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Biomedical subjects

F Jiménez

Publications and source records attributed to F Jiménez.

At least 19 recordsLinked to original sources

Ras pathway specificity is determined by the integration of multiple signal-activated and tissue-restricted transcription factors.

Ras signaling elicits diverse outputs, yet how Ras specificity is generated remains incompletely understood. We demonstrate that Wingless (Wg) and Decapentaplegic (Dpp) confer competence for receptor tyrosine kinase-mediated induction of a subset of Drosophila muscle and cardiac progenitors by acting both upstream of and in parallel to Ras. In addition to regulating the expression of proximal Ras pathway components, Wg and Dpp coordinate the direct effects of three signal-activated (dTCF, Mad, and Pointed-functioning in the Wg, Dpp, and Ras/MAPK pathways, respectively) and two tissue-restricted (Twist and Tinman) transcription factors on a progenitor identity gene enhancer. The integration of Pointed with the combinatorial effects of dTCF, Mad, Twist, and Tinman determines inductive Ras signaling specificity in muscle and heart development.

Animals↗

The EGF and FGF receptors mediate neuroglian function to control growth cone decisions during sensory axon guidance in Drosophila.

Cell adhesion molecules (CAMs) implement the process of axon guidance by promoting specific selection and attachment to substrates. We show that, in Drosophila, loss-of-function conditions of either the Neuroglian CAM, the FGF receptor coded by the gene heartless, or the EGF receptor coded by DER display a similar phenotype of abnormal substrate selection and axon guidance by peripheral sensory neurons. Moreover, neuroglian loss-of-function phenotype can be suppressed by the expression of gain-of-function conditions of heartless or DER. The results are consistent with a scenario where the activity of these receptor tyrosine kinases is controlled by Neuroglian at choice points where sensory axons select between alternative substrates for extension.

Animals↗

Use of partial least-squares regression for multicomponent determinations based on kinetic spectrofluorimetric data. Simultaneous determination of canrenone and spironolactone in urine.

A new spectrofluorimetric method for the simultaneous determination of canrenone and spironolactone in urine is proposed. The method is based on the different rates at which the two analytes react with hot sulfuric acid to form a trienone. The kinetic spectrofluorimetric data are processed by partial least-squares regression. The effects of sulfuric acid concentration and temperature on the system under study were also evaluated and the optimum values for carring out the reaction were 50% and 50 degrees C, respectively. The method was checked by analyzing urine samples that they contained both diuretics. The accuracy and the precision of the method were tested. The relative standard errors in the quantification of each analyte in all tested samples were 3.69 and 3.59%. The proposed method was validated by comparison with a high performance liquid chromatographic method for urine samples.

Canrenone↗

Predictors in the treatment of difficult-to-control seizures by electrical stimulation of the centromedian thalamic nucleus.

OBJECTIVE: To evaluate the efficacy of chronic electrical stimulation of centromedian thalamic nuclei (ESCM) in the treatment of difficult-to-control seizures. METHODS: Thirteen patients underwent ESCM for periods ranging from 12 to 94 months (mean, 41.2 mo) with electrodes stereotactically placed in both centromedian nuclei and connected to internalized stimulation systems. Electrode placement was guided by ventriculography and confirmed with magnetic resonance imaging before stimulation systems were internalized. Anatomic and electrophysiological confirmation of the electrodes' position was accomplished by plotting electrode position on anatomic sections of Schaltenbrand and Bailey's atlas, and testing cortical recruiting responses and electroencephalogram desynchronization elicited by acute low- or high-frequency stimulation, respectively. RESULTS: Improvement was highly significant for generalized tonicoclonic seizures and atypical absences. Better results were obtained for Lennox-Gastaut syndrome. These results were accompanied by a significant decrease in generalized spike-wave and secondary synchronous discharges, as well as focal spikes in the frontal regions. In contrast, ESCM reduced neither complex partial seizures nor focal spikes in temporal regions. Outcomes using ESCM for generalized epilepsy were better in patients in whom anatomic and electrophysiological confirmation of electrode placement was correct than in those in whom the target was missed bilaterally (P < 0.001). The effect was sustained during the observation period and was better for longer-term than for shorter-term stimulation periods. CONCLUSION: ESCM is an efficient and safe procedure for controlling certain seizure types, if patient selection and stereotactic placement are satisfactory.

Adolescent↗

Nifedipine prevents changes in nitric oxide synthase mRNA levels induced by cyclosporine.

Cyclosporine toxicity mainly affects kidney and liver function. We have previously shown that cyclosporine nephrotoxicity alters kidney nitric oxide synthase mRNA pattern of expression. To determine if nitric oxide synthase expression changes are mediated directly by cyclosporine or by secondary hemodynamic alterations induced by cyclosporine, we evaluated if these effects are tissue specific and if nifedipine-induced vasodilation prevents these alterations. Uninephrectomized Wistar rats treated for 7 days with olive oil, cyclosporine (30 mg/kg), nifedipine (3 mg/kg), and nifedipine+cyclosporine were studied. In vehicle and cyclosporine groups, the gene expression of the neuronal, inducible, and endothelial nitric oxide synthases in cerebellum, heart, intestine, liver, renal cortex, and medulla was evaluated. The administration of cyclosporine was associated with nephrotoxicity and hepatotoxicity, increased endothelial nitric oxide synthase mRNA levels in renal cortex and liver, and a decrease in inducible nitric oxide synthase and neuronal nitric oxide synthase in renal medulla. The mRNA levels of the 3 nitric oxide synthase isoforms were not affected in any other tissue. Nifedipine did not alter nitric oxide synthase expression in the control group but prevented changes associated with cyclosporine. These results suggest that cyclosporine-induced changes in the pattern of expression of the nitric oxide synthases may be secondary to its hemodynamic effects.

Animals↗

[Double pylorus...?? To be or not to be. Case report and review of the literature].

In this rare condition, that could be congenital or acquired, there is an abnormal communication between the stomach and the duodenum. First reported in 1861 was not consider as a real entity till 1969. There are not classical symptoms for the disease, and most of the times it is an incidental finding during other studies, up to 25% of the cases remain undiagnosed. Other than the standard surgical treatment, the use of I.P.Ps. became the common practice with good results. In the acquired cases, this is a complication of gastric ulcers, we recommend its understanding and acknowledgement for a better control and follow up.

Duodenal Diseases↗

Dexamethasone increases eNOS gene expression and prevents renal vasoconstriction induced by cyclosporin.

Cyclosporin A (CsA)-induced renal vasoconstriction (RV) is attributed to an imbalance in vasoactive factors release. Dexamethasone (Dex) exerts a renal vasodilatory effect by a mechanism not yet characterized. This study evaluates whether the effect of Dex is mediated by NO and whether it prevents CsA-induced RV. Micropuncture studies were performed in six groups of uninephrectomized rats treated for 7 days with the following: vehicle (Veh); Veh + 4 mg/kg dexamethasone (Veh+Dex); 30 mg/kg CsA; CsA+Dex; vehicle + 10 mg/kg nitro-L-arginine methyl ester (Veh+L-NAME); and Veh+Dex+L-NAME. NO synthase (NOS) isoform mRNA levels were evaluated in renal cortex and medulla by semiquantitative RT-PCR analysis in the first four groups. Dex produced renal vasodilation, which was blocked by concomitant L-NAME administration, and the effect of Dex was associated with higher cortical and medullary endothelial NOS (eNOS) and cortical inducible NOS (iNOS) mRNA levels. In the CsA group, Dex prevented RV, restoring glomerular hemodynamics to control values. These changes were associated with further enhancement of eNOS and restoration of medullary iNOS and neuronal NOS (nNOS) expression. We conclude that Dex prevents CsA-induced RV, and its vasodilator effect could be mediated by increased intrarenal generation of NO, secondary to enhanced expression of eNOS and iNOS.

Animals↗

An evolutionary algorithm for interval solid transportation problems.

The Solid Transportation Problem arises when bounds are given on three item properties. Usually, these properties are source, destination and mode of transport (conveyance), and may be given in an interval way. This paper deals with solid transportation problems in which the data in the constraint set are expressed in an interval form, i.e. when sources, destinations and conveyances have interval values instead of point values. An arbitrary linear or nonlinear objective function is also considered. To solve the problem, an Evolutionary Algorithm which extends and generalizes other approaches considering only point values, is proposed.

Algorithms↗

[Cancer of the esophagus and stomach: 3-year evaluation].

Esophagus cancer has a very bad pathological prognosis. Risk factors considered are: smoking consumption and deficiency of vitamins A and C. The mortality rates of cancer of the stomach vary notably according to geographic region. Factors such as genetics, races, smoking, socioeconomic conditions are some of stomach cancer development. 646 symptomatic patients were studied in the gastroenterology unit at. J.M. Cullen hospital. Histopathologically, 22 (3.3%) cancer of the esophagus and 13 (2%) cancers of stomach were detected. All esophagus cancers were squamous cells; 82% were males and 18% females. 50% were located on the middle third zone. 92.3% of stomach cancers were adenocarcinoma; 83% were males and 17% females. A 50.8% were located in corporo-fundic zone. All the cancers both of the esophagus as well as of the stomach, were in the advanced phase. The cancer of esophagus has appeared most frequently among cancers of the tract in our hospital, with significant difference among province and national registers.

Adenocarcinoma↗

Combinatorial signaling codes for the progressive determination of cell fates in the Drosophila embryonic mesoderm.

Mesodermal progenitors arise in the Drosophila embryo from discrete clusters of lethal of scute (l'sc)-expressing cells. Using both genetic loss-of-function and targeted ectopic expression approaches, we demonstrate here that individual progenitors are specified by the sequential deployment of unique combinations of intercellular signals. Initially, the intersection between the Wingless (Wg) and Decapentaplegic (Dpp) expression domains demarcate an ectodermal prepattern that is imprinted on the adjacent mesoderm in the form of a L'sc precluster. All mesodermal cells within this precluster are competent to respond to a subsequent instructive signal mediated by two receptor tyrosine kinases (RTKs), the Drosophila epidermal growth factor receptor (DER) and the Heartless (Htl) fibroblast growth factor receptor. By monitoring the expression of the diphosphorylated form of mitogen-associated protein kinase (MAPK), we found that these RTKs are activated in small clusters of cells within the original competence domain. Each cluster represents an equivalence group because all members initially resemble progenitors in their expression of both L'sc and mesodermal identity genes. Thus, localized RTK activity induces the formation of mesodermal equivalence groups. The RTKs remain active in the single progenitor that emerges from each cluster under the subsequent inhibitory influence of the neurogenic genes. Moreover, DER and Htl are differentially involved in the specification of particular progenitors. We conclude that distinct cellular identity codes are generated by the combinatorial activities of Wg, Dpp, EGF, and FGF signals in the progressive determination of embryonic mesodermal cells.

Animals↗

Formation and specification of ventral neuroblasts is controlled by vnd in Drosophila neurogenesis.

During Drosophila neural development, neuroblasts delaminate from the neuroectoderm of each hemisegment in a stereotypic orthogonal array of five rows and three columns (ventral, intermediate, and dorsal). Prevailing evidence indicates that the individual neuroblast fate is determined by the domain-specific expression of genes along the dorsoventral and anteroposterior axis. Here, we analyze the role of Vnd, a NK-2 homeodomain protein, expressed initially in the ventral neuroectoderm adjacent to the ventral midline, in the dorsoventral patterning of the neuroectoderm and the neuroblasts. We show that in vnd null mutants most ventral neuroblasts do not form and the few that form do not develop ventral fates, but instead develop intermediate-like fates. Furthermore, we demonstrate that Vnd influences the gene expression patterns in the ventral proneural clusters and neuroectoderm, and that its action in neuroblast formation includes, but is not exclusive to the activation of proneural AS-C genes. Through the use of GAL4/UAS gene-expression system we show that ectopic Vnd expression can promote ventral-like fates in intermediate and dorsal neuroblasts and can suppress certain normal characteristics of the intermediate and dorsal neuroectoderm. Our results are discussed in the context of the current evidence in dorsoventral patterning in the Drosophila neuroectoderm.

Animals↗

Inscuteable and numb mediate asymmetric muscle progenitor cell divisions during Drosophila myogenesis.

Each larval hemisegment comprises approximately 30 uniquely specified somatic muscles. These derive from muscle founders that arise as distinct sibling pairs from the division of muscle progenitor cells. We have analyzed the progenitor cell divisions of three mesodermal lineages that generate muscle (and pericardial cell) founders. Our results show that Inscuteable and Numb proteins are localized as cortical crescents on opposite sides of dividing progenitor cells. Asymmetric segregation of Numb into one of the sibling myoblasts depends on inscuteable and is essential for the specification of distinct sibling cell fates. Loss of numb or inscuteable results in opposite cell fate transformations-both prevent sibling myoblasts from adopting distinct identities, resulting in duplicated or deleted mesodermal structures. Our results indicate that the muscle progenitor cell divisions are intrinsically asymmetric; moreover, the involvement of both inscuteable and numb/N suggests that the specification of the distinct cell fates of sibling myoblasts requires intrinsic and extrinsic cues.

Animals↗

[Heart rate variability during the first 24 hours of acute myocardial infarction].

BACKGROUND: To evaluate the heart rate variability (HRV) during the first 24 h after a myocardial infarction (MI), and to study its relationship with other clinical variables and in-hospital follow-up. PATIENTS AND METHODS: 101 patients (age < 80 years) with MI in sinus rhythm were prospectively studied. A Holter monitoring was performed during the first 24 h. The heart rate (HR), standard deviation of RR intervals (SDRR) and the histogram at different levels were analyzed, as well as the mean and standard deviation of RR intervals in an early 5 min record. The results were compared with the clinical characteristics and the in-hospital outcome of the patient. RESULTS: HRV was lower in women, hypertensives and patients who did not receive thrombolytic agents. In patients without heart failure, inferior MI's had lower HR and higher HRV than anterior MI's (SDRR: 52.8 [20.6] and 42.2 [16.9], respectively; p < 0.05). HRV was significantly decreased as Killip group increased, as well as in patients who developed late heart failure. The development of ventricular tachycardia or fibrillation was associated to a low HRV in the 24 h analysis (SDRR: 30.2 [15.6] for the 6 patients with VF/VT vs 46.8 [20.1] for the rest; p < 0.05), as well as in the early 5 min record (29.8 [14.8] and 50.8 [35.8], respectively; p < 0.05). CONCLUSIONS: During the first 24 h after MI the HRV is related to some clinical variables and to MI location (higher in inferior MI). Patients who develop heart failure or ventricular arrhythmias before hospital discharge have a higher HR and a significantly decreased HRV.

Aged↗

Neurotactin functions in concert with other identified CAMs in growth cone guidance in Drosophila.

We have isolated and characterized mutations in Drosophila neurotactin, a gene that encodes a cell adhesion protein widely expressed during neural development. Analysis of both loss and gain of gene function conditions during embryonic and postembryonic development revealed specific requirements for neurotactin during axon outgrowth, fasciculation, and guidance. Furthermore, embryos of some double mutant combinations of neurotactin and other genes encoding adhesion/signaling molecules, including neuroglian, derailed, and kekkon1, displayed phenotypic synergy. This result provides evidence for functional cooperativity in vivo between the adhesion and signaling pathways controlled by neurotactin and the other three genes.

Alleles↗

Prospective biochemical and scintigraphic evaluation of autografted normal parathyroid glands in patients undergoing thyroid operations.

BACKGROUND: Parathyroid autotransplantation has been widely used in thyroid operations. Few studies have assessed the function of the autotransplanted glands. The aim of this study was to evaluate the success rate, pattern of biochemical function, and scintigraphic appearance of parathyroid autografts in patients undergoing thyroid operations. METHODS: Twelve patients in whom 1 parathyroid gland was removed during thyroid operation were included. Glands were fragmented and autografted into individual pockets in the brachioradialis muscle of the nondominant forearm. Parathyroid hormone levels were measured in both arms the day of autotransplantation and 2 weeks and 1, 2, 3, and 6 months after operation. Serum calcium levels were also measured at each interval. Sestamibi scanning was performed 6 months after operation in 7 patients. RESULTS: All patients were women with a mean age of 50 +/- 15 years. Serum calcium levels were normal during follow-up. A gradient of parathyroid hormone level of 1.5 or greater between the autotransplanted and nontransplanted arm was found in 10 patients. Isotope uptake at the site of the parathyroid autotransplant was demonstrated in the 7 patients evaluated. CONCLUSIONS: Biochemical function of autotransplanted normal parathyroid tissue was documented in 83% of the patients. Sestamibi scintiscans were able to identify the autotransplanted tissue.

Adult↗

Signalling by the Drosophila epidermal growth factor receptor is required for the specification and diversification of embryonic muscle progenitors.

Muscle development initiates in the Drosophila embryo with the segregation of single progenitor cells, from which a complete set of myofibres arises. Each progenitor is assigned a unique fate, characterized by the expression of particular identity genes. We now demonstrate that the Drosophila epidermal growth factor receptor provides an inductive signal for the specification of a large subset of muscle progenitors. In the absence of the receptor or its ligand, SPITZ, specific progenitors fail to segregate. The resulting unspecified mesodermal cells undergo programmed cell death. In contrast, receptor hyperactivation generates supernumerary progenitors, as well as the duplication of at least one SPITZ-dependent myofibre. The development of individual muscles is differentially sensitive to variations in the level of signalling by the epidermal growth factor receptor. Such graded myogenic effects can be influenced by alterations in the functions of Star and rhomboid. In addition, muscle patterning is dependent on the generation of a spatially restricted, activating SPITZ signal, a process that may rely on the localized mesodermal expression of RHOMBOID. Thus, the epidermal growth factor receptor contributes both to muscle progenitor specification and to the diversification of muscle identities.

Animals↗

Electrocortical and behavioral responses produced by acute electrical stimulation of the human centromedian thalamic nucleus.

Incremental, desynchronizing and spike-wave electrocortical responses and concomitant symptoms to acute electrical stimulation of the centromedian thalamic nucleus (CM) were studied in 12 patients with intractable complex partial and tonic-clonic generalized seizures. Low-frequency (6/s), 320-800 microA stimulation of the caudal-basal and central portions of CM elicited incremental recruiting and augmenting-like responses with a bilateral regional scalp distribution, with emphasis at the ipsilateral frontal (recruiting) and central (augmenting) regions, while ventral-basal CM stimulation elicited primary-like responses with a focal distribution at the ipsilateral parietal region. High-frequency (60/s), 320-800 microA stimulation of caudal-basal and central, but not ventral-basal CM, elicited EEG desynchronization and a slow negative shift of the EEG baseline with scalp distribution similar to that showed by recruiting- and augmenting-like responses. Neither incremental nor desynchronization EEG responses were accompanied by evident patient sensory or motor responses. Low-frequency (3/s), high-intensity (30 V = 2400 microA) combined stimulation of the right CM and left non-specific mesencephalic ascending pathways elicited a response similar to the typical absence attack with all EEG and clinical ingredients: S1, S2, P1 and W components of the individual spike-wave complex and generalized spike-wave discharges followed by sleep spindle EEG afterdischarges, accompanied by motionless stare, 3/s eye blinking, lip smacking and total failure to respond to visual stimuli in patients under a simple responding task.

Behavior↗

Biochemical bone markers, bone mineral content, and bone mineral density in rats with experimental nephrotic syndrome.

The human nephrotic syndrome (NS) is accompanied by important alterations of mineral and bone metabolism. The purpose of the present study was to examine bone metabolism in rats with experimental NS and normal creatinine clearance, and to evaluate the reversibility of this alteration. NS was induced by three injections of puromycin aminonucleoside (PAN) on days 0, 21, and 35 (10, 5, and 5 mg/100 g body weight, respectively). The biochemical markers of bone formation (osteocalcin and alkaline phosphatase) and bone resorption (hydroxyproline and pyridinoline), bone mineral content (BMC), and bone mineral density (BMD), determined by dual-energy x-ray absorptiometry (DEXA), were studied on days 0, 7, 14, 28, 42, 56, 84, and 112. Proteinuria was present throughout the study. Hypoproteinemia was seen on days 7, 28, 42, and 56, returning to control values on days 84 and 112. In serum, osteocalcin (OC) concentration increased (p < 0.001), and alkaline phosphatase (ALP) decreased (p = 0.002). In urine, hydroxyproline increased (p < 0.001), but urinary pyridinoline was not different from the control group throughout the study. Increased serum parathyroid hormone concentration and decreased levels of 25-hydroxy and 1,25-dihydroxyvitamin D were found from day 7. During the intense proteinuria, bone resorption predominates and decreased BMC and BMD ensues in PAN-nephrotic rats. PAN-nephrotic rats showed low BMC and BMD compared to control group (p < 0.001). At the end of the study, when proteinuria persisted but total serum protein returned to control values, the biochemical bone markers, BMC, and BMD returned to normal. In conclusion, PAN-nephrotic rats had reversible bone alterations that were related to the magnitude of proteinuria and the concentration of total serum protein.

Alkaline Phosphatase↗