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Biomedical subjects

P Ferrer

Publications and source records attributed to P Ferrer.

At least 37 records · Page 2Linked to original sources

Role of nitric oxide on papillary blood flow and pressure natriuresis.

This study examined whether nitric oxide synthesis blockade or potentiation (with N omega-nitro-L-arginine methyl ester [L-NAME] or N-acetylcysteine, respectively) can shift the relations between sodium excretion, papillary blood flow, and renal perfusion pressure. Papillary blood flow was measured by laser Doppler flowmetry. A low dose of L-NAME (3.7 nmol/kg per minute) reduced papillary blood flow only at high arterial pressure (140 mm Hg), but it had no effect on pressure natriuresis. Infusion of 37 nmol/kg per minute L-NAME reduced cortical blood flow by 9% at all perfusion pressures studied, lowered papillary blood flow by 8% and 19% at 120 and 140 mm Hg, respectively, and blunted the pressure-natriuresis response. The administration of 185 nmol/kg per minute L-NAME reduced cortical blood flow by 30% and decreased papillary blood flow by 25% in the range of 100 to 140 mm Hg of arterial pressure. Blockade of nitric oxide synthesis with L-NAME at all doses studied reduced papillary blood flow only at high renal perfusion pressures, but papillary blood flow remained essentially unchanged at low perfusion pressures, thus restoring papillary blood flow autoregulation. N-Acetyl-cysteine (1.8 mmol/kg) increased papillary blood flow by 9% and shifted the relations between papillary blood flow, sodium excretion, and renal perfusion pressure toward lower pressures. This effect of N-acetylcysteine on papillary blood flow was blocked by subsequent L-NAME administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗

Reduced contractile function after balloon denudation of rat carotid arteries.

In rat carotid arteries isolated 2 weeks after balloon denudation, a significant neointima developed with little change in medial size. Associated with this neointimal hyperplasia was a marked decrease in contraction to various agents including angiotensins I and II, big endothelin-1, endothelin-1, norepinephrine, phenylephrine, and serotonin. Vasodilator responses to acetylcholine were significantly reduced. In contrast, vasodilator responses to nitroglycerin were unaffected. It is suggested that modulation of the neointimal cells to a more non-contractile phenotype may be responsible for the loss in contractile ability.

Acetylcholine↗

Interspecific comparison of Drosophila serendipity delta and beta: multimodular structure of these C2H2 zinc finger proteins.

The Drosophila serendipity (sry) beta and delta genes, which resulted from a gene duplication event, provide an interesting model for the evolutionary diversification in structure and function of C2H2 zinc finger proteins. We examined here the divergence of the sry beta and delta proteins over an estimated period of 45 million years by comparing their predicted sequences in D. melanogaster, D. pseudoobscura, and D. subobscura. Between orthologs, i.e., pairs of either sry beta or sry delta, the NH2-proximal region delineated by pairs of C-X2-C motifs and the DNA-binding finger domain are highly conserved. Sequence conservation operates over the entire finger domain, including the links separating adjacent fingers, even though each has a unique sequence different from the widespread TGEKP motif. In contrast, the sequence of the central acidic region has extensively diverged and differs between species in the number of amino acids, probably because of slippage-driven mutations. The NH2-terminal region and fingers 1, 5, and 6 differentiate the sry beta and delta proteins while zinc fingers 2, 3, and 4 are virtually identical in these two paralogs. A nuclear localization signal of the SV40T antigen type, preceded by a potential CKII phosphorylation regulatory site, is conserved in sry delta but not found in sry beta. The interspecific conserved regions correlate well with the positions of zygotic lethal mutations in the D. melanogaster sry delta protein. Furthermore, P-element transformation experiments show that a transgenic copy of the D. pseudoobscura sry delta gene rescues the sry delta mutant phenotype. Convergence of genetic and structural data on the sry proteins supports a multimodular function and mode of evolution of these C2H2 finger proteins.

Amino Acid Sequence↗

Regulation of water balance between blood and lymph in the frog, Rana pipiens.

To determine the relative importance of the lymphatic system and transcapillary reabsorption in maintaining water distribution between blood and lymph in Rana pipiens, the hematocrit (HCT) was measured (12 frogs) when each frog was: 1) under tricaine methanesulfonate (MS222) anesthesia, which inactivates the lymph hearts, 2) conscious at rest (control), and 3) conscious after activity. Arterial pressure (AP), lymph-heart rate (LHR), and plasma and lymph protein concentrations and colloid osmotic pressures (COP) were also measured. The average HCT during control state was 26.0 +/- 5.2% (SD), AP was 21.9 +/- 5.2 mmHg, and LHR was 86 +/- 13 bpm. MS222 increased HCT (42.6 +/- 7.9%), and did not affect AP. Experiments, in which plasma volumes were determined by intra-arterial injection of Evans blue-labeled albumin (EB-BSA) (16 frogs), showed that the increased HCT reflected a reduced plasma volume. Activity did not affect HCT, but increased AP (33.1 +/- 6.4 mmHg, p < 0.01), and LHR (115 +/- 26 bpm, p < 0.01). Thus lymph hearts are largely responsible for maintaining blood volume, and changes in transcapillary filtration rate are rapidly mirrored by changes in lymph heart function. Plasma and lymph COP values after MS222 or activity were not significantly different from control. This observation is consistent with the protein and fluid fluxes resulting from Starling forces if an average reflection coefficient to protein, sigma, of 0.5 is assumed, which is consistent with our EB-BSA data.

Animals↗

Changes in depressive status associated with topical beta-blockers.

Depression and sexual dysfunction have been related to side effects of topical beta-blockers. We performed a preliminary study in order to determine any difference between a non selective beta-blocker (timolol) and a selective beta-blocker (betaxolol) regarding CNS side effects. Eight glaucomatous patients chronically treated with timolol 0.5%/12h, suffering from depression diagnosed through DMS-III-R criteria, were included in the study. During the six-month follow up, depression was quantified through the Beck and Zung-Conde scales every two months. In a double blind cross-over study with control group, the patients under timolol treatment presented higher depression values measured through the Beck and the Zung-Conde scales (p < 0.001 vs control). These results suggest that betaxolol could be less of a depression-inducer than timolol in predisposed patients.

Adult↗

Single amino acid exchanges in separate domains of the Drosophila serendipity delta zinc finger protein cause embryonic and sex biased lethality.

The Drosophila serendipity (sry) delta (delta) zinc finger protein is a sequence-specific DNA binding protein, maternally inherited by the embryo and present in nuclei of transcriptionally active cells throughout fly development. We report here the isolation and characterization of four ethyl methanesulfate-induced zygotic lethal mutations of different strengths in the sry delta gene. For the stronger allele, all of the lethality occurs during late embryogenesis or the first larval instar. In the cases of the three weaker alleles, most of the lethality occurs during pupation; moreover, those adult escapers that emerge are sterile males lacking partially or completely in spermatozoa bundles. Genetic analysis of sry delta thus indicates that it is an essential gene, whose continued expression throughout the life cycle, notably during embryogenesis and pupal stage, is required for viability. Phenotypic analysis of sry delta hemizygote escaper males further suggests that sry delta may be involved in regulation of two different sets of genes: genes required for viability and genes involved in gonadal development. All four sry delta alleles are fully rescued by a wild-type copy of sry delta, but not by an additional copy of the sry beta gene, reinforcing the view that, although structurally related, these two genes exert distinct functions. Molecular characterization of the four sry delta mutations revealed that these mutations correspond to single amino acid replacements in the sry delta protein. Three of these replacements map to the same (third out of seven) zinc finger in the carboxy-terminal DNA binding domain; interestingly, none affects the zinc finger consensus residues. The fourth mutation is located in the NH2-proximal part of the protein, in a domain proposed to be involved in specific protein-protein interactions.

Alleles↗

Molecular cloning of Xenopus fibrillarin, a conserved U3 small nuclear ribonucleoprotein recognized by antisera from humans with autoimmune disease.

Autoantibodies against U3 small nuclear ribonucleoprotein are associated with scleroderma autoimmune disease. They were shown to react with fibrillarin, a 34- to 36-kilodalton protein that has been detected in all eukaryotes tested from humans to yeasts. We isolated a 1.6-kilobase cDNA encoding fibrillarin from a Xenopus laevis cDNA library. The protein contains a 79-residue-long Gly-Arg-rich domain in its N-terminal region and a putative RNA-binding domain with ribonucleoprotein consensus sequence in its central portion. This is the first report of cloning of fibrillarin, and the deduced protein sequence is in agreement with the involvement of the protein in a ribonucleoprotein particle.

Amino Acid Sequence↗

Effects of captopril on atherosclerosis in cynomolgus monkeys.

A study was performed to investigate if oral dosing of captopril could influence the development of atherosclerosis in cholesterol-fed cynomolgus monkeys. Twenty-four monkeys were divided into four groups: (a) a control group given a normal monkey diet and placebo medication; (b) a high cholesterol group given a high cholesterol diet and placebo medication; (c) a low-dose captopril group given the cholesterol diet and 25 mg/kg of captopril twice daily; and (d) a high-dose captopril group given the cholesterol diet and 50 mg/kg of captopril twice daily. The doses of captopril used in this study did not change the levels of total serum cholesterol, high-density lipoprotein (HDL), or triglycerides. The total cholesterol/HDL ratio was also unaffected by captopril. The animals were killed after 6 months of treatment. The progression of atherosclerosis was assessed by gross pathology, histopathology, and biochemical methods. The results showed a significantly reduced progression of arterial lesions in monkeys given captopril; the effects of captopril were most evident in the coronary arteries, which were practically free from atherosclerosis in captopril-treated animals.

Animals↗

The maternal-infant center in the control of hepatitis B.

A seroepidemiologic survey of HBV infection was carried out in four population groups served by the Maternity Hospital of Majorca, an island in the Mediterranean. The prevalence of HBV markers (HBsAg, anti-HBs, anti-HBc), determined by enzyme-immunoassay, reached 17.2% among 864 parturients, 17.2% in 783 hospital personnel, 2.7% and 19.2% among the 186 children and 73 husbands of parturients with no HBV markers, 22.8% and 43.8%, respectively, among the 44 children and 48 husbands of HBsAg chronic carrier parturients. The prevalences of HBsAg in the same groups reached 0.9%, 1.5%, 0% and 0%, 11.4% and 2.1%, respectively. The carrier state represents 50% of all infection cases among children and 4.8% among husbands of carrier women. The prevalence of markers, which was especially high among personnel working in maintenance services (39.1%), on surgical wards (35.3%), among midwives (27.6%) and in cleaning and laundry services (27.1%), and laboratories (21.4%), is used as an indicator in defining priorities for the vaccination of people at risk. Sixty-seven newborn babies of HBsAg carrier mothers were administered one dose of HBIG and three doses of hepatitis B vaccine; at 12 months of age, the seroconversion rate was 98.5%, whereas 1 child (1.5%) became a chronic carrier. Maternity hospitals represent the ideal centers in which to carry out the detection of HBsAg in pregnant women prior to parturition, to ensure that all newborns of chronic carrier women receive passive-active immunization, and to screen their family contacts and vaccinate those who are found susceptible to the infection.

Adult↗

A U3 RNA pseudogene in mouse: sequence and organization in genomic DNA.

A mouse U3 RNA pseudogene has been identified; it corresponds to a U3B full length coding sequence with a 3'-oligo(A) tail, precisely flanked at both ends by a pair of 15 bp direct repeats. These structural features suggest that it has arisen through an RNA-mediated mechanism involving an insertion at staggered nicks in the genome. Sequence data indicate that this mouse specimen has been generated by a different event as compared to the recently described rat pseudogenes. It represents the first reported case, for a pseudogene of this class, to be present at more than one copy per genome.

Animals↗

Widened E point septal separation in a normal pediatric population.

To determine the age and gender distribution of the E point septal separation (EPSS), M-mode echocardiograms were obtained from 121 normal subjects aged four months to 82 years. A small but consistent age factor was found. In subjects less than age 20, EPSS was 3.0 +/- 2.6 mm, whereas in those greater than 20 years, EPSS was 1.4 +/- 1.8 (p less than .001). In females EPSS did not vary appreciably at different ages. By contrast, in males EPSS increased with age, peaking between ages 15 and 19 and then decreasing. Between ages 10 and 19, EPSS was significantly wide in males than in females. Thus, EPSS is wide in male adolescents than in adults. The cause for this phenomenon is unclear, but judging from its age and gender distribution, it may be related to the effect of androgens on the myocardium.

Adolescent↗

Hemodynamics and intracardiac conduction after operative repair of tetralogy of Fallot.

Electrophysiologic studies were performed in 47 children aged 3 to 18 years, 15 of whom had cardiac arrhythmias 1 to 15 years after repair of tetralogy of Fallot. Six exhibited sinus or atrioventricular nodal dysfunction, 8 had ventricular extrasystoles, and 1 had supraventricular tachycardia. Hemodynamic and electrophysiologic data were obtained at postoperative catheterization. Although electrophysiologic responses were abnormal in a proportion of both the children with and those without arrhythmia, hemodynamic values were similar. Three of 6 children with impaired sinus impulse generation or atrioventricular nodal conduction had a prolonged A-H interval, and in 3 Wenckebach heart block developed at low pacing rates. Ventricular ectopic rhythm was not associated with any particular abnormality of basic intracardiac conduction intervals. Thus, arrhythmias and conduction abnormalities are not consistently related to residual right ventricular hypertension. Abnormalities in electrophysiologic function are common after repair of tetralogy of Fallot in patients with sinus rhythm and may have prognostic implications for these patients.

Adolescent↗

Takayasu's arteritis associated with glomerulonephritis. A case report.

Takayasu's disease is a nonspecific arteritis of unknown cause with predilection for the aortic arch and its branches; approximately 20% of those affected are children or adolescents, predominantly females. The purpose of this article is to report the case of a young girl in which the mode of presentation was microscopic hematuria and proteinuria. Subsequently, aortic valvular insufficiency developed and there was evidence of aortitis in the thoracic and abdominal aorta, as well as in the arch. All functional and anatomical cardiac derangements were documented by ultrasound and angiocardiography. Renal biopsies showed progressive glomerular involvement characterized by focal and segmental glomerulonephritis. It is postulated that a common immunologic mechanism was responsible for the aortic and glomerular lesions.

Adolescent↗

Atrioventricular reciprocal rhythm and chronic reciprocating tachycardia in a newborn infant with concealed Wolff-Parkinson-White syndrome.

A case of atrioventricular reciprocal rhythm and chronic reciprocating tachycardia in a newborn infant is presented. Electrophysiological studies suggest that these rhythm disturbances are related to the presence of a right-sided atrioventricular accessory pathway capable only of retrograde conduction (concealed Wolff-Parkinson-White syndrome). The technique of recording the sequence of atrial activation during the tachycardia is described and its clinical importance emphasised.

Cardiac Catheterization↗