Search PubMed⌕ Search

Biomedical subjects

G Aguirre

Publications and source records attributed to G Aguirre.

At least 19 recordsLinked to original sources

Furoxan derivatives as cytotoxic agents: preliminary in vivo antitumoral activity studies.

Furoxan derivatives with in vitro cytotoxic activity were investigated as antitumoral agents in vivo. The compounds were tested in murine models of both CCRFS-180 II sarcoma and mammary adenocarcinoma. Two of the furoxan derivatives considered here, 3-formyl-4-phenyl-1,2,5-oxadiazole N2-oxide and 3-carbonitrile-4-phenyl-1,2,5-oxadiazole N2-oxide, present in vivo antitumoral activity. They were able to produce more than 90% of tumoral necrosis under the experimental protocol of administration and posology employed. NO-releasing capacity of furoxans may explain the anti-neoplastic activity of these compounds.

Animals↗

Radiation hybrid map, physical map, and low-pass genomic sequence of the canine prcd region on CFA9 and comparative mapping with the syntenic region on human chromosome 17.

Progressive rod-cone degeneration (prcd) is a canine retinal disease that maps to the centromeric end of CFA9 in a region of synteny with the distal part of HSA17q. As such, prcd has been postulated as the only animal model of RP17, a human retinitis pigmentosa locus that maps to 17q22. In an effort to establish more detailed regions of synteny between dog CFA9 and the HSA17q-ter region, we created a robust gene-enriched CFA9-RH08(3000) map with 34 gene-based markers and 12 microsatellites, with the highest resolution and number of markers for the centromeric end of CFA9. Furthermore, we built an approximately 1.5-Mb physical map containing both GRB2 and GALK1, genes so far identified by meiotic linkage analysis as being closest to the prcd locus, and generated about 1.2 Mb low-pass (3.2x) canine sequence. Canine to human comparative sequence analysis identified 49 transcripts that had been previously mapped to the HSA17q25 region. The generated low-pass canine sequence was annotated with a working draft of human sequence from HSA17q25, and we used this scaffold to order and orient the canine sequence against human. This order and orientation are preliminary, as high-throughput genomic sequencing of HSA17q-ter has not been fully completed.

Animals↗

Chromosome evolution in the annual killifish genus Cynolebias and mitochondrial phylogenetic analysis.

Extensive chromosome variation involving Robertsonian and non-Robertsonian changes were proposed to explain chromosomal evolution within killifishes of the aplocheiloid group belonging to the order Cyprinodontiforms. In the present work we describe the karyotypes of four Cynolebias species and analyze chromosome changes by means of mitochondrial phylogenetic studies, including 10 taxa of this genus. Diploid numbers varied from 48 to 44 and the number of chromosome arms from 50 to 54. Molecular phylogenetic analyses allow us to corroborate previous hypothesis about chromosome evolution in aplocheiloid fishes. The tree topology based on a combined dataset of mitochondrial cytochrome b and 12S genes shows that recent cladogenetic events within the genus Cynolebias could have occurred by allopatric or 'in-situ' differentiation involving chromosomal rearrangements. Our analyses of approximately 10% of mitochondrial genome can be helpful in determining these recent cladogenetic events but it showed limited phylogenetic resolution at intermediate levels of divergence. This can be explained in part by the high levels of DNA sequence divergence (ranging from 0.015 to 0.245) detected at intrageneric level. Different methodological approaches suggest that chromosomal changes in Cynolebias have occurred during their differentiation, supporting the hypothesis that the unresolved basal polytomy could be the result of rapid speciation events, like a true 'star polytomy'.

Animals↗

Posterior segment approach for subretinal transplantation or injection in the canine model.

A posterior segment approach for cell transplantation or injection into the subretinal space of the dog has been developed. Controlled penetration to the subretinal space was achieved using a 29-gauge injection cannula, either blunted or with a 30 degrees sharpened bevel, and partially ensheathed with moveable plastic tubing. Depending on the injection volume used, the retina detached, and the fluid was reabsorbed within 1-3 weeks, although for smaller volumes the retina reattached within a matter of days. The optimal injection volume used was between 100 and 150 microl, or two injections of 55 microl each. By ophthalmoscopy following the surgery, it was possible to serially monitor the injection site and retinal bleb through fundus photography. Light microscopy demonstrates the distribution of stable, viable RPE cells in the subretinal space up to 6 months. The transplantation technique developed for the dog is atraumatic and free from any major surgical or clinical complications. It can be readily used to deliver cells or fluids to localized regions of the subretinal space.

Animals↗

Synthesis and structure of isomeric palladium(II)-pyrazole chelate complexes with and without an N-H group as hydrogen bond donor.

Four new ligands containing a pyrazole ring and either a phosphine or thioether were prepared and converted to their cis-dichloropalladium(II) complexes. Two of the ligands are especially notable for the attachment of a side chain at pyrazole carbon, rather than at nitrogen. The new metal complexes include dichloro[3-(diphenylphosphinomethyl)pyrazole]palladium(II) (1-PdCl2) and dichloro[3-(methylthiomethyl)pyrazole]palladium(II) (2-PdCl2), which both feature an N-H group as a potential proton or hydrogen bond donor. For comparison, isomeric complexes lacking an NH group were prepared: dichloro[1-(diphenylphosphinomethyl)pyrazole]palladium(II) (3-PdCl2) and dichloro[1-(methylthiomethyl)pyrazole]palladium(II) (4-PdCl2). As determined by X-ray crystallography, all four complexes were found to have slightly distorted square planar geometry. Complexes 1-PdCl2 and 2-PdCl2, which contain an NH group, exhibit both intermolecular and intramolecular hydrogen bonding, whereas isomers 3-PdCl2 and 4-PdCl2 do not. Single-crystal X-ray structure determinations on the following compounds are reported: 1-PdCl2, space group P1, a = 8.4488(9) A, b = 8.9175(13) A, c = 12.731(2) A, Z = 2, V = 871.8(2) A3; 2-PdCl2, space group Pbca, a = 10.8827(10) A, b = 11.7721(7) A, c = 14.874(2) A, Z = 8, V = 1905.6 A3; 3-PdCl2, space group P2(1)/c, a = 20.520(2) A, b = 12.549(2) A, c = 13.9784(13) A, Z = 8, V = 3401.1(6) A3; 4-PdCl2, space group Pbca, a = 10.6545(10) A, b = 12.0205(11) A, c = 14.6474(14) A, Z = 8, V = 1875.9(3) A3.

Journal Article↗

Replication and further studies of neural mechanisms of spatial mnemonic processing in humans.

Changes in neuronal firing rates during periods of time when subjects are required to remember information (retention delays) have been reported in non-human primates. In humans, tests for such functional changes using hemodynamic markers of neural activity have typically relied on cognitive subtraction. However, the temporal resolution of fMRI allows a more direct test than that afforded by cognitive subtraction of the idea that certain brain regions may increase their neural activity during retention delays in humans. Using a method that exploits this temporal resolution, increased functional activity attributable to a retention delay for spatial information in regions proximate to/within the right frontal eye field and the right superior parietal lobule were detected (in four out of four and three out of four subjects, respectively; this is an internal replication of the results of [E. Zarahn, G.K. Aguirre, M. D'Esposito, Temporal isolation of the neural correlates of spatial mnemonic processing with fMRI, Cognit. Brain Res., 7 (1999) 255-268. ]). Second, a model in which ventral and not dorsal prefrontal cortex in humans is involved in simply maintaining spatial information was tested. The results disputed this model as increases in fMRI signal attributable to the retention delay were detected more frequently in dorsal than ventral prefrontal cortex. Third, a model which posited that the intensity of neural activity is causally related to the accuracy of spatial mnemonic representation was tested by comparing retention delay signal between correct and incorrect trials. The results did not support this model in any of the regions tested.

Adult↗

A trial-based experimental design for fMRI.

An experimental design for functional MRI (fMRI) is presented whose conceptual units of analysis are behavioral trials, in contrast to blocks of trials. This type of design is referred to as a trial-based (TB) fMRI design. It is explained how TB designs can afford the ability to: (1) randomize the presentation of behavioral trials and (2) utilize intertrial variance in uncontrolled behavioral measures to examine their functional correlates. A particular type of TB design that involves modeling trial-evoked fMRI responses with one or more shifted impulse response functions is described. This design is capable of discriminating functional changes occurring during temporally separated behavioral subcomponents within trials. An example of such a design is implemented and its statistical specificity, functional sensitivity, and functional specificity are tested.

Adult↗

Corneal endothelium in mucopolysaccharide storage disorders. Morphologic studies in animal models.

In the systemic mucopolysaccharidoses (MPS) in animals, corneal clouding resulted from storage of glycosaminoglycans (GAG) in stromal keratocytes. The corneal epithelium was normal (MPS VI and VII) or minimally affected (MPS I), and stromal edema was not a feature even though the corneal endothelium demonstrated variable pathology. The MPS I (cat) cornea showed endothelial cells with large numbers of secondary lysosomal inclusions that were vacuolated or had a granular matrix. The endothelium was uniformly affected, but was not markedly hypertrophied. In contrast, the MPS VI (cat) cornea showed no endothelial cell disease. The MPS VII (dog) cornea had the most significant and dramatic endothelial pathology. The cells were massively hypertrophied and contained large numbers of vacuolated lysosomal inclusions. Regardless of the severity of the morphologic disease, the endothelial cells in these animal models functioned normally in maintaining the relative dehydration of the cornea. The corneal clouding was the result of storage in stromal keratocytes rather than corneal edema from endothelial dysfunction.

Animals↗

A polymerase chain reaction-based method for the identification of DNA samples from common vertebrate species.

Polymerase chain reaction (PCR) amplification of vertebrate genomic DNAs using a (CAC)n primer was found to generate species-specific patterns which are resolvable by agarose gel electrophoresis. Of the thirteen species tested (trout, frog, chicken, mouse, rat, cow, dog, African green monkey, chimpanzee, orangutan, gorilla, rhesus macaque, and human), all species showed discrete amplification products ranging in size from 1.0 to 3.2 kbp although trout and frogs had only weak (CAC)n amplification products. Most species had three to six bands except rodents, who had eight bands, and cows, who had a single band at 2.2 kbp. Importantly, within a single species, different unrelated individuals had highly similar amplification band patterns although the relative intensities of the bands varied. This held true even when different unrelated humans of different racial backgrounds were tested. We conclude that this technique is potentially useful for identifying which vertebrate species contributed DNA to a given biological sample (e.g., bloodstains, semen, hair) and that only a very small amount of sample is necessary for the analysis.

Animals↗

[Profile of health services utilization during the XVII Central American and Caribbean Sport Games: Delegation of Puerto Rico, Ponce 1993].

During the XVII Central American and Caribbean Sports Games held in Ponce in 1993 the health services offered to the Puerto Rico Delegation included medical, dental and psychological assistance, physical therapy and services on the playing field. Information about the use of these services was obtained from the encounter sheets. The Puerto Rican delegation of 750 members had 1,800 encounters with the health team; 612 (34.0%) individual consults; 896 (54.8%) physical therapy sessions; 166 (9.2%) encounters in the sports venues; and 36 (20%) group therapies. The most common diagnoses were athletic injuries (304; 58.2%) and diseases of the respiratory system (76; 14.5%). The most frequent athletic injuries were first degree strains (75; 24.7%) and tendinitis (73, 24.0%). This pattern is similar to that observed in other sports games and delegations with mild conditions prevailing. An interdisciplinary work and biopsychosocial approach will be important for the better health and performance of our athletes.

Adolescent↗

Patterns of injuries in athletes evaluated in an interdisciplinary clinic.

The pattern of sports injuries appears to be population-specific. The purpose of the present study is to describe 1750 injuries evaluated between April 1988 and April 1994 in our Olympic Training Center Interdisciplinary Sports Injury Clinic. Our patient population included elite and recreational athletes of both sexes between the ages of 7 and 71 years. Males comprised 73% of the patient population and approximately 80% of the injuries corresponded to the 10 to 29 age range. The most frequent sports in males were baseball (21.9%) and basketball (15.9%) and in females were track and field (17.1%) and gymnastics (15.1%). Most injuries (52%) were traumatic in nature, chronic (71.6%), and occurred during training sessions (57.4%). The most commonly affected anatomical areas were the knee (31.2%) and shoulder (15.5%). The most common diagnoses were tendinitis (25.4%), and first degree strains (11.8%) and sprains (9.3%). Finally, treatment strategies included medications (61.0%), physical therapy (48.9%), relative rest (35.7%), and home exercise programs (35.2%). The variety of musculoskeletal disorders seen in combination with the frequent use of conservative treatment confirms the importance of an interdisciplinary approach to sports injuries.

Adolescent↗

Spatial and temporal differences between the expression of short- and middle-wave sensitive cone pigments in the mouse retina: a developmental study.

In an earlier study we found a topographic separation of middlewave-sensitive (M) and shortwave-sensitive (S) cones in the adult mouse retina. In the present study we investigated the development of the two colour-specific cone types to see whether there is also a temporal difference between the expression of the specific cone visual pigments. Using two anti-cone visual pigment antibodies, COS-1 and OS-2, we compared the densities of immunopositive cone outer segments on retinal whole mounts derived from mice of various ages. The first detectable cone outer segments were the S-cones which appeared in the inferior half of the retina on postnatal day 4. At this stage, the density of the S-cones was very low (30-40 cones/retina) but increased steadily on the following days to reach a value comparable to that of adults by P30 (18,000/mm2). This cone type always remained much more abundant in the lower part of the retina throughout the whole retinal development. In the superior half of the retina, a few S-cones appeared from postnatal day 7; however, their number always remained about one order of magnitude lower than in the inferior part. In contrast, M-cone outer segments were not identifiable earlier than postnatal day 11 and were confined exclusively to the superior part of the retina during the whole developmental process. On postnatal day 12, their density was 1,900/mm2 and increased to a value of 11,000/mm2 by postnatal day 30, which represented the adult stage. As shown by comparison of isodensity lines derived from immunocytochemical reactions of whole mount retinas, the two cone types occupied complementary halves of the mouse retina with maximum density centres located in opposite retinal quadrants. We conclude that 1) in contrast to the primate retina, mouse S-cones precede the M-cones in their development, and 2) the spatial arrangements of the two cone types is maintained throughout the whole differentiation process.

Animals↗

Cloning of a polymorphic canine genetic marker which maps to human chromosome 9.

We describe the cloning of a novel canine polymorphic genetic marker which maps to human chromosome 9. The sequence is 2092 bp, 59% GC rich, and contains three GC boxes. Chemiluminescent probing of zooblots showed evolutionary conservation. Dogs have three BamHI alleles: 2.3 kb, 2.1 kb and 1.7 kb. Allele frequencies in 17 unrelated dogs representing 13 breeds are presented. Polymorphism for the 1.7-kb allele in beagles is common. The 2.1-kb allele is probably the ancestral allele since it is the most common and is also noted in the Cape hunting dog. Interestingly, in more than 50 dogs tested to date, the 2.3-kb allele has been found only in miniature and giant schnauzers. This points to a common origin for these two breeds.

Animals↗

[Morbidity during the XVI Central American and Caribbean Games: Puerto Rican delegation, Mexico 1990].

The health services offered to the Puerto Rican Delegation during the XVI Central American and Caribbean Sports Games in México in 1990 included: medical, dental and psychological assistance, physical therapy and services on the playing field. From the consultation sheets completed during the Games we obtained information about the use of these services. The 336 members of the Puerto Rico Delegation in the village at México City had 1,838 encounters with the health team. Of these, 991 were medical consults, 55 group therapies, 466 physical therapy sessions and 326 encounters in the sports venues. Among the encounters for medical evaluation the most frequent problems were athletic injuries (318; 32.1%), respiratory problems (240; 24.2%), gastrointestinal conditions (126; 12.7%) and dental services (119; 12.0%). The most frequent athletic injuries were first degree strains (83; 26.1%), tendinitis (56; 17.6%), contusions (42; 13.2%), myositis (40; 12.6%) and first degree sprains (28; 8.8%). The health problems found were diversed and in the majority of cases mild in character, which can be attend by adequately trained on sports health primary health professionals.

Adolescent↗

Unique topographic separation of two spectral classes of cones in the mouse retina.

We have found two immunologically distinguishable cone types in the retina of the mouse, each localized to two opposite halves of the eye. One cone type was labelled by the monoclonal antibody COS-1 specific to the middle-to-long wave sensitive visual pigment of the mammals, while the other type was stained by the shortwave-specific monoclonal antibody (OS-2). These results were confirmed with other antibodies directed against specific sequences of the visual pigments. As a result of the uneven distribution of the two cone types the mouse retina is divided into two fields separated by an oblique meridional line. The middlewave sensitive cones were present exclusively in the dorsal half of the mouse retina (M-field). The overwhelming majority of the shortwave sensitive cones occupied the ventral half (S-field), and only a small number was scattered among the middlewave sensitive cones in the dorsal retina. The ratio of the two cone types in the M-field corresponds to what has been found in the retina of other mammals, including rodents such as the gerbil and the rat. The S-field represents an entirely unique area with the unusually great number of shortwave sensitive cones and with the complete lack of the middlewave sensitive ones. The present study provides the structural basis for dichromacy in a rodent species considered for a long time to be monochromat. In addition, it shows that the ventral retina, containing exclusively S-cones in a relatively high density, is a unique retinal field not present in other mammalian species studied so far.

Animals↗

The beta subunit of cyclic GMP phosphodiesterase mRNA is deficient in canine rod-cone dysplasia 1.

Irish setter dogs affected with rod-cone dysplasia 1 have elevated levels of retinal cGMP resulting from deficient rod-specific cGMP phosphodiesterase (cGMP PDE) activity. We investigated the mRNAs coding for the three subunits of cGMP PDE and for the proteins involved in the activation/deactivation of this enzyme in the retinas of developing affected and control dogs. While the photoreceptor cells are viable in the diseased retinas, opsin, transducin alpha 1 and beta 1, 48 and 33 kd proteins, and cGMP PDE alpha and gamma mRNAs have normal transcript sizes and levels. In contrast, a different pattern of cGMP PDE beta mRNAs with lower than normal concentrations is present in the developing affected retinas prior to degeneration. Our observations suggest that an abnormality involving cGMP PDE beta expression is implicated in rod-cone dysplasia 1.

3',5'-Cyclic-GMP Phosphodiesterases↗