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Biomedical subjects

R Bernal

Publications and source records attributed to R Bernal.

At least 19 recordsLinked to original sources

A simple processing method allowing comparison of renal enhancing volumes derived from standard portal venous phase contrast-enhanced multidetector CT images to derive a CT estimate of differential renal function with equivalent results to nuclear medicine quantification.

As iodinated contrast medium is cleared by glomerular filtration, it should be possible to apply the same principles utilized in radionuclide studies to derive differential renal function by comparison of enhancing renal volumes derived from contrast enhanced multidetector CT (CEMDCT). Having established a technique iteratively which appeared successful, a retrospective study was performed using 25 consecutive patients with a wide range of urological conditions who had undergone both CEMDCT, including the renal area in the portal venous phase, and nuclear medicine (NM) assessment of renal function with no urological intervention between the studies. Proprietary volume software was used to quantify the volume and attenuation of each kidney, the products of which (after subtraction of soft tissue attenuation derived from a region of interest over psoas) gave right and left enhancing renal volumes. The contribution by each kidney as a percentage of total renal enhancing tissue was derived. Comparison with NM studies resulted in excellent correlation of relative renal function by CEMDCT and NM assessments having a regression of near unity and a Pearson's correlation coefficient of 0.96. Bland Altman and Passing Bablock tests confirmed good agreement between the two methods with no bias. This is a simple, practicable processing technique using standard portal venous phase CEMDCT images to quantify differential function. This technique may allow a one-stop CT assessment of both anatomy and function.

Adult↗

Optically stimulated luminescence dosimetry performance of natural Brazilian topaz exposed to beta radiation.

Optically stimulated luminescence (OSL) has become the technique of choice in many areas of dosimetry. Natural materials like topaz are available in large quantities in Brazil and other countries. They have been studied to investigate the possibility of use its thermoluminescence (TL) properties for dosimetric applications. In this work, we investigate the possibility of utilising the OSL properties of natural Brazilian topaz in dosimetry. Bulk topaz samples were exposed to doses up to 100 Gy of beta radiation and the integrated OSL as a function of the dose showed linear behaviour. The fading occurs in the first 20 min after irradiation but it is <6% of the integrated OSL measured shortly after exposure. We conclude that natural colourless topaz is a very suitable phosphor for OSL dosimetry.

Beta Particles↗

Thermoluminescence response of new KCl(X)Br(1-X):EuCl3 sintered phosphors exposed to beta and gamma radiation.

Alkali halides crystals have been the subject of intense research for an understanding of their radiation-induced defects and luminescence properties. They exhibit noteworthy thermoluminescence (TL) properties when exposed to ionising radiation. Currently, these materials are grown employing expensive and rather complicated techniques. In this work, the results on the TL properties of new alkali halides phosphors fabricated by a simple and inexpensive procedure are presented. The samples were made by mixing KCl, KBr and EuCl3 salts, and compressing them at a pressure of 3.2 x 10(7) Pa during 3 min, followed by sintering at 700 degrees C during 24 h under air atmosphere. The dosimetric response of the samples showed an increase with radiation dose in the 1.5-20.0 Gy dose range for beta and gamma radiation. The TL glow curves in sintered samples presented significant differences in their peak structures compared with monocrystalline samples, indicating that the nature of the trapping states and the recombination mechanisms may be different.

Beta Particles↗

Performance of CVD diamond as an optically and thermally stimulated luminescence dosemeter.

Diamond is a material with extreme physical properties. Its radiation hardness, chemical inertness and tissue equivalence qualify it as an ideal material for radiation dosimetry. In the present work, the optically stimulated luminescence (OSL) and thermoluminescence (TL) characteristics of a 10 microm thick CVD diamond (polycrystalline diamond films prepared by chemical vapor deposition) film were studied in order to test its performance as a beta radiation dosemeter. The TL response is composed of four main TL glow peaks; two of these are in the range of 150-200 degrees C and two additional peaks in the 250-400 degrees C temperature range. The integrated TL as a function of radiation dose is linear up to 100 Gy and increases with increasing dose exposure. The dose dependence of the integrated OSL exhibits a similar behavior. The observed OSL/TL behavior for the CVD diamond film clearly demonstrate its capability for applications in radiation dosimetry with special relevance in medical dosimetry owing to the diamond's intrinsic material properties.

Diamond↗

Wrinkle formations in axi-symmetrically stretched membranes.

We study experimentally the main features of wrinkles that form in an initially stretched and flat elastic membrane when subjected to an axi-symmetric traction force at the center. The wavelength and amplitude of the wrinkle pattern are accurately characterized as the membrane tension and the traction forced are varied. We show that wrinkles are the result of a supercritical instability and appear for a well-defined critical traction force that is a function of the membrane tension. Wrinkle length and amplitude increase as the traction force is increased further. By contrast, both quantities decrease as the membrane tension is increased. Calculations based on symmetry arguments and elastic-energy minimization are in good agreement with experiments and provide a simple way to investigate configurations that are difficult to access experimentally. Such problems include wrinkles in elastic nano-films on finite-thickness viscous substrates used in semiconductor technology or in cellular forces detection.

Cell Movement↗

Normal-mode-vortex interactions.

Standing surface waves that interact with a confined, vertical, vorticity field with zero net circulation are studied both analytically and experimentally. The surface waves are generated by vertical vibration, and constant vorticity injection is achieved by a rotating disk flush mounted in the cell. Experimental results are indicative of a local wave-vortex interaction (no dislocation), and a simple theoretical model is able to explain them in quantitative detail.

Journal Article↗

Localisation of endothelin-1 mRNA expression and immunoreactivity in the retina and optic nerve from human and porcine eye. Evidence for endothelin-1 expression in astrocytes.

We have investigated the localisation of endothelin-1 (ET-1) mRNA and ET-1-like immunoreactivity in retina and anterior portion of optic nerve from human and porcine eyes. In situ hybridisation method revealed expression of ET-1 mRNA mainly in the innermost layers of the retinas, in the retinal pigment epithelium cells as well as in the astrocytes of the optic nerve. Immunohistochemical studies showed that ET-1-like immunoreactivity appeared in the same regions where ET-1 mRNA was expressed as well as in the inner nuclear layer and in the inner segments of photoreceptors. In the nerve fibre and ganglion cell layers, astrocytes expressed both glial fibrillary acidic protein and ET-1 proteins suggesting that these cells may secrete ET-1. Expression of ETA and ETB receptors in human retina were demonstrated by reverse transcription-polymerase chain reaction. Our results demonstrated expression of ET-1 in glial, neural and vascular components of retina and optic nerve from human and porcine eyes.

Aged↗

Combining electron microscopic with x-ray crystallographic structures.

Analgorithm has been developed for placing three-dimensional atomic structures into appropriately scaled cryoelectron microscopy maps. The first stage in this process is to conduct a three-dimensional angular search in which the center of gravity of an X-ray crystallographically determined structure is placed on a selected position in the cryoelectron microscopy map. The quality of the fit is measured by the sum of the density at each atomic position. The second stage is to refine the three angles and three translational parameters for the best (usually 25 to 100) fits. Useful criteria for this refinement include the sum of densities at atomic sites, the lack of atoms in negative or low density, the absence of atomic clashes between symmetry-related positions of the atomic structure, and the distances between identifiable features in the map and their positions on the fitted atomic structure. These refinements generally lead to a convergence of the originally chosen, top scoring fits to just a few (about 3 to 8) acceptable possibilities. Usually, the best remaining fit is clearly superior to any of the others.

Cryoelectron Microscopy↗

Renal tubulointerstitial damage caused by persistent proteinuria is attenuated in AT1-deficient mice: role of endothelin-1.

Using angiotensin II (AngII) type 1A receptor-deficient mice [AT1(-/-)], in which we induced protein overload nephropathy, we explored the potential implication of AngII and endothelin-1 (ET-1) in the tubulointerstitial damage because of persistent proteinuria. At day 7, AT1(-/-) showed marked proteinuria to a similar extent to that of wild-type mice (WT). However, at day14, AT1(-/-) had significantly less proteinuria, renal damage, transforming growth factor-beta, and matrix mRNA expression and mortality. AT1(-/-) also showed a significant diminution in the activation of the transcriptional factors nuclear factor-kappaB and AP-1. Unexpectedly, AT1(-/-) had a higher interstitial infiltration than WT. The administration of the angiotensin-converting enzyme inhibitor quinapril to WT caused a marked improvement in proteinuria and renal lesions, resembling that seen in untreated AT1(-/-). However, the interstitial infiltration persisted in AT1(-/-) when treated with quinapril. Because ET-1 may participate in the recruitment of mononuclear cells, we also studied the implication of this peptide. AT1(-/-) had a significantly higher ET-1 expression in tubular epithelial cells than WT. The administration of the dual ETA/ETB antagonist bosentan to AT1(-/-) considerably reduced the interstitial infiltrates. Bosentan also exerted a beneficial effect on proteinuria, renal lesions, and mortality in WT. These data show that in overload nephropathy, proteinuria and renal lesions are, to a large extent, AngII-dependent. The up-regulation of ET-1 in tubular epithelial cells in AT1(-/-), associated with interstitial infiltrates, suggests that the combination of drugs interfering with both vasopeptides may be of therapeutic interest in renal diseases with severe proteinuria and tubulointerstitial damage.

Angiotensin-Converting Enzyme Inhibitors↗

Psychometric properties of a Spanish version of the McGill Pain Questionnaire in several Spanish-speaking countries.

OBJECTIVE: Versions of the McGill Pain Questionnaire are available in a several languages and are used in clinical studies and sociocultural or ethnic comparisons of pain issues. However, there is a lack of studies that compare the validity and reliability of the instrument in the countries where it is used. The current study investigates the psychometric properties of a Spanish version of the McGill Pain Questionnaire in five Spanish-speaking countries. DESIGN: The authors conducted a multicenter and transnational study with one investigator in each center. Patients were evaluated once with a Spanish version of the McGill Pain Questionnaire, a visual analog scale, and a verbal rating scale. SETTING: The study was performed in pain clinics and acute pain units of four Latin American countries (Argentina, Costa Rica, Mexico, and Panama) and Spain. PATIENTS: The study included 205 patients (84 with acute pain, 121 with chronic pain) from Latin America. Their data were compared with those of 282 Spanish patients. INTERVENTIONS: The McGill Pain Questionnaire, visual analog scale, and verbal rating scale were administered once to all patients. The McGill Pain Questionnaire was administered again to patients from Latin America countries to ascertain descriptor comprehension. OUTCOME MEASURES: Demographic data, McGill Pain Questionnaire parameters, and visual analog scale and a verbal rating scale scores were obtained from patients with chronic and acute pain. Psychometric properties of the Spanish version of the McGill Pain Questionnaire were established for each country by calculating the ordinal consistency by means of rank-scale correlation (Spearman test), intercategory correlation, and interparameter correlation (Pearson test). Concurrent validity was also calculated by comparing scores from the visual analog scale (Pearson test) and verbal rating scale (Spearman test) with questionnaire parameters (qualitative-to-quantitative comparisons). RESULTS: The Spanish version of the McGill Pain Questionnaire maintained a high internal validity when tested in different countries. Ordinal consistency, intercategory, interparameter, and qualitative-to-quantitative parameter correlations were similar in all countries. Few descriptors were considered to be inappropriate or difficult to understand. CONCLUSIONS: The psychometric properties of the Spanish version of the McGill Pain Questionnaire assessed in different Latin-American countries suggest that the questionnaire may be used to evaluate Spanish-speaking patients. The validity of this test should be extended with reliability studies to further establish its usefulness in the evaluation of pain.

Argentina↗

Changes in the density and localisation of endothelin receptors in the early stages of rat diabetic retinopathy and the effect of insulin treatment.

AIMS/HYPOTHESIS: The endothelin system (ET system) has been implicated in the retinal blood flow abnormalities that precede the onset of diabetic retinopathy. This study was undertaken to assess whether the density and localisation of both the immunoreactive endothelin-1 and endothelin receptors in rat retina change in the early stages of diabetes and the insulin treatment would affect those changes. METHODS: Untreated streptozotocin-diabetic, insulin-treated streptozotocin-diabetic and age-matched control rats were killed 15, 45 and 90 days after the induction of diabetes. Binding assays were used to determine the density and proportion of endothelin receptors in neural retinal membranes. Localisation of endothelin receptors and immunoreactive endothelin-1 were analysed by microautoradiography and immunohistochemistry, respectively. RESULTS: Fifteen days after the induction of diabetes, the neural retinal membranes of untreated streptozotocin-diabetic rats showed a statistically significant decrease in the density of both endothelin receptor subtypes when compared with age-matched control rats. At 90 days, however, the density of endothelin receptors type B was statistically significantly higher than that of control rats, and the innermost layers of the diabetic retina also showed an increase of both endothelin receptor type B receptor and immunoreactive endothelin-1 signal. Insulin treatment during 90 days up-regulated endothelin receptor type A in neural retinal membranes and in the innermost layers of the retina when compared with control retinas. CONCLUSION/INTERPRETATION: These results show that the endothelin system is altered in both vascular and neuronal components of the retina in early diabetic retinopathy. The up-regulation of endothelin receptor type A induced by insulin treatment suggests that insulin might be involved in retinal microangiopathy.

Animals↗

Type B and type C natriuretic peptide receptors modulate intraocular pressure in the rabbit eye.

We investigated (1) the in vivo functional significance of the type B (ANP(B)) and type C (ANP(C)) natriuretic peptide receptors in the rabbit eye by evaluating the effect of intracameral administration of C-type natriuretic peptide (CNP) and C-ANP-(4-23) on intraocular pressure, and (2) the action of CNP on guanylate cyclase activity in the rabbit ciliary process membranes. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were also studied for comparison. We demonstrated that the natriuretic peptides decrease intraocular pressure and stimulate guanylate cyclase activity, CNP being the most potent. The duration of the effect of C-ANP-(4-23) on intraocular pressure reduction was almost 9-fold that of the BNP and 20-fold that of ANP and CNP effect. This ligand increased threefold the immunoreactive natriuretic peptides levels in aqueous humour. Our data demonstrate the presence of functional ANP(A) and ANP(B) receptors in the rabbit eye and that the ANP(C) receptor modulates the concentration of the natriuretic peptides in the aqueous humour.

Animals↗

Higher proportions of type C than of types A and B natriuretic peptide receptors exist in the rat ciliary body.

We investigate the interaction of atrial natriuretic peptide (ANP) brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) with their receptors (NPRA, NPRB and NPRC), as well as the proportion and localization of those receptors in the rat ciliary body. Binding assays and affinity cross-linking experiments demonstrated the presence of the NPRC receptor type. However, the three natriuretic peptides stimulate the guanylate cyclase activity in the ciliary body membranes suggesting the presence of the NPRA and NPRB receptor type. Microautoradiographic data show that the NPRs are localized in the whole ciliary body. Our results indicated that NPRC is the most prominent receptor type in this tissue.

Animals↗

Endothelial apoptosis in Braf-deficient mice.

Tyrosine kinase growth factor receptors and Ras/Raf/MEK/MAPK signalling have been implicated in the suppression as well as augmentation of programmed cell death. In addition, a Ras-independent role for Raf as a suppressor of programmed cell death has been suggested by the recent finding that Craf1 interacts with members of the Bcl-2 family at mitochondrial membranes. However, genetic studies of C. elegans and Drosophila, as well as the targeted mutagenesis of the murine Araf gene, have failed to support such a role. Here we show that mice with a targeted disruption in the Braf gene die of vascular defects during mid-gestation. Braf -/- embryos, unlike Araf -/- or Craf1 -/- embryos (L.W. et al., unpublished), show an increased number of endothelial precursor cells, dramatically enlarged blood vessels and apoptotic death of differentiated endothelial cells. These results establish Braf as a critical signalling factor in the formation of the vascular system and provide the first genetic evidence for an essential role of Raf gene in the regulation of programmed cell death.

Animals↗

Beta-thalassaemia in south-western Spain: high frequency of G-->A (IVS I-1) mutation.

Huelva province is situated in southwestern Spain; its historic and geographic characteristics contribute to the existence of erythrocyte genetic anomalies, such as beta thalassaemia. We have carried out a prenatal study of microcytosis, with a preliminary beta-gene analysis. Our findings show a beta-thalassaemia trait prevalence of 0.81%. In the molecular research there was a high frequency of G-->A (IVS I-1) injury: 55%. By comparing the rates of this mutation neighbouring Cáceres province in western Spain (47%) and Algarve in south Portugal (32%), it demonstrates that this beta-gene defect has a high frequency in the southwest of the Iberian Peninsula.

Child↗

3pK, a new mitogen-activated protein kinase-activated protein kinase located in the small cell lung cancer tumor suppressor gene region.

NotI linking clones, localized to the human chromosome 3p21.3 region and homozygously deleted in small cell lung cancer cell lines NCI-H740 and NCI-H1450, were used to search for a putative tumor suppressor gene(s). One of these clones, NL1G210, detected a 2.5-kb mRNA in all examined human tissues, expression being especially high in the heart and skeletal muscle. Two overlapping cDNA clones containing the entire open reading frame were isolated from a human heart cDNA library and fully characterized. Computer analysis and a search of the GenBank database to reveal high sequence identity of the product of this gene to serine-threonine kinases, especially to mitogen-activated protein kinase-activated protein kinase 2, a recently described substrate of mitogen-activated kinases. Sequence identitiy was 72% at the nucleotide level and 75% at the amino acid level, strongly suggesting that this protein is a serine-threonine kinase. Here we demonstrate that the new gene, referred to as 3pK (for chromosome 3p kinase), in fact encodes a mitogen-activated protein kinase-regulated protein serine-threonine kinase with a novel substrate specificity.

Amino Acid Sequence↗

Safety, immunogenicity and protective effect of the SPf66 malaria synthetic vaccine against Plasmodium falciparum infection in a randomized double-blind placebo-controlled field trial in an endemic area of Ecuador.

A total of 537 subjects were randomized to receive either SPf66 malaria vaccine against Plasmodium falciparum or placebo in three doses (days 0, 30 and 180). Subjects completing the course of vaccination (230 in the vaccine and 238 in the placebo group) were followed up for a further 12 months. Case detection surveillance was implemented by parasitological cross-sectional surveys every 2 months and by monthly household visits to each participant. Symptomatic subjects were also diagnosed in a local health centre. Minor local side-effects were observed mainly after the second dose in about 19% of the vaccinated subjects and in 3.7% of the placebo group. Thirty days after the third dose the prevalence of anti-SPf66 antibodies was 57% in the vaccine and 8.8% in the placebo groups. The prevaccination prevalence of antibodies measured by indirect immunofluorescence assay increased with age and seemed to be inversely related to anti-SPf66 antibody production. Immune response to SPf66 was independent of age. Vaccine efficacy was calculated based on person-time of exposure. The protective effect considering any malaria episode was 66.8% (95% confidence interval = -2.7-89.3%) and considering only one episode per individual was 60.2% (95% confidence interval = -26-87.5%).

Adolescent↗