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Biomedical subjects

A Mendoza

Publications and source records attributed to A Mendoza.

At least 19 recordsLinked to original sources

Efficacy and safety of flexible-dose oral sildenafil citrate (Viagra) in the treatment of erectile dysfunction in Brazilian and Mexican men.

A 12-week, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of flexible-dose sildenafil citrate (Viagra) treatment (25, 50 or 100 mg) in Brazilian and Mexican men with erectile dysfunction (ED) of broad-spectrum etiology. Efficacy was assessed on the basis of responses to the 15-item International Index of Erectile Function (IIEF) questionnaire, completed at baseline and after 12 weeks of treatment. At end point, mean scores for all IIEF domains of sexual function (erectile function, orgasmic function, sexual desire, intercourse satisfaction and overall satisfaction) were significantly (P<0.0001) higher in the sildenafil group (n=109) than in the placebo group (n=105). These findings confirm the significant increases in frequency of penetration and frequency of maintained erections reported previously. Sildenafil treatment was well tolerated. The most common adverse events were headache and flushing. In conclusion, sildenafil is a well-tolerated and effective treatment for ED of broad-spectrum etiology in Latin American men.

Administration, Oral↗

Development of a homologous transformation system for the opportunistic human pathogen Aspergillus fumigatus based on the sC gene encoding ATP sulfurylase.

The development of a homologous transformation system for the opportunistic human pathogenic fungus Aspergillus fumigatus is described. The system is based on the sC gene encoding ATP sulfurylase. Several A. fumigatus sC mutant strains were readily isolated by strong selection for selenate resistance. The coding region plus upstream and downstream regulatory sequences of the A. fumigatus sC gene were cloned by inverse PCR and then sequenced. Sequencing of the sC cDNA revealed the presence of five introns located within the first half of the gene. The A. fumigatus sC gene encodes a protein of 574 amino acids which is highly similar to ATP sulfurylases from the filamentous fungal species Aspergillus nidulans, Aspergillus terreus and Penicillium chrysogenum. By contrast, ATP sulfurylases from the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe lack the C-terminal adenosine-5'-phosphosulfate kinase-like domain present in the filamentous fungal orthologues. A 3.8-kb DNA fragment amplified by PCR and containing the sC gene plus 5' and 3' flanking regions was cloned into pUC19 to give the vector pSCFUM. Transformation of two different sC mutant isolates with the plasmid pSCFUM established the functionality of this new homologous transformation system. Molecular analysis of sC+ transformants showed that up to 44% of transformed clones contained one or more copies of the entire plasmid integrated at the sC locus. This result also demonstrates the utility of the sC marker for targeting specific genetic constructs to the A. fumigatus sC locus, facilitating studies of gene regulation and function.

Amino Acid Sequence↗

Prenatal sonographic diagnosis of vasa previa: ultrasound findings and obstetric outcome in ten cases.

OBJECTIVE: To assess the specificity of sonographic diagnosis of vasa previa and pregnancy outcome in sonographically diagnosed cases. METHODS: We prospectively collected cases of vasa previa diagnosed by color Doppler sonography. Delivery by elective Cesarean section after demonstration of fetal pulmonary maturity and prior to the onset of labor was recommended unless obstetric complications supervened. Data regarding maternal obstetric courses and newborn status were collected. RESULTS: Eleven cases of vasa previa without placenta previa were diagnosed among 33 208 women over an 8-year period. Ten patients had confirmation of the diagnosis by the delivering obstetrician and/or placental examination, giving a specificity of diagnosis of 91%. Among the 10 patients with confirmed vasa previa, two were delivered at 31.5 and 35.5 weeks' gestation prior to demonstration of lung maturity, and the remainder were delivered at 34-37.5 weeks, after lung maturity. All infants had normal Apgar scores and survived. One baby had Scimitar syndrome, which was not suspected from sonography. CONCLUSIONS: The specificity of sonographic diagnosis of vasa previa at our center was 91%. Antenatal diagnosis permitted us to prevent the catastrophic outcomes commonly associated with vasa previa.

Adult↗

Annotated draft genomic sequence from a Streptococcus pneumoniae type 19F clinical isolate.

The public availability of numerous microbial genomes is enabling the analysis of bacterial biology in great detail and with an unprecedented, organism-wide and taxon-wide, broad scope. Streptococcus pneumoniae is one of the most important bacterial pathogens throughout the world. We present here sequences and functional annotations for 2.1-Mbp of pneumococcal DNA, covering more than 90% of the total estimated size of the genome. The sequenced strain is a clinical isolate resistant to macrolides and tetracycline. It carries a type 19F capsular locus, but multilocus sequence typing for several conserved genetic loci suggests that the strain sequenced belongs to a pneumococcal lineage that most often expresses a serotype 15 capsular polysaccharide. A total of 2,046 putative open reading frames (ORFs) longer than 100 amino acids were identified (average of 1,009 bp per ORF), including all described two-component systems and aminoacyl tRNA synthetases. Comparisons to other complete, or nearly complete, bacterial genomes were made and are presented in a graphical form for all the predicted proteins.

DNA, Bacterial↗

[Morphogenesis of the sexual phase of six Mexican species of the Dryopteris (Dryopteridaceae), Part II].

The development of the sexual phase of six Mexican species of Dryopteris is described and compared. Spores of all studied species are monolete, ellipsoid and have a rugose surface; the perine is folded, brown to dark brown, with a tubercled outline. Germination pattern is of the Vittaria-type and the development pattern of the prothallia is of the Aspidium-type. Gametangia are of the common type for the leptosporangiate advanced ferns. First leaves of the sporophytes appear 258-265 after sowing and apparently in Dryopteris pseudo-filix-mas the sporophyte have an apogamic origin (80 days). To make a comparative analysis of gametophytic characteristics in the twelve Mexican species and conclude of germination is of the Vittaria-type and development pattern prothallial is of the Aspidium-type, and unicelular trichomes on margin and superficial gametophytic to yield irregular aspect are characteristics to yield unit and characteristic to genera to conform Dryopteridaceae family (sensu Moran 1995) with the exception of Didymochlaena genus.

Germination↗

Translation elongation factor 2 is encoded by a single essential gene in Candida albicans.

Translation elongation factor 2 (eEF2) is a large protein of more than 800 amino acids which establishes complex interactions with the ribosome in order to catalyze the conformational changes needed for translation elongation. Unlike other yeasts, the pathogenic fungus Candida albicans was found to have a single gene encoding this factor per haploid genome, located on chromosome 2. Expression of this locus is essential for vegetative growth, as evidenced by placing it under the control of a repressible promoter. This C. albicans gene, named EFT2, was cloned and sequenced (EMBL accession number Y09664). Genomic and cDNA sequence analysis identified common transcription initiation and termination signals and an 842 amino acid open reading frame (ORF), which is interrupted by a single intron. Despite some genetic differences, CaEFT2 was capable of complementing a Saccharomyces cerevisiae Deltaeft1 Deltaeft2 null mutant, which lacks endogenous eEF2, indicating that CaEFT2 can be expressed from its own promoter and its intron can be correctly spliced in S. cerevisiae.

Candida albicans↗

NifA-dependent expression of glutamate dehydrogenase in Rhizobium etli modifies nitrogen partitioning during symbiosis.

Constitutive expression of foreign glutamate dehydrogenase in Rhizobium etli inhibits bean plant nodulation (A. Mendoza, A. Leija, E. Martínez-Romero, G. Hernández, and J. Mora. Mol. Plant-Microbe Interact. 8:584-592, 1995). Here we report that this inhibition is overcome when controlling gdhA expression by NifA, thus delaying the GDH activity onset after nodule establishment. Expression of gdhA modifies the nitrogen partitioning inside the bacteroid, where newly synthesized ammonia is preferentially incorporated into the amino acid pool instead of being exported to the infected cells. As a consequence, the fixed nitrogen transport to the leaves, measured as the ureides content in xylem sap, is significantly reduced. Nitrogenase activity, although not nifHDK expression, is significantly reduced in bacteroids expressing gdhA, probably due to the utilization of energy and reducing power for nitrogen assimilation. Here we show that ammonia assimilation inside R. etli bacteroids is active, albeit at low levels, and when enhanced is deleterious to the symbiotic performance. This leads us to believe that further reduction of the basal nitrogen metabolism in the bacteroid might stimulate the nitrogenase activity and increase the nitrogen supply to the plant.

Bacterial Proteins↗

Translation elongation factor 2 is part of the target for a new family of antifungals.

Translation elongation factor 2 (EF2), which in Saccharomyces cerevisiae is expressed from the EFT1 and EFT2 genes, has been found to be targeted by a new family of highly specific antifungal compounds derived from the natural product sordarin. Two complementation groups of mutants resistant to the semisynthetic sordarin derivative GM193663 were found. The major one (21 members) consisted of isolates with mutations on EFT2. The minor one (four isolates) is currently being characterized but it is already known that resistance in this group is not due to mutations on EFT1, pointing to the complex structure of the functional target for these compounds. Mutations on EF2 clustered, forming a possible drug binding pocket on a three-dimensional model of EF2, and mutant cell extracts lost the capacity to bind to the inhibitors. This new family of antifungals holds the promise to be a much needed and potent addition to current antimicrobial treatments, as well as a useful tool for dissection of the elongation process in ribosomal protein synthesis.

Amino Acid Sequence↗

Liver transplantation for fulminant hepatic failure: importance of renal failure.

One hundred eighty-one consecutive patients with fulminant hepatic failure (FHF) presenting in a 2-year period were reviewed. In this cohort we examined the impact of pretransplant renal failure on mortality and morbidity following orthotopic liver transplantation (OLTx). Twenty-seven patients (18 female, 9 male) with a median age of 43.5 years (range 19-65 years) underwent OLTx. FHF was due to idiosyncratic drug reaction (n = 4), paracetamol overdose (n = 3), seronegative hepatitis (n = 17), hepatitis B (n = 1), veno-occlusive disease (n = 1), and Wilson's disease (n = 1). Renal failure was present in 14 patients, 7 of whom died (whereas there was 100% survival in patients without renal failure). Pretransplant renal failure was associated with prolonged mechanical ventilation (13 days vs 6 days, P = 0.05), prolonged intensive care stay (17 days vs 8 days, P = 0.01) and prolonged hospital stay (27 vs 21 days, P = NS). Pretransplant renal failure did not predict renal dysfunction at 1 year after OLTx. We conclude that the survival of patients transplanted for FHF is inferior to that of patients transplanted for chronic liver disease (67% vs 88% 1-year survival in Birmingham). For patients with FHF undergoing transplantation, pretransplant renal failure strongly predicts poor outcome with significantly greater consumption of resources.

Adult↗

Characterization of SKM1, a Saccharomyces cerevisiae gene encoding a novel Ste20/PAK-like protein kinase.

Ste20/PAK serine/threonine protein kinases have been suggested as playing essential roles in cell signalling and morphogenesis as potential targets of Cdc42 and Rac GTPases. We have isolated and characterized the Saccharomyces cerevisiae SKM1 gene, which codes for a novel member of this family of protein kinases. The amino acid sequence analysis of Skm1p revealed the presence of a PH domain and a putative p21-binding domain near its amino terminus, suggesting its involvement in cellular signalling or cytoskeletal functions. However, deletion of SKM1 produced no detectable phenotype under standard laboratory conditions. Moreover, disruption of each of the two other S. cerevisiae Ste20/PAK-like kinase-encoding genes, STE20 and CLA4, in skm1 backgrounds, showed that Skm1p is not redundant with Ste20p or Cla4p. Interestingly, overexpression of SKM1 led to morphological alterations, indicating a possible role for this protein in morphogenetic control. Furthermore, overproduction of Skm1p lacking its N-terminus caused growth arrest. This effect was also seen when similarly truncated versions of Ste20p or Cla4p were overexpressed. We further observed that overproduction of this C-terminal fragment of Skm1p complements the mating defect of a ste20 mutant strain. These results suggest that the N-terminal domains of S. cerevisiae Ste20/ PAK-like protein kinases share a negative regulatory function and play a role in substrate specificity.

Amino Acid Sequence↗

The Candida albicans PKC1 gene encodes a protein kinase C homolog necessary for cellular integrity but not dimorphism.

Using a DNA fragment derived from the Saccharomyces cerevisiae protein kinase C gene (PKC1) as a probe to screen an ordered array library of genomic DNA from the dimorphic pathogenic fungus Candida albicans, the C. albicans PKC1 gene (CaPKC1) was isolated. The CaPKC1 gene is predicted to encode a protein of 1079 amino acids with 51% sequence identity over the entire length with the S. cerevisiae Pkc1 protein and is capable of functionally complementing the growth defects of a S. cerevisiae pkc1 delta mutant strain on hypo-osmotic medium. Deletion of both endogenous copies of the CaPKC1 gene in diploid C. albicans cells resulted in an osmotically remedial cell lysis defect of both the budding and the hyphal growth form and morphologically aberrant cells of the budding form. Despite these abnormalities, the transition between the two growth forms of C. albicans occurred normally in pkc1/pkc1 double disruptants. Capkc1p was modified at its C-terminus with two repeats of the Staphylococcus aureus protein A IgG-binding fragment (ZZ-sequence tag) and partially purified by chromatography on DEAE-Sepharose and IgG-Sepharose. In vitro, Capkc1p preferably phosphorylated the S. cerevisiae Pkc1p pseudosubstrate peptide and myelin basic protein, but not histones, protamine or dephosphorylated casein, and failed to respond to cofactors known to activate several mammalian PKC isozymes.

Amino Acid Sequence↗

Cervical flexion: its contribution to normal and abnormal cardiac morphogenesis.

Although His in 1881 and Patten in 1922 suggested that cervical flexion could play an important role in normal cardiac morphogenesis, until recently this hypothesis has been largely neglected. The purpose of this report is to present data indicating that prevention of cervical flexion leads to double outlet right ventricle (DORV), which is unrelated to any affect on neural crest cell migration. At stage 11-12, suture material was inserted into the neural tube to prevent cervical flexion. Six out of 22 experimental embryos survived until stage 38 and 5 out of 6 had DORV. Neither abnormalities of the aortico-pulmonary septum nor interruption of the aortic arch were observed at dissection. Hemodynamic studies performed at stage 18 revealed distinctive characteristics that are inconsistent with hemodynamic studies previously reported following neural crest ablation. With respect to immunohistochemical studies using neural crest associated antigen HNK-1 antibody, normal migration of neural crest cells was noted in the outflow tract in the experimental embryos at stage 22. These hemodynamic and immunohistochemical studies suggest that insertion of suture material into the neural tube at stage 11-12 does not jeopardize neural crest migration. We propose that reduction in cervical flexion increases the distance between the future aorta and the left ventricle, which prevents the transition of intracardiac flow pattern from a serial circulation to a parallel one, leaving persistence of a "double outlet" from the right ventricle.

Animals↗

Clinical spectrum, investigations and treatment of Budd-Chiari syndrome.

The clinical presentation, investigations, therapeutic modalities, prognosis and outcome of 44 patients with Budd-Chiari syndrome (BCS) were reviewed. There were 27 women and 17 men. Median age at presentation was 37 years (range 14-60). Possible aetiological factors were identified in 31 patients (70%). Myeloproliferative disorders were the commonest aetiology. Abdominal pain and swelling were the commonest presenting symptoms. Sixteen patients underwent a shunt operation (14 mesocaval, 2 mesoatrial). Ten patients had liver transplantation. Eleven patients had angioplasty/stent as their only treatment, and seven were treated medically or died before any treatment was instituted. Radiological intervention was comparable to mesocaval shunt in relieving patients' symptoms and in achieving good long-term results. Medical treatment and liver transplantation both yielded poor results. Radiological intervention in the form of balloon angioplasty or stent placement gives good results in a subgroup of BCS patients, and should be tried first to relieve the hepatic outflow obstruction. Mesocaval shunts provide good results in selected cases. Underlying haematological causes should be intensively investigated and promptly treated.

Adult↗

Placental cord insertion visualization with prenatal ultrasonography.

Color Doppler and gray scale sonography can be used prenatally to identify the location of the cord insertion into the placenta. The purposes of this paper were to (1) relate sonographic identification of placental cord insertion with placental pathology; (2) evaluate the possibility that a marginal cord insertion may evolve into a velamentous cord insertion; and (3) determine the frequency and factors affecting sonographic visualization of cord insertion. Our results show that the sonographic assessment of cord insertion correlated with the pathologic outcome in 83% (106 of 128) of singleton pregnancies and at least one of the fetuses in 72% (8 of 11) of twin or triplet pregnancies. Although the sensitivity for identification of an abnormal cord insertion was low (42%), the specificity was high (95%). Our data suggest that marginal cord insertion evolved into velamentous cord insertion in one singleton and one twin. Our results showed that cord insertion was visualized in 54% of fetuses scanned in a routine clinical practice. Cord insertion visualization was possible at all gestational ages, although it was more difficult at later gestational ages. In conclusion, this study provides evidence that (1) ultrasonography (either gray scale or color Doppler) is useful in identifying normal, marginal, and velamentous cord insertion; (2) marginal cord insertion may evolve into velamentous cord insertion as pregnancy progresses; (3) in clinical practice the cord insertion site was visualized in just over half of the cases, and (4) prenatal identification of marginal and velamentous cord insertion potentially may be useful for planning obstetrical management.

Female↗

Prenatal sonographic diagnosis of intracranial haemorrhage: report of a case with a sinusoidal fetal heart rate tracing, and review of the literature.

The sinusoidal fetal heart rate pattern has been described in association with severe fetal anaemia, with fetal hypoxaemia, and with the administration of parenteral narcotics. Here, we report a case of decreased fetal movement in which a sinusoidal tracing was recorded. The sonographic diagnosis of a massive fetal intracranial haemorrhage was made. A non-interventive approach was taken and the fetus died soon after in utero. We review 28 previous cases in which the prenatal sonographic diagnosis of fetal intracranial haemorrhage was made, including the underlying maternal and fetal factors and neonatal outcomes. We propose that the sinusoidal tracing in this case was due to the intracranial bleed and suggest that fetal intracranial haemorrhage be considered in the sonographic evaluation of the fetus with a sinusoidal pattern.

Cerebral Hemorrhage↗