Search PubMed⌕ Search

Biomedical subjects

P Martinez

Publications and source records attributed to P Martinez.

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

Identification of genes that modify ataxin-1-induced neurodegeneration.

A growing number of human neurodegenerative diseases result from the expansion of a glutamine repeat in the protein that causes the disease. Spinocerebellar ataxia type 1 (SCA1) is one such disease-caused by expansion of a polyglutamine tract in the protein ataxin-1. To elucidate the genetic pathways and molecular mechanisms underlying neuronal degeneration in this group of diseases, we have created a model system for SCA1 by expressing the full-length human SCA1 gene in Drosophila. Here we show that high levels of wild-type ataxin-1 can cause degenerative phenotypes similar to those caused by the expanded protein. We conducted genetic screens to identify genes that modify SCA1-induced neurodegeneration. Several modifiers highlight the role of protein folding and protein clearance in the development of SCA1. Furthermore, new mechanisms of polyglutamine pathogenesis were revealed by the discovery of modifiers that are involved in RNA processing, transcriptional regulation and cellular detoxification. These findings may be relevant to the treatment of polyglutamine diseases and, perhaps, to other neurodegenerative diseases, such as Alzheimer's and Parkinson's disease.

Animals↗
PubMed2000

A sea urchin genome project: sequence scan, virtual map, and additional resources.

Results of a first-stage Sea Urchin Genome Project are summarized here. The species chosen was Strongylocentrotus purpuratus, a research model of major importance in developmental and molecular biology. A virtual map of the genome was constructed by sequencing the ends of 76,020 bacterial artificial chromosome (BAC) recombinants (average length, 125 kb). The BAC-end sequence tag connectors (STCs) occur an average of 10 kb apart, and, together with restriction digest patterns recorded for the same BAC clones, they provide immediate access to contigs of several hundred kilobases surrounding any gene of interest. The STCs survey >5% of the genome and provide the estimate that this genome contains approximately 27,350 protein-coding genes. The frequency distribution and canonical sequences of all middle and highly repetitive sequence families in the genome were obtained from the STCs as well. The 500-kb Hox gene complex of this species is being sequenced in its entirety. In addition, arrayed cDNA libraries of >10(5) clones each were constructed from every major stage of embryogenesis, several individual cell types, and adult tissues and are available to the community. The accumulated STC data and an expanding expressed sequence tag database (at present including >12, 000 sequences) have been reported to GenBank and are accessible on public web sites.

Aging↗
PubMed2000

Determination of inorganic cations in brine solutions by ion chromatography.

The method for analysis of inorganic cations in brine solutions was developed. Ion chromatography is a well-established and accepted technique in the determination of a variety of inorganic ions. However, there are significant complications when ion chromatography is used to determine trace concentrations of inorganic ions in brine matrices. The brine solution in our study was made to simulate the solution from the Waste Isolation Pilot Plant. Instrumental parameters such as eluent composition, flow-rates, and sample loop volumes were investigated to arrive at the optimum condition for the determination of the cations with minimal dilution. Separation was carried out in a Dionex CG12A/CS12A with 8.25 mM H2SO4 as eluent at 1.2 ml/min flow-rate. Our results indicated that ion chromatography is an accurate and a good alternative method for the analysis of cations in brine solution.

Cations↗
PubMed2000

Bronchiectasis in Alaska Native children: causes and clinical courses.

Although bronchiectasis has become a rare condition in U.S. children, it is still commonly diagnosed in Alaska Native children in the Yukon Kuskokwim Delta. The prevalence of bronchiectasis has not decreased in persons born during the 1980s as compared with those born in the 1940s. We reviewed case histories of 46 children with bronchiectasis. We observed that recurrent pneumonia was the major preceding medical condition in 85% of patients. There was an association between the lobes affected by pneumonia and the lobes affected by bronchiectasis. Eight (17%) patients had surgical resection of involved lobes. We conclude that the continued high prevalence of bronchiectasis appears to be related to extremely high rates of infant and childhood pneumonia. Pediatr Pulmonol. 2000;29:182-187. Published 2000 Wiley-Liss, Inc.

Adolescent↗
PubMed2000

Orientation of the body response to galvanic stimulation as a function of the inter-vestibular imbalance.

We proposed to study and quantify the anteroposterior component, on top of the lateral one, of the body sway induced by different configurations of galvanic vestibular stimulation (GVS) in order to advance the understanding of the orientation of the response. Four stimulation configurations were used in two separate experiments: monaural, binaural, and opposite double monaural in the first experiment (11 subjects); monaural and double monaural in the second (13 subjects). The postural response of the subjects, standing with their eyes closed, to the stimulus (0.6 mA, 4 s) was assessed by measuring the displacement of the center of pressure (CoP) using a force platform. As usual, binaural GVS induced a strictly lateral deviation of the center of pressure. The opposite double monaural condition induced a similar lateral sway to that obtained in the binaural mode, although with a very different stimulation configuration. Monaural GVS induced an oblique, stereotyped deviation in each subject. The anteroposterior component comprised a forward deviation when the anode was on the forehead and a backward deviation when the anode was on the mastoid. The lateral component, directed towards the anode as in the binaural design, was twice as large in the binaural than in the monaural mode. The second experiment showed that double monaural stimulation elicited an anteroposterior deviation (backwards when the anode was on the mastoids and forwards when it was on the forehead) that was equivalent to the addition of two complementary monaural configurations. The present results show that monaural stimulation activates one side of the vestibular apparatus and induces reproducible, stereotyped deviations of the CoP in both the anteroposterior and lateral plane. Secondly, binaural GVS appears to result from the addition of two complementary monaural stimulations. Lateral components of the response to each stimulation, being in the same direction, are summed, whilst anteroposterior components, being in opposite directions, cancel each other out. The opposite happens when both labyrinths are polarized in the same way, as in the double monaural configuration. We suggest that the orientation of the response to GVS is a function of the imbalance between right and left vestibular polarization, rather than a function of the actual position of the electrodes.

Electric Stimulation↗
PubMed2000

A population analysis of the structure and variability of NOR in Salmo trutta by Ag, CMA3 and ISH.

An analysis of the variation in the number and location of rDNA genes has been carried out in two populations of brown trout (Salmo trutta) from Poland by using Ag and CMA3-staining, and rDNA in situ hybridisation. We observed an interindividual variation in arm number with NF = 100, 101, and 102. This variation was connected with the size polymorphism of the short (NOR-bearing) arm of the chromosome pair 11. The population studied showed a multichromosomal distribution of active NORs. Atypical Ag-NORs consisted of rDNA genes, as evidenced by rDNA-ISH. In addition to individuals with standard NORs, specimens with extra NORs as well as others with only one active NOR and single interphase nucleolus were observed.

Animals↗
PubMed1999

Tubulin binding sites on gamma-tubulin: identification and molecular characterization.

gamma-Tubulin is essential to microtubule organization in eukaryotic cells. It is believed that gamma-tubulin interacts with tubulin to accomplish its cellular functions. However, such an interaction has been difficult to demonstrate and to characterize at the molecular level. gamma-Tubulin is a poorly soluble protein, not amenable to biochemical studies in a purified form as yet. Therefore basic questions concerning the existence and properties of tubulin binding sites on gamma-tubulin have been difficult to address. Here we have performed a systematic search for tubulin binding sites on gamma-tubulin using the SPOT peptide technique. We find a specific interaction of tubulin with six distinct domains on gamma-tubulin. These domains are clustered in the central part of the gamma-tubulin primary amino acid sequence. Synthetic peptides corresponding to the tubulin binding domains of gamma-tubulin bind with nanomolar K(d)s to tubulin dimers. These peptides do not interfere measurably with microtubule assembly in vitro and associate with microtubules along the polymer length. On the tertiary structure, the gamma-tubulin peptides cluster to surface regions on both sides of the molecule. Using SPOT analysis, we also find peptides interacting with gamma-tubulin in both the alpha- and beta-tubulin subunits. The tubulin peptides cluster to surface regions on both sides of the alpha- and beta- subunits. These data establish gamma-tubulin as a tubulin ligand with unique tubulin-binding properties and suggests that gamma-tubulin and tubulin dimers associate through lateral interactions.

Amino Acid Sequence↗
PubMed1999

Organization of an echinoderm Hox gene cluster.

The Strongylocentrotus purpuratus genome contains a single ten-gene Hox complex >0.5 megabase in length. This complex was isolated on overlapping bacterial artificial chromosome and P1 artificial chromosome genomic recombinants by using probes for individual genes and by genomic walking. Echinoderm Hox genes of Paralog Groups (PG) 1 and 2 are reported. The cluster includes genes representing all paralog groups of vertebrate Hox clusters, except that there is a single gene of the PG4-5 types and only three genes of the PG9-12 types. The echinoderm Hox gene cluster is essentially similar to those of the bilaterally organized chordates, despite the radically altered pentameral body plans of these animals.

Amino Acid Sequence↗
PubMed1999

Persistent hypokalemia after successful adrenalectomy in a patient with Cushing's syndrome due to ectopic ACTH secretion: possible role of 11beta-hydroxysteroid dehydrogenase inhibition.

Ectopic ACTH secretion is characterized by a high incidence of hypokalemia. The pathophysiology of hypokalemia has not been totally clarified, although it has been postulated that excessive amounts of adrenal steroids may play a role, as well as a possible role of the inhibition of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-OHSD). This enzyme normally converts cortisol to cortisone avoiding the mineralocorticoid action of cortisol. We present a patient with ectopic ACTH secretion due to a metastatic carcinoid tumor. The clinical picture was characterized by maintained hypokalemia (1.4 mmol/l) resistant to potassium, spironolactone and ketoconazole administration. A bilateral adrenalectomy was performed but the hypokalemia persisted while he was receiving a physiological dose of cortisol. Eight days after adrenalectomy cortisol was replaced by an equivalent dose of dexamethasone. This change was followed by a rapid and persistent normalization of hypokalemia suggesting a mineralocorticoid effect of cortisol. In conclusion, the origin of hypokalemia in our patient with ectopic ACTH secretion was secondary to cortisol. We postulate that this peculiar effect of cortisol could have happened if an inhibition of 11beta-OHSD occurred.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

Genetic structure of brown trout, salmo trutta l., at the southern limit of the distribution range of the anadromous form

Genetic variation at 33 protein loci was investigated in 41 wild brown trout populations from four river basins in Galicia (northwest Spain) to analyse the amount and distribution of genetic diversity in a marginal area, located in the distribution limit of the anadromous form of this species. The genetic diversity detected within populations (H between 0 and 6%) lies within the range quoted for this species in previous reports. The Mino, the most southern river basin analysed, showed a significantly lower genetic diversity and the highest genetic differentiation among the river basins studied. The hierarchical gene diversity analysis showed high population differentiation in a restricted area (GST = 27%), mostly due to differences among populations within basins (GSC = 22%). The reduction of GST observed when the isolated samples were excluded from the analysis (GST = 17%) showed the importance of habitat fragmentation on the heterogeneity detected. Gene flow among populations was comparatively evaluated by three indirect methods, which in general revealed low figures of absolute number of migrants per generation, slightly higher than 1. The gene flow among basins reflected a positive relationship with geographical distance. This trend was confirmed by the significant correlation observed between geographical and genetic distances, including all population pairs, which suggests a component of isolation by distance in brown trout genetic structure. Nevertheless, the nonsignificant intrabasin correlation demonstrates the complexity of genetic relationships among populations in this species. The model of genetic structure in brown trout is discussed in the light of the results obtained.

Journal Article↗
PubMed1999

Genomics of the major histocompatibility complex: haplotypes, duplication, retroviruses and disease.

The genomic region encompassing the Major Histocompatibility Complex (MHC) contains polymorphic frozen blocks which have developed by local imperfect sequential duplication associated with insertion and deletion (indels). In the alpha block surrounding HLA-A, there are ten duplication units or beads on the 62.1 ancestral haplotype. Each bead contains or contained sequences representing Class I, PERB11 (MHC Class I chain related (MIC) and human endogenous retrovirus (HERV) 16. Here we consider explanations for co-occurrence of genomic polymorphism, duplication and HERVs and we ask how these features encode susceptibility to numerous and very diverse diseases. Ancestral haplotypes differ in their copy number and indels in addition to their coding regions. Disease susceptibility could be a function of all of these differences. We propose a model of the evolution of the human MHC. Population-specific integration of retroviral sequences could explain rapid diversification through duplication and differential disease susceptibility. If HERV sequences can be protective, there are exciting prospects for manipulation. In the meanwhile, it will be necessary to understand the function of MHC genes such as PERB11 (MIC) and many others discovered by genomic sequencing.

Animals↗
PubMed1999

Hypovitaminosis D in an Italian population of healthy subjects and hospitalized patients.

The present study aimed to investigate the prevalence and seasonal variation of hypovitaminosis D (defined as serum 25-hydroxyvitamin D level below 30 nmol/l) among healthy subjects and hospitalized patients living in central Italy. We studied 297 subjects, 131 in February 1997 and 166 in July 1997, subdivided into four groups: (a) young healthy blood donors; (b) healthy postmenopausal women; (c) inpatients with various medical diseases and (d) inpatients engaged in long-term rehabilitation programmes because of various neurological disorders. In all subjects and patients serum levels of 25-hydroxyvitamin D were measured by radioimmunoassay. We found a significant seasonal variation (P < 0.0001) of serum 25-hydroxyvitamin D levels, mean values being higher in summer in all groups, except in patients with a longer hospitalization time (group (d)). In each group, a significantly higher prevalence of hypovitaminosis D was found in winter compared with summer time (P < 0.001), being unexpectedly high in postmenopausal women (winter 32% and summer 4.5%); furthermore, in both seasons, inpatients were characterized by the highest incidences of hypovitaminosis, particularly those in group (d) (winter 82.3% and summer 57.8%). The results of the present study emphasize the importance of 25-hydroxyvitamin D measurement, and the need to increase vitamin D intake in Italy; foodstuff fortification and supplement use must be considered in order to prevent negative effects of vitamin D deficiency on skeletal integrity.

25-Hydroxyvitamin D 2↗
PubMed1999

Prognostic value of ornithine decarboxylase and polyamines in human breast cancer: correlation with clinicopathologic parameters.

The polyamines putrescine, spermidine, and spermine and ornithine decarboxylase (ODC), the rate-limiting enzyme in their biosynthetic pathway, play an important role in cell proliferation, differentiation, and transformation. In the present study, we have analyzed polyamine concentrations and ODC activity in samples from benign breast diseases (n = 36), benign breast tissue adjacent to the primary carcinoma (n = 19), and breast carcinoma (n = 104). ODC activity in primary carcinoma was significantly higher (2.42 +/- 0.22 nmol CO2/h g; P < 0.001) than that found in benign breast (0.62 +/- 0.15 nmol CO2/h g) or in breast tissue adjacent to the primary carcinoma (0.52 +/- 0.16 nmol CO2/h g). The total polyamine content of breast cancer tissues was higher than in benign breast diseases (704.3 +/- 38.3 nmol/g wet weight versus 295.8 +/- 27.4 nmol/g wet weight) and correlated well with ODC activity (Pearson, r = 0.42; P < 0.001). ODC activity correlated with histological grade, peritumoral lymphatic or blood vessel invasion, S-phase fraction, and cathepsin D. Total polyamine concentration increased with S-phase fraction, cathepsin D, and aneuploidy. No significant correlation was found between ODC or polyamines and tumor size, lymph node involvement, or steroid receptor status. A major finding in our study was that ODC activity was an independent prognostic factor for recurrence and death. The results indicate that the estimation of ODC activity and polyamines in human breast carcinoma might be useful to determine tumor aggressiveness and suggest that ODC may have a potential value as both a prognostic factor and a chemoprevention target in human breast cancer.

Adolescent↗