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Biomedical subjects

R Bernal

Publications and source records attributed to R Bernal.

At least 19 recordsLinked to original sources
PubMed2002

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1994

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↗
PubMed1989

Ivermectin for human strongyloidiasis and other intestinal helminths.

Since ivermectin, a mixture of 2 closely related macrocyclic lactones, has proven highly effective against animal intestinal nematodes, trials were undertaken to determine its efficacy against human intestinal nematodes. We tested 110 patients with strongyloidiasis and 90 with enterobiasis; many had other intercurrent intestinal nematode infections. Stool examinations were done before and after patients were given a single dose of oral ivermectin capsules (50, 100, 150, or 200 micrograms/kg body wt); 55 recipients of 100 or 200 micrograms/kg doses received a second identical dose the next day. Kato and saline smears, ethyl acetate concentration, modified Baermann's technique, and Harada-Mori cultures were repeated; cure was defined as complete absence of eggs and/or larvae from stools tested 30 days after dosing. Ivermectin was well tolerated. Overall cure rates at all doses 30 days after therapy averaged 88% for strongyloidiasis, 100% for ascariasis, 85% for trichuriasis, and 85% for enterobiasis. Ancylostoma duodenale and Necator americanus were little affected.

Adolescent↗
PubMed1987

The antihypertensive effect of lisinopril compared to atenolol in patients with mild to moderate hypertension.

In a multicenter, parallel, double-blind study, lisinopril was compared with atenolol in the treatment of mild to moderate essential hypertension. Four hundred ninety patients were randomized to a once-a-day treatment with lisinopril 20 mg or atenolol 50 mg for 4 weeks, and the doses of lisinopril or atenolol were increased up to 80 mg or 200 mg, respectively, at 4-week intervals if sitting diastolic blood pressure (SDBP) was not well controlled. Hydrochlorothiazide (HCTZ) 12.5 or 25 mg was added after 12 weeks, if necessary, and titrated upward after 4 weeks to a maximum dose of 25 or 50 mg/day. Lisinopril and atenolol reduced SDBP to a similar extent. All reductions from baseline in sitting diastolic and systolic blood pressure were significant (less than 0.01). Lisinopril produced a significant (less than 0.01) greater reduction in sitting systolic blood pressure (SSBP) than atenolol. Addition of HCTZ caused further blood pressure reductions (p less than 0.01). Five patients (1.7%) on lisinopril and four (2.0%) on atenolol developed skin rashes during weeks 1-12. Two patients (0.7%) on lisinopril 80 mg developed proteinuria (greater than 1 g/day). Cough occurred more often with lisinopril (4.5%), and elevated triglycerides occurred more often with atenolol (2.0%).

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1982

A possible hepatic factor in the control of plasma free fatty acid levels.

Insulin acts as a regulator of lipid metabolism by inhibiting the rate of lipolysis. Hyperinsulinemia, produced by the peripheral infusion of glucose, therefore, causes a lowering of plasma free fatty acids (FFA) by decreasing the mobilization of fats from peripheral deposits. Based on previous studies, it was postulated that a lowering of plasma FFA could be produced, in the absence of hyperinsulinemia, by the infusion of glucose directly into the liver. This study was undertaken to investigate the existence of endogenous factors other than insulin, which inhibit lipolysis. It was determined that glucose at a dosage of 0.125 gm/kg/hr could be infused into the portal vein of dogs without increasing plasma insulin levels. This dosage significantly lowered plasma FFA levels when injected into the portal vein but had no effect on plasma FFA when infused peripherally. There were significant decreases in FFA turnover following portal glucose administration, with no changes in fractional turnover. This indicated that the lowered plasma FFA concentrations found following portal infusions of glucose, were due to reduced lipid mobilization from adipose tissue, rather than increased tissue uptake of FFA. These results suggested the existence of an hepatic factor, stimulated by portal glucose infusion, which lowered FFA mobilization from adipose tissue.

Animals↗
PubMed1976

Continuous negative chest-wall pressure. Successful use for severe respiratory distress in an adult.

Continuous negative pressure (CNP) around the chest-wall and lower parts of the body was used to treat progressively alveolar disease. Therapy with CNP produced a substantial increase in arterial oxygen tension that was sustained and permitted a decrease in oxygen requirements to 40% within 24 hours. There were concomitant decreases in intrapulmonary right-to-left shunt and respiratory frequency. During CNP therapy, no adverse effects on heart rate or blood pressure were detected.

Adult↗