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Biomedical subjects

M Mora

Publications and source records attributed to M Mora.

At least 55 records · Page 3Linked to original sources
PubMed1999

Fatty acid composition of platelet membrane lipids after administration of two different fat emulsions in critically ill patients.

OBJECTIVE: To determine the effects on platelet membrane fatty acid composition following administration of two different fat emulsions. DESIGN: Prospective, randomized, double-blind study. SETTING: Intensive care unit in a university-affiliated hospital. PATIENTS: 12 adult critically ill patients in need of total parenteral nutrition. INTERVENTIONS: Patients were treated with total parenteral nutrition (TPN) for 7 days, receiving for fat intake either a long-chain triglyceride (20% LCT) emulsion (group 1, n=6) or a medium-chain triglyceride-LCT (20% MCT/LCT) emulsion (group 2, n=6). MEASUREMENTS AND RESULTS: High-performance liquid chromatography of membrane fatty acids was carried out before and after 7 days of TPN. In the LCT group, an increase in C18:2n-6 and a decrease in caprylic acid and docosahexaenoic acid, which resulted in a decreased ratio of n-3/n-6 fatty acid content, was observed. In the MCT/LCT group, a reduced percentage of palmitoleic acid and arachidonic acid was shown. CONCLUSIONS: The observed changes in fatty acid composition are in agreement with the lipid composition of the fat emulsions used. Because the C18:2n-6/C18:3n-3 ratio in both emulsions is close (approximately 9.0), the observed changes in the fatty acid composition of platelets may not be relevant for platelet function.

APACHE↗
PubMed1999

Development of muscle pathology in canine X-linked muscular dystrophy. I. Delayed postnatal maturation of affected and normal muscle as revealed by myosin isoform analysis and utrophin expression.

Canine X-linked muscular dystrophy (CXMD) is genetically homologous to Duchenne muscular dystrophy and shares the severe myopathy and lethal clinical development of the human disease. We used immunohistochemistry to characterize the time course of postnatal expression of adult fast, adult slow and developmental myosin in the muscle of CXMD dogs, carriers and healthy controls. We also characterized the expression of utrophin and dystrophin. This detailed immunolocalization study confirmed that postnatal muscle maturation is delayed in normal dogs compared to other animals and humans, and is only achieved at around 60 days. In CXMD dogs major derangement of myosin expression became evident from about 15 days; there was a selective loss of fibers expressing fast myosin and persistence of developmental fibers compared to controls. In carriers, the proportion of dystrophin-deficient fibers, which mainly expressed fast myosin, decreased with age. In controls and carriers utrophin was absent from muscle fiber surfaces in 2-day-old animals but present between 15 and 30 days, to mostly disappear by 60 days. In dystrophic animals, sarcolemmal expression of utrophin was more marked and persistent. That immature neonatal muscle from control dogs normally contains sarcolemmal utrophin may have implications for the success of utrophin up-regulation therapy to correct the dystrophic phenotype. The data of this study provide important baseline information for further studies on the development and progression of pathological changes in the muscle of CXMD dogs.

Aging↗
PubMed1999

Transforming growth factor-beta1 and fibrosis in congenital muscular dystrophies.

We evaluated transforming growth factor-beta1 (TGF-beta1) expression in the muscle of four laminin alpha2-negative, four laminin alpha2-positive and seven partial laminin alpha2-deficient congenital muscular dystrophy (CMD) patients, and compared it to Duchenne muscular dystrophy (DMD) patients and controls. TGF-beta1 mRNA levels in skeletal muscle from laminin alpha2-negative and laminin alpha2-positive CMD patients were significantly greater than in controls (P < 0.05 and P < 0.005, respectively), while in partial laminin alpha2-deficient muscular dystrophy patients the amount was not significantly higher than in controls (P > 0.1). The TGF-beta1 values were lower than those found in DMD, although the extent of fibrosis was greater in CMD than in DMD and controls. Our findings suggest that TGF-beta1 is involved in CMD muscle fibrosis, but differently from what we observed in DMD muscles as it seems not to be the major player in connective tissue proliferation.

Adult↗
PubMed1999

A novel mutation (8342G-->A) in the mitochondrial tRNA(Lys) gene associated with progressive external ophthalmoplegia and myoclonus.

We describe a patient who suffered from impaired ocular motility from age 10 years and at 16 years developed ptosis, proximal weakness and progressive fatigability. At 35 years she developed massive myoclonic jerks, and head and distal tremor. A muscle biopsy showed a high percentage of cytochrome c oxidase negative fibers but no ragged-red fibers. A novel heteroplasmic mutation (8342G-->A) was found in the mitochondrial transfer RNA(Lys) gene by single-strand conformation polymorphism screening, followed by sequence and restriction fragment length polymorphism analysis. Approximately 80% of muscle mitochondrial DNA (mtDNA) harbored the mutation, while the mutation was absent in lymphocyte DNA of the proband, as well as of her mother, daughter and a maternal aunt. However, the pathogenicity of the mutation was confirmed by restriction fragment length polymorphism analysis of single muscle fibers, which revealed a significantly greater level of mutant mtDNA in cytochrome c oxidase negative over cytochrome c oxidase positive fibers.

Adenine↗
PubMed1999

Evaluation of institutional cancer registries in Colombia.

The four primary objectives of this descriptive study were to: 1) design a quality-measurement instrument for institutional cancer registries (ICRs), 2) evaluate the existing ICRs in Colombia with the designed instrument, 3) categorize the different registries according to their quality and prioritize efforts that will efficiently promote better registries with the limited resources available, and 4) determine the institution with the greatest likelihood of successfully establishing Colombia's second population-based cancer registry. In 1990 the National Cancer Institute of Colombia developed 13 institution-based cancer registries in different Colombian cities in order to promote the collection of data from a large group of cancer diagnostic and treatment centers. During the first half of 1997, this evaluation reviewed 12 registries; one of the original 13 no longer existed. All of the Colombian institutions (hospitals) that maintain institution-based cancer registries were included in the study. At each institution, a brief survey was administered to the hospital director, the registry coordinator, and the registrar (data manager). Researchers investigated the institutions by looking at six domains that are in standard use internationally. Within each domain, questions were developed and selected through the Delphi method. Each domain and each question were assigned weights through a consensus process. In most cases, two interviewers went to each site to collect the information. The university hospitals in Cali, Pereira, and Medellín had substantially higher scores, reflecting a good level of performance. Four of the 12 institutions had almost no cancer registry work going on. Five of the 12 hospital directors considered that the information provided by the cancer registries influenced their administrative decisions. Three of the registries had patient survival data. Four of the institutions allocated specific resources to operate their cancer registries; in the other 8 hospitals there was no clear budget allocation. Seven of the hospital directors could not identify five or more objectives of a cancer registry. Data management was usually poor and resources insufficient at most of the institutions. In summary, the cancer registry system in Colombia varies greatly from institution to institution. A few of the hospitals do a good job while others have neglected the registries. The high, identical total scores for Pereira and Medellín suggest they would be good locations to establish new population-based cancer registries similar to the existing one in Cali. However, the overall characteristics in Pereira may provide a more appropriate environment for the second registry, with Medellín as an alternative.

Colombia↗
PubMed1998

Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease.

Hereditary spastic paraplegia (HSP) is characterized by progressive weakness and spasticity of the lower limbs due to degeneration of corticospinal axons. We found that patients from a chromosome 16q24.3-linked HSP family are homozygous for a 9.5 kb deletion involving a gene encoding a novel protein, named Paraplegin. Two additional Paraplegin mutations, both resulting in a frameshift, were found in a complicated and in a pure form of HSP. Paraplegin is highly homologous to the yeast mitochondrial ATPases, AFG3, RCA1, and YME1, which have both proteolytic and chaperon-like activities at the inner mitochondrial membrane. Immunofluorescence analysis and import experiments showed that Paraplegin localizes to mitochondria. Analysis of muscle biopsies from two patients carrying Paraplegin mutations showed typical signs of mitochondrial OXPHOS defects, thus suggesting a mechanism for neurodegeneration in HSP-type disorders.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1998

A novel mutation in the mitochondrial tRNA(Val) gene associated with a complex neurological presentation.

We describe a patient who presented with progressive ataxia, seizures, mental deterioration, mild myopathy, and hearing loss. A novel heteroplasmic G-to-A transition was found, affecting the acceptor stem of the mitochondrial (mt) tRNA(Val) gene. Mutant mtDNA was 67% of total mtDNA in the muscle of the proband and was also present at low levels in the muscle of his healthy mother. It was absent in all of the numerous control DNA samples that were tested. Analysis of single muscle fibers revealed a significantly greater level of mutant mtDNA in cytochrome c oxidase-negative fibers. Mutations of mtDNA may be responsible of neurological syndromes that, like the case reported here, are clinically puzzling, and lack typical "mitochondrial" clues, such as elevated levels of blood lactate, overt defects of the respiratory complexes, and clinically documented maternal inheritance.

Base Sequence↗
PubMed1998

Congenital muscular dystrophy with merosin deficiency: MRI findings in five patients.

We present the MRI findings in five patients with congenital muscular dystrophy (CMD) and merosin (laminin alpha2) deficiency, which was total in one and partial in four. In one patient with partial merosin deficiency, MRI was normal. The other four patients had supratentorial white matter abnormalities. In three, T2-weighted images revealed subcortical, deep lobar and periventricular high signal in white matter, while in the other there were only small peritrigonal areas of increased signal. On T1-weighted images, there was slightly low signal. Cortical abnormalities were absent. None of these changes were accompanied by symptoms or signs of central nervous system involvement. White matter abnormalities in a patient with CMD should prompt investigation of merosin.

Adult↗
PubMed1998

PCR based mutation screening of the laminin alpha2 chain gene (LAMA2): application to prenatal diagnosis and search for founder effects in congenital muscular dystrophy.

Classical congenital muscular dystrophy with merosin deficiency is caused by mutations in the laminin alpha2 chain gene (LAMA2). Extended sequencing of the introns flanking the 64 LAMA2 exons was carried out and, based on these sequences, oligonucleotide primers were designed to amplify the coding region of each exon separately. By PCR-SSCP analysis, we identified eight new mutations in nine families originating from various countries. All induced a premature truncation of the protein, either in the short arm or in the globular C-terminal domain. A 2 bp deletion in exon 13, 2098delAG, was found in three French non-consanguineous families and a nonsense mutation of exon 20, Cys967stop, in two other non-consanguineous families originating from Italy. Determination of rare intragenic polymorphisms permitted us to show evidence of founder effects for these two mutations suggesting a remote degree of consanguinity between the families. Other, more frequent polymorphisms, G to A 1905 (exon 12), A to G 2848 (exon 19), A to G 5551 (exon 37), and G to A 6286 (exon 42), were used as intragenic markers for prenatal diagnosis. This study provides valuable methods for determining the molecular defects in LAMA2 causing merosin deficient congenital muscular dystrophy.

Child↗
PubMed1998

Kidneys derived from mice transgenic for human complement blockers are protected in an in vivo model of hyperacute rejection.

PURPOSE: The major obstacle to successful discordant kidney xenotransplantation is hyperacute rejection (HAR). Complement plays a key role in the induction of HRA, defined by endothelial cell activation, loss of vascular integrity, hemorrhage and thrombosis. The activation of complement is tightly controlled by a number of species-specific regulatory proteins which inhibit, at different points, the cascade of events leading to the formation of the membrane attack complex (MAC). We have tested the hypothesis that kidneys derived from transgenic mice expressing two human complement inhibitors, Decay Accelerating Factor (hDAF) and Membrane Cofactor Protein (MCP), could be protected from human complement-mediated damage. MATERIALS AND METHODS: Control and transgenic mice were perfused with human plasma by cannulation of the right jugular vein, at a perfusion rate of 10 microL./min. for two hours. Complement C3 deposition was detected on kidney sections by immunohistochemistry using specific FITC antibody. Complement-induced tissue damage was evaluated by histopathological examination. RESULTS: Heavy deposition of complement C3 was observed on kidneys derived from perfused control mice. This was associated with a characteristic HAR pathology of severe interstitial hemorrhage, inflammatory reaction, loss of glomerula and tubuli structure. Kidneys derived from mice transgenic for hDAF or hMCP were partially protected from both complement C3 deposition and tissue damage. The expression of both hDAF and hMCP in double transgenic mice significantly increases the protection from human complement-mediated damage. CONCLUSION: A novel model of in vivo perfusion with human plasma has been adopted to recreate the initial event of HAR. Our data show that this murine model could be very valuable to determine the effect of transgenic human molecules in protecting vascularized organs from human complement attack.

Acute Disease↗
PubMed1997

Laminin-alpha2 but not -alpha1-mediated adhesion of human (Duchenne) and murine (mdx) dystrophic myotubes is seriously defective.

It has been suggested that alpha-dystroglycan links the dystrophin-associated protein complex and extracellular matrix and that the absence of dystrophin and alpha-dystroglycan in Duchenne muscular dystrophy (DMD) may lead to the breakdown of this linkage. In the present study, myotubes from DMD patients and murine X-linked muscular dystrophic mice (mdx) were used to measure their adhesive force to the physiological laminin-alpha2 substrate, and it was found that the dystrophic myotubes were selectively unable to sustain adhesion. However, normal and dystrophic myotubes attached equally well to the laminin-alpha1 substrate. As far as we know, this is the first experimental evidence that the absence of dystrophin causes the complete loss of a still unknown laminin-alpha2-dependent adhesion force, therefore suggesting that the primary consequence of Duchenne dystrophy consists of the loss of an authentic mechanical linkage at the level of the alpha-dystroglycan/basal lamina interface.

Animals↗
PubMed1997

Outbreak of trichinosis in France associated with eating horse meat.

The investigation of a trichinosis outbreak in Auvergne, France identified 23 cases in 12 households living in two cities-Clermont-Ferrand and Montluçon-between 15 February and 7 March 1991. One patient required intensive care, 15 had major symptoms, and seven had minor or no symptoms. Two case control studies demonstrated a significant (p < 0.01) association between eating horse meat and acute trichinosis. Veterinary services found that three supermarkets where the patients had bought horse meat during the suspected period had been supplied by a single wholesaler. The analysis of the wholesaler's records revealed that the implicated horse meat had been imported from a slaughterhouse in the United States. This outbreak occurred despite a requirement in France for all meat from horses slaughtered in France and in countries exporting meat to France to be examined systematically for trichinella.

Adult↗
PubMed1997

Human CD46 aberrant splicing in transgenic mice.

RNA analysis of mice transgenic for human CD46 reveals almost undetectable levels of the expected transcript and the accumulation of a 900 nt shorter species. cDNA cloning and sequence analysis of this variant demonstrate an aberrant splicing of the transgene RNA. This aberrant splicing is present at low levels in cells that normally express the gene, suggesting that the transgene is lacking regulatory elements influencing the abundance of the shorter transcript.

3T3 Cells↗
PubMed1997

X-linked Emery-Dreifuss muscular dystrophy can be diagnosed from skin biopsy or blood sample.

We have raised an anti-emerin polyclonal antibody against a fusion protein encompassing most of the hydrophilic portion of emerin. Using this antibody, we have analyzed emerin expression in Emery-Dreifuss muscular dystrophy (EDMD) patients and controls, by immunocytochemistry, in skeletal muscle and skin, and by immunoblot, in peripheral blood mononuclear cells and lymphoblasts. Emerin was localized on the surfaces of nuclei in control skeletal muscle and skin but was absent or reduced in patient skeletal muscle, was absent from the skin of patients, and was expressed only in a few nuclei in a patient's mother. Immunoblot of peripheral blood cells from EDMD patients showed absence of the emerin band, altered-size emerin, or a protein of normal molecular mass but slightly reduced quantity. The diagnosis of X-linked EDMD is normally confirmed by genetic analysis of the STA gene coding for emerin. We propose immunocytochemical evaluation of emerin expression in skin biopsies as a sensitive and more convenient tool for diagnosing X-linked EDMD and, in particular, for distinguishing it from the autosomal dominant form. This technique may be applied to suspected EDMD patients, especially sporadic cases or those with incomplete clinical phenotype, and also suspected carriers. Immunoblot of peripheral blood cells is also useful, but it may not unequivocally identify carriers and some patients.

Adolescent↗
PubMed1997

Mechanism of action of clozapine-induced modification of motor behavior in an animal model of the "super-off" phenomenon.

We tested the effects of clozapine, and "atypical" neuroleptic with high affinity for the D4 (dopaminergic), and the 5-HT1c and 5-HT2 (serotonergic) receptor subtypes on locomotor activity in an animal model of Parkinson's disease showing a bimodal response curve to increasing doses of a D2 agonist. Sulpiride (D2 antagonist) and ritanserin (5-HT1c and 5-HT2 antagonist) were used for comparison. The D1 agonist SKF 38393 at a dose of 8 mg/kg significantly reversed the akinesia induced by chronic reserpine treatment (1 mg/kg for 5 days) and alpha-methyl-p-tyrosine pretreatment (300 mg/kg). In this model, the addition of a low dose of a D2 agonist, LY 171555 (quinpirole, 1 microgram/kg), inhibited the effects of SKF 38393, whereas the same drug at higher doses (5-50 microgram/kg) restored and potentiated the stimulatory response to D1 stimulation. Clozapine inhibited the inhibitory phase and potentiated the stimulatory phase of the curve. Sulpiride inhibited both phases of the dose-response curve (inhibitory/stimulatory), whereas ritanserin had no effect. We believe these results may reflect a disinhibition phenomenon possible mediated by the blockade by clozapine of a subpopulation of inhibitory, dopamine (DA) receptors belonging to the D2 "family."

Animals↗
PubMed1997

Concomitant deficiency of beta- and gamma-sarcoglycans in 20 alpha-sarcoglycan (adhalin)-deficient patients: immunohistochemical analysis and clinical aspects.

We have investigated the expression, using immunohistochemistry, of beta- and gamma-sarcoglycans in the muscles of 20 patients in whom previous screening had revealed a deficiency of alpha-sarcoglycan. alpha-, beta- and gamma-sarcoglycans were absent in 7 patients and variably reduced in 8 patients, in 2 of whom beta-sarcoglycan was more reduced than the alpha- and gamma-proteins. In 5 other patients with variably reduced alpha- and beta-sarcoglycans, gamma-sarcoglycan was completely absent. In all patients the distribution of hyposthenia at disease onset was similar, and predominantly involved pelvic girdle muscles; however, the age at onset and rate of disease progression were highly variable. In severely compromised patients, the onset of disease was before 10 years of age and gamma-sarcoglycan or all three sarcoglycans were absent from muscles. Immunohistochemical analysis of sarcoglycans should be part of routine screening for muscle dystrophies to identify patients with sarcoglycanopathy. Gene analysis is necessary to identify the primary defect; however, sarcoglycan immunohistochemistry may be useful for indicating which gene to investigate. Further biochemical characterization of the interactions between these proteins is required to fully elucidate their roles in causing severe, moderate or mild muscular dystrophy.

Adolescent↗
PubMed1997

Handling and aflatoxin contamination of white maize in Costa Rica.

Projects funded by International Development Research Centre (IDRC) of Canada and the European Commission have enabled the examination of more than 3000 samples of maize collected from all regions of Costa Rica at different stages, from the growing crop through storage to final sale, and at different water contents. Contamination with Aspergillus flavus was frequent and about 80% of samples contained more than 20 ng aflatoxins g(-1) grain. Average contamination with aflatoxins in the Brunca Region was > 274 ng g(-1) while that in other regions was < 70 ng g(-1). Except in Brunca region, where it averaged 376 ng g(-1), contamination of grain from commercial sources was slightly less than of that from farms (< or = 15 ng g(-1)). It appeared that samples kept on the cob after harvest contained almost no aflatoxin while shelled samples were frequently highly contaminated. Experiments were therefore done in Brunca and Huetar Atlantic Regions, utilising 34 experimental maize crops to study in detail the development of A. flavus and aflatoxin from before harvest, through postharvest treatment before drying and through storage for six months. A. flavus was isolated more frequently from maize shelled immediately after harvest than from that kept on the cob until it could be dried, and from more samples from the Brunca Region than from the Huetar Atlantic Region. Samples harvested with > or = 18% water content often contains > 70% of grains infected with A. flavus but sometimes there were few grains infected. As found in the initial survey, more aflatoxin contamination developed in shelled maize than in that handled on the cob during the period from harvesting to drying, especially if the delay was more than 5 days, and more in Brunca than in Huetar. Shelled grain contained 400-800 ng aflatoxin g(-1) in Brunca but < 100 ng g(-1) in Huetar while grain kept on the cob contained < 30 ng g(-1), even with > 18% water content. Incidence of Fusarium spp. exceeded 50% except where A. flavus colonized more than 80% of grains.

Aflatoxins↗