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C Flores

Publications and source records attributed to C Flores.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2000

Northwest African distribution of the CD4/Alu microsatellite haplotypes.

We have analysed a linked microsatellite/Alu polymorphism at the CD4 locus (CD4/Alu) in 666 chromosomes from samples of the Iberian Peninsula, Northwest Africa, and West sub-Saharan Africa. The Iberian Peninsula differs from other European populations by its higher levels of haplotype diversity (0.75), and weaker association between the microsatellite allele 90 and Alu(-) chromosomes. These results are explainable by a substantial gene flow from Northwest Africa. Significant geographic clines for the five major haplotypes suggest a south to north migration from sub-Saharan Africa into Northwest Africa. In spite of this, the consistent presence of haplotype 110(-) in this area is congruent with an ancient and autochthonous human presence in Northwest Africa.

Africa South of the Sahara↗
PubMed2000

Vertebral hemangioma mimicking a metastatic bone lesion in well-differentiated thyroid carcinoma.

The authors report a case of abnormal accumulation of I-131 in a thoracic vertebra in a patient with a well-differentiated thyroid carcinoma. The presumptive diagnosis was metastatic bone disease. Further diagnostic work-up confirmed a benign bone lesion. Bone metastasis, when shown on I-131 whole-body scintigraphy, usually supports a change in the staging and therapeutic approach to a patient with thyroid carcinoma. The authors believe that, although an infrequent lesion, the differential diagnosis of abnormal accumulation of I-131 in the body of a vertebra in patients with well-differentiated thyroid carcinoma should raise the possibility of a benign hemangioma. Complete work-up of the suggested bone metastatic lesion should be performed before tumor restaging and I-131 therapy is recommended.

Carcinoma, Papillary↗
PubMed2000

[Tumorogenesis and mdm2 protein].

Tumorogenesis is associated with several events by which a normal cell transforms itself into a tumour cell with an increased proliferation rate. One of the most important research initiatives in this area is the characterization of the molecular mechanisms involved in tumorogenesis and cancer. Oncogenes and tumour suppressor genes are directly involved in the cell cycle, differentiation, and apoptosis. The cellular oncogene MDM2 seems to be abnormally elevated in several human tumours, specially in sarcomas. The MDM2 gene product, mdm2 protein, pS3 and retinoblastoma (Rb) proteins, play crucial roles in the control of the cell cycle. The molecular interactions between mdm2, pS3 and Rb in cancer, are associated with a loss of control in the G1 phase of the cell cycle leading to uncontrolled cell proliferation. Studies by gene amplification appear to show an incomplete picture of mdm2 protein levels in tumour cells. The simultaneous determination of mdm2 protein and mRNA levels seems to give a more accurate interpretation of the abnormal function of the mdm2 protein. Thus, in addition to gene amplification, different mechanisms by which mdm2 is overexpressed in cancer cells also play an important role in tumorogenesis.

Cell Transformation, Neoplastic↗
PubMed2000

Endovascular therapy in the treatment of head and neck lesions.

Recent advances in microcatheter technology, refinements in embolic agents and improvements in navigational techniques have allowed for endovascular embolization to become an important adjunct in the treatment of vascular head and neck lesions. We describe several case reports where endovascular embolization was utilized in the treatment of such lesions.

Adolescent↗
PubMed2000

[Severe Henoch-Schonlein purpura in a patient with multiple myeloma].

A Multiple Myeloma (MM), IgG-lambda stage III-A was diagnosed in a 41-year-old-man. After VAD cycles IgG decreased from 7.5 to 2.4 g/dL. were mobilized with cyclophosphamide and 10 micrograms/Kg G-CSF. Three days after the collection of peripheral stem cell, the patient had fever, nausea, vomiting, liquid stools, shoulder and knee arthralgia and dehydration. Upper GI endoscopy showed esophageal candidiasis and ulcerative necrotic lesions both in stomach and duodenum; the biopsy confirmed necrosis. Simultaneously, the appearance of purpura with maculopapular lesions of diverse sizes appeared in the feet progressing to the limbs and trunk. Hematuria and proteinuria were also observed. Skin biopsy showed leukocytoclastic vasculitis. Renal biopsy showed focal and segmental glomerulonephritis. Serum ANCA, cryoglobulins, anti-HCV and RF were negative, and serum monoclonal IgG was 1290 mg/dL. Daily treatment with i.v. methylprednisolone pulses for 3 days improved skin lesions and digestive involvement. Macroscopic hematuria and proteinuria improved after two months of steroid treatment.

Adult↗
PubMed1999

Ovariectomy of adult rats leads to increased expression of astrocytic basic fibroblast growth factor in the ventral tegmental area and in dopaminergic projection regions of the entorhinal and prefrontal cortex.

Changes in astrocytic function may underlie the neurochemical and morphological alterations in limbic and cortical areas after estrogen loss in adult females. We assessed whether increased expression of basic fibroblast growth factor (bFGF), an astrocytic response involved in injury-induced neuronal plasticity, occurs after ovariectomy. We examined bFGF immunoreactivity (IR) in ovariectomized rats with oil or estradiol benzoate (5 microgram every 4 d; Experiment 1) and in ovariectomized and intact animals (Experiment 2). In the ventral tegmental area (VTA), bFGF-IR and glial fibrillary acidic protein (GFAP)-IR were greater in ovariectomized animals than in animals with estrogen replacement. bFGF-IR in the VTA was greater in ovariectomized than in intact females. In the dorsal raphe, no differences between groups were found in GFAP-IR or bFGF-IR. In mesolimbic dopaminergic target areas within entorhinal cortex (Ent), prefrontal cortex, and nucleus accumbens, bFGF-IR was higher in Ent of ovariectomized animals 4 weeks after surgery in both experiments, but no differences were seen in nucleus accumbens or in an occipital cortical, control, area in either study. In Experiment 2, small increases in bFGF-IR were seen in the prefrontal cortex after ovariectomy. In the VTA and Ent, changes in bFGF-IR developed gradually, peaking at 4 weeks and waning at 40 weeks. Furthermore, increased dendritic arbor of Ent layer II/III pyramidal cells was found in ovariectomized females with the use of a modified Golgi-Cox staining procedure. These findings suggest that, within specific regions, ovariectomy induces astrocytic responses similar to those observed after injury that may affect neuronal chemistry and morphology.

Animals↗
PubMed1999

Microsatellite instability in Drosophila spellchecker1 (MutS homolog) mutants.

We have cloned a mutS homolog from Drosophila melanogaster called spellchecker1 (spel1) and have constructed spel1 mutant flies. MutS proteins promote the correction of DNA mismatches and serve important roles in DNA replication, recombination, and repair. The spel1 gene belongs to a subfamily of mutS first characterized by the MSH2 gene of yeast and which also includes hMSH2, one of the two major hereditary nonpolyposis colon cancer loci of humans. Like msh2 mutants in other species, we find that flies lacking the spel1 gene suffer a highly increased rate of instability in long runs of dinucleotide repeats when analyzed after 10-12 fly generations. Using a new assay, we have also discovered that mutations in spel1 decrease the stability of a dinucleotide repeat when it is copied into the site of a double-strand break during gene conversion. Contrary to the case in mammalian cells, spel1 deficiency does not affect tolerance of flies to a methylating agent nor does it affect resistance to gamma-irradiation.

Adenosine Triphosphatases↗
PubMed1999

Recurrent ectopic adrenocorticotropic hormone producing thymic carcinoid detected with octreotide imaging.

Primary thymic carcinoids are rare tumors in which the tumor cells retain functional somatostatin receptors. In-111-labeled octreotide imaging has been used to diagnose abdominal carcinoids with a sensitivity rate of approximately 87%. The authors describe a case of a recurrent, ectopic cortisol-releasing hormone that produced thymic carcinoid localized as a focal area of increased activity in the upper mediastinum when planar and tomographic octreotide scintigraphy was used. Chest CT and MRI failed to localize the tumor. This may be the first reported case of In-111-labeled octreotide used to identify Cushing's syndrome caused by a cortisol-releasing hormone that produced thymic carcinoid.

Adult↗
PubMed1999

[Segmental short bowel stenosis after a superior mesenteric vein thrombosis. Report of a case].

We report a 24 years old female with a Superior Mesenteric and Portal Vein Thrombosis due to an Antithrombin III factor deficiency, associated to oral contraceptive use and smoking. She presented with severe abdominal pain and the diagnosis was reached after surgery with a CT scan. The patient was treated with intravenous heparin and oral anticoagulation, with a good clinical and Doppler endo-sonographic response. One month after the onset, she developed an intestinal occlusion caused by two concentric jejunal stenoses, measuring 2 and 0.7 cm in length and demonstrated with a barium jejunogram. A 35 cm intestinal resection was done and the patient recovered uneventfully. The pathological study showed granulation tissue on both stenotic zones with an ulcer near to the distal stricture, that reached the internal muscularis propria, with subserosal fibrosis. The development of segmental stenosis is a rare complication superior mesenteric vein thrombosis, that must be bore in mind.

Adult↗