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Biomedical subjects

M Fernandes

Publications and source records attributed to M Fernandes.

At least 19 recordsLinked to original sources
PubMed2003

Genetic distinction of wildcat (Felis silvestris) populations in Europe, and hybridization with domestic cats in Hungary.

The genetic integrity and evolutionary persistence of declining wildcat populations are threatened by crossbreeding with widespread free-living domestic cats. Here we use allelic variation at 12 microsatellite loci to describe genetic variation in 336 cats sampled from nine European countries. Cats were identified as European wildcats (Felis silvestris silvestris), Sardinian wildcats (F. s. libyca) and domestic cats (F. s. catus), according to phenotypic traits, geographical locations and independently of any genetic information. Genetic variability was significantly partitioned among taxonomic groups (FST = 0.11; RST = 0.41; P < 0.001) and sampling locations (FST = 0.07; RST = 0.06; P < 0.001), suggesting that wild and domestic cats are subdivided into distinct gene pools in Europe. Multivariate and Bayesian clustering of individual genotypes also showed evidence of distinct cat groups, congruent with current taxonomy, and suggesting geographical population structuring. Admixture analyses identified cryptic hybrids among wildcats in Portugal, Italy and Bulgaria, and evidenced instances of extensive hybridization between wild and domestic cats sampled in Hungary. Cats in Hungary include a composite assemblage of variable phenotypes and genotypes, which, as previously documented in Scotland, might originate from long lasting hybridization and introgression. A number of historical, demographic and ecological conditions can lead to extensive crossbreeding between wild and domestic cats, thus threatening the genetic integrity of wildcat populations in Europe.

Animals↗
PubMed2003

Evaluation of a nutrition supplementation programme in the Northern Cape Province of South Africa.

AIM: This study aimed at assessing the effectiveness regarding implementation and impact of a take-home nutrition supplementation programme, the Protein Energy Malnutrition (PEM) Scheme, that targets malnourished pre-school children and pregnant and lactating women in the Northern Cape Province of South Africa. METHODOLOGY: In assessing implementation of the PEM Scheme, a cross-sectional descriptive study was undertaken over a 6-month period in the six regions of the Northern Cape Province. Interviews were conducted with programme managers and health personnel at clinics who were responsible for implementing the PEM Scheme. In assessing the impact of the PEM Scheme on growth, a retrospective review was done of the clinic records (including anthropometric data) of children enrolled in the PEM Scheme over a 1-year period. RESULTS: About 76% of the budget allocated to the PEM Scheme had been utilised over the 1-year period. The budget for the following financial year was based solely on food supplements purchased in the previous year. Coverage of malnourished pre-school children and eligible pregnant and lactating women for enrolment was estimated to be 50% and 60%, respectively. Eighty-five per cent of health facilities in the province participated in the PEM Scheme. Some of the main problems identified included: lack of training, inappropriate targeting of certain groups, incorrect application especially of discharge criteria for pregnant and lactating women, inadequate assessment for nutrition-related disease, inadequate nutrition counselling and no standardised monitoring. Of the 319 children enrolled over a year, the mean age was 16.2 (standard deviation 16.2) months, 41% had been low-birth-weight and 18% had been diagnosed with tuberculosis. Ten per cent of the children with a weight-for-age Z-score of <-2 moved into the normal Z-score range after being on the PEM Scheme for a mean duration of 8 months. There was an overall improvement in the weight-for-age Z-scores of 25% of the sample, with a significant difference between the mean weight-for-age Z-scores at enrolment and follow-up This was mainly related to significant improvement in the mean weight-for-age Z-scores of children <2 years. CONCLUSIONS: Numerous problems with the PEM Scheme have been identified which could have limited its impact. Recommendations are proposed for improving the effectiveness and impact of the PEM Scheme in the province.

Adolescent↗
PubMed2001

Double aortic arch in a dog (Canis familiaris): a case report.

We herein report a case of a double aortic arch in a 10-week-old male dog of no defined race, which presented episodes of regurgitation at the time of weaning. This vascular malformation was characterized by the persistence of two aortic arches, right and left, of varying dimensions. The right aortic arch was observed to be larger. During post mortem examination the vessels of the animal were injected with coloured latex bi-centrifuged CIS 1-4 polisopreno which revealed the patency of the two aortic arches. Concomitantly, dilation of the cranial oesophagus causing constriction was observed, indicating megaesophagus. Apart from the constriction, the oesophagus presented normal morphometric parameters in relation to its dimensions.

Animals↗
PubMed2001

Crack cocaine--a two-year follow-up of treated patients.

OBJECTIVES: To investigate the 2-year outcome of the first 131 crack cocaine users who had been admitted for a period of inpatient treatment. DESIGN: Follow-up study of consecutive patients admitted between 1992 and 1994. SETTING: Inpatient detoxification unit of a public general hospital in São Paulo City, Brazil. PARTICIPANTS: 131 consecutive crack cocaine users. MEASURES: Reported crack use during last 12 months, incarceration and death. FINDINGS: After 2 years, 50 patients reported crack use in the last 12 months, 29 said that they had not used it during this period, 9 were in prison, 13 had died, 2 had disappeared and no information was available on 28. CONCLUSIONS: Crack cocaine use seems to be associated with a high mortality rate and criminal involvement but about one-third of patients give up using the drug within 2 years of inpatient treatment.

Adolescent↗
PubMed2001

Crystal-induced neutrophil activation. VII. Involvement of Syk in the responses to monosodium urate crystals.

The inflammatory response in acute gouty arthritis is in large part a result of the interaction between neutrophils and monosodium urate (MSU) crystals. The tyrosine kinase Syk, which has been largely associated with the phagocytic response by Fc receptors and with spreading mediated by integrins, has been identified as one of the major proteins tyrosine-phosphorylated in human neutrophils upon stimulation by MSU crystals and is known to be mediated in part by the Fc receptor, CD16. This has led to the present examination of the implication of Syk in the activation pathways used by MSU crystals. The tyrosine-phosphorylation patterns induced by MSU crystals and by the ligation of CD16 were inhibited by piceatannol, which, conversely, only slightly delayed but did not diminish the peak of tyrosine phosphorylation induced by cross-linking CD32 or by the addition of fMet-Leu-Phe. Moreover, piceatannol inhibited the activity of Syk as monitored by in vitro kinase assays, by its in situ tyrosine phosphorylation, and by its activity toward exogenous substrates after stimulation by MSU crystals. We also measured the impact of piceatannol on the mobilization of calcium, the production of superoxide anions, and the activity of PLD stimulated by MSU crystals. We noted a distinct inhibition of all these responses by piceatannol. Finally, the morphological changes observed in neutrophils as characteristic of MSU crystal internalization were diminished significantly by piceatannol. The results obtained show that Syk plays a critical and central role in the signal-transduction pathways called upon by MSU crystals subsequent to their interaction with human neutrophils.

Adult↗
PubMed2000

Targeted localized degradation of Paired protein in Drosophila development.

BACKGROUND: Selective spatial regulation of gene expression lies at the core of pattern formation in the embryo. In the fruit fly Drosophila, localized transcriptional regulation accounts for much of the embryonic pattern. RESULTS: We identified a gene, partner of paired (ppa), whose properties suggest that localized receptors for protein degradation are integrated into regulatory networks of transcription factors to ensure robust spatial regulation of gene expression. We found that the Ppa protein interacts with the Pax transcription factor Paired (Prd) and contains an F-box, a motif found in receptors for ubiquitin-mediated protein degradation. In normal development, Prd functions only in cells in which ppa mRNA expression has been repressed by another segmentation protein, Even-skipped (Eve). When ppa was expressed ectopically in these cells, Prd protein, but not mRNA, levels diminished. When ppa function was removed from cells that express prd mRNA, Prd protein levels increased. CONCLUSIONS: Ppa co-ordinates Prd degradation and is important for expression of Prd to be correctly localized. In the presence of Ppa, Prd protein is targeted for degradation at sites where its mis-expression would disrupt development. In the absence of Ppa, Prd is longer-lived and regulates downstream target genes.

Amino Acid Sequence↗
PubMed2000

Envelope glycoprotein determinants of increased fusogenicity in a pathogenic simian-human immunodeficiency virus (SHIV-KB9) passaged in vivo.

Changes in the envelope glycoprotein ectodomains of a nonpathogenic simian-human immunodeficiency virus (SHIV-89.6) that was serially passaged in vivo have been shown to be responsible for the increased pathogenicity of the resulting virus, SHIV-KB9 (G. B. Karlsson, et al., J. Exp. Med. 188:1159-1171, 1998). The 12 amino acid changes in the envelope glycoprotein ectodomains resulted in increased chemokine receptor-binding and syncytium-forming abilities. Here we identify the envelope glycoprotein determinants of these properties. A single amino acid change in the gp120 third variable (V3) loop was both necessary and sufficient for the observed increase in the binding of the SHIV-KB9 gp120 glycoprotein to the CCR5 chemokine receptor. The increased syncytium-forming ability of SHIV-KB9 involved, in addition to the V3 loop change, changes in the second conserved (C2) region of gp120 (residue 225) and in the gp41 ectodomain (residues 564 and 567). The C2 and gp41 ectodomain changes influenced syncytium formation in a cooperative manner. Changes in the V1/V2 gp120 variable loops exerted a negative effect on syncytium formation and chemokine receptor binding, supporting a previously described role of these changes in immune evasion. The definition of the passage-associated changes that determine the efficiency of chemokine receptor binding and membrane fusogenicity will allow evaluation of the contribution of these properties to in vivo CD4-positive lymphocyte depletion.

Animals↗
PubMed2000

[Visualization of the vibratory movements of the vocal cords under asymmetrical conditions].

In this study, we present a new system for measuring the vibration signal of the larynx which allows the vibration of each vocal cord in an excised larynx to be studied using a method of distant optical measurement. The set-up consisted of an insufflator and a device for immobilising the larynx, together with microprobes capable of creating mechanical pressure at the laryngeal ventricles. The whole system was computer-controlled. The measurements were carried out under normal and asymmetrical conditions on seven excised pig larynges. Measurement of the individual vibration of each vocal cord showed that the transient period of commencement of vibration (vocal onset) is influenced to a significant extent by the degree of asymmetry. Under conditions of extreme asymmetry, movement of the cords appeared to be aberrant, but not random because of the coupling mechanisms which cause "anchoring" of the two cords during the phase of closure. Thus one cord may vibrate at twice the frequency of the other. The method described has given us a better understanding of the mechanism of laryngeal vibration, and one which is in conflict with the theoretical harmonic model in many details.

Animals↗
PubMed1999

Nutritional status and mortality of refugee and resident children in a non-camp setting during conflict: follow up study in Guinea-Bissau.

OBJECTIVE: To study the effects on children of humanitarian aid agencies restricting help to refugee families (internally displaced people). DESIGN: Follow up study of 3 months. SETTING: Prabis peninsular outside Bissau, the capital of Guinea-Bissau, which has functioned as a refugee area for internally displaced people in the ongoing war, and the study area of the Bandim health project in Bissau. PARTICIPANTS: 422 children aged 9-23 months in 30 clusters. MAIN OUTCOME MEASURES: Mid-upper arm circumference and survival in relation to residence status. RESULTS: During the refugee situation all children deteriorated nutritionally, and mortality was high (3.0% in a 6 week period). Rice consumption was higher in families resident in Prabis than in refugees from Bissau but there was no difference in food expenditure. Nutritional status, measured by mid- upper arm circumference, was not associated with rice consumption levels in the family, and the decline in circumference was significantly worse for resident than for refugee children; the mid-upper arm circumference of refugee children increased faster than that of resident children. For resident children, mortality was 4.5 times higher (95% confidence interval 1.1 to 30.0) than for refugee children. Mortality for both resident and refugee children was 7.2 times higher (1.3 to 133.9) during the refugee's stay in Prabis compared with the period after the departure of the refugees. CONCLUSION: In a non-camp setting, residents may be more malnourished and have higher mortality than refugees. Major improvements in nutritional status and a reduction in mortality occurred in resident and refugee children as soon as refugees returned home despite the fact that there was no improvement in food availability.

Eating↗
PubMed1999

Identification of bothrojaracin-like proteins in snake venoms from Bothrops species and Lachesis muta.

Bothrojaracin, a 27 kDa protein isolated from Bothrops jararaca venom, forms a non-covalent complex with thrombin, thus blocking its activity. We have previously identified a bothrojaracin-like protein in B. alternatus venom [Castro, H.C., Dutra, D.L.S., Oliveira-Carvalho, A.L., Zingali, R.B., 1998. Bothroalternin, an inhibitor of thrombin from the venom of Bothrops alternatus. Toxicon 36, 1903-1912]. In this report, we have examined snake venoms from six different Bothrops species (B. atrox, B. cotiara, B. jararacussu, B. moojeni and B. neuwiedi), from Lachesis muta and from Crotalus durissus terrificus for the presence of bothrojaracin-like proteins, which we define here as 27 kDa proteins that are immunologically related to bothrojaracin and that inhibit thrombin-induced platelet aggregation. The immunological analysis of these venoms by different techniques indicated the existence of at least one protein recognized by anti-bothrojaracin serum in all venoms tested. Bothrojaracin-like proteins were purified from all crude venoms, except for C. d. terrificus, by a single-step procedure using a thrombin affinity column (PPACK-thrombin-Sepharose). Retained material that inhibits thrombin-induced platelet aggregation was found in a different proportion in each species. Under non-reducing conditions, SDS-PAGE of this material revealed several bands between 20-60 kDa; only those bands corresponding to 27 kDa were recognized by anti-bothrojaracin serum. ELISA confirmed the greater bothrojaracin immunoreactivity of proteins present in B. atrox and B. cotiara as compared to other Bothrops species. Smaller amounts of proteins related to bothrojaracin were found in L. muta venom and were absent from the venom of C. d. terrificus. Our results thus suggest that bothrojaracin-like proteins are widely distributed among Bothrops genera.

Animals↗
PubMed1998

In search of novel water soluble forskolin analogues for positive inotropic activity.

Using the novel lead from hydroxy acetyl substituted forskolin analogues, such as 7 beta-hydroxyacetyl-7 beta-deacetyl forskolin or 6 beta-hydroxyacetyl forskolin, a number of water soluble omega-amino acyl derivatives were synthesized. Two such compounds 6 and 18 showed better in vitro activity but failed to show in vivo activity.

Acetylation↗
PubMed1998

Sequence-specific binding by Aspergillus nidulans AflR, a C6 zinc cluster protein regulating mycotoxin biosynthesis.

The Aspergillus nidulans aflR gene is found within a 60 kb gene cluster that includes approximately 24 other genes that putatively function in the production of the aflatoxin-related mycotoxin sterigmatocystin. Previous work showed that AflR is a C6 zinc binuclear cluster protein that is conserved across Aspergillus spp. and functions as a pathway-specific transcription factor in activating expression of other cluster genes. In this report, we demonstrate that A. nidulans AflR (AnAflR) is a 45kDa protein that binds to the palindromic sequence 5'-TCG(N5)CGA-3' found in the promoter regions of several aflatoxin and sterigmatocystin cluster genes (stc genes). The in vivo relevance of this AnAflR binding site was assessed by examining the contribution of the three TCG(N5)CGA elements in the 1.1 kb promoter region of stcU using gene fusions with the bacterial uidA gene encoding beta-glucuronidase (GUS). By mutating one, two or all three of the AnAflR-binding elements and examining GUS activity in wild-type aflR or delta aflR A. nidulans strains, we found that stc gene activation required both AnAflR and at least one TCG(N5)CGA AflR binding site.

Aflatoxins↗
PubMed1998

Characterization of simian-human immunodeficiency virus envelope glycoprotein epitopes recognized by neutralizing antibodies from infected monkeys.

We characterized human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein epitopes recognized by neutralizing antibodies from monkeys recently infected by molecularly cloned simian-human immunodeficiency virus (SHIV) variants. The early neutralizing antibody response in each infected animal was directed mainly against a single epitope. This primary neutralizing epitope, however, differed among individual monkeys infected by identical viruses. Two such neutralization epitopes were determined by sequences in the V2 and V3 loops of the gp120 envelope glycoprotein, while a third neutralization epitope, apparently discontinuous, was determined by both V2 and V3 sequences. These results indicate that the early neutralizing antibody response in SHIV-infected monkeys is monospecific and directed against epitopes composed of the gp120 V2 and V3 variable loops.

Animals↗