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Biomedical subjects

P Rodríguez

Publications and source records attributed to P Rodríguez.

At least 19 recordsLinked to original sources

Ras protein is involved in the physiological regulation of phospholipase D by platelet derived growth factor.

Lipid-derived metabolites play an important role in the regulation of cell responses to external stimuli, including cell growth control, transformation and apoptosis. Phospholipase D (PLD) is one of the critical elements in the regulation of lipid metabolism and the generation of second messengers, some of them involved in cell growth control. Oncogenic Ras proteins affect the activity of PLD by two alternate mechanisms, involving a positive activation and a feedback negative loop. Here we investigate the involvement of the proto-oncogenic Ras protein in the physiological activation of PLD induced by platelet-derived growth factor (PDGF). Over-expression of the wild type Ras protein or some of its regulatory components, such as Shc or Grb2, induces an amplification of PLD activation by PDGF challenge. Furthermore, blocking the endogenous Ras by expression of the dominant negative mutant, H-Ras-Asn17 completely eliminated the activation of PLD by PDGF. Thus, PDGF requires a complex system for PLD regulation implying the existence of at least two positive regulatory pathways, a Ras-dependent and a PKC-dependent mechanism. These results imply that PLD is an important element in signaling by Ras proteins that is altered after ras-induced transformation.

3T3 Cells↗

Comparison of IS1245 restriction fragment length polymorphism and pulsed-field gel electrophoresis for typing clinical isolates of Mycobacterium avium subsp avium.

SETTING: Little is still known about the epidemiology and pathogenesis of Mycobacterium avium subsp avium (MASA) infection. OBJECTIVE: Examination of the reproducibility and the stability over time of pulsed-field gel electrophoresis (PFGE) and IS1245 restriction fragment length polymorphism (IS1245-RFLP) techniques. The ability of these typing systems for differentiating clinical isolates of MASA was also assessed. DESIGN: Clinical isolates recovered from 63 patients (59 human immunodeficiency virus [HIV] positive and four HIV-negative) were studied by insertion sequence IS1245 and PFGE. For the study of in vivo and in vitro stability, strains collected over time from four patients and five strains chosen at random, respectively, were used. RESULTS: The stability of PFGE and IS1245-RFLP in vitro was excellent. PFGE was also stable in vivo, but IS1245-RFLP patterns showed some variation. The discriminatory power of IS1245-RFLP and PFGE was 0.995 and 0.989, respectively. The cluster analysis did not reveal differences between strains recovered from HIV-negative and HIV-positive patients or between patients with colonisation, local infection or disseminated disease. CONCLUSION: IS1245-RFLP and PFGE are useful tools for typing MASA strains. However, IS1245 variations in vivo may complicate the analysis of epidemiological relationships.

Adult↗

[Recurring invasive thymoma of the diaphragm].

Diaphragmatic recurrence of a thymoma is rare. We report the case of a 70-year-old woman who underwent transternal thymectomy and adjuvant radiation therapy, and who was admitted four years later with recurrence of the thymoma in the left hemidiaphragm with infiltration of the inferior ipsilateral pulmonary lobe. The thymoma was excised along with the left hemidiaphragm, chest wall and three ribs and an atypical segmentectomy of the left lower lobe was performed. The hemidiaphragm was reconstructed and the chest wall was repaired with synthetic mesh. Surgery was complemented with radiotherapy.

Aged↗

Optimizing the balance between false positive and false negative error probabilities of confirmatory methods for the detection of veterinary drug residues.

GC-MS data on veterinary drug residues in bovine urine are used for controlling the illegal practice of fattening cattle. According to current detection criteria, peak patterns of preferably four ions should agree within 10 or 20% from a corresponding standard pattern. These criteria are rigid, rather arbitrary and do not match daily practice. A new model, based on multivariate modeling of log peak abundance ratios, provides a theoretical basis for the identification of analytes and optimizes the balance between the avoidance of false positives and false negatives. The performance of the model is demonstrated on data provided by five laboratories, each supplying GC-MS measurements on the detection of clenbuterol, dienestrol and 19 beta-nortestosterone in urine. The proposed model shows a better performance than confirmation by using the current criteria and provides a statistical basis for inspection criteria in terms of error probabilities.

Animals↗

Prothymosin alpha is a chromatin-remodelling protein in mammalian cells.

Prothymosin alpha (ProTalpha) is an abundant mammalian acidic nuclear protein whose expression is related to cell proliferation. Here we report that in HL-60 cells overexpressing ProTalpha, the accessibility of micrococcal nuclease to chromatin is strongly increased. In the DNA ladder generated by the nuclease activity, the sizes of the mononucleosome (146 bp, the DNA fragment that is bound to the histone octamer) and its multimers correspond to nucleosomes lacking histone H1. The percentage of histone-H1-depleted chromatin (active chromatin) is also higher in the cells overexpressing ProTalpha. On the basis of these and previous findings, we propose a biological role for ProTalpha in the remodelling of chromatin fibres through its interaction with histone H1.

Cell Nucleus↗

[Subarachnoid hemorrhage: electrocardiographic, left ventricular wall motion abnormalities and mortality analysis in 14 cases].

BACKGROUND: Electrocardiographic (ECG) changes have been frequently observed in patients with subarachnoid hemorrhage (SAH). Their association with wall motion abnormalities of the left ventricle (LV) have not been well established. PATIENTS AND METHODS: Sixteen patients with SAH were included; 2 patients with previous history of heart disease were subsequently excluded. We studied the neurological damage (Hunt-Hess grading scale), ECG (ST segment, T wave) and echocardiography (LV regional and global contractility) of 14 patients. RESULTS: The ECG was abnormal in 11 patients (T wave: 6 patients; ST segment: 5 patients). Echocardiography showed alterations in 5 patients, all of them with ECG changes (T wave: one patient; ST segment: 4 patients). The neurological lesion was higher in patients with abnormal echocardiogram (Hunt-Hess mean grade: 4.6 vs 2.7 in patients with normal echocardiogram; p < 0.001). An intravenous infusion of dobutamine in a 23 years old male, improved the LV ejection fraction, which was severely depressed at baseline. Mortality, in all cases secondary to the neurological damage, was higher in patients with abnormal ECG (91% vs 0% in patients with normal ECG; p = 0.01) and when the echocardiogram showed alterations although in the last case no statistical differences were found. CONCLUSIONS: Echocardiography abnormalities in patients with SAH and without previous history of heart disease are more frequently related to ECG changes affecting ST segment, and to a higher cerebral damage.

Adult↗

Overexpression of prothymosin alpha accelerates proliferation and retards differentiation in HL-60 cells.

Prothymosin alpha (ProTalpha) is an acidic nuclear protein the expression of which is related to the proliferation and differentiation processes in mammalian cells. In the present study we have stably transfected HL-60 cells, a biological system that allows the study of both proliferation and differentiation, with recombinant vectors encoding sense and antisense ProTalpha mRNA. In the HL-60 cell clones overexpressing ProTalpha we observed an acceleration in the growth rate, whereas expression of the antisense orientation showed the opposite effect. Moreover, cell-cycle analysis demonstrated that the G1-phase was shortened in the cells expressing the sense construct. Before studying how ProTalpha affects differentiation, we showed that the down-regulation of ProTalpha gene during differentiation occurs in all mammalian cell lines (HL-60, K562, U937, MEL C88, N2A and PC12) analysed. The biological effect evoked by the induction of the ProTalpha sense vector was the retardation of cell differentiation, although expression of the antisense construct showed no effect on differentiation. In conclusion, our findings provide evidence that ProTalpha is directly implicated in cellular proliferation and that the maintenance of high levels of ProTalpha inside HL-60 cells is incompatible with their ability to differentiate.

Cell Differentiation↗

Unilateral femoral deformity due to a focal fibrous tether.

The purpose of this paper is to assess the radiological features of the unilateral angular deformity of the distal end of the femur secondary to a focal fibrous tether. Only five cases of this entity have been reported in the literature. We report another two patients. Magnetic resonance study was performed on one of them, which has not been used in previous cases. Both cases are described with illustrations of the typical radiographic appearances supplemented by CT and MR imaging.

Female↗

[The rights of the hospital patient: the knowledge and perception of their fulfillment on the part of the professional. The Group in Catalonia of the Spanish Society of Care for the Health Services User].

BACKGROUND: The Customer Service Department includes the protection of the patient's rights. To analyze the work performed in this setting, we planned to quantitate and evaluate the knowledge and perception of fulfillment by medical staff. METHODS: Multicentric cross-sectional study. The population included health care professionals in nine Catalonian hospitals. The sample was selected at random with reposition and was segmented according to professional category. Data collection was carried out by personal interview supported by a questionnaire. Differences according to institution size were analyzed. RESULTS: A total of 1,014 professionals were interviewed; 84.4% reported to know the patient's rights and 64.4% to observe them. Significant differences (p < 0.05) according to institution size were observed. CONCLUSIONS: Discussion and diffusion of patient's rights is an useful tool to improve knowledge and evaluate the perception of its fulfillment by health care professionals.

Adult↗

[Molecular diagnosis in an Argentinian family with multiple endocrine neoplasia type-1 (MEN-1)].

MEN-1 is a hereditary autosomal dominant syndrome characterized by the involvement of parathyroid glands, pancreatic islet cells and anterior pituitary gland. Today molecular genetics permit gene carrier analysis to compare the data obtained with the clinical biochemical tests. The twenty living members of the first, second and third generation of a family with MEN-1 were studied to determine the presence of genetic markers in MEN-1 loci 11q13, by linkage analysis and in affected individuals by biochemical tests and clinical examination. Two very informative polymorphic markers immediately flanking the MEN-1 gene on chromosome 11 band q13 were detected: PYGM and D11S987, haplotypes segregated by two members of the second generation, inherited from their father and two of the third generation: the affected one and one presymptomatic. The third generation had the affected member with renal stones and elevated PTH, PRL and glucagon. The presymptomatic carrier of MEN-1 allele showed elevated PTH. Among the members who inherited the normal allele we found one with elevated gastrin, one with elevated glucagon and one with elevated PTH, all asymptomatic. Of one Argentine family studied, molecular diagnosis allowed us to detect one presymptomatic carrier in the members at risk. As suggested by the available literature, accuracy of molecular diagnosis seems to make it the test of choice to exclude those members at risk for MEN-1 inheriting the normal allele.

Adult↗

Rapid kinetic studies of SH oxidation-induced calcium release from sarcoplasmic reticulum vesicles.

We studied the kinetics of calcium release induced by SH oxidation in triads isolated from frog and rabbit skeletal muscle by measuring calcium fluxes by a fast filtration method. In both species SH oxidation induced release of 70-80% of the passively loaded calcium with a rate constant of 1 s-1. This rate constant is 3 times higher than the rate constant of calcium-induced calcium release and 15 times lower than the rate constant of ATP-induced release. Calcium release induced by SH oxidation exhibited the same calcium dependence of calcium-induced calcium release and was also inhibited by physiological [MG2+]. Neither SH oxidation-induced calcium release nor calcium-induced calcium release were regulated by luminal calcium. The redox state of thiol groups does not seem to control ATP-induced calcium release since the rate constant of calcium release after SH oxidation was not different from the rate constant measured in the presence of the reducing agent dithiothreitol. Our results do not support a role for SH oxidation, per se, as an essential step for the release of calcium from sarcoplasmic reticulum.

2,2'-Dipyridyl↗

Effect of ouabain on insulin secretion in the amphibian pancreas.

We investigated the influence of ouabain on glucose-induced insulin release from toad pancreatic minces in the same nanomolar range as that of an ouabain-like compound found in human blood. Ouabain increased insulin secretion at basal (2 mM), but not maximally stimulatory (8 mM), glucose levels in a dose-dependent manner up to an optimal concentration of 1 nM, with the values declining progressively thereafter. Ouabain at 3 nM changed the shape of the overall dose-response curve for glucose from sigmoidal to hyperbolic and displaced the optimal insulinotropic glucose concentration from 8 to 2 mM. Preincubation with ouabain (3 nM) followed by glycoside washout potentiated insulin induction at 2 mM, but not at 8 mM glucose, but this same pretreatment followed by incubation in Ca(2+)-free medium depressed insulin release under all conditions, and especially at high glucose; here, however, the preexposure to ouabain partially prevented the drop in insulin secretion at 8 mM glucose. Acetylcholine at 8 microM augmented insulin release at both levels of glucose, and ouabain potentiated this effect synergistically at high, but not low glucose. Ouabain, at physiologic concentrations, thus appears to regulate the effect of secretagogues such as glucose and acetylcholine in amphibians.

Acetylcholine↗

Acquired drug resistance in Mycobacterium tuberculosis isolates recovered from compliant patients with human immunodeficiency virus-associated tuberculosis.

We describe five compliant patients with human immunodeficiency virus (HIV)-associated tuberculosis (TB) that relapsed, with acquisition of resistance by the original Mycobacterium tuberculosis strains. Both the first and second isolates from each patient had the same IS (insertion sequence) 6110-based DNA fingerprint patterns. Three of the five patients developed TB that was resistant to rifampin alone; no mutation in the region of the rpoB gene was detected by a line probe assay in two of the isolates from these patients. We discuss several factors presumably associated with acquired drug resistance in HIV-infected patients, including exogenous reinfection, drug interactions, malabsorption of drugs, and the presence of a large organism burden.

AIDS-Related Opportunistic Infections↗