA-OUT.

Bacteriophage lambda↗
PubMed1988

An endosomal model for acid triggering of diphtheria toxin translocation.

An endosomal model system was developed for studying the effects of pH on vesicle-entrapped diphtheria toxin. The "endosomes" were prepared from dioleoylphosphatidylcholine (1 mg), diphtheria toxin (0.25 mg), and lysozyme (2.25 mg) in water at pH 8.4. The method used for preparing large unilamellar vesicles was adapted from the procedure of Shew and Deamer (Shew, R. L., and Deamer, D. W. (1985) Biochim. Biophys. Acta 816, 1-8). Efficiencies of trapping (typically 45-75%) and separation from untrapped proteins (typically 95-100%) were assessed by fluorescamine assays conducted before and after column chromatography and in the presence and absence of Tergitol Nonidet P-40. Intramembranous photolabeling revealed that diphtheria toxin inserts into the vesicle bilayer when the pH is dropped to 4; surface labeling revealed that the same treatment leads to exposure of diphtheria toxin at the trans surface of the vesicles. Release of toxin to the solution was not detected under the experimental conditions employed (i.e. with nicked or unnicked toxin, +/- exogenous trypsin, pH 4 or 8.4). Preliminary results indicate that this model system will be a valuable tool for elucidating the pathway by which the ADP ribosyltransferase domain of diphtheria toxin gains access to the cytoplasmic compartment of cells after endosomal uptake.

ADP Ribose Transferases↗
PubMed1977

Solitary cerebral falx plasmacytoma.

An unusual lesion, a solitary plasmacytoma of the falx cerebri is reported. Surgical treatment and subsequent radiotherapy have been effective therapeutic modalities with no signs of recurrence or disseminated disease after two and a half years.

Adult↗