Biomedical subjects

C Menéndez

Publications and source records attributed to C Menéndez.

At least 19 recordsLinked to original sources

PubMed2004

The sick placenta-the role of malaria.

The human placenta is an ideal site for the accumulation of Plasmodium falciparum malaria parasites, and as a consequence serious health problems arise for the mother and her baby. The pathogenesis of placental malaria is only partially understood, but it is clear that it leads to a distinct epidemiological pattern of malaria during pregnancy. The objectives of this review are: (1) To review recent data on the epidemiology of malaria in pregnancy, with emphasis on placental malaria; (2) to describe the pathological changes and immunological factors related to placental malaria; and (3) to discuss briefly the functional consequences of this infection for the mother and her baby. The review attempts to bring together local events at the maternal-fetal interface which encompass immunological and pathological processes which relate to the epidemiological pattern of malaria in pregnancy in areas of both high and low malaria transmission. An integrated understanding of the epidemiological, immunological and pathological processes must be achieved in order to understand how to control malaria in pregnancy. The yearly exposure of at least 50 million pregnancies to malaria infection makes it the commonest and most recurrent parasitic infection directly affecting the placenta. These statistics and our limited understanding of its pathogenesis suggest the research priorities on this subject.

Cytokines↗

PubMed2001

Human papillomavirus genotypes in rural Mozambique.

We studied the genotype distribution of cervical human papillomavirus (HPV) infections in an age-stratified sample of 262 women in Mozambique using the PGMYO9-PGMY11 primer system in a reverse line-blot strip-based assay with high sensitivity in type-specific amplification. Despite the low precision of the estimates, we found that HPV-16 was not the dominant type. Instead, HPV 35 was the most commonly identified genotype among HPV-positive women (16/96 [17%]) and women with cervical neoplasia (7/23 [30%]). Certain genotypes might have been under-detected in previous studies, and type-specific HPV distributions might vary across populations. Therefore, the estimated proportion of cervical neoplasia that could be prevented by an HPV-16-based vaccine could be lower than expected.

Adolescent↗

PubMed2001

Diagnostic accuracy and case management of clinical malaria in the primary health services of a rural area in south-eastern Tanzania.

Malaria control continues to rely on the diagnosis and prompt treatment of both suspected and confirmed cases through the health care structures. In south-eastern Tanzania malaria is one of the leading causes of morbidity and mortality. The absence of microscopic examination in most of the health facilities implies that health workers must rely on clinical suspicion to identify the need of treatment for malaria. Of 1558 randomly selected paediatric consultations at peripheral health facilities throughout Kilombero District, 41.1% were diagnosed by the attending health worker as clinical malaria cases and 42.5% prescribed an antimalarial. According to our malaria case definition of fever or history of fever with asexual falciparum parasitaemia of any density, 25.5% of all children attending the health services had malaria. This yielded a sensitivity of 70.4% (IC95% = 65.9-74.8%) and a specificity of 68.9% (IC95% = 66.2-71.5%). Accordingly, 30.4% of confirmed cases left with no antimalarial treatment. Among malaria-diagnosed patients, 10% were underdosed and 10.5% were overdosed. In this area, as in many African rural areas, the low diagnostic accuracy may imply that the burden of malaria cases may be overestimated. Greater emphasis on the functioning and quality of basic health services in rural endemic areas is required if improved case management of malaria is to help roll back this scourge.

Antimalarials↗

PubMed2000

Frequency-domain analysis of heart rate variability during positive and negative head-up tilt test: importance of age.

The study of autonomic behavior during a head-up tilt test (HUT) has been deemed important to understand the loss of consciousness mechanism. Though HRV in patients with HUT(+) and HUT(-) has been compared, few trials emphasized the importance of age. HRV in frequency domain was analyzed based on 5-minute samples in the supine position, and between 5 and 10 minutes during early tilt test (R1) in 102 patients with one or more episodes of syncope (mean age 44.3 +/- 20.8, range 15-85 years, 55 women). Two subgroups were selected afterwards: (1) young patients between 15 and 35 years of age (41 patients) and (2) elderly patients aged 60 or more (36 patients). The following parameters were taken into account: the sum of low (LF) and high frequency (HF) (LF and HF in absolute values and in normalized units), the LF/HF ratio (L/H ratio), and the percentage of change between baseline and R1 values. The HRV behavior in young and elderly patients with positive and negative HUT was established. We then analyzed the correlation between HRV and age and HUT outcome. A multiple regression analysis encompassing age, HUT outcome, gender, and number of syncope episodes was performed. In young patients, the LF and HF areas and the L/H ratio changed significantly between baseline and R1. The L/H ratio increases from baseline to R1. Conversely, these differences were not significant in the elderly. No differences between HUT(+) and HUT(-) within the same age group were observed. Age related significantly to practically all HRV parameters analyzed, whereas the tilt test outcome correlates poorly with HF normalized units and LF normalized units during R1, and the L/H ratio changes between baseline and R1. By means of a multivariate analysis, only age shows a significant correlation with the HRV values. Despite an all age triggering of vasovagal syncope during HUT, the young and elderly patients' autonomic behavior differs. The young considerably increase their sympathovagal balance during HUT, whereas the elderly have a mitigated autonomic response. No significant differences were observed during the first minutes of the test between those with a HUT(+) and those with a HUT(-) within the same age group. Age, and not the HUT response, is the major determinant of the autonomic behavior during early HUT.

Adolescent↗

PubMed2000

Cold exposure inhibits leptin secretion in vitro by a direct and non-specific action on adipose tissue.

OBJECTIVE: Leptin secretion is reduced by low temperatures in experimental animals, and this effect has been explained as an adaptive mechanism to cold environments. This study investigated the in vitro effects of cold exposure on human white adipose tissue. DESIGN: To understand whether the low temperature action is a direct or a mediated effect, leptin secretion was assessed in vitro in human omental adipose tissue incubated at varied temperatures, from 38 donors. As an internal control, the effect of reduced temperatures on in vitro GH secretion by GH3 cells was assessed. METHODS: Measurement of hormones secretion was carried out with an RIA, while human ob gene mRNA expression was assessed with reverse transcription PCR. RESULTS: Compared with the standard temperature of 37 degrees C, leptin secretion by human adipose tissue was significantly (P<0.05) reduced when the incubations were carried out at 34.5 degrees C (41% inhibition), and 32 degrees C (68% inhibition), with no parallel changes in the ob mRNA expression. At these reduced temperatures, glucocorticoid-mediated leptin secretion was well preserved. When the effect of reduced temperatures was assessed on in vitro GH secretion, a superimposable reduction was observed. CONCLUSIONS: These results indicate: (i) that low temperatures reduce leptin secretion by acting directly on the adipose tissue and (ii) that the similar reduction in a hormone unrelated to energy metabolism, such as GH, suggests that the observed reduction is a mechanical perturbation of leptin secretion, which may be devoid of physiological implications.

Adipose Tissue↗

PubMed2000

Cost-effectiveness of iron supplementation and malaria chemoprophylaxis in the prevention of anaemia and malaria among Tanzanian infants.

Prerequisites for effective interventions against severe anaemia and malaria among infants are economic evaluations to aid the setting of priorities and the making of health policy. In the present study we analysed the cost and effectiveness of three control strategies hypothetically delivered through the Expanded Programme on Immunization (EPI). For the prevention of severe anaemia and from the perspective of the health provider, the cost-effectiveness ratios were, respectively, US$ 8, US$ 9, and US$ 21 per disability-adjusted life year (DALY) for malaria chemoprophylaxis with Deltaprim (a combination of 3.125 mg pyrimethamine and 25 mg dapsone) + iron, Deltaprim alone, or iron supplementation alone. For malaria prevention, Deltaprim + iron cost US$ 9.7 per DALY and Deltaprim alone cost US$ 10.2 per DALY. From a sociocultural perspective the cost-effectiveness ratios ranged from US$ 9 to US$ 26 for severe anaemia prevention and from US$ 11 to US$ 12 for the prevention of clinical malaria. These ratios were highly cost-effective, as defined by the World Bank's proposed threshold of less than US$ 25 per DALY for comparative assessments. Furthermore, all the preventive interventions were less costly than the current malaria and anaemia control strategies that rely on clinical case management. This economic analysis supports the inclusion of both malaria chemoprophylaxis and iron supplementation delivered through EPI as part of the control strategies for these major killers of infants in parts of sub-Saharan Africa.

Anemia, Iron-Deficiency↗

PubMed1999

Substitution of Asp-309 by Asn in the Arg-Asp-Pro (RDP) motif of Acetobacter diazotrophicus levansucrase affects sucrose hydrolysis, but not enzyme specificity.

beta-Fructofuranosidases share a conserved aspartic acid-containing motif (Arg-Asp-Pro; RDP) which is absent from alpha-glucopyranosidases. The role of Asp-309 located in the RDP motif of levansucrase (EC 2.4.1.10) from Acetobacter diazotrophicus SRT4 was studied by site-directed mutagenesis. Substitution of Asp-309 by Asn did not affect enzyme secretion. The kcat of the mutant levansucrase was reduced 75-fold, but its Km was similar to that of the wild-type enzyme, indicating that Asp-309 plays a major role in catalysis. The two levansucrases showed optimal activity at pH 5.0 and yielded similar product profiles. Thus the mutation D309N affected the efficiency of sucrose hydrolysis, but not the enzyme specificity. Since the RDP motif is present in a conserved position in fructosyltransferases, invertases, levanases, inulinases and sucrose-6-phosphate hydrolases, it is likely to have a common functional role in beta-fructofuranosidases.

Acetobacter↗

PubMed1999

Levansucrase from Acetobacter diazotrophicus SRT4 is secreted via periplasm by a signal-peptide-dependent pathway.

Acetobacter diazotrophicus SRT4 secretes a constitutive levansucrase (LsdA) (EC 2.4.1.10) that is responsible for sucrose utilization. Immunogold electron microscopical studies revealed that LsdA accumulates in the periplasm before secretion. The periplasmic and extracellular forms of the enzyme were purified to homogeneity. Both proteins exhibited similar physical and biochemical characteristics indicating that LsdA adopts its final conformation in the periplasm. The N-terminal sequence of mature LsdA was pGlu-Gly-Asn-Phe-Ser-Arg as determined by PSD-MALDI-TOFMS (post-source decay-matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry). Comparison of this sequence with the predicted precursor protein revealed the cleavage of a 30-residue typical signal peptide followed by the formation of the pyroglutamic acid (pGlu) residue. Thus, in contrast with other Gram-negative bacteria, A. diazotrophicus secretes levansucrase by a signal-peptide-dependent mechanism.

Acetobacter↗

PubMed1999

Molecular evidence of mother-to-infant transmission of hepatitis G virus among women without known risk factors for parenteral infections.

Hepatitis G virus (HGV) RNA was detected in 18 of 133 pregnant women from Tanzania without known risk factors for HGV infection and in 7 of 18 children born to HGV RNA-positive mothers. Molecular evidence of mother-to-infant transmission was obtained only for three of seven children. HGV RNA was also detected in 4 of 42 children born to non-HGV-infected women. Thus, mechanisms other than materno-filial may play an important role in HGV transmission during early childhood.

Female↗

PubMed1999

Prolactin stimulates leptin secretion by rat white adipose tissue.

Leptin, the obese (Ob) gene product, is an adipocyte-derived satiety factor that is involved in the regulation of food intake and body weight. Leptin signals nutritional status to several other physiological systems and modulates their function. As PRL is involved in energy and lipid metabolism, this study was undertaken to investigate the role of PRL on in vivo regulation of leptin serum concentration and Ob messenger RNA expression in white adipose tissue in rats. It was found that increased serum PRL levels, obtained by pituitary graft or exogenous injected ovine PRL (oPRL, 5 mg/kg), significantly stimulate serum leptin concentration. A significant increase (P < 0.01) in serum leptin concentration was present in hyperprolactinemic animals (4.7+/-0.4 microg/liter) in comparison to controls (1.2+/-0.1 microg/liter and 1.09+/-0.09 microg/liter of intact sham operated and ovariectomized rats, respectively). Similar results were obtained in oPRL-treated animals where leptin levels were 5.4+/-0.1 microg/liter vs. 1.1+/-0.1 microg/liter and 0.8+/-0.08 microg/liter of intact sham operated rats and ovariectomized, respectively (P < 0.001). This stimulatory effect of PRL on serum leptin levels was significantly reduced by food deprivation (P < 0.01) where serum leptin levels were 12.5+/-0.65 microg/liter in grafted animals vs. 3.2+/-0.36 microg/liter of grafted animals subjected to 48 h of food deprivation. Moreover, in vivo, PRL was able to induce leptin messenger RNA levels in several areas of rat white adipose tissue. The data demonstrate that PRL acts on the adipose tissue increasing leptin synthesis and secretion, suggesting a new role for this lactogenic hormone in the regulation of food intake.

Adipose Tissue↗

PubMed1998

Diagnostic yield of stimulation and voluntary single-fiber electromyography in myasthenia gravis.

Voluntary and stimulation single-fiber electromyography were performed in the extensor digitorum communis muscle of 15 myasthenic patients. The increase in mean and individual mean consecutive difference as well as the proportion of blocking in the volitional activation were greater than in the stimulation method. These differences may be explained in part by the different degree of alteration in large as compared with small motor units in patients with myasthenia gravis.

Aged↗

PubMed1998

Cis-unsaturated free fatty acids block VIP-mediated GH and PRL secretion by perturbing the cAMP/protein kinase A pathway.

Cis-unsaturated free fatty acids (FFA) like oleic acid are strong blockers of both basal and stimulated GH secretion in vivo by acting directly on the somatotroph cell. Several lines of evidence suggest that this inhibitory action is the result of a perturbation of the function of several plasma membrane integral proteins. It has been reported recently that cis-FFA are able to block several steps in the inositolphosphates/phospholipase C/Ca2+ (InsPs/PLC/Ca2+) signal transduction pathway triggered by the activation of the TRH receptor. In this paper we present evidence showing that the inhibition of growth hormone (GH) and prolactin (PRL) secretion by cis-FFA in vitro is also exerted at several different levels on the cAMP-protein kinase A (cAMP/PKA) pathway triggered by the stimulation of the vasoactive intestinal peptide (VIP) receptor in pituitary clonal cells. By means of a sequential analysis of signal transduction events, we observed that cis-unsaturated FFA; (1) reduce the activity of adenylate cyclase; (2) perturb the activity of protein kinase A; (3) suppress the VIP-triggered Ca2+ influx, and (4) do not perturb VIP binding or the homologous desensitization of the VIP receptor.

Adenylyl Cyclases↗

PubMed1998

[Tables of normal values of average and long latency auditory potentials].

INTRODUCTION AND OBJECTIVE: In view of the disparity of data and methodology concerning medium (MAEP) and long latency (LAEP) acoustic evoked potentials, we have obtained tables of normal values using a reliable method and statistical study of these potentials in 30 healthy persons, in order to serve as a basis for clinical reference and for possible further studies. MATERIAL AND METHODS: In the MAEP we used the two types of stimuli most commonly employed, first a click and then a rising-plateau-falling tone (2-6-2). We observed that this did not affect the latency or amplitude of the different waves, although the best defined waves are obtained with tones. In the LAEP we always used a tone with rise-plateau-fall of 10-50-10, as recommended by the American Electroneurophysiological Society. In all cases the intensity was of 70 db, with rarefaction and masking of the contralateral ear with an intensity of 50 db. Self-adhesive electrodes were used for captation; the active one was placed on the ipsilateral ear lobe and the reference electrode in Cz for the LAEP. For the LAEP the lower filter was of 1 Hz and the higher of 70 Hz. In view of the variety of filters recommended, 10 Hz at the lower level and 500, 1000 and 2000 at the higher level were used successively for the MAEP. We observed that these did not affect the latency or amplitude of the waves, so these three values may all be used equally well. RESULTS AND CONCLUSIONS: In the inter-sexual study, no differences were seen between men and women. Nor were there significant differences between the acoustic evoked potentials on the right and left sides of the same person.

Adolescent↗

PubMed1997

Molybdate-uptake genes and molybdopterin-biosynthesis genes on a bacterial plasmid--characterization of MoeA as a filament-forming protein with adenosinetriphosphatase activity.

A gene cluster consisting of homologs to Escherichia coli moaA, moeA, moaC and moaE, which encode enzymes involved in the biosynthesis of molybdopterin cofactor (MoCo), and to modA, modB and modC, which encode a high-affinity molybdate transporter, were identified on pAO1 of Arthrobacter nicotinovorans near genes of molybdopterin-dependent enzymes involved in nicotine degradation. This gene arrangement suggests a coordinated expression of the MoCo-dependent and the MoCo-biosynthesis genes and shows that catabolic plasmids may carry the transport and biosynthetic machinery for the synthesis of the cofactors needed for the functioning of the enzymes they encode. pAO1 MoeA functionally complemented E. coli moeA mutants. The overexpressed and purified protein, of molecular mass 44,500 Da, associated into high-molecular-mass complexes and spontaneously formed gels at concentrations above 1 mg/ml. Transmission electron microscopy and atomic force microscopy revealed that MoeA forms fibrilar structures. In the presence of Mg2+ MoeA exhibited ATPase activity (0.020 pmol ATP x pmol protein(-1) x min(-1)). ATP, ADP or AMP induced the disassembly of the MoeA fibers into aggregates. pAO1 MoeA shows 39% identity to the C-terminal domain of the rat neuroprotein gephyrin. Like gephyrin it binds to neurotubulin, but binds with preference to tubulin dimers.

Adenosine Triphosphatases↗

PubMed1997

IS1473, a putative insertion sequence identified in the plasmid pAO1 from Arthrobacter nicotinovorans: isolation, characterization, and distribution among Arthrobacter species.

A putative insertion sequence (IS1473) has been cloned and sequenced. The 1087-bp element was found between the moaA and the ndhA genes in the upstream region of the nicotine dehydrogenase (ndh) operon in the 160-kb pAO1 plasmid of Arthrobacter nicotinovorans. It is flanked by an imperfect repeat of 33 bp and carries two overlapping open reading frames which, by programmed -1 translational frameshifting, may produce a transposase of 36.735 Da with a pI = 10. 18. The deduced protein is similar to the transposases IS481 and IS1002 from Bordetella and IS476 from Xanthomonas campestris, all members of the IS3 family. The putative insertion element was found as a single copy in the pAO1 plasmid and absent on the chromosome of the A. nicotinovorans genome. Similar sequences were detected by hybridization on total DNA from Arthrobacter globiformis, Arthrobacter ramosus, and Arthrobacter ureafaciens.

Amino Acid Sequence↗

PubMed1996

MoaA of Arthrobacter nicotinovorans pAO1 involved in Mo-pterin cofactor synthesis is an Fe-S protein.

MoaA, involved in an early step in the biosynthesis of the molybdopterin cofactor (MoCo), has not yet been characterized biochemically and the reaction it catalyzes is unknown. We overexpressed MoaA from pAO1 of Arthrobacter nicotinovorans in Escherichia coli as a N-terminal fusion with either glutathione-S-transferase or a 6-histidine tag. The pAO1 encoded MoaA as well as the fusion proteins functionally complement E. coli moaA mutants. Here we show that purified MoaA contains approximately 4 microM Fe and approximately 3 microM acid-labile S/microM protein. EPR spectroscopy revealed a predominant signal at g(av) = 2.01, indicative of a [3Fe-xS] cluster.

Amino Acid Sequence↗

PubMed1995

A pAO1-encoded molybdopterin cofactor gene (moaA) of Arthrobacter nicotinovorans: characterization and site-directed mutagenesis of the encoded protein.

A gene homologous to moaA, the gene responsible for the expression of a protein involved in an early step in the synthesis of the molybdopterin cofactor of Escherichia coli, was found to be located 2.7-kb upstream of the nicotine dehydrogenase (ndh) operon on the catabolic plasmid pAO1 of Arthrobacter nicotinovorans. The MoaA protein, containing 354 amino acids, migrated on an SDS-polyacrylamide gel with an apparent molecular weight of 40,000, in good agreement with the predicted molecular weight of 38,880. The pAO1-encoded moaA gene from A. nicotinovorans was expressed in E. coli as an active protein that functionally complemented moaA mutants. Its deduced amino acid sequence shows 43% identity to the E. coli MoaA, 44% to the NarAB gene product from Bacillus subtilis, and 42% to the gene product of two contiguous ORFs from Methanobacterium formicicum. N-terminal sequences, including the motif CxxxCxYC, are conserved among the MoaA and NarAB proteins. This motif is also present in proteins involved in PQQ cofactor synthesis in almost all the NifB proteins reported so far and in the fixZ gene product from Rhizobium leguminosarum. Mutagenesis of any of these three conserved cysteine residues to serine abolished the biological activity of MoaA, while substitution of the tyrosine by either serine, phenylalanine, or alanine did not alter the capacity of the protein to complement the moaA mutation in E. coli. A second Cys-rich domain with the motif FCxxC(13x)C is found close to the C-terminus of MoaA and NarAB proteins. These two Cys-rich sequences may be involved in the coordination of a metal ions. The pAO1 copy of moaA may not be unique in the A. nicotinovorans genome since the molybdopterin cofactor oxidation products were detected in cell extracts from a plasmidless strain.

Amino Acid Sequence↗

PubMed1994

Effects of percutaneous oestradiol versus oral oestrogens on bone density.

In order to compare the effects on bone density of 1.5 mg/day percutaneous 17 beta-oestradiol (E2) and of 0.625 mg/day oral conjugated oestrogens (CEE), 68 women who had undergone hysterectomy were studied. The subjects were randomly allocated to one of three study groups. A total of 15 women dropped out from these groups during the study. The percutaneous group (n = 20) received treatment for 36 months and the oral group (n = 17) for 24 months, while the untreated group (n = 16) served as controls over a period of 24 months. Bone mineral density (BMD) was measured by dual gammagraphic densitometry (Novo 22A densitometer) in the lumbar spine (L2-L4). The percentage gain in the percutaneous group was 1.7% +/- 3.9% after 12 months, 5.6% +/- 2.9% (P < 0.001) after 24 months and 4.7% +/- 3.2% (P < 0.01) after 36 months. In the oral group the gain was 3.5% +/- 13.0% after 12 months and 4.3% +/- 9.2% (P < 0.001) after 24 months. In the untreated group the bone density loss was 6.6% +/- 3.5% (P < 0.001) after 12 months and 9.1% +/- 3.4% (P < 0.001) after 24 months. On the basis of our results we concluded that both 1.5 mg/day percutaneous E2 and 0.625 mg/day oral CEE not only prevented bone loss but also increased BMD, as was confirmed by our findings after 36 and 24 months of treatment, respectively.

Administration, Cutaneous↗