Biomedical subjects

C Flores

Publications and source records attributed to C Flores.

At least 19 recordsLinked to original sources

PubMed2003

Molecular epidemiology of oxacillin-resistant Staphylococcus aureus in Brooklyn, New York.

Although oxacillin-resistant Staphylococcus aureus (ORSA) are well-established pathogens in many hospitals, the impact of infection control measures on the clonal distribution of ORSA is poorly defined. A citywide surveillance study of Staphylococcus aureus in Brooklyn, New York revealed that 36% of isolates were ORSA. Molecular typing showed that one strain (Cluster A) accounted for more than half of the isolates and was present in all 15 hospitals. In one hospital, a distinct strain (Cluster B) accounted for 20% of ORSA isolates. Infection control measures in this hospital significantly decreased the percentage of clinical isolates that belonged to Cluster B, but did not have an effect on the strain endemic to the city (Cluster A). Regional infection control strategies may need to be developed to limit the spread of the ORSA clone endemic to this area.

Anti-Bacterial Agents↗

PubMed2003

A predominant European ancestry of paternal lineages from Canary Islanders.

We genotyped 24 biallelic sites and 5 microsatellites from the non-recombining portion of the Y chromosome in 652 males from the Canary Islands. The results indicate that, contrary to mtDNA data, paternal lineages of the current population are overwhelmingly (>90%) of European origin, arguing for a highly asymmetric pattern of mating after European occupation. However, the presence of lineages of indisputable African assignation demonstrates that an aboriginal background still persists (<10%). On the basis of distribution and dating of some of these lineages we derived a genetic perspective of settlement processes of the archipelago in two stages, congruent with anthropological, archaeological and linguistic findings.

Africa↗

PubMed2003

Y chromosome and mitochondrial DNA characterization of Pasiegos, a human isolate from Cantabria (Spain).

Mitochondrial DNA sequences and Y chromosome haplotypes were characterized in Pasiegos, a human isolate from Cantabria, and compared with those of other Cantabrian and neighbouring Northern Spain populations. Cantabria appears to be a genetically heterogeneous community. Whereas Lebaniegos do not differ from their eastern Basque and western Asturian and Galician neighbours, Pasiegos and other non-Lebaniego Cantabrians show significant differences with all of them. Pasiegos are peculiar for their high frequencies of Y chromosomal markers (E-M81) with North African assignation, and Y chromosomal (R-SRY2627) and mtDNA (V, I, U5) markers related to northern European populations. This dual geographic contribution is more in agreement with the complex demographic history of this isolate, as opposed to recent drift effects. The high incidence in Cantabrians with pre-V and V mtDNA haplotypes, considered as a signal of Postglacial recolonization in Europe from south-western refugees, points to such refugees as a better candidate population than Basques for this expansion. However, this does not discount a conjoint recolonization.

Chromosomes, Human, Y↗

PubMed2002

Bioavailability of ranitidine in healthy Mexican volunteers: effect of food.

Is well known that food can affect the bioavailability of several drugs, its impact is major for those drugs that have to act near of drug absorption. Documentation about alterations of ranitidine bioavailability by effect of food is poor. The purpose of this work was to evaluate the effect of food over the bioavailability of ranitidine. Twenty healthy Mexican volunteers were included for the study. The study was made in two stages, in the first one the volunteers had 12 hour fast and took a 300 mg of oral dose of ranitidine (without food, WOF) and blood samples were drawn. Two weeks later, the volunteers took a normal diet just before ranitidine intake (with food, WF). The area under the curve (AUC) was 30% greater in WOF, Cmax was 921.5 ng/ml (WF) vs. 1685.2 (WOF), and t1/2 was 2.70 +/- 1.38 (WF) h vs 3.66 +/- 1.34 (WOF). The AUC, Cmax and t1/2 were statistically different. It is evident that there are differences in the drug disposition due to the presence of food, then, it is possible that the efficacy of ranitidine as inhibitor of gastric secretion being limited by food.

Adolescent↗

PubMed2001

Major genomic mitochondrial lineages delineate early human expansions.

BACKGROUND: The phylogeographic distribution of human mitochondrial DNA variations allows a genetic approach to the study of modern Homo sapiens dispersals throughout the world from a female perspective. As a new contribution to this study we have phylogenetically analysed complete mitochondrial DNA(mtDNA) sequences from 42 human lineages, representing major clades with known geographic assignation. RESULTS: We show the relative relationships among the 42 lineages and present more accurate temporal calibrations than have been previously possible to give new perspectives as how modern humans spread in the Old World. CONCLUSIONS: The first detectable expansion occurred around 59,000-69,000 years ago from Africa, independently colonizing western Asia and India and, following this southern route, swiftly reaching east Asia. Within Africa, this expansion did not replace but mixed with older lineages detectable today only in Africa. Around 39,000-52,000 years ago, the western Asian branch spread radially, bringing Caucasians to North Africa and Europe, also reaching India, and expanding to north and east Asia. More recent migrations have entangled but not completely erased these primitive footprints of modern human expansions.

Base Sequence↗

PubMed2001

Modulation of adenosine transport by insulin in human umbilical artery smooth muscle cells from normal or gestational diabetic pregnancies.

1. Adenosine transport was measured in human cultured umbilical artery smooth muscle cells, isolated from non-diabetic or gestational diabetic pregnancies, under basal conditions and after pretreatment in vitro with insulin. 2. Adenosine transport in non-diabetic smooth muscle cells was significantly increased by insulin (half-maximal stimulation at 0.33 +/- 0.02 nM, 8 h) and characterized by a higher maximal rate (V(max)) for nitrobenzylthioinosine (NBMPR)-sensitive (es) saturable nucleoside transport (17 +/- 5 vs. 52 +/- 12 pmol (microg protein)(-1) min(-1), control vs. insulin, respectively) and maximal binding sites (B(max)) for [(3)H]NBMPR (0.66 +/- 0.07 vs. 1.1 +/- 0.1 fmol (microg protein)(-1), control vs. insulin, respectively), with no significant changes in Michaelis-Menten (K(m)) and dissociation (K(d)) constants. 3. In contrast, in smooth muscle cells from diabetic pregnancies, where the values of V(max) for adenosine transport (59 +/- 4 pmol (microg protein)(-1) min(-1)) and B(max) for [(3)H]NBMPR binding (1.62 +/- 0.16 fmol (microg protein)(-1)) were significantly elevated by comparison with non-diabetic cells, insulin treatment (1 nM, 8 h) reduced the V(max) for adenosine transport and B(max) for [(3)H]NBMPR binding to levels detected in non-diabetic cells. 4. In non-diabetic cells, the stimulatory effect of insulin on adenosine transport was mimicked by dibutyryl cGMP (100 nM) and reduced by inhibitors of phosphatidylinositol 3-kinase (10 nM wortmannin), nitric oxide synthase (100 microM N (G)-nitro-L-arginine methyl ester, L-NAME) or protein synthesis (1 microM cycloheximide), whereas inhibition of adenylyl cyclase (100 microM SQ-22536) had no effect. 5. Wortmannin or SQ-22536, but not L-NAME or cycloheximide, attenuated the inhibitory action of insulin on the diabetes-induced stimulation of adenosine transport. 6. Protein levels of inducible NO synthase (iNOS) were similar in non-diabetic and diabetic cells, but were increased by insulin (1 nM, 8 h) only in non-diabetic smooth muscle cells. 7. Our results suggest that adenosine transport via the es nucleoside transporter is modulated differentially by insulin in either cell type. Insulin increased adenosine transport in non-diabetic cells via NO and cGMP, but inhibited the diabetes-elevated adenosine transport via activation of adenylyl cyclase, suggesting that the biological actions of adenosine may be altered under conditions of sustained hyperglycaemia in uncontrolled diabetes.

Adenosine↗

PubMed2001

The potential application of aqueous two-phase systems for in situ recovery of 6-pentyl-infinity-pyrone produced by Trichoderma harzianum.

Commercial production of aroma compounds by de novo microbial biosynthesis has been principally limited by the low productivity so far achieved. Production of 6-pentyl-alpha-pyrone (6PP), a coconut-like aroma compound, by Trichoderma harzianum has been limited by the toxic effect that occurs even at low concentration (<100 ppm). This work evaluated the feasibility of the use of aqueous-two phase systems (ATPS), as in situ extraction systems, in order to overcome the toxic effects of 6PP and to improve culture productivity. The partition behaviour of 6-pentyl-alpha-pyrone and Trichoderma harzianum mycelium in polyethylene glycol (PEG)-salt and PEG-dextran two-phase systems was investigated and it is reported for the first time. The evaluation of system parameters such as PEG molecular mass, concentration of PEG as well as salt, volume ratio (Vr) and dextran molecular mass, was carried out to determine under which conditions the 6PP partitions to the opposite phase that mycelium does. PEG-dextran systems proved to be unsuitable for the in situ recovery of 6PP because either 6PP and biomass partitioned to the same phase or a large extraction phase was required for the process. ATPS extraction comprising Vr = 0.26, PEG 1450 (7.2% w/w) and sulphate (16.6% w/w) provided the best conditions for the maximum accumulation of the biomass into the bottom phase and concentrated the 6PP in the opposite phase (i.e. 86% of biomass and 56% of 6PP of the total amount loaded from the fermentation extract into the ATPS) for ex situ bioseparation. However, this system caused complete inhibition of the growth of the microorganism during the in situ bioseparation, probably as a consequence of the high ionic strength resulting from the salt concentration. Consequently, two ATPS PEG 8000-sulphate (12%/7% and 6%/14%) were evaluated and proved to be more suitable in the potential application for the in situ recovery of 6PP.

Journal Article↗

PubMed2001

Polymorphism and distribution of HLA-DR2 alleles in Mexican populations.

DRB1*15/16 nucleotide polymorphism was analyzed in 68 DR2 positive individuals (18 Mexican Mestizos, 30 Mazatecans and 20 Nahuas), carrying a total of 75 DR2 haplotypes. HLA-DR2 was one of the most frequent specificities detected in Mazatecans and Nahuas with gene frequency (gf) of 0.232 and 0.141, respectively. In these populations DRB1*16 was the most frequent DR2 split (gf = 0.183 in Mazatecans and gf = 0.135 in Nahuas), whereas in Mexican Mestizos the most frequent was DRB1*15 (gf = 0.065). Four DRB1-DQB1 combinations in Mexican Mestizos, two in Mazatecans and one in Nahuas were in linkage disequilibrium. In spite of the restricted polymorphism, there were differences on DRB1*15/16 alleles found in Mexicans. DRB1*1501 a Caucasian allele was predominant in Mexican Mestizos, whereas DRB1*1602 an Amerindian allele was characteristic on Indian populations. An important difference was detected among the Amerindian populations studied since DRB1*1502 was only present in Mazatecans. This data corroborates the restricted polymorphism of DRB1*15/16 and the high frequency of DRB1*16 subtype in autochthonous American populations and suggest that the differences in gene frequencies of DRB1*15/16 alleles could be helpful in distinguishing each of these population.

Alleles↗

PubMed2001

The peopling of the Canary Islands: a CD4/Alu microsatellite haplotype perspective.

A new CD4 microsatellite allele with three TTTTC complete repetitions, previously described only in hominoids, has been found in this screening. The number of haplotypes and heterozygosities in the Canary Islands (15 and 0.746+/-0.007) is more similar to Iberian (14 and 0.748+/-0.015) than to North African (18 and 0.827+/-0.009) values. However, in some islands, with less European migratory impact, haplotypes with major African assignation (90[+] and 130[+]) reach frequencies similar to African populations. There is a significant negative correlation between geographic distances to Africa and insular heterozygosity values, which suggests a main aborigine colonization from East to West still detectable today.

Alleles↗

PubMed2001

Mitochondrial DNA characterisation of European isolates: the Maragatos from Spain.

Mitochondrial DNA analysis confirms that Maragatos from Spain are a genetically isolated human group. Genetic distances between Maragatos and the comparison samples are significantly different even with the León sample (P<0.001) which shares the same geographic area as the Maragatos. Although the north-African haplogroup U6 is present in them, their attributed Berber origin is weakened, as this haplogroup is also detected in surrounding populations with which, in addition, Maragatos have the smaller genetic distances. These U6 haplotypes are ascribed to a pre-historic African colonisation that influenced all the Iberian Peninsula. The presence of Neolithic haplogroups in this sample suggests that their isolation culture was not absolute until recent times.

Alleles↗

PubMed2001

Tubular NF-kappaB and AP-1 activation in human proteinuric renal disease.

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) and activated protein-1 (AP-1) are transcription factors that regulate many genes involved in the progression of renal disease. Recent data have shown that NF-kappaB is activated in tubules and glomeruli in various experimental models of renal injury. In vitro studies also suggest that proteinuria could be an important NF-kappaB activator. We therefore approached the idea that NF-kappaB may be an indicator of renal damage progression. METHODS: Paraffin-embedded renal biopsy specimens from 34 patients with intense proteinuria [14 with minimal change disease (MCD) and 20 with idiopathic membranous nephropathy (MN)] and from 7 patients with minimal or no proteinuria (IgA nephropathy) were studied by Southwestern histochemistry for the in situ detection of activated transcription factors NF-kappaB and AP-1. In addition, by immunohistochemistry, we performed staining for the NF-kappaB subunits (p50 and p65) and AP-1 subunits (c-fos, c-jun). By immunohistochemistry and/or in situ hybridization, the expression of some chemokines [monocyte chemoattractant protein-1 (MCP-1), RANTES, osteopontin (OPN)] and profibrogenic cytokines [transforming growth factor-beta (TGF-beta)], whose genes are regulated by NF-kappaB and/or AP-1, were studied further. RESULTS: NF-kappaB was detected mainly in the tubules of proteinuric patients, but rarely in nonproteinuric IgA nephropathy (IgAN) patients. In addition, there was a significant relationship between the intensity of proteinuria and NF-kappaB activation in MCD (r = 0.64, P = 0.01) and MN patients (r = 0.64, P < 0.01). Unexpectedly, patients with MCD had a significantly higher NF-kappaB tubular activation than those with MN (P < 0.01). To assess whether there was a different composition of NF-kappaB protein components, immunostaining was performed for the NF-kappaB subunits p50 and p65. However, no differences were noted between MCD and MN patients. In those patients, there was a lower tubular activation of AP-1 compared with NF-kappaB. Moreover, a strong correlation in the expression of both transcription factors was observed only in MN (r = 0.7, P = 0.004). Patients with progressive MN had an overexpression of MCP-1, RANTES, OPN, and TGF-beta, mainly in the proximal tubules, while no significant expression was found in MCD patients. CONCLUSIONS: On the whole, our results show that a tubular overactivation of NF-kappaB and AP-1 and a simultaneous up-regulation of certain proinflammatory and profibrogenic genes are markers of progressive renal disease in humans. Increased activation of solely NF-kappaB and/or AP-1 may merely indicate the response of tubular renal cells to injury.

Adolescent↗

PubMed2001

Comparison of automated ribotyping to pulsed-field gel electrophoresis for genetic fingerprinting of Streptococcus pneumoniae.

Fifty-two isolates of Streptococcus pneumoniae were characterized by pulsed-field gel electrophoresis (PFGE) and automated ribotyping by using HindIII and PvuII. HindIII ribotypes correlated well with PFGE. PvuII produced fewer bands and was less discriminatory. Automated ribotyping with HindIII is an accurate method for genetic fingerprinting of S. pneumoniae and can complement PFGE.

DNA Fingerprinting↗

PubMed2001

Y-chromosome differentiation in Northwest Africa.

Variation of seven Y-chromosomal DNA polymorphisms, one microsatellite (DYS19), and six biallelic markers (DYS287, DYS271, SRY-2627, SRY-1532, 92R7, and M9), were studied in males from Northwest Africa. To evaluate the degree of differentiation in this region, males from neighboring areas such as the Iberian Peninsula and sub-Saharan Africa were also typed. The results show a large number of paternal lineages of Northwest African origin (over 75%), supporting a long-term population continuity in the area. When the analysis of molecular variance (AMOVA) was performed both on the microsatellite and biallelic marker combinations or haplogroups, a large degree of differentiation among areas was revealed. In spite of these geographic differences, some gene flow between areas was detected by the presence of haplogroups with other geographical origins.

Africa South of the Sahara↗

PubMed2000

Regulation of adenosine transport by D-glucose in human fetal endothelial cells: involvement of nitric oxide, protein kinase C and mitogen-activated protein kinase.

The effects of elevated D-glucose on adenosine transport were investigated in human cultured umbilical vein endothelial cells isolated from normal pregnancies. Elevated D-glucose resulted in a time- (8-12 h) and concentration-dependent (half-maximal at 10+/-2 mM) inhibition of adenosine transport, which was associated with a reduction in the Vmax for nitrobenzylthioinosine (NBMPR)-sensitive (es) saturable nucleoside with no significant change in Km. d-Fructose (25 mM), 2-deoxy-D-glucose (25 mM) or D-mannitol (20 mM) had no effect on adenosine transport. Adenosine transport was inhibited following incubation of cells with the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA; 100 nM, 30 min to 24 h). D-Glucose-induced inhibition of transport was abolished by calphostin C (100 nM, an inhibitor of PKC), and was not further reduced by PMA. Increased PKC activity in the membrane (particulate) fraction of endothelial cells exposed to D-glucose or PMA was blocked by calphostin C but was unaffected by NG-nitro-L-arginine methyl ester (L-NAME; 100 microM, an inhibitor of nitric oxide synthase (NOS)) or PD-98059 (10 microM, an inhibitor of mitogen-activated protein kinase kinase 1). D-Glucose and PMA increased endothelial NOS (eNOS) activity, which was prevented by calphostin C or omission of extracellular Ca2+ and unaffected by PD-98059. Adenosine transport was inhibited by S-nitroso-N-acetyl-l, d-penicillamine (SNAP; 100 microM, an NO donor) but was increased in cells incubated with L-NAME. The effect of SNAP on adenosine transport was abolished by PD-98059. Phosphorylation of mitogen-activated protein kinases p44mapk (ERK1) and p42mapk (ERK2) was increased in endothelial cells exposed to elevated D-glucose (25 mM for 30 min to 24 h) and the NO donor SNAP (100 microM, 30 min). The effect of D-glucose was blocked by PD-98059 or L-NAME, which also prevented the inhibition of adenosine transport mediated by elevated D-glucose. Our findings provide evidence that D-glucose inhibits adenosine transport in human fetal endothelial cells by a mechanism that involves activation of PKC, leading to increased NO levels and p42-p44mapk phosphorylation. Thus, the biological actions of adenosine appear to be altered under conditions of sustained hyperglycaemia.

Adenosine↗

PubMed2000

Mutations in GAL2 or GAL4 alleviate catabolite repression produced by galactose in Saccharomyces cerevisiae.

Galactose does not allow growth of pyruvate carboxylase mutants in media with ammonium as a nitrogen source, and inhibits growth of strains defective in phosphoglyceromutase in ethanol-glycerol mixtures. Starting with pyc1, pyc2, and gpm1 strains, we isolated mutants that eliminated those galactose effects. The mutations were recessive and were named dgr1-1 and dgr2-1. Strains bearing those mutations in an otherwise wild-type background grew slower than the wild type in rich galactose media, and their growth was dependent on respiration. Galactose repression of several enzymes was relieved in the mutants. Biochemical and genetic evidence showed that dgr1-1 was allelic with GAL2 and dgr2-1 with GAL4. The results indicate that the rate of galactose consumption is critical to cause catabolite repression.

Journal Article↗

PubMed2000

Requirement of endogenous basic fibroblast growth factor for sensitization to amphetamine.

Repeated exposure to amphetamine produces long-lasting increases in sensitivity to its effects. We reported previously that repeated amphetamine treatment results in increased astrocytic expression of basic fibroblast growth factor (bFGF) in the ventral tegmental area (VTA) and substantia nigra compacta (SNc) and that this effect is prevented by coadministration of a nonspecific glutamate receptor antagonist. Here we show that the development of sensitization to amphetamine is prevented when amphetamine injections are preceded by infusions of a neutralizing antibody to bFGF into the VTA. In addition, we show that astrocytic bFGF expression is increased in the VTA and SNc of animals that exhibit behavioral sensitization and that the number of bFGF-immunoreactive astrocytes in these regions is strongly and positively correlated with the magnitude of sensitization. Cotreatment with an NMDA glutamate receptor antagonist blocks both the development of behavioral sensitization and bFGF induction. These results show that endogenous bFGF is necessary for the development of sensitization to amphetamine and suggest that bFGF mediates the glutamatergic-dopaminergic interaction that initiates the long-term consequences of repeated drug use.

Amphetamine↗

PubMed2000

Basic fibroblast growth factor as a mediator of the effects of glutamate in the development of long-lasting sensitization to stimulant drugs: studies in the rat.

RATIONALE: Repeated exposure to stimulant drugs, such as the indirect dopaminergic agonists amphetamine or cocaine, results in increased sensitivity to their effects on behavior and dopaminergic function. Neuroadaptations initiated in the ventral tegmental area (VTA), a cell body region of midbrain dopaminergic neurons, and dependent on glutamatergic transmission, underlie the development of this persistent drug-induced sensitization. How precisely drug actions in the VTA initiate long-lasting changes in dopaminergic function, and how glutamate participates in these events is not clear. OBJECTIVES: To discuss the idea that neurotrophic, neuroprotective factors are involved. RESULTS: We review the few studies that have been concerned with a role for neurotrophic factors in the changing response to stimulant drugs and present a summary of those conducted in our laboratory on basic fibroblast growth factor (bFGF), a neurotrophic factor produced by astrocytes. CONCLUSION: We argue that repeated exposure to stimulant drugs increases the demands on dopaminergic cell functioning, and, by stimulating glutamate release, recruits neurotrophic and neuroprotective substances such as bFGF. We propose that the actions of these factors, in turn, give rise to long-lasting neuronal adaptations that underlie sensitized responding to further drug exposure. Possible mechanisms whereby bFGF participates in the development of sensitization, including interactions with other neurotrophic factors, are discussed. In addition, we show how the evidence reviewed in this paper provides further support for the idea that repeated treatment with stimulant drugs induces synaptic plasticity.

Animals↗

PubMed2000

Changes in astrocytic basic fibroblast growth factor expression during and after prolonged exposure to escalating doses of amphetamine.

We have shown that brief exposure to amphetamine leads to sustained glutamate-dependent increases in expression of the neurotrophic, neuroprotective factor, basic fibroblast growth factor, in astrocytes in dopaminergic cell body regions and that blockade of basic fibroblast growth factor in this region prevents the development of behavioral sensitization to amphetamine. Here we examine the effects of prolonged exposure to an escalating-dose regimen of amphetamine known to induce long-lasting sensitization to amphetamine and leading to increases in neuronal dendritic length and spine density in nucleus accumbens and prefrontal cortex and to decreases in spine density in occipital cortex. Astrocytic basic fibroblast growth factor immunoreactivity was increased in both dopaminergic cell body and terminal regions one week after termination of a two-week amphetamine treatment (1-4mg/kg). These effects were not evident one week after a five-week treatment (1-9mg/kg) and, in fact, one month later basic fibroblast growth factor levels in cell body regions were decreased. In the occipital cortex, basic fibroblast growth factor immunoreactivity was decreased one week after the two-week amphetamine treatment, but was not different from that seen in saline-treated animals after the five-week treatment. Increased astrocytic basic fibroblast growth factor expression appears to be an early, but relatively prolonged, response to amphetamine exposure and seems to parallel structural changes induced by repeated drug exposure.These findings suggest that basic fibroblast growth factor may participate in the development of structural changes brought about by amphetamine. The fact that the basic fibroblast growth factor response is not maintained after prolonged intense exposure to amphetamine suggests that the factors that initially induce basic fibroblast growth factor expression are self-regulating.

Amphetamine↗