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Biomedical subjects

A Cabello

Publications and source records attributed to A Cabello.

At least 37 records · Page 2Linked to original sources
PubMed2001

Antimicrobial activity of ergokonin A from Trichoderma longibrachiatum.

AIMS: Natural fungal products were screened for antifungal compounds. The mode of action of one of the hits found and the taxonomy of the producing organism were analysed. METHODS AND RESULTS: An extract from a Trichoderma species showed a more potent activity in an agar-based assay against the null mutant fks1::HIS strain than against the wild-type strain, suggesting that it could contain a glucan synthesis inhibitor. The active component was identified as the known compound ergokonin A. The compound exhibited activity against Candida and Aspergillus species, but was inactive against Cryptococcus species. It induced alterations in the hyphal morphology of Aspergillus fumigatus. The identification of the producing isolate was confirmed by sequencing of the rDNA internal transcribed spacers and comparison with the sequences of other Trichoderma species. The analysis showed that the producing fungus had a high homology with other strains classified as Trichoderma longibrachiatum and its teleomorph Hypocrea schweinitzii. CONCLUSIONS: The antifungal activity spectrum of ergokonin A and the morphology alterations induced on A. fumigatus are consistent with glucan synthesis as the target for ergokonin A. The production of ergokonin A is not uncommon, but is probably restricted to Trichoderma species. SIGNIFICANCE AND IMPACT OF THE STUDY: The discovery that ergokonin A could be an inhibitor of glucan synthesis, having a structure very different to other inhibitors, increases the likelihood that orally active agents with this fungal-specific mode of action may be developed.

Animals↗
PubMed2001

Molecular heterogeneity of myophosphorylase deficiency (McArdle's disease): a genotype-phenotype correlation study.

We report on 54 Spanish patients with McArdle's disease from 40 unrelated families. Molecular analysis revealed that the most common R49X mutation was present in 70% of patients and 55% of alleles. The G204S mutation was less frequent and found in 14.8% of patients and 9% of mutant alleles. The W797R mutation was observed in 16.5% of patients, accounting for 13.7% of mutant alleles. Moreover, 78% of mutant alleles among Spanish patients can be identified by using polymerase chain reaction-restriction fragment length polymorphism analysis for the R49X, G204S, and W797R mutations, which makes noninvasive diagnosis possible through molecular genetic analysis of blood DNA. Six novel mutations were found. Three were missense mutations, E348K, R601W, and A703V; two nonsense mutations, E124X and Q754X; and one single base pair deletion, 533 delA. No clear genotype-phenotype correlation emerges from our study. Most of the mutations of uncharged and solvent inaccessible residues and the truncations must disrupt the basic structure of the protein. The mutations of charged residues would be expected to interfere with internal hydrogen bonding networks, introducing severe incompatible partnering that is caused by poor packing or electrostatic repulsions.

Adolescent↗
PubMed2000

Quantum key distribution in the Holevo limit.

A theorem by Shannon and the Holevo theorem impose that the efficiency of any protocol for quantum key distribution, E, defined as the number of secret (i.e., allowing eavesdropping detection) bits per transmitted bit plus qubit, is E < or = 1. The problem addressed here is whether the limit E = 1 can be achieved. It is showed that it can be done by splitting the secret bits between several qubits and forcing Eve to have only a sequential access to the qubits, as proposed by Goldenberg and Vaidman. A protocol with E = 1 based on polarized photons and in which Bob's state discrimination can be implemented with linear optical elements is presented.

Journal Article↗
PubMed2000

Time window for clinical effectiveness of mass evacuation in a rat balloon model mimicking an intraparenchymatous hematoma.

The purpose of this study is to evaluate in a rat model if the early removal of an experimental intracerebral mass mimicking an extensive subcortical hematoma improves neurological outcome. Fifty six male Wistar rats were studied. A balloon was placed sterotactically at the level of the striatum. The balloon was inflated to 100 microl for periods of 10, 60 or 120 min (with 10 animals in each group). In 10 animals the balloon was not deflated and there were four sham operated cases. Neurological deficit was evaluated by a blinded observer by means of a clinical scale from 0 to 8 points at 24 and 72 h after inflation. Three additional animals at each inflation period were sacrificed after 6 h for pathological study with hematoxylin-eosin staining. Death rate was 9/10 animals who had permanent inflation, 4/10 in those with 2 h inflation, 2/10 for 1 h inflation and 0/10 for 10 min inflation (P<0.01 in chi square test). Many animals developed a particular clinical syndrome not previously described. Mean 72 h clinical scores (0-8 points) were 7.6 (S.D.: 1. 2) for the permanent inflation group, 4.4 (S.D.: 3.2) for 2 h of inflation, 2.3 (S.D.: 3.2) for 1 h and 0.4 (0.9) for 10 min of inflation (P<0.01 in Kruskal Wallis test). In the pathological study the rate of damaged neurons was significantly higher in the permanent than in transient inflation groups. In conclusion, in this balloon model evacuation of an extensive acute expanding subcortical (hematoma-like) mass must be performed within a limited time window to prevent the development of irreversible neurological deficits or death.

Animals↗
PubMed2000

A missense mutation W797R in the myophosphorylase gene in a Spanish patient with McArdle's disease.

We identified a novel missense mutation in the myophosphorylase gene (PYGM) in a Spanish patient with McArdle's disease. This homozygous T-to-C transition results in the replacement of a highly conserved tryptophan at amino acid position (aa) 797 with an arginine in the C-terminal domain of the PYGM protein. The lack of enzyme activity in the proband's muscle is consistent with a crucial role of the aa 797 in the normal function of the PYGM protein. Our data further expand the genetic heterogeneity in patients with McArdle's disease.

Adult↗
PubMed2000

Two homozygous mutations (R193W and 794/795 delAA) in the myophosphorylase gene in a patient with McArdle's disease.

We report two novel homozygous mutations in the myophosphorylase gene (PYGM) in a patient with McArdle's disease. A C-to-T transition that changed an arginine to tryptophan at codon 193 (R193W) in exon 5, and a deletion of two adenine base pairs in exon 20 at codon 794/795 (794/795 delAA) were identified. Several lines of evidence suggest the pathogenicity of both mutations: (i) they were the only nucleotide alteration in the coding region and adjacent exon/intron boundaries of the PYGM gene; (ii) the R193W mutation leads to the replacement of a highly conserved amino acid residue involved in glucose-6-P binding, and the 794/795 delAA mutation predicts a frameshift and premature termination of the protein; (iii) 60 normal controls and 20 disease controls did not have the mutations in their 160 alleles. Hum Mutat 15:294, 2000.

Adolescent↗
PubMed2000

Molecular analysis of Spanish patients with AMP deaminase deficiency.

We found six patients with AMPD deficiency in muscle who were homozygous for the most common mutation, Q12X in the AMPD gene (AMPD1), associated with this disease. Three patients had AMPD deficiency alone, showing a mild clinical phenotype. Two patients showed a defect of PPL in muscle, and were homozygous for the most common mutation associated with McArdle's disease, R49X in the muscle PPL gene (PYGM). In one of these patients, the clinical phenotype was more severe than usually seen in patients with McArdle's disease. The remaining patient harbored the mtDNA A3243G mutation, showing one of the usual clinical patterns associated with this mutation. We conclude that the Q12X mutation in AMPD1 may result in a mild clinical effect; that it is frequent in the Spanish population, and therefore frequently associated with other metabolic diseases; and that the effect of the association of AMPD and PPL deficiencies seems to be neutral.

AMP Deaminase↗
PubMed2000

Identification of novel mutations in Spanish patients with muscle carnitine palmitoyltransferase II deficiency.

Carnitine palmitoyltransferase II (CPT II) deficiency is the most common recessively inherited disorder of lipid metabolism affecting skeletal muscle and the most frequent cause of hereditary myoglobinuria. We studied 5 Spanish patients with CPT II deficiency from four unrelated families. Four patients had the typical clinical phenotype of muscle CPT II deficiency with recurrent episodes of myoglobinuria, triggered by prolonged exercise, fasting, or fever, and marked elevation of creatine kinase values during metabolic crisis. One patient had exercise-related myalgia, cramps and moderate elevation of serum CK values, but had never had myoglobinuria. Molecular analysis showed that three patients were heterozygous for the S113L mutation and one patient heterozygous for the P50H substitution. To identify the mutations in the other alleles of our patients we amplified and sequenced genomic DNA fragments encompassing the entire coding region and intron/exon boundaries of the CPT2 gene. We found the recently reported 178 insT/del 25 bp in one patient. Three novel mutations were identified: a Y120C substitution that leads to a nonconservative amino acid replacement; a 36-38 insGC mutation that results in premature termination of the translation; and an I502T substitution that affects a conserved amino acid residue in the CPT II protein. Our data confirm the molecular heterogeneity of patients with CPT II deficiency, and suggest that the ethnic origin has to be taken into account before performing mutation analysis in these patients.

Adolescent↗
PubMed2000

Suprasellar chordoid glioma.

Brat et al. (J Neuropathol Exp Neurol 57:288-290, 1998) reported eight cases of a new clinico-pathological entity, which occurs mainly in the third ventricle of middle-aged females, which they described as chordoid glioma of the third ventricle. We report a new case of a 41-year-old woman with a suprasellar chordoid glioma with histological, immunohistochemical and ultrastructural studies. We discuss the differential diagnosis between chordoma, chordoid meningioma, germinoma and pituitary adenoma. Histologically, the tumour showed cords and lobules of isomorphic epithelioid cells in a vacuolated matrix with prominent multifocal lymphoplasmacytic infiltrates in which some histiocytes and isolated Touton-type giant cells were seen; cells were immunoreactive for glial fibrillary acidic protein but negative for epithelial membrane antigen. Ultrastructural examination revealed abundant intermediate filament but no desmosomes, microvilli nor cilia were seen.

Adult↗
PubMed2000

The discovery of enfumafungin, a novel antifungal compound produced by an endophytic Hormonema species biological activity and taxonomy of the producing organisms.

In a screening of natural products with antifungal activity derived from endophytic fungi, we detected a potent activity in a culture belonging to the form-genus Hormonema, isolated from leaves of Juniperus communis. The compound is a new triterpene glycoside, showing an antifungal activity highly potent in vitro against Candida and Aspergillus and with moderate efficacy in an in vivo mouse model of disseminated candidiasis. The agent is especially interesting since its antifungal spectrum and its effect on morphology of Aspergillus fumigatus is comparable to that of the glucan synthase inhibitor pneumocandin B,,, the natural precursor of the clinical candidate MK-0991 (caspofungin acetate). An additional search for other Hormonema isolates producing improved titers or derivatives resulted in the isolation of two more strains recovered from the same plant host showing identical activity. The producing isolates were compared with other non-producing Hormonema strains by DNA fingerprinting and sequencing of the rDNA internal transcribed spacers. Comparison of rDNA sequences with other fungal species suggests that the producing fungus could be an undetermined Kabatina species. Kabatina is a coelomycetous genus whose members are known to produce Hormonema-like states in culture.

Animals↗
PubMed2000

A homozygous missense mutation (A659D) in the myophosphorylase gene in a Spanish patient with McArdle's disease.

We identified a novel missense mutation in the myophosphorylase gene (PYGM) in a Spanish patient with McArdle's disease. This homozygous C-to-A mutation results in the replacement of a highly conserved alanine at amino acid position 659 with an aspartic acid in the C-terminal domain of the myophosphorylase gene protein, near binding sites for pyridoxal phosphate and glucose. Our data further expand the genetic heterogeneity in patients with McArdle's disease.

Adult↗
PubMed2000

Discovery of novel antifungal (1,3)-beta-D-glucan synthase inhibitors.

The increasing incidence of life-threatening fungal infections has driven the search for new, broad-spectrum fungicidal agents that can be used for treatment and prophylaxis in immunocompromised patients. Natural-product inhibitors of cell wall (1,3)-beta-D-glucan synthase such as lipopeptide pneumocandins and echinocandins as well as the glycolipid papulacandins have been evaluated as potential therapeutics for the last two decades. As a result, MK-0991 (caspofungin acetate; Cancidas), a semisynthetic analogue of pneumocandin B(o), is being developed as a broad-spectrum parenteral agent for the treatment of aspergillosis and candidiasis. This and other lipopeptide antifungal agents have limited oral bioavailability. Thus, we have sought new chemical structures with the mode of action of lipopeptide antifungal agents but with the potential for oral absorption. Results of natural-product screening by a series of newly developed methods has led to the identification of four acidic terpenoid (1,3)-beta-D-glucan synthase inhibitors. Of the four compounds, the in vitro antifungal activity of one, enfumafungin, is comparable to that of L-733560, a close analogue of MK-0991. Like the lipopeptides, enfumafungin specifically inhibits glucan synthesis in whole cells and in (1,3)-beta-D-glucan synthase assays, alters the morphologies of yeasts and molds, and produces a unique response in Saccharomyces cerevisiae strains with point mutations in FKS1, the gene which encodes the large subunit of glucan synthase.

Antifungal Agents↗
PubMed2000

Fatal familial insomnia: clinical, neuropathological, and genetic description of a Spanish family.

The clinical presentation and evolution, neuropathological findings, and genotyping of three members of a Spanish family affected with fatal familial insomnia are reported. The mother and two of her offspring developed a rapidly evolving disease with insomnia and behavioural disorders as the initial symptoms and died between 5 and 10 months after the onset of the illness. Frontal brain biopsy in the mother disclosed only non-significant spongiosis, and full neuropathological examination of her offspring showed thalamic and olivary degeneration with isolated focal cortical spongiosis. Genetic examination could only be performed in the contemporary patients and both harboured the prion protein (PrP) 178Asn mutation and homozygous 129 Met/Met genotype.

Biopsy↗
PubMed2000

Multi-minicore disease--searching for boundaries: phenotype analysis of 38 cases.

Multi-minicore disease (MmD) is a congenital myopathy morphologically defined by the presence of multiple small zones of sarcomeric disorganization and lack of oxidative activity ("minicores") in muscle fibers. The dinical expression of MmD is considered to be greatly variable, and the morphological lesions are nonspecific; therefore, its boundaries are poorly defined, and its molecular bases are not known. To better define the phenotypic characteristics of MmD, we analyzed a large series of 38 patients with multiple minicores in muscle fibers in the absence of any other potential cause. According to clinical features, 4 subgroups were identified. Most patients (30 cases) shared a common highly consistent phenotype marked by the axial predominance of muscle weakness and a high occurrence of severe respiratory insufficiency and scoliosis ("classical" form). Other forms were characterized by pharyngolaryngeal involvement and total lack of head control (2 cases), antenatal onset with arthrogryposis (3 cases), and slowly progressive weakness with marked hand amyotrophy (3 cases). Type 1 fiber predominance and hypotrophy as well as centrally located nuclei were found in every subgroup. MmD is thus phenotypically heterogeneous, but a typical recognizable phenotype does exist. This phenotype classification should be helpful when undertaking research into the molecular defects that cause MmD.

Biopsy↗
PubMed2000

[Early erythropoietin use for the prevention of anemia in infant premature].

BACKGROUND: Anemia is common among very low birth weight newborns and requires frequent blood transfusions. Erythropoietin was been reported to be useful in the prevention of this anemia. AIM: To assess the benefits of early (before the third week of life) Human recombinant Erythropoietin (r-EPO) administration to reduce the requirement of blood transfusions in very low birth weight newborns. PATIENTS AND METHODS: Sixty newborns under 1500 g of birthweight were randomly assigned to receive r-EPO (n = 29) or placebo (n = 31) three times per week, during four weeks. Packed red cell volume and reticulocyte counts were measured weekly. Serum erythropoietin was measured prior to eighth dose. Transfusion requirements were recorded. RESULTS: r-EPO reduced transfusions from 1.41 +/- 1.1 to 0.69 +/- 1 transfusions/newborns (p < 0.001). At the fourth week of treatment, reticulocyte count was 14.8 +/- 7 and 6.4 +/- 4.9% in the active treatment group and placebo group respectively (p < 0.001). CONCLUSIONS: r-EPO reduces the requirement of transfusions in low birth weight infants.

Anemia, Neonatal↗
PubMed2000

[Technology for the whole utilization of brewer's yeast in food industry].

A flexible scheme for the fractionation of brewer's yeast was developed. The procedure allows the production of different products such as: dry yeast flakes, dry yeast pills, yeast-extract based table sauce, yeast protein concentrates and soy-like sauce. The investment required for the processing of one ton per day is below 2 million dollars with an overall profitability higher than 53%. Investment is recovered in 0.75 years. The production of food ingredients from yeast upgrades its biomass about 25 fold. Present procedure is compared with other biomass fractionation processes taking into account the utilization of all technological streams where the process becomes environmentally friendly since effluent production significantly lower than similar technologies.

Analysis of Variance↗
PubMed1999

Molecular analysis in Spanish patients with muscle carnitine palmitoyltransferase deficiency.

The most common mutation in muscle carnitine palmitoyltransferase II (CPT II) deficiency is a missense mutation that replaces a leucine for a serine residue at amino acid position 113 of the CPT II protein (S113L). We performed molecular analysis in a group of 14 Spanish patients with CPT II deficiency from ten unrelated families. The S113L mutation was observed in 8 of the 14 patients studied. Seven patients were homozygous for the mutation, 1 patient was heterozygous, and 6 patients did not carry the mutation on either allele. Seven healthy relatives belonging to three different families carried the mutation on one allele. One patient carried the missense mutation that replaces a tyrosine for a serine at amino acid position 628 on one allele. Our data indicate that the S113L is also the most common mutation in Spanish patients with CPT II deficiency in muscle, and that further pathogenic mutations remain to be identified.

Carnitine O-Palmitoyltransferase↗