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Biomedical subjects

S Prieto

Publications and source records attributed to S Prieto.

At least 19 recordsLinked to original sources

Rubella and measles seroprevalence among women of childbearing age, Argentina, 2002.

To assess rubella and measles susceptibility among women of childbearing age we conducted a cross-sectional seroprevalence study in four cities and one rural area in Argentina. A convenience sample of women aged 15-49 years seeking care in public health-care institutions was selected (n=2804). Serum specimens were tested for rubella and measles IgG antibody titres. The overall susceptibility to rubella and measles was 8.8 and 12.5% respectively. Seroprevalence differences were found for both rubella (P<0.001) and measles (P=0.002) across sites. Rubella seroprevalence was higher in women aged >or=40 years than in younger women (P=0.04). Measles seroprevalence tended to increase with age (P<0.001). Approximately 15% of women aged 15-29 years were not immune to measles. No risk factors were associated with rubella seronegativity; however, age (P<0.001) and having less than four pregnancies (P<0.001) were factors associated with measles seronegativity. Our findings support the introduction of supplemental immunization activities targeting adolescents and young adults to prevent congenital rubella syndrome and measles outbreaks over time.

Adolescent↗

Efficacy of amoxicillin-sulbactam, given twice-a-day, for the treatment of community-acquired pneumonia: a clinical trial based on a pharmacodynamic model.

The present multicenter study reports the results of a clinical trial, designed on the basis of a pharmacodynamic study published previously (Bantar et al., J. Chemother 2000; 12: 223-227) to assess the efficacy of amoxicillin/sulbactam (875 mg/125 mg), given orally twice-a-day for 7 days in the treatment of patients with community-acquired pneumonia (CAP). Eighty-four evaluable subjects older than 19 years with clinical symptoms and features suggestive of CAP, consulting from June 2000 to March 2002 and meeting the PORT risk class I through III, were enrolled in the study. Mean age (y +/- standard deviation) was 46.7 +/- 16.3 and 62% of the patients had some co-morbidity predisposing for CAP. Several individuals (77.4%) fell into a low-risk class (i.e. PORT I or II) and 22.6% of patients belonged to a moderate-risk class at the start of treatment. Six patients (6.45%) had pneumococcal bacteremia. Streptococcus pneumoniae was the organism most frequently isolated (61.9% of all the patients in whom an etiologic diagnosis was made), followed by Haemophilus influenzae. Clinical success was observed in 97.6% of the patients (confidence interval 95%, 94.3%-100%). Almost all the individuals with clinical success became afebrile within the first 3 days of therapy. Ten patients (11.8%) reported mild or moderate adverse events (especially diarrhea) possibly related to the antimicrobial therapy, but this did not lead to withdrawal from the trial. The results of this study suggest that amoxicillin/sulbactam (875 mg/125 mg) is an efficacious and well tolerated option for treating patients with CAP belonging to a low-moderate risk class and support the use of a short, oral (7-day) b.i.d. regimen.

Administration, Oral↗

Human caliciviruses are a significant pathogen of acute sporadic diarrhea in children of Santiago, Chile.

Human caliciviruses (HuCVs) are increasingly recognized as common pathogens that cause acute sporadic diarrhea in children; however, regional antigenic and genetic diversity complicate detection techniques. Stool samples from children seeking medical attention in 2 outpatient clinics, a large emergency department, and 2 hospital wards were evaluated for HuCVs by reverse transcription-polymerase chain reaction, using primers based on a conserved sequence of the polymerase region of a previously sequenced Chilean strain. HuCVs were detected in 53 (8%) of 684 children 1 month to 5 years of age (mean, 13 months). Detection occurred year-round without a clear seasonal peak, and detection frequency declined from 16% in 1997 to 2% in 1999. The decline may have been due to a change in virus genotype. HuCVs are a significant pathogen of acute sporadic diarrhea in Chilean children, and continuous characterization of genetic diversity will be crucial for appropriate detection.

Acute Disease↗

Glucose-regulated turnover of mRNA and the influence of poly(A) tail length on half-life.

Glucose repression in Saccharomyces cerevisiae can now be seen to operate at two levels: regulation of transcription of certain genes and control of the half-life of the corresponding mRNAs (Scheffler, I. E., de la Cruz, B. J., and Prieto, S. (1998) Int. J. Biochem Cell Biol. 30, 1175-1193). For example, the steady state levels of SDH2 mRNA and SUC2 mRNA are significantly determined by their differential rates of turnover. A current model for the mechanism of mRNA turnover includes three distinct steps: a rate-limiting deadenylation, removal of the 5'-7-methyl-G (decapping), and 5'-3' exonuclease digestion. We have investigated the same three reactions during glucose-induced degradation of these transcripts. Our results indicate that while decapping (by Dcp1p) and 5'-3' exonuclease digestion (by Xrn1p) are obligatory steps for the rapid degradation of these mRNAs, the dependence on deadenylation is more complicated. At steady state in glycerol these transcripts have very short poly(A) tails but are nevertheless very stable; the addition of glucose causes immediate decapping and degradation without further deadenylation; in contrast, newly made SUC2 mRNA (after a shift from glucose to glycerol) has significantly longer poly(A) tails, and such transcripts are not rapidly degraded upon addition of glucose. A constitutive deadenylation reaction that is independent of the carbon source eventually makes the stability of these transcripts very sensitive to glucose. These results are interpreted in terms of a working hypothesis proposing a competition between translational initiation and decapping influenced by the carbon source. The presence of a long poly(A) tail may also affect this competition in favor of translational initiation and mRNA stabilization.

Base Sequence↗

Transmission of Pneumocystis carinii DNA from a patient with P. carinii pneumonia to immunocompetent contact health care workers.

The transmission of Pneumocystis carinii from person to person was studied by detecting P. carinii-specific DNA in prospectively obtained noninvasive deep-nasal-swab samples from a child with a documented P. carinii pneumonia (PCP), his mother, two contact health care workers, and 30 hospital staff members who did not enter the patient's room (controls). Nested-DNA amplification was done by using oligonucleotide primers designed for the gene encoding the mitochondrial large subunit rRNA of rat P. carinii (P. carinii f. sp. carinii) that amplifies all forms of P. carinii and internal primers specific for human P. carinii (f. sp. hominis). P. carinii f. sp. hominis DNA was detected in samples from the patient and all of his contacts versus none of the 30 hospital staff members. The results, as previously shown in murine models of P. carinii pneumonia, document that person-to-person transmission of P. carinii is possible. This observation suggests that immunocompromised patients not on PCP prophylaxis should not enter the room of a patient with PCP, and it also raises the question as to whether healthy contacts can transmit the disease to immunocompromised patients at risk.

Adult↗

Genotypic survey of recent beta-lactam-resistant pneumococcal nasopharyngeal isolates from asymptomatic children in Chile.

To assess pneumococcal strain variability among young asymptomatic carriers in Chile, we used serotyping, antibiotic susceptibility testing, and genotyping to analyze 68 multidrug-resistant pneumococcal isolates recovered from 54 asymptomatic children 6 to 48 months of age. The isolates represented capsular serotypes 19F (43 isolates), 14 (14 isolates), 23F (7 isolates), 6B (3 isolates), and 6A (1 isolate). Genotypic analysis, which included pulsed-field gel electrophoresis (PFGE) of chromosomal digests, penicillin binding protein (PBP) gene fingerprinting, and dhf gene fingerprinting, revealed that the isolates represented six different genetic lineages. Clear circumstantial evidence of capsular switching was seen within each of four of the genetically related sets. The majority of the isolates, consisting of the 43 19F isolates and 2 type 6B isolates, appeared to represent a genetically highly related set distinct from previously characterized pneumococcal strains. Each of three other genetically defined lineages was closely related to one of the previously characterized clones Spain(6B)-2, France(9V)-3, or Spain(23F)-1. A fifth lineage was comprised of four type 23F isolates that, by the techniques used for this study, were genetically indistinguishable from three recent type 19F sterile-site isolates from the United States. Finally, a sixth lineage was represented by a single type 23F isolate which had a unique PFGE type and unique PBP and dhf gene fingerprints.

Base Sequence↗

Control of mRNA turnover as a mechanism of glucose repression in Saccharomyces cerevisiae.

The phenomenon of glucose repression in yeast is concerned with the repression of a large number of genes when glucose is an abundant carbon source and almost all of the energy requirements of the cell can be satisfied from glycolysis. Prominent among the repressed genes are those encoding mitochondrial proteins required for respiration and oxidative phosphorylation. Past studies have characterized a pathway by which a signal generated from extracellular glucose is transmitted to the nucleus. The ultimate outcome is the repression of transcription of numerous genes, but also the induction of a limited number of others. The emphasis has been almost exclusively on transcriptional control mechanisms. A discovery made originally with the transcript of the SDH2 gene prompted an investigation of post-transcriptional mechanisms, and more specifically a study of the turnover rate of this mRNA in the absence and presence of glucose. SDH2 mRNA has a very short half-life in medium with glucose (YPD) and a significantly longer half-life in medium with glycerol (YPG). Experimental evidence and recent progress in understanding of (1) mRNA turnover in yeast and (2) initiation of translation on the 5' untranslated region of mRNAs, lead to a working hypothesis with the following major features: the carbon source, via a signaling pathway involving kinase/phosphatase activities, controls the rate of initiation, and thus influences a competition between eukaryotic initiation factors (prominently eIF4E, eIF4G, eIF3) binding to the capped mRNA and a decapping activity (DCP1) which is one of the rate limiting activities in the turnover of such mRNAs.

Carbohydrate Dehydrogenases↗

[Cervical radiculopathy as a form of presentation of non-Hodgkin's lymphoma].

INTRODUCTION: Neurological involvement in no-Hodgkin lymphoma is usually a serious problem leading to subacute compression of the spinal cord secondary to invasion of the spinal extradural space. This condition may be the presenting form of the illness, although relatively infrequently. Onset with involvement of the cauda equina or as an isolated radiculopathy is even rarer and has mainly been described at lumbar level. CLINICAL CASE: We present the case of a 27 year old man with no significant previous clinical history who had progressive, insidious onset of moderate-serious senso-motor radiculopathy at C8. On MR there was an infiltrating mass affecting the nerve root and reaching the spinal extradural space. Following decompression laminectomy the patient's leg recovered and on histology there was a large cell B lymphoma. The other complementary tests showed disseminated disease, although analysis of the cerebro-spinal fluid (including cytology) was normal. HIV seriology was also normal. CONCLUSION: Although isolated nerve root involvement is unusual in the presentation of lymphoma it should be considered to be part of the differential diagnosis of nerve root syndromes in young patients with no history of trauma or degenerative lesions.

Adult↗

Calcitonin, etidronate, and calcidiol treatment in bone loss after cardiac transplantation.

Cardiac transplantation is associated with severe bone loss caused by glucocorticoids, immunosuppressive treatment, and other factors. Treatment protocols for the prevention of bone loss is being studied. Forty patients who underwent cardiac transplantation were randomly given calcitonin (n = 13; 100 UI/d, nasal route), etidronate (n = 14; cyclical treatment 400 mg p.o./d/2 weeks/3 months), or calcidiol (n = 13; 32,000 IU/weekly) therapy for at least 18 months. Serum parameters (Ca, P, alkaline phosphatase, osteocalcin, intact PTH), urinary calcium, and vertebral mineral density (VMD; L2-L4, DXA Hologic QDR 1000) were measured immediately before treatment and after 6, 12, and 18 months of therapy after cardiac transplantation. Patients with cardiac transplantation had a VMD significantly lower than age and sex-matched Spanish controls. Prevalence of osteoporosis (Z-score below -2 SD) was 30%. Osteocalcin levels increased at 6, 12, and 18 months of treatment in the three groups. After 18 months of treatment, VMD increased significantly in the calcidiol 4.9%, vs. -1.19% and -0.19% in the calcitonin and etidronate groups, respectively. A lower incidence of fracture was found in patients treated with calcidiol during the study. In summary, we have found in this open randomized study that calcidiol was the most effective drug in the prevention and treatment of bone loss in patients after cardiac transplantation.

Alkaline Phosphatase↗

The nature and regulation of the ATP-induced anion permeability in Saccharomyces cerevisiae mitochondria.

ATP lowers the efficiency of oxidative phosphorylation in Saccharomyces cerevisiae mitochondria by a mechanism that involves the activation of cytochrome c oxidase and the increase in anion permeability of the mitochondrial inner membrane (S. Prieto, F. Bouillaud, and E. Rial (1995) Biochem. J. 307, 657-661). In this study, we have carried out experiments to determine the transport specificity of the ATP-induced permeability pathway and its regulation. The pathway allows permeation of anions such as Cl- or Br- , while NO3-, N02-, or Tes are not transported. Transport is activated by ATP, GTP, dATP, dGTP, and GDP, while ADP, AMP, GMP, and pyrimidine nucleotides are ineffective. Analysis of transport inhibition by ADP and phosphate suggests that ADP is a competitive inhibitor of ATP while phosphate inhibition is noncompetitive. These effectors are operative in the physiological range of concentrations.

Adenosine Diphosphate↗

Evidence for a selective and electroneutral K+/H(+)-exchange in Saccharomyces cerevisiae using plasma membrane vesicles.

The existence of a K+/H+ transport system in plasma membrane vesicles from Saccharomyces cerevisiae is demonstrated using fluorimetric monitoring of proton fluxes across vesicles (ACMA fluorescence quenching). Plasma membrane vesicles used for this study were obtained by a purification/reconstitution protocol based on differential and discontinuous sucrose gradient centrifugations followed by an octylglucoside dilution/gel filtration procedure. This method produces a high percentage of tightly-sealed inside-out plasma membrane vesicles. In these vesicles, the K+/H+ transport system, which is able to catalyse both K+ influx and efflux, is mainly driven by the K+ transmembrane gradient and can function even if the plasma membrane H(+)-ATPase is not active. Using the anionic oxonol VI and the cationic DISC2(5) probes, it was shown that a membrane potential is not created during K+ fluxes. Such a dye response argues for the presence of a K+/H+ exchange system in S. cerevisiae plasma membrane and established the non-electrogenic character of the transport. The maximal rate of exchange is obtained at pH 6.8. This reversible transport system presents a high selectivity for K+ among other monovalent cations and a higher affinity for the K+ influx into the vesicles (exit from cells). The possible role of this K+/H+ exchange system in regulation of internal potassium concentration in S. cerevisiae is discussed.

Biological Transport, Active↗

The mechanism for the ATP-induced uncoupling of respiration in mitochondria of the yeast Saccharomyces cerevisiae.

We have recently reported that ATP induces an uncoupling pathway in Saccharomyces cerevisiae mitochondria [Prieto, Bouillaud, Ricquier and Rial (1992) Eur. J. Biochem. 208, 487-491]. The presence of this pathway would explain the reported low efficiency of oxidative phosphorylation in S. cerevisiae, and may represent one of the postulated energy-dissipating mechanisms present in these yeasts. In this paper we demonstrate that ATP exerts its action in two steps: first, at low ATP/Pi ratios, it increases the respiratory-chain activity, probably by altering the kinetic properties of cytochrome c oxidase. Second, at higher ATP/Pi ratios, an increase in membrane permeability leads to a collapse in membrane potential. The ATP effect on cytochrome c oxidase corroborates a recent report showing that ATP interacts specifically with yeast cytochrome oxidase, stimulating its activity [Taanman and Capaldi (1993) J. Biol. Chem. 268, 18754-18761].

Adenosine Triphosphate↗

Permeabilization of the mitochondrial inner membrane by short cecropin-A-melittin hybrid peptides.

A number of cecropin-A-melittin hybrid peptides have previously been shown to be potent antibacterial agents [Andreu, D., Ubach, J., Boman, A., Wahlin, B., Wade, D., Merrifield, R. B. & Boman, H. G. (1992) FEBS Lett. 296, 190-194]. In the present report we analyze their action on biological systems using rat liver mitochondria as a test system. We demonstrate that the longest peptide, cecropin-A-(1-8)-melittin(1-18) permeabilizes the mitochondrial inner membrane allowing the movement of both charged and non-charged solutes. Concentrations used have already been shown to be bactericidal. This effect is also demonstrated under respiring conditions where succinate oxidation is uncoupled. Shorter analogs also permeabilize mitochondria although at ten-fold higher concentrations. Heparin potentiates the peptide effects at low concentrations, while at high concentration it becomes inhibitory. We propose that the cecropin-melittin analogs disrupt the mitochondrial membrane in a detergent-like mode rather than by creating selective channels as had been previously suggested.

Amino Acid Sequence↗

Cysteine residues are not essential for uncoupling protein function.

The uncoupling protein (UCP) of brown adipose tissue is a regulated proton carrier which allows uncoupling of mitochondrial respiration from ATP synthesis and, therefore, dissipation of metabolic energy as heat. In this article we demonstrate that, when UCP is expressed in Saccharomyces cerevisiae, it retains all its functional properties: proton and chloride transport, high-affinity binding of nucleotides and regulation of proton conductance by nucleotides and fatty acids. Site-directed mutagenesis demonstrates that sequential replacement by serine of cysteine residues in the UCP does not affect either its uncoupling activity or its regulation by nucleotides and fatty acids, and therefore establishes that none of the seven cysteine residues present in the wild-type UCP is critical for its activity. These data indicate that transport models involving essential thiol groups can be discounted and that chemical modification data require critical re-evaluation.

Base Sequence↗

Activation by ATP of a proton-conducting pathway in yeast mitochondria.

The growth of Saccharomyces cerevisiae cells under aerobic conditions, in the presence of an energy-rich source, leads to production of an excess of NAD(P)H. Since the redox balance must be maintained, it has been postulated that NAD(P)H reoxidation is accelerated by the activation of energy-dissipating reactions, which would, in turn, explain the low growth efficiencies observed. It has been demonstrated already in S. cerevisiae cultures that these putative energy-dissipating reactions are stimulated both by oxygen and high cytosolic ATP levels. In this paper, we show that ATP induces a proton-permeability pathway in mitochondria at concentrations which are within the physiological range, as revealed both from the ATP stimulation of respiration and from the induction of H(+)-dependent swelling. We also demonstrate that phosphate acts as a competitive inhibitor of the nucleotide, and since activation is observed even in the presence of atractylate, we postulate that the ATP-binding site is located in the outer face of the mitochondrial inner membrane.

Adenosine Triphosphate↗

[Tubercular disease in a general hospital. Apropos of 445 cases].

Four hundred and forty-five patients diagnosed of active thoracic or extrathoracic tuberculosis during a 6 year period were retrospectively reviewed. An increase in the rate of cases was found through the surveyed period. Less than 20% of patients were over 60 years of age at the time of diagnosis. Although the most common localizations were pulmonary and pleural, the disease was exclusively extrathoracic in one fifth of patients. Ten patients died of tuberculosis; 9.6% of patients had untoward side effects of tuberculostatic drugs and 14% did not comply with the scheduled follow up.

Adolescent↗