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Biomedical subjects

A Redondo

Publications and source records attributed to A Redondo.

At least 19 recordsLinked to original sources

Imaging does not predict the clinical outcome of bacterial vertebral osteomyelitis.

OBJECTIVES: Magnetic resonance imaging (MRI) and computed tomography (CT) are useful for initial assessment of bacterial spondylodiscitis. However, clinical relevance of imaging changes during treatment is less well-documented. METHODS: Between October 1997 and March 2005, 29 patients with documented bacterial spondylodiscitis were prospectively enrolled. They had clinical, biological and imaging examinations (MRI and/or CT) at M0 and M3, and in 22 cases, at M6. RESULTS: Mean age was 58 yrs. Antimicrobial chemotherapy lasted an average of 98 days. The median follow-up was 18 months, including 12 months after the completion of treatment. Infection was cured in every patient. Biological markers of inflammation returned to normal at M3. Six patients had painful and/or neurological sequelae. Decreased disc height was a consistent and early sign, and remained stable during the follow-up. Vertebral oedema, present in 100% of cases initially, persisted in 67 and 15% of cases at M3 and M6, respectively. Discal abscesses and paravertebral abscesses, present in 65 and 39% of cases initially, persisted in, respectively, 42 and 9% of cases at M3 and in 18 and 3% of cases at M6. Epidural abscesses were present at diagnosis in 30% of cases, and had always disappeared by M3. Imaging abnormalities found at M0 and M3 did not differ between patients with and without late neurological or painful sequelae. CONCLUSIONS: Imaging abnormalities often persist in patients with bacterial spondylodiscitis despite a favourable clinical and biological response to antibiotic treatment. They are not associated with relapses, neurological sequelae or persistent pain. Imaging controls are not necessary when bacterial spondylodiscitis responds favourably to treatment.

Adult↗

Probing the mechanical unzipping of DNA.

A study of the micromechanical unzipping of DNA in the framework of the Peyrard-Bishop-Dauxois model is presented. We introduce a Monte Carlo technique that allows accurate determination of the dependence of the unzipping forces on unzipping speed and temperature. Our findings agree quantitatively with experimental results for homogeneous DNA, and for lamda-phage DNA we reproduce the recently obtained experimental force-temperature phase diagram. Finally, we argue that there may be fundamental differences between in vivo and in vitro DNA unzipping.

Bacteriophage lambda↗

Sequencing DNA by dynamic force spectroscopy: limitations and prospects.

Using a well established model, we systematically analyze fundamental limitations on the viability of using mechanical unzipping of DNA as a fast and inexpensive sequencing method. Standard unzipping techniques, where double-stranded DNA is unzipped through the application of a force at one end of the molecule, are shown to be inadequate. Emerging techniques that unzip DNA by local force application are more promising, and we establish the necessary experimental requirements that must be met for these techniques to succeed as single molecule sequencing tools.

Microscopy, Atomic Force↗

Breast cancer prognosis determined by gene expression profiling: a quantitative reverse transcriptase polymerase chain reaction study.

PURPOSE: We sought to reproduce with quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) the results obtained with a 70-gene expression profile that has been described previously in breast cancer. PATIENTS AND METHODS: Frozen breast cancer samples from patients who were operated on were used to isolate tumor RNA. Ninety-six patients with stage I to II disease were included. Median age was 57 years (range, 27 to 80 years). Forty-eight patients had lymph node-negative and 48 lymph node-positive disease. qRT-PCR amplifications were performed and the results were correlated with clinical data. RESULTS: After a minimum follow-up of 5 years, 25 patients had a relapse. The gene profile divided patients into two groups with poor and good prognosis. Significant differences with regard to grade of differentiation, size and hormone receptors were seen between the two groups. The gene profile was significantly associated with relapse-free survival and overall survival in the whole group of 96 patients. Multivariate analysis showed that only lymph node status and gene profile were significantly correlated to overall survival. CONCLUSION: qRT-PCR reproduced the results obtained with microarrays for a prognostic gene profile in women with early-stage breast cancer.

Adult↗

Localisation of COX-2 protein is different in breast ductal carcinoma and adjacent non-tumour ductal epithelium.

INTRODUCTION: A number of findings suggest that cyclooxygenase-2 (COX-2) is overexpressed in breast tumours. However, there is a lack of consensus in the literature regarding the pattern of expression of this protein in invasive breast ductal carcinoma and in the adjacent non-tumour ductal epithelium. This study compares the expression of COX-2 mRNA and protein in breast ductal carcinoma relative to non-tumour breast tissue. MATERIAL AND METHODS: We analysed the expression of COX-2 mRNA by quantitative PCR, and COX-2 protein by immunohistochemistry in invasive ductal carcinoma as well as in non-tumour adjacent ductal epithelium from 34 breast biopsies diagnosed as being invasive ductal carcinoma. As control, we analysed expression of COX-2 protein by immunohistochemistry in surgically-resected benign breast lesions. RESULTS: Our results show that COX-2 mRNA and protein are overexpressed in non-tumour ductal epithelium compared with invasive ductal carcinoma. However, the pattern of the protein expression is different in tumour and non-tumour tissue: COX-2 protein is expressed predominantly in the membrane of the non-tumour ductal epithelium (including in benign breast lesions) while, in invasive ductal carcinoma cells, it is localised in the cytoplasm. CONCLUSIONS: The non-tumour ductal epithelium adjacent to invasive ductal carcinoma shows a higher COX-2 expression than does the invasive ductal carcinoma. However, the different localisation of the immunohistochemically-detected protein suggests a possible post-translational regulation of the protein.

Adult↗

[Intraosseous meningioma of the skull: radiologic pathologic correlation].

Intraosseous meningiomas are rare ectopic meningiomas. The authors report the case of a hyperostotic intraosseous meningioma of the parietal bone without dural extension. The preoperative imaging findings, as well as imaging features of the surgical specimen and pathologic findings are discussed.

Female↗

Diffusion-weighted MR imaging and pathologic findings in adult cerebellar medulloblastoma.

UNLABELLED: OBJECTIVES, MATERIALS AND METHODS: The authors present the diffusion-weighted MR imaging and pathologic findings in two adult patients with cerebellar medulloblastoma. RESULTS: Both presented with a vermian mass of the posterior fossa with low signal on SE T1 weighted images, and moderate enhancement of the mass after gadolinium injection. The tumors were of high intensity on diffusion-weighted images with low ADC value. The ADC values (x10(-3) mm2/s) were respectively 0.60 +/- 0.06 and 0.59+/-0.11 (tumor), and 0.65 +/- 0.04 and 0.67 +/- 0.07 (cerebellar white matter). Tumors were highly cellular and composed of densely packed small round cells with hyperchromatic nuclei and scanty cytoplasm. CONCLUSION: diffusion-weighted MR imaging may be useful for the diagnosis of cerebellar medulloblastoma, due to their high cellularity and high nuclear-to-cytoplasmic ratio.

Adult↗

Cell signalling of the GLP-1 action in rat liver.

GLP-1, incretin with insulin-independent antidiabetic properties, is insulinomimetic upon glucose metabolism in extrapancreatic tissues, acting through specific receptors not associated to adenylate cyclase activation. We investigated the role of enzymes mediating insulin actions, in the GLP-1-induced glycogen synthase a activation in rat hepatocytes. GLP-1, like insulin, activates PI3K/PKB, p70s6k, p44 and p42 MAP-kinase. Wortmannin (PI3K/PKB inhibitor) blocked the stimulatory action of insulin on glycogen synthase a and reduced that of GLP-1; rapamycin (p70s6k inhibitor) was ineffective and PD98059 (MEK/MAPK inhibitor) decreased only the insulin effect; okadaic acid (PP-2A inhibitor) was ineffective, while TNFalpha (PP-1 inhibitor) blocked the action of insulin and reduced that of GLP-1; H-7 or Ro 31-8220 (PKC inhibitors) decreased the GLP-1 effect, while only H-7 reduced that of insulin. The activation of PI3K/PKB, PKC and PP-1, but not PP-2A, seems to mediate the GLP-1 stimulatory action on glycogen synthase a in rat hepatocytes, while MAPKs and p70s6k could participate in other GLP-1 effects.

Animals↗

Glucagon-like peptide-1 (GLP-1) and glucose metabolism in human myocytes.

Glucagon-like peptide-1 (GLP-1) has been shown to have insulin-like effects upon the metabolism of glucose in rat liver, muscle and fat, and on that of lipids in rat and human adipocytes. These actions seem to be exerted through specific receptors which, unlike that of the pancreas, are not - at least in liver and muscle - cAMP-associated. Here we have investigated the effect, its characteristics, and possible second messengers of GLP-1 on the glucose metabolism of human skeletal muscle, in tissue strips and primary cultured myocytes. In muscle strips, GLP-1, like insulin, stimulated glycogen synthesis, glycogen synthase a activity, and glucose oxidation and utilization, and inhibited glycogen phosphorylase a activity, all of this at physiological concentrations of the peptide. In cultured myotubes, GLP-1 exerted, from 10(-13) mol/l, a dose-related increase of the D-[U-(14)C]glucose incorporation into glycogen, with the same potency as insulin, together with an activation of glycogen synthase a; the effect of 10(-11) mol/l GLP-1 on both parameters was additive to that induced by the equimolar amount of insulin. Synthase a was still activated in cells after 2 days of exposure to GLP-1, as compared with myotubes maintained in the absence of peptide. In human muscle cells, exendin-4 and its truncated form 9-39 amide (Ex-9) are both agonists of the GLP-1 effect on glycogen synthesis and synthase a activity; but while neither GLP-1 nor exendin-4 affected the cellular cAMP content after 5-min incubation in the absence of 3-isobutyl-1-methylxantine (IBMX), an increase was detected with Ex-9. GLP-1, exendin-4, Ex-9 and insulin all induced the prompt hydrolysis of glycosylphosphatidylinositols (GPIs). This work shows a potent stimulatory effect of GLP-1 on the glucose metabolism of human skeletal muscle, and supports the long-term therapeutic value of the peptide. Further evidence for a GLP-1 receptor in this tissue, different from that of the pancreas, is also illustrated, suggesting a role for an inositolphosphoglycan (IPG) as at least one of the possible second messengers of the GLP-1 action in human muscle.

Analysis of Variance↗

Kinetic proofreading models for cell signaling predict ways to escape kinetic proofreading.

In the context of cell signaling, kinetic proofreading was introduced to explain how cells can discriminate among ligands based on a kinetic parameter, the ligand-receptor dissociation rate constant. In the kinetic proofreading model of cell signaling, responses occur only when a bound receptor undergoes a complete series of modifications. If the ligand dissociates prematurely, the receptor returns to its basal state and signaling is frustrated. We extend the model to deal with systems where aggregation of receptors is essential to signal transduction, and present a version of the model for systems where signaling depends on an extrinsic kinase. We also investigate the kinetics of signaling molecules, "messengers," that are generated by aggregated receptors but do not remain associated with the receptor complex. We show that the extended model predicts modes of signaling that exhibit kinetic discrimination for some range of parameters but for other parameter values show little or no discrimination and thus escape kinetic proofreading. We compare model predictions with experimental data.

Animals↗

Effect of GLP-1 treatment on GLUT2 and GLUT4 expression in type 1 and type 2 rat diabetic models.

Glucagon-like peptide-1 (G LP-1) is an incretin with glucose-dependent insulinotropic and insulin-independent antidiabetic properties that exerts insulin-like effects on glucose metabolism in rat liver, skeletal muscle, and fat. This study aimed to search for the effect of a prolonged treatment, 3 ds, with GLP-1 on glucotransporter GLUT2 expression in liver, and on that of GLUT4 in skeletal muscle and fat, in rats. Normal rats and streptozotocin-induced type 1 and type 2 diabetic models were used; diabetic rats were also treated with insulin for comparison. In normal rats, GLP-1 treatment reduced in the three tissues the corresponding glucotransporter protein level, without modifying their mRNA. In the type 2 diabetic model, GLP-1, like insulin, stimulated in liver and fat only the glucotransporter translational process, while in the muscle an effect at the GLUT4 transcriptional level was also observed. In the type 1 diabetic model, GLP-1 apparently exerted in the liver only a posttranslational effect on GLUT2 expression; in muscle and fat, while insulin was shown to have an action on GLUT4 at both transcriptional and translational levels, the effect of GLP-1 was restricted to glucotransporter translation. In normal and diabetic rats, exogenous GLP-1 controlled the glucotransporter expression in extrapancreatic tissues participating in the overall glucose homeostasis-liver, muscle, and fat-where the effect of the peptide seems to be exerted only at the translational and/or posttranslational level; in muscle and fat, the presence of insulin seems to be required for GLP-1 to activate the transcriptional process. The stimulating action of GLP-1 on GLUT2 and GLUT4 expression, mRNA or protein, could be a mechanism by which, at least in part, the peptide exerts its lowering effect on blood glucose.

Adipose Tissue↗

[Acute intracranial hypertension and anicteric cholestasis revealing Whipple's disease without digestive involvement].

Whipple's disease is a rare infectious disease with potential central nervous system manifestations and a poor prognosis. We report the case of a young woman who presented with acute intracranial hypertension associated with cholestasis which revealed Whipple's disease without digestive involvement. The diagnosis was supported by the presence of PAS-diastase positive hepatic granulomas. A long course of antibiotics resulted in complete remission of the disease without relapse. An acute neurologic syndrome associated with cholestasis should suggest Whipple's disease.

Adolescent↗

Antioxidant activity and radioprotective effects against chromosomal damage induced in vivo by X-rays of flavan-3-ols (Procyanidins) from grape seeds (Vitis vinifera): comparative study versus other phenolic and organic compounds.

The quantitative distribution of several flavan-3-ols was determined using HPLC in a grape (Vitis vinifera) seed extract (GSE) of four cultivars grown in the region of Murcia. Polymer >/= C(4) units made up the largest group of procyanidins in the GSE (90.92%, expressed as HPLC % area). The antioxidant activity of GSE and other reference compounds was investigated by measuring their ability to scavenge the ABTS(*)(+) radical cation (TEAC). The most effective compounds were, in order: GSE > rutin > (+)-catechin > diosmin >/= ascorbic acid. The radioprotective effects of GSE and other reference compounds were determined by using the micronucleus test for anticlastogenic activity, any reduction of the frequency of micronucleated polychromatic erythrocytes (MnPCEs) being evaluated in the bone marrow of mouse exposed to X-rays. The most effective compounds were, in order: GSE > rutin > dimethyl sulfoxide (DMSO) > ascorbic acid > 6-n-propyl-2-thiouracil-6c (PTU) > diosmin. The higher ABTS(*)(+) scavenging capacity and anticlastogenic activity of GSE can be explained, structurally, by the high number of conjugated structures between the catechol groups in the B-rings and the 3-OH free groups of the polymeric polyphenolic skeleton and, in addition, by the stability of the aroxyl flavonoid radical generated in the above processes.

Animals↗

[Cerebral amyloid angiopathy presenting as a pseudotumor: 2 cases with spontaneously favorable outcomes].

A rare clinical and radiographical presentation of cerebral amyloid angiopathy mimicking a brain neoplasm was observed in 2 patients. The signs and symptoms included seizures and focal parieto-occipital dysfunction in 1 case, massive left hemisphere dysfunction and akinetic mutism in the other. Brain CT and MRI showed nonspecific focal white matter abnormalities suggestive of the diagnosis of low-grade glioma. Gradient echo T1 and T2-weighted images showing multiple areas of signal void suggesting multiple disseminated petechial hemorrhages led to the diagnosis of cerebral amyloid angiopathy. An eventless brain biopsy confirmed the diagnosis. The neuropathology examination disclosed amyloid angiopathy of the pial and cortical vessels selectively stained by anti A-beta protein antibodies. The clinical course was remarkable in the two cases with almost complete clinical recovery without any particular treatment.

Aged↗

[Intracranial abscess and empyema: neurosurgical management].

Brain abscesses and empyemas are severe infections with lethal outcomes in the case of inappropriate treatment. The files of 34 patients with brain abscesses, and nine with intracranial empyemas treated over eight years (1990-1997) were analyzed retrospectively. Cases were evaluated for treatment and compared with data from the literature. Patients with brain abscess underwent either aspiration of the lesion through a burr hole (79.5% of the cases), or craniotomy and excision (8.8% of the cases); 11.7% were treated only with antibiotics. The operative mortality was 2.9% and the outcome was satisfactory in 85% of patients. These results are in agreement with data from the literature. Prognosis is strongly related to the initial clinical status. Current methods of treatment include surgical aspiration of large abscesses with a mass effect, and are usually associated with a poor clinical status. Excision is suggested whenever aspiration procedures have failed, or in the presence of foreign material or fungal abscess. Medical treatment is indicated for small and deeply located abscesses in patients with satisfactory clinical states. Empyemas in our series were treated with burr hole and pus aspiration. The mortality rate was 11%, and 62.5% of the patients made a good recovery. In agreement with other reported studies, the method of treating subdural empyema is much less significant than an aggressive early drainage of the infection. Although brain abscesses and empyema remain a significant neurosurgical concern, aggressive treatment can result in an excellent outcome in the majority of patients.

Adolescent↗