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Biomedical subjects

R Ballester

Publications and source records attributed to R Ballester.

At least 19 recordsLinked to original sources
PubMed2002

Use of 201Tl SPECT imaging to assess the response to therapy in patients with high grade gliomas.

PURPOSE: To assess the potential role of 201Tl single photon emission tomography (201-Thallium SPECT) when compared to other imaging modalities in the evaluation of the response to therapy in high grade gliomas. MATERIALS AND METHODS: Twenty patients with histologically proved high grade glioma have been included: 15 with glioblastoma (GBM), 3 with anaplastic astrocytoma (AA) and 2 with anaplastic oligoastrocytoma (AOA). Patients were assessed by 201Tl SPECT, computed tomography (CT) and magnetic resonance imaging (MRI) at (a) either at the moment of maximum response to first line chemotherapy, or after the completion of radiotherapy and chemotherapy if post-surgical residual disease was present, and (b) after the completion of second line chemotherapy if disease persisted, or either a relapse or disease progression was confirmed. Final response was evaluated according to the McDonald criteria, and by comparing SPECT, CT and MRI results. RESULTS: According to the McDonald criteria, clinical response after first line chemotherapy was 5 partial response, 7 stable disease and 8 progressive disease. Evaluation by 201Tl SPECT was in agreement with such criteria in nearly all patients (90%). MRI findings closely agreed with the clinical follow-up. CT findings clearly differed from those observed by SPECT and MRI. After second line therapy, 10 patients progressed, 3 had stable disease and 7 had partial response. 201Tl SPECT agreed with the clinical status in 89% cases, whereas MRI and, specially CT, fared significantly lower. CONCLUSION: Compared to conventional neuroimaging, 201Tl SPECT added valuable information in the assessment of the response to therapy in our patient population; whenever findings were not conclusive and in the case of disagreement between CT and MRI findings.

Adult↗
PubMed2001

Mutations in WSC genes for putative stress receptors result in sensitivity to multiple stress conditions and impairment of Rlm1-dependent gene expression in Saccharomyces cerevisiae.

Intracellular signaling by mitogen-activated protein (MAP) kinase cascades plays an essential role in the cellular response to environmental stress. In the yeast Saccharomyces cerevisiae, the PKC1-regulated, stress-activated MAP kinase pathway, the MPK1 cascade, is activated by heat and by a decrease in osmolarity. The genes WSC1, WSC2 and WSC3 encode putative receptors that maintain cell wall integrity under conditions of heat stress. Genetic studies place the function of the WSC genes upstream of the MPK1 kinase cascade. To further define the role of the WSC family in the stress response we determined whether: (1) the wscdelta mutants are sensitive to other environmental stress conditions, in addition to heat shock; (2) expression from four transcriptional control elements, known to be activated by stress, is impaired in wscdelta mutants; and (3) Wsc4, a Wsc homolog, has functions that overlap with those of the other Wsc family members. We report here that deletion of WSC and PKC1 causes hypersensitivity to ethanol, hydrogen peroxide and DNA-damaging drugs. In wscdelta mutants expression of beta-galactosidase from the AP-1 response element (ARE), the heat shock response element (HSE) or the stress response element (STRE) is not reduced. In contrast, expression of a reporter gene placed under the control of the Rlm1 (transcription factor)-dependent response element is significantly reduced in wscdelta mutants. This suggests that the lysis defect of wscdelta mutants is at least in part caused by a defect in transcriptional regulation by Rlm1. Phenotypic analysis of the effect of deleting WSC4 in a wsc1delta mutant show that, unlike WSC2 or WSC3, deletion of WSC4 does not exacerbate the lysis defect of a wsc1delta strain. In contrast, deletion of WSC4 enhances the sensitivity of the wsc1delta mutant to heat shock, ethanol, and a DNA-damaging drug, suggesting that WSC4 plays a role in the response to environmental stress but that its function may differ from those of the other WSC family members.

Ethanol↗
PubMed2000

Effects of antidepressants in adrenergic neurotransmission of human vas deferens.

OBJECTIVES: To evaluate the effects of sertraline, fluoxetine, and amitriptyline on the contractile responses of the human vas deferens muscle elicited by norepinephrine, electrical field stimulation, and KCl, because the therapeutic action of antidepressants may be accompanied by sexual dysfunction related to the contractility of the vas deferens smooth muscle. METHODS: Ring segments of the epididymal part of the vas deferens were taken from 32 elective vasectomies and mounted in organ baths for isometric recording of tension. We then studied the effects of sertraline, fluoxetine, and amitriptyline on the neurogenic and agonist-induced contractile responses. RESULTS: Amitriptyline caused concentration-dependent inhibition of neurogenic and norepinephrine-induced contractions. In contrast, only the highest concentration (10(-5) M) of sertraline and fluoxetine reduced the adrenergic contractions. The dihydropyridine calcium antagonist nifedipine (10(-6) M) completely prevented the inhibitory effect of sertraline and fluoxetine on neurogenic and norepinephrine-induced contractions but did not change the inhibition caused by amitriptyline. Sertraline, fluoxetine, and amitriptyline (all at 10(-5) M) attenuated contractions elicited by KCl and reduced contractions induced by CaCl(2) in KCl-depolarized preparations. CONCLUSIONS: The results indicate that sertraline and fluoxetine inhibit vas deferens motility through inhibition of Ca(2+) entry, with no effect on the adrenergic receptors, and amitriptyline acts as an adrenoceptor antagonist and inhibitor of the entry of calcium.

Amitriptyline↗
PubMed2000

A role for the noncatalytic N terminus in the function of Cdc25, a Saccharomyces cerevisiae Ras-guanine nucleotide exchange factor.

The Saccharomyces cerevisiae CDC25 gene encodes a guanine nucleotide exchange factor (GEF) for Ras proteins. Its catalytic domain is highly homologous to Ras-GEFs from all eukaryotes. Even though Cdc25 is the first Ras-GEF identified in any organism, we still know very little about how its function is regulated in yeast. In this work we provide evidence for the involvement of the N terminus of Cdc25 in the regulation of its activity. A truncated CDC25 lacking the noncatalytic C-terminal coding sequence was identified in a screen of high-copy suppressors of the heat-shock-sensitive phenotype of strains in which the Ras pathway is hyper-activated. The truncated gene acts as a dominant-negative mutant because it only suppresses the heat-shock sensitivity of strains that require the function of CDC25. Our two-hybrid assays and immunoprecipitation analyses show interactions between the N terminus of Cdc25 and itself, the C terminus, and the full-length protein. These results suggest that the dominant-negative effect may be a result of oligomerization with endogenous Cdc25. Further evidence of the role of the N terminus of Cdc25 in the regulation of its activity is provided by the mapping of the activating mutation of CDC25HS20 to the serine residue at position 365 in the noncatalytic N-terminal domain. This mutation induces a phenotype similar to activating mutants of other genes in the Ras pathway in yeast. Hence, the N terminus may exert a negative control on the catalytic activity of the protein. Taken together these results suggest that the N terminus plays a crucial role in regulating Cdc25 and consequently Ras activity, which in S. cerevisiae is essential for cell cycle progression.

Base Sequence↗
PubMed1999

A novel role for the mating type (MAT) locus in the maintenance of cell wall integrity in Saccharomyces cerevisiae.

The cell wall and stress response component (Wsc) protein family in the yeast Saccharomyces cerevisiae is encoded by at least three genes, WSC1, WSC2, and WSC3. The Wsc proteins are putative upstream activators of the RHO1-regulated PKC1-MAP kinase cascade, and are required for maintenance of cell wall integrity and the stress response. Deletion of WSC1 causes a cell lysis defect that is exacerbated by deleting WSC2 or WSC3. This cell lysis defect can be rescued by adding osmotic stabilizers, such as 1 M sorbitol, to the medium, and by overexpressing PKC1 or RHO1. To advance our understanding of the function of the WSC genes, we performed a genetic screen to identify other components of the pathways they regulate. Here we report our findings. MATa1 and MATalpha2 were identified as dosage-dependent suppressors of the lysis defect of a wsc delta mutant. Overexpression of MATa1 or MATalpha2 was found to suppress the heat shock sensitivity, in addition to the lysis defect, of the wsc delta mutant. Phenotypic suppression by these two genes, MATa1 and MATalpha2, is significantly stronger when they are overexpressed in cells of the opposite mating type. Deletion of MATa1 exacerbates the lysis defect of haploid and diploid wsc delta strains. Our results suggest that the MAT locus plays a role in responses similar to those regulated by WSC and provide evidence for a regulatory effect of the MAT locus outside the realm of cell type determination.

Cell Wall↗
PubMed1999

Characterization of the Wsc1 protein, a putative receptor in the stress response of Saccharomyces cerevisiae.

Wsc1p, Wsc2p, Wsc3p, and Wsc4p, members of a novel protein family in the yeast Saccharomyces cerevisiae, are putative sensors or receptors in the stress response. Genetic characterization suggests that the WSC family are upstream regulators of the stress-activated PKC1-MAP kinase cascade and are required for the heat shock response and for maintenance of cell wall integrity. The Wsc proteins share sequence characteristics: at their N terminus they have a cysteine motif and a serine/threonine-rich domain predicted to be extracellular, a hydrophobic domain suggested to be transmembranous, and a variable, highly charged C terminus that may be involved in intracellular signaling. Although a role for the WSC genes in maintenance of cell wall integrity has been firmly established, little is known about the properties of the proteins. As reported here, to study its properties in vivo, we epitope tagged the Wsc1 protein. Wsc1p was found to fractionate with the membrane pellet after high-speed centrifugation. Extraction experiments show that Wsc1p is an integral membrane protein present in two forms: one solubilized by detergent, the other Triton X-100 insoluble. Our results also show that Wsc1p is glycosylated and phosphorylated. To characterize the contribution of different domains to the function of Wsc1p, we generated various deletion constructs. Analysis of the properties and function of the mutant proteins shows that the predicted extracellular serine/threonine-rich domain is required for Wsc1p functionality, as well as its glycosylation. A mutant Wsc1 protein lacking the putative transmembrane domain is not functional and partitions to the soluble fraction. Overexpression of full-length Wsc1p inhibits cell growth, with the N terminus alone being sufficient for this inhibition. This suggests that Wsc1p may function in a complex with at least one other protein important for normal cell growth.

Amino Acid Sequence↗
PubMed1998

[Health and primary education in the regenerationist ideology at the open educational institution].

The objective of this work is to reconstruct the discourse of the authors who published about issues establishing links between health and primary education in the Boletin de la Institucion Libre de Ensenanza at the time of the Spanish colonial crisis in 1898. This source has been chosen due to its relevance to Spanish pedagogical renovation. Physical education was taken as a model for analysis for two reasons: firstly, it is the aspect that received the most attention; secondly, it became the engine for change in the renovation programme. In addition, its holistic nature was intended to lead to the new citizen that was needed by the country after the loss of the colonies.

Colonialism↗
PubMed1998

Microleakage of a universal adhesive used as a fissure sealant.

PURPOSE: To evaluate the microleakage of a universal hydrophilic adhesive (OptiBond dual-cure) by itself as a pit and fissure sealant compared to that of an ionomeric product (VariGlass) and two hydrophobic sealants (Delton and Fluroshield). MATERIALS AND METHODS: Sixty-four extracted human third molars were sealed with one of these four materials under either a conventional procedure (free of humidity) or after contamination of the etched surfaces with 3 microliters of human plasma. The sealed teeth were subjected to 1,500 thermocycles (1 min/5-55 degrees C) and to 450,000 mechanical cycles under an 8.5 kgf average load at 37 degrees C. The tooth crowns were partially coated with nail varnish, immersed in a 50% aqueous solution of AgNO3 for 2 h in darkness, washed and then developed for 8 h under fluorescent light. The teeth were sectioned and dye penetration was scored according to a 4-point scale by four trained professionals. RESULTS: An ANOVA suggested that under no humidity conditions, the average score for VariGlass (1.92 +/- 0.36) was significantly higher (P = 0.0006) than that corresponding to the three remaining materials (1.28 +/- 0.20) which were considered equivalent. Under humid (plasma contaminated) conditions, there was complete loss of Delton and Fluroshield in all cases, whereas the average score for VariGlass (1.98 +/- 0.36) was slightly higher (P = 0.0444) than that for OptiBond (1.62 +/- 0.36). These results suggest that OptiBond may be used by itself as a pit and fissure sealant instead of the combination of adhesive plus sealant.

Acrylic Resins↗
PubMed1997

A family of genes required for maintenance of cell wall integrity and for the stress response in Saccharomyces cerevisiae.

The PKC1-MPK1 pathway in yeast functions in the maintenance of cell wall integrity and in the stress response. We have identified a family of genes that are putative regulators of this pathway. WSC1, WSC2, and WSC3 encode predicted integral membrane proteins with a conserved cysteine motif and a WSC1-green fluorescence protein fusion protein localizes to the plasma membrane. Deletion of WSC results in phenotypes similar to mutants in the PKC1-MPK1 pathway and an increase in the activity of MPK1 upon a mild heat treatment is impaired in a wscDelta mutant. Genetic analysis places the function of WSC upstream of PKC1, suggesting that they play a role in its activation. We also find a genetic interaction between WSC and the RAS-cAMP pathway. The RAS-cAMP pathway is required for cell cycle progression and for the heat shock response. Overexpression of WSC suppresses the heat shock sensitivity of a strain in which RAS is hyperactivated and the heat shock sensitivity of a wscDelta strain is rescued by deletion of RAS2. The functional characteristics and cellular localization of WSC suggest that they may mediate intracellular responses to environmental stress in yeast.

Amino Acid Sequence↗
PubMed1996

Intravenous amiodarone in treatment of recent-onset atrial fibrillation: results of a randomized, controlled study.

OBJECTIVES: This study was designed to determine the efficacy of intravenous amiodarone in the management of recent-onset atrial fibrillation. BACKGROUND: The optimal approach for acute atrial fibrillation has not been established. Amiodarone is a unique antiarrhythmic agent with activity in both supraventricular and ventricular tachyarrhythmias, but its value for the restoration of sinus rhythm in patients with recent-onset atrial fibrillation has not been demonstrated. METHODS: Sample size was calculated to detect a 25% increase in reversion rate with amiodarone with a statistical power of 80%. One hundred consecutive patients with recent-onset (<1 week) atrial fibrillation and not taking antiarrhythmic agents were randomized to receive either intravenous amiodarone, 5 mg/kg body weight in 30 min followed by 1,200 mg over 24 h, or an identical amount of saline. Both groups received intravenous digoxin, 0.5 mg initially, followed by 0.25 mg at 2 h and 0.25 mg every 6 h thereafter, to complete 24 h while the ventricular rate was >100 beats/min. Amiodarone and digoxin blood levels were determined. Both groups were homogeneous regarding underlying heart disease, time from onset to treatment, initial ventricular rate and left atrial size. RESULTS: By the end of the 24-h treatment period, 34 patients (68%, 95% confidence interval [CI] 53% to 80%) in the amiodarone group and 30 (60%, 95% CI 45% to 74%) in the control group had returned to sinus rhythm (p = 0.532). Mean times (+/-SD) of conversion were 328 +/- 335 and 332 +/- 359 min, respectively (p =0.957). Among patients who did not convert to sinus rhythm, treatment with amiodarone was associated with a slower ventricular rate (82 +/- 15 beats/min in the amiodarone group vs. 91 +/- 23 beats/min in the control group, p = 0.022). After restoration of sinus rhythm, atrial fibrillation recurred during a 15-day follow-up period in 4 (12%) of 34 patients (95% CI 3% to 27%) in the amiodarone group and in 3 (10%) of 30 (95% CI 2% to 26%) in the control group (p = 0.861). CONCLUSIONS: Intravenous amiodarone, at the doses used in this study, produces a modest but not significant benefit in converting acute atrial fibrillation to sinus rhythm.

Adult↗
PubMed1995

A functional assay for heterozygous mutations in the GTPase activating protein related domain of the neurofibromatosis type 1 gene.

The GTPase-activating protein related domain of the human neurofibromatosis type 1 protein (NF1GRD) can down-regulate RAS in Saccharomyces cerevisiae. Using a technique termed the FASAY method, for Functional Analysis of Separated Alleles in Yeast, we designed a rapid method for detection of heterozygous NF1GRD loss-of-function mutations. In our method, PCR amplified NF1GRD cDNA is directly cloned into a centromeric vector by homologous recombination in a cdc25 temperature-sensitive mutant strain expressing human Ha-ras. This strain is dependent on the Ha-ras for growth, allowing a simple growth assay for NF1GRD loss-of-function mutations. In a test of our method, two alternatively spliced NF1GRD cDNAs (type I and II) inhibited yeast growth whereas four mutants with amino acid substitutions at highly conserved residues did not. This simple method thus permits the rapid screening for heterozygous germline or somatic NF1GRD mutations. In an initial application of this method, no mutations disrupting NF1GRD function were detected in lymphoblasts from 11 previously untested neurofibromatosis type 1 patients.

Base Sequence↗
PubMed1995

[Childhood as a value and a problem in the campaigns for health at the beginning of the twentieth century in Spain].

The paper explores how, through a process that began in the last decades of the nineteenth century and continued during the first part of the present century, especially in the 1920's infancy and infant health were regarded as objects of great value and as a social problem. The child's body was studied and analyzed by doctors, a situation that had important repercussions in other spheres of social life. Children were considered to have a series of characteristics which formed, as a whole, an ideal model within the family and home setting. Care, protection and intervention are the three components underlying the sanitary reform process that supported the health and welfare of children in Spain during this period.

Child↗
PubMed1994

Two types of RAS mutants that dominantly interfere with activators of RAS.

In the fission yeast Schizosaccharomyces pombe, ras1 regulates both sexual development (conjugation and sporulation) and cellular morphology. Two types of dominant interfering mutants were isolated in a genetic screen for ras1 mutants that blocked sexual development. The first type of mutation, at Ser-22, analogous to the H-rasAsn-17 mutant (L. A. Feig and G. M. Cooper, Mol. Cell. Biol. 8:3235-3243, 1988), blocked only conjugation, whereas a second type of mutation, at Asp-62, interfered with conjugation, sporulation, and cellular morphology. Analogous mutations at position 64 of Saccharomyces cerevisiae RAS2 or position 57 of human H-ras also resulted in dominant interfering mutants that interfered specifically and more profoundly than mutants of the first type with RAS-associated pathways in both S. pombe or S. cerevisiae. Genetic evidence indicating that both types of interfering mutants function upstream of RAS is provided. Biochemical evidence showing that the mutants are altered in their interaction with the CDC25 class of exchange factors is presented. We show that both H-rasAsn-17 and H-rasTyr-57, compared with wild-type H-ras, are defective in their guanine nucleotide-dependent release from human cdc25 and that this defect is more severe for the H-rasTyr-57 mutant. Such a defect would allow the interfering mutants to remain bound to, thereby sequestering RAS exchange factors. The more severe interference phenotype of this novel interfering mutant suggests that it functions by titrating out other positive regulators of RAS besides those encoded by ste6 and CDC25.

Base Sequence↗
PubMed1993

RAS function and protein kinase cascades.

This paper reviews recent progress in understanding the function of RAS in three systems: the budding yeast (Saccharomyces cerevisiae), the fission yeast (Schizosaccharomyces pombe) and Xenopus laevis oocytes. One of the functions of RAS in S. cerevisiae is the stimulation of adenylate cyclase. This leads to the activation of the cAMP-dependent protein kinases--a function that has probably not been conserved in evolution. The immediate function of RAS in S. pombe is not known, but it may lead to the activation of a protein kinase cascade. This cascade has likely been conserved in evolution and linkage between it and RAS can be demonstrated in cell-free extracts from Xenopus oocytes. The Xenopus cell-free system provides a means to test specific hypotheses about RAS function and to isolate targets of RAS.

Adenylyl Cyclases↗
PubMed1993

A conserved alternative splice in the von Recklinghausen neurofibromatosis (NF1) gene produces two neurofibromin isoforms, both of which have GTPase-activating protein activity.

Sequence analysis has shown significant homology between the catalytic regions of the mammalian ras GTPase-activating protein (GAP), yeast Ira1p and Ira2p (inhibitory regulators of the RAS-cyclic AMP pathway), and neurofibromin, the protein encoded by the NF1 gene. Yeast expression experiments have confirmed that a 381-amino-acid segment of neurofibromin, dubbed the GAP-related domain (GRD), can function as a GAP. Using the RNA polymerase chain reaction with primers flanking the NF1-GRD, we have identified evidence for alternative splicing in this region of the NF1 gene. In addition to the already published sequence (type I), an alternative RNA carrying a 63-nucleotide insertion (type II) is present in all tissues examined, although the relative amounts of types I and II vary. The insertion is conserved across species but is not present in GAP, IRA1, or IRA2. GenBank searches have failed to identify significant similarity between the inserted sequence and known DNA or protein sequences, although the basic amino acid composition of the insertion shares features with nuclear targeting sequences. Expression studies in yeasts show that despite the partial disruption of the neurofibromin-IRA-GAP homology by this insertion, both forms of the NF1-GRD can complement loss of IRA function. In vivo assays designed to compare the GAP activity of the two alternatively spliced forms of the NF1-GRD show that both can increase the conversion of GTP-bound ras to its GDP-bound form, although the insertion of the 21 amino acids weakens this effect. The strong conservation of this alternative splicing suggests that both type I and II isoforms mediate important biological functions of neurofibromin.

Amino Acid Sequence↗
PubMed1993

Analysis of the neurofibromatosis type 1 (NF1) GAP-related domain by site-directed mutagenesis.

The gene for von Recklinghausen neurofibromatosis type 1 (NF1) was recently identified by positional cloning and found to encode a protein with sequence similarity to a family of eucaryotic GTPase-activating proteins (GAPs). Expression of the NF1-GAP-related domain (NF1GRD) has been shown to complement yeast strains deficient in the yeast GAP homologs, IRA1 and IRA2, to interact with human RAS proteins and to accelerate the conversion of ras-GTP to ras-GDP. Further analysis of this region has revealed a number of residues that are highly conserved between members of the GAP family. Mutational analysis of a representative number of these residues produced one of three effects: (1) no change in NF1GRD function, (2) complete disruption of NF1GRD function and (3) intermediate retention of NF1GRD function. One of these mutations at residue 1423 was shown to have reduced ability to negatively regulate ras in yeast, which is interesting in light of a recent report demonstrating a similar naturally occurring mutation in human malignancies.

Amino Acid Sequence↗
PubMed1990

The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins.

The von Recklinghausen neurofibromatosis locus, NF1, encodes a protein with homology restricted to the catalytic region of the RAS GTPase-activating protein, GAP, and with extensive homology to the IRA1 and IRA2 gene products of the yeast S. cerevisiae. A segment of the NF1 cDNA gene, expressed in yeast, can complement loss of IRA function and can inhibit both wild-type and mutant activated human H-ras genes that are coexpressed in yeast. Yeast expressing the NF1 segment have increased H-ras GTPase-stimulating activity. These studies indicate that the NF1 gene product can interact with RAS proteins and demonstrate structural and functional similarities and differences among the GAP, IRA1, IRA2, and NF1 proteins.

Amino Acid Sequence↗