Biomedical subjects

J Mendes

Publications and source records attributed to J Mendes.

At least 19 recordsLinked to original sources

PubMed2000

Evolution of the thyroid hormone-binding protein, transthyretin.

Transthyretin (TTR) belongs to a group of proteins, which includes thyroxine-binding globulin and albumin, that bind to and transport thyroid hormones in the blood. TTR is also indirectly implicated in the carriage of vitamin A through the mediation of retinol-binding protein (RBP). It was first identified in 1942 in human serum and cerebrospinal fluid and was formerly called prealbumin for its ability to migrate faster than serum albumin on electrophoresis of whole plasma. It is a single polypeptide chain of 127 amino acids (14,000 Da) and is present in the plasma as a tetramer of noncovalently bound monomers. The major sites of synthesis of TTR in eutherian mammals, marsupials, and birds are the liver and choroid plexus but in reptiles it is synthesised only in the choroid plexus. The observation that TTR is strongly expressed in the choroid plexus but not in the liver of the stumpy-tailed lizard and the strong conservation of expression in the choroid plexus from reptiles to mammals have been taken as evidence to suggest that extrahepatic synthesis of TTR evolved first. The identification and cloning of TTR from the liver of an amphibian, Rana catesbeiana, and a teleost fish, Sparus aurata, and its absence from the choroid plexus of both species suggest an alternative model for its evolution. Protein modelling studies are presented that demonstrate differences in the electrostatic characteristics of the molecule in human, rat, chicken, and fish, which may explain why, in contrast to TTR from human and rat, TTR from fish and birds preferentially binds triiodo-l-thyronine.

Amino Acid Sequence↗

PubMed2000

Latin american experience with two low-dose oral contraceptives containing 30 microg ethinylestradiol/75 microg gestodene and 20 microg ethinylestradiol/150 microg desogestrel.

The objective of this study was to compare cycle control, efficacy and tolerance of an oral contraceptive containing 20 microg ethinylestradiol and 150 microg desogestrel with a preparation containing 30 microg ethinylestradiol combined with 75 microg gestodene. This study involved 342 women and 4104 cycles use in Argentina, Brazil, Chile, and Mexico. Contraceptive efficacy was good with both formulations. Two pregnancies occurred in the desogestrel group but were not due to method failure. With respect to cycle control, the incidence of intermenstrual bleeding was higher during the first 3 cycles in the desogestrel group; it was significant (p <0.01) during the first 3 days of the cycle for a normal or heavy bleeding only in the Mexican group. Amenorrhea was not reported for any group, but the incidence of dysmenorrhea was significantly higher (p <0.01) in the Brazilian desogestrel group (13.8%) and was significantly lower (p <0.01) in the Mexican gestodene group (8.5%). Adverse events were similar in all the countries with headache, breast tension, and nausea, the most frequently reported symptoms. The range of mean increase in body weight varied from 0.2 kg in the Argentine group to 2.6 kg in the Chilean group (95% confidence limit, +/- 2.51) in the gestodene group, and 0.2 kg in the Argentine group to 2.5 kg in Brazilian group (95% confidence limit, +/- 2.36) in the desogestrel group. Fifteen women discontinued because of headache, but there were no significant differences between the groups regarding discontinuation for this and other medical or non-medical reasons. Both oral contraceptive preparations are reliable and well tolerated, and both have favorable effects on control cycle.

Adolescent↗

PubMed1999

Improved modeling of side-chains in proteins with rotamer-based methods: a flexible rotamer model.

Side-chain modeling has a widespread application in many current methods for protein tertiary structure determination, prediction, and design. Of the existing side-chain modeling methods, rotamer-based methods are the fastest and most efficient. Classically, a rotamer is conceived as a single, rigid conformation of an amino acid sidechain. Here, we present a flexible rotamer model in which a rotamer is a continuous ensemble of conformations that cluster around the classic rigid rotamer. We have developed a thermodynamically based method for calculating effective energies for the flexible rotamer. These energies have a one-to-one correspondence with the potential energies of the rigid rotamer. Therefore, the flexible rotamer model is completely general and may be used with any rotamer-based method in substitution of the rigid rotamer model. We have compared the performance of the flexible and rigid rotamer models with one side-chain modeling method in particular (the self-consistent mean field theory method) on a set of 20 high quality crystallographic protein structures. For the flexible rotamer model, we obtained average predictions of 85.8% for chi1, 76.5% for chi1+2 and 1.34 A for root-mean-square deviation (RMSD); the corresponding values for core residues were 93.0%, 87.7% and 0.70 A, respectively. These values represent improvements of 7.3% for chi1, 8.1% for chi1+2 and 0.23 A for RMSD over the predictions obtained with the rigid rotamer model under otherwise identical conditions; the corresponding improvements for core residues were 6.9%, 10.5% and 0.43 A, respectively. We found that the predictions obtained with the flexible rotamer model were also significantly better than those obtained for the same set of proteins with another state-of-the-art side-chain placement method in the literature, especially for core residues. The flexible rotamer model represents a considerable improvement over the classic rigid rotamer model. It can, therefore, be used with considerable advantage in all rotamer-based methods commonly applied to protein tertiary structure determination, prediction, and design and also in predictions of free energies in mutational studies.

Amino Acids↗

PubMed1999

The caa3 terminal oxidase of the thermohalophilic bacterium Rhodothermus marinus: a HiPIP:oxygen oxidoreductase lacking the key glutamate of the D-channel.

The respiratory chain of the thermohalophilic bacterium Rhodothermus marinus contains a novel complex III and a high potential iron-sulfur protein (HiPIP) as the main electron shuttle (Pereira et al., Biochemistry 38 (1999) 1268-1275 and 1276-1283). In this paper, one of the terminal oxidases expressed in this bacterium is extensively characterised. It is a caa3-type oxidase, isolated with four subunits (apparent molecular masses of 42, 19 and 15 kDa and a C-haem containing subunit of 35 kDa), which has haems of the A(s) type. This oxidase is capable of using TMPD and horse heart cytochrome c as substrates, but has a higher turnover with HiPIP, being the first example of a HiPIP:oxygen oxidoreductase. The oxidase has unusually low reduction potentials of 260 (haem C), 255 (haem A) and 180 mV (haem A3). Subunit I of R. marinus caa3 oxidase has an overall significant homology with the subunits I of the COX type oxidases, namely the metal binding sites and most residues considered to be functionally important for proton uptake and pumping (K- and D-channels). However, a major difference is present: the putative essential glutamate (E278 in Paraccocus denitrificans) of the D-channel is missing in the R. marinus oxidase. Homology modelling of the R. marinus oxidase shows that the phenol group of a tyrosine residue may occupy a similar spatial position as the glutamate carboxyl, in relation to the binuclear centre. Moreover, sequence comparisons reveal that several enzymes lacking that glutamate have a conserved substitution pattern in helix VI: -YSHPXV- instead of -XGHPEV-. These observations are discussed in terms of the mechanisms for proton uptake and it is suggested that, in these enzymes, tyrosine may play the role of the glutamate in the proton channel.

Amino Acid Sequence↗

PubMed1999

An iterative structure-assisted approach to sequence alignment and comparative modeling.

Correct alignment of the sequence of a target protein with those of homologues of known three-dimensional structure is a key step in comparative modeling. Usually an iterative approach that takes account of the local and overall structural features is required. We describe such an approach that exploits databases of structural alignments of homologous proteins (HOMSTRAD, http:/(/)www-cryst.bioc.cam.ac.uk/ approximately homstrad) and protein superfamilies (CAMPASS, http:/(/)www-cryst.bioc.cam.ac.uk/ approximately campass), in which structure-based alignments are analyzed and formatted with the program JOY (http:/(/)www-cryst.bioc.cam.ac.uk/ approximately joy) to reveal conserved local structural features. The databases facilitate the recognition of a family or superfamily, they assist in the selection of useful parent structures, they are helpful in alignment of the target sequences with the parent set, and are useful for deriving relationships that can be used in validating models. In the iterative approach, a model is constructed on the basis of the proposed sequence alignment and this is then reexpressed in the JOY format and realigned with the parent set. This is repeated until the model and sequence alignment is optimized. We examine the case for comparison and use of multiple structures of family members, rather than a single parent structure. We use the targets attempted by our group in CASP3 to assess the value of such procedures.

Algorithms↗

PubMed1999

Improvement of side-chain modeling in proteins with the self-consistent mean field theory method based on an analysis of the factors influencing prediction.

With the objective of improving side-chain conformation prediction, we have analyzed the influence of various factors on prediction by the Self-Consistent Mean Field Theory method, applied to a set of high resolution x-ray protein structure models. These factors may be classed as variations in the mean field optimization protocol, variations in the potential energy function, and variations in rotamer library completeness. We have developed an optimization protocol that consistently reached lower mean field conformational free energies than two other protocols. This protocol led to an important improvement in prediction. We observed a major improvement in prediction with two more detailed van der Waals parameter sets, which we found to be due mainly to the introduction of scaling of 1-4 interactions. In a comparison of two knowledge-based rotamer libraries of considerably different size, we observed an unexpected decrease in prediction with an increase in library completeness. However, when we introduced a torsion potential term in the potential energy function, we found an important increase in average prediction and in the prediction of almost all residue types with a more complete rotamer set. The two knowledge-based rotamer libraries now became equivalent in terms of average prediction. The results we obtained in an analysis of the effect of the introduction of an additional electrostatic term in the potential energy function were largely inconclusive. However, we found a small increase in average prediction for an electrostatic potential term with a fixed dielectric constant of 15. The combined effect of all the factors we analyzed in this study resulted in average prediction accuracies of 79.9% for X1, 68.1% for X1 + 2, and 1.590 A for global rms deviation (RMSD); the corresponding values for core residues were 88.2%, 78.6%, and 1.171 A. These values represent improvements in average prediction of 6.5% for X1, 9.1% for X1 + 2, and 0.163 A for global RMSD over the original conditions; the corresponding improvements in the core were 5.9%, 9.0%, and 0.180 A, respectively.

Amino Acids↗

PubMed1999

Diapause, pupation sites and parasitism of the horn fly, Haematobia irritans, in south-eastern Brazil.

In order to verify the occurrence of diapause, preference for pupation sites and hymenopteran parasitism, the pupae of the horn fly, Haematobia irritans (Diptera: Muscidae), were collected from undisturbed cattle dung pats in pastures, and adults of the fly were sampled from cattle in São Paulo State, south-eastern Brazil, from April 1993 to July 1994. Diapause was verified in 7.7% of pupae sampled from pastures in June and July of 1993 and in 9.9% of those sampled in May, June and July of 1994 (overall rate of 9.1%). Approximately 8.3% of the pupae were parasitized by microhymenopterans, mostly Spalangia nigroaenea and S. cameroni (Hymenoptera: Pteromalidae). Horn fly pupae were found almost exclusively inside the pat or in the soil immediately beneath and adjacent to it, and very few were collected elsewhere. Pupa mortality was 54.4% and did not change significantly during the year, but mortality was greater among pupae collected in pastures when compared to those obtained from experimental pats, lacking natural enemies.

Animals↗

PubMed1999

[Comparative study of Toronto SPV prosthesis and bileaflet mechanical aortic prosthesis with 2D-Doppler echocardiography].

AIM: The aim of this study was to make a noninvasive comparison, by means of Doppler echocardiography, of the hemodynamic performance of biological stentless xenografts and mechanical bileaflet (MB) prostheses (P) in aortic position. METHODS: We studied 20 patients (pts) with normofunctional (nf) aortic Toronto (T) Stentless Porcine valves (SPV)--Group I--8 males, aged 69 +/- 12 years, 32 +/- 9 months after surgery, and 30 pts with nf MB aortic P (Carbomedics or St. Jude Medical)--Group II--17 males (p = NS vs G I), aged 61 +/- 12 years (p < 0.01 vs G I), 30 +/- 12 months after implantation (p = NS vs G I). Both groups were comparable with regard to body surface area and surgical indication. P diameters ranged from 21 to 25 mm (G I: 22.9 +/- 1.7; G II: 22.8 +/- 1.7 - p = NS), the number of pts with the same P diameter in each group being similar. We analysed, at rest: aortic orifice diameter (AoOd - cm), maximal (GMax) and mean (GMean) transprosthesic pressure gradients, P functional area (PFA) and P resistance (PRes). Gradients (mm Hg) were calculated by means of the Bernoulli equation, PFA (cm2) by means of the continuity equation and PRes (dynes.s.cm-5) as 1333 x Gmean x SEP/SV (SEP = systolic ejection period; SV = stroke volume). RESULTS: AoOd (G I vs G II): P 21--1.78 +/- 0.04 vs 2.00 +/- 0.10 (p < 0.001); P 23--1.91 +/- 0.10 vs 2.19 +/- 0.10 (p = 0.01); P 25--2.22 +/- 0.24 vs 2.29 +/- 0.19 (NS). Doppler parameters: [table: see text] CONCLUSIONS: P T SPV show better hemodynamic performance when compared to P MB with the same diameter, in aortic position. In addition, our results suggest that P T SPV allow the use of larger valve sizes for the same aortic orifice diameter.

Aged↗

PubMed1998

Molecular dynamics simulation of cytochrome c3: studying the reduction processes using free energy calculations.

The tetraheme cytochrome c3 from Desulfovibrio vulgaris Hildenborough is studied using molecular dynamics simulation studies in explicit solvent. The high heme content of the protein, which has its core almost entirely made up of c-type heme, presents specific problems in the simulation. Instability in the structure is observed in long simulations above 1 ns, something that does not occur in a monoheme cytochrome, suggesting problems in heme parametrization. Given these stability problems, a partially restrained model, which avoids destruction of the structure, was created with the objective of performing free energy calculations of heme reduction, studies that require long simulations. With this model, the free energy of reduction of each individual heme was calculated. A correction in the long-range electrostatic interactions of charge groups belonging to the redox centers had to be made in order to make the system physically meaningful. Correlation is obtained between the calculated free energies and the experimental data for three of four hemes. However, the relative scale of the calculated energies is different from the scale of the experimental free energies. Reasons for this are discussed. In addition to the free energy calculations, this model allows the study of conformational changes upon reduction. Even if the precise details of the structural changes that take place in this system upon individual heme reduction are probably out of the reach of this study, it appears that these structural changes are small, similarly to what is observed for other redox proteins. This does not mean that their effect is minor, and one example is the conformational change observed in propionate D from heme I when heme II becomes reduced. A motion of this kind could be the basis of the experimentally observed cooperativity effects between heme reduction, namely positive cooperativity.

Biophysical Phenomena↗

PubMed1998

[Congenital bronchopulmonary cystic disease].

From September 1989 to December 1994, 12 children with congenital bronchopulmonary cystic disease were operated in the Department of Pediatric Surgery, Santa Maria Hospital. Four cases of bronchogenic cyst (BC), 2 of cystic adenomatoid malformation (CAM), 3 of pulmonary sequestration (PS), and 3 of congenital lobar emphysema (CLE) were found. Age ranged between 9 days and 10 years without predominance of gender. Seven were younger than one year of age, of which 5 were less than 6 months old at the time of surgery. The CAT scan was most useful in the diagnosis and follow-up of these children. The review of these cases helped evaluate our experience in the diagnosis and surgical approach for these congenital malformations. Successful treatment depends on early diagnosis and the planning of therapeutic priorities, based on the embryological and pathophysiological knowledge at these anomalies. The embryological mechanisms implicated in the development are discussed and the results of surgical treatment are presented.

Bronchogenic Cyst↗

PubMed1997

[Mitral valve insufficiency caused by tendinous cord rupture and mitral valve aneurysm. Significance of the echocardiographic study].

Mitral valve aneurysm is a rare complication that may occur in a myxomatous valve. We report the case of a 73 year old male patient with severe mitral regurgitation and heart failure-class IV NYHA. Echocardiography showed perforation of an aneurysm of the anterior leaflet of the mitral valve associated with rupture of tendinous cords of the posterior mitral leaflet. Diagnosis was made by transthoracic echocardiography and confirmed by transesophageal echocardiography. The patient was urgently operated with success and a mitral valve prosthesis was implanted.

Aged↗

PubMed1996

Paramagnetic NMR analysis of the seven-iron ferredoxin from the hyperthermoacidophilic archaeon Desulfurolobus ambivalens reveals structural similarity to other dicluster ferredoxins.

The seven-iron ferredoxin from the hyperthermophilic archaeon Desulfurolobus ambivalens has been investigated by one-dimensional and two-dimensional 1H-NMR in its oxidized and dithionite-reduced states. All iron atoms of both the three-iron and the four-iron cluster are bound to cysteine residues whose hyperfine-shifted resonances were characterized. The pattern of these resonances is similar to those from three-iron, four-iron and eight-iron ferredoxins previously described in the literature, but the four-iron cluster has a shift pattern different from that in other seven-iron proteins. A second set of hyperfine-shifted resonances clearly indicates sample heterogeneity, which possibly involves the four-iron cluster. The observation of interresidue NOEs between two different cysteine residues proves the existence of close spatial proximity of the two clusters in D. ambivalens ferredoxin and therefore indicates structural homology to other dicluster ferredoxins. Moreover, this feature is crucial for the sequence-specific assignment of the hyperfine-shifted resonances. The C alpha-C beta-S-Fe dihedral angles of the cysteine residues coordinating the four-iron cluster could be estimated, and the electronic structure of the three-iron cluster is discussed.

Ferredoxins↗

PubMed1995

A seven-iron ferredoxin from the thermoacidophilic archaeon Desulfurolobus ambivalens.

A seven-iron ferredoxin was isolated from aerobically grown cells of the hyperthermoacidophilic archaeon Desulfurolobus ambivalens (DSM 3772). The protein is monomeric, with an apparent molecular mass of 15 kDa and contains 7 iron atoms/molecule. The N-terminal sequence shows a large similarity (70% identity) with that of the ferredoxin isolated from the archaeon Sulfolobus acidocaldarius. The EPR characteristics in both the native (oxidized) and dithionite-reduced states of this protein allowed an unequivocal identification of a [3Fe-4S]1+/0 center, with a reduction potential of -270 +/- 20 mV, at pH 7.5. The protein also contains a [4Fe-4S]2+/1+ center with a very low reduction potential (Eo = -540 mV, pH 7.0), which yields a rhombic EPR spectrum upon reduction with sodium dithionite at high pH. The reduction potentials of both centers are slightly pH dependent between pH 6 and 9. The [3Fe-4S] ferredoxin center is able to accept electrons from pyruvate oxidase and NADH oxidase isolated from D. ambivalens. This ferredoxin is present in large amounts (at least 130 mg/kg wet cells), which allowed the unequivocal observation of oxidized [3Fe-4S] clusters in intact D. ambivalens cells.

Amino Acid Sequence↗

PubMed1994

[Fecal incontinence. What to do?].

There are various functional or organic pathologies that can interfere with the defecation mechanism. The authors present 4 clinical cases with fecal incontinence: 1 false enconprese--2 myelomeningoceles--1 ileo-anal anastomose (total colectomy in Behçet disease). All cases were evaluated manometrically and operated with myorrhaphy of the rectum levators, plasty of gluteus muscles with approximation and median suture, (without rectum circumferential dissection), associating contiguous muscles of independent enervation. In incontinence due to ileo-anal anastomose, a prior ileostomy was made and an S ileal anal-pouch reconstructed. In other cases any intestinal derivation was made. In 3 cases, post operation treatment went well without incidents and there was a clear improvement in the continence. In the other case (myelomeningocele) a complication developed-an abscess with suture dehiscence-which most likely contributed to a less satisfactory result. After the incontinence cases being entirely studied the technique followed is easy to use, adopting neighboring muscular groups capable of improving the continence mechanism.

Adolescent↗

PubMed1994

[Vasculitis associated with ANCA].

The authors present a case report of a 62-year old woman, with hypertension for many years. She suffered from weakness, anorexia and weight loss in the last 6 months. On admission, anemia, elevated ESR, haematuria, proteinuria and renal failure were present. Renal biopsy was compatible with chronic glomerulonephritis. The clinical picture and positivity for P-ANCA suggested systemic vasculitis. Later evidence of maxillary sinusitis and nasal mucosae ulcers as well as pneumonitis, although biopsy did not reveal granulomas, suggested the diagnosis of Wegener Vasculitis. Medicated with Cyclophosphamide and Prednisolone, for a year, with improvement. The authors make a brief discussion of the clinical criteria for classification of ANCA-associated systemic vasculitis.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed1994

[Ritual circumcision and the plastic repair of phimosis].

The AA. describe two variations of their personal technique of foreskin plasty for phimosis treatment. They utilize a variation of Duhamel procedure, with incision of foreskin dorsal face in italic S in cases where the striction ring is moderate and allows a slipping with glandular exposure. They resected ad minima the foreskin in the cases of very serious phimosis and make a YV plasty on the dorsal face, and if necessary a small excision à la demande of the remaining ventral skin. They achieve a good aesthetic result in both techniques and most of operated cases are hard to distinguish from a normal foreskin. The plasties with foreskin maintenance tend to be used in the modern European culture, where the rites disappeared and hygienic habits gained roots. With the exception of religious reasons or strict medical indications (diabetes, skin lesions, etc.) the phimosis repair by mutilation procedures tends to disappear.

Circumcision, Male↗

PubMed1992

Wuchereria bancrofti microfilarial density of autochthonous cases and natural Culex infectivity rates in northeast Brazil.

Autochthonous Wuchereria bancrofti microfilaraemic cases from three neighbouring cities of Northeast Brazil (Recife, Jaboatao and Olinda) were selected from thick smear or filtration positive individuals and classified by their microfilarial (mf) densities through polycarbonate membrane blood filtration. Individuals were subdivided into two groups: autochthonous cases without any previous specific drug administrations (group A) and those with one or more previous DEC treatments (group B). In Recife, unlike Jaboatao and Olinda (P less than 0.05), the majority of autochthonous cases were over 20 years old and no microfilaraemics were found under the age of 10. The majority of cases in Recife had lower levels of mf density (66.6%), while in Jaboatao and Olinda higher mf carriers (65.6%) prevailed when group A (n = 141) individuals were rearranged in mf density above and below 500 mf ml-1 (P less than 0.01). All subjects in group B (n = 110) had less than 501 mf ml-1 and the great majority less than 100 mf ml-1, but a significant difference (P less than 0.05) between Recife and the two other cities was observed. Captured mosquitoes in Recife, Jaboatao and Olinda totalled 7856, 8010 and 8003 respectively. The infectivity rate found in Recife (0.61%) was significantly lower than in Jaboatao (1.21%) and Olinda (1.31%) (P less than 0.001). The authors discuss the possible influences of previous disease control programmes (medicated salt and individual treatments) applied only to the city of Recife in relation to the outcome of this investigation.

Animals↗

PubMed1988

[Torsion of the spleen].

The authors describe, a case of torsion of the splenic hilum complicated with a Salmonella typhimurium infection in a child aged 14 months. The existence of a defect of the spleen fixation to the parietal peritoneum, the wandering spleen, that occurs during foetal life is responsible for this situation. The etiology of this entity as well as its clinical presentation and differential diagnosis are analysed. the therapeutic indications os splenectomy and splenopexy are discussed.

Diagnosis, Differential↗