Search PubMed⌕ Search

Biomedical subjects

E Bonilla

Publications and source records attributed to E Bonilla.

At least 109 records · Page 6Linked to original sources
PubMed1994

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical, biochemical, and genetic features of an autosomal recessive mitochondrial disorder.

We studied the clinical, biochemical, and genetic features of eight patients with the autosomal recessive mitochondrial syndrome mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). MNGIE is clinically characterized by ophthalmoparesis, peripheral neuropathy, leukoencephalopathy, gastrointestinal symptoms (recurrent nausea, vomiting, or diarrhea) with intestinal dysmotility, and histologically abnormal mitochondria in muscle. Brain MRI scans were consistent with leukodystrophy in seven patients examined. Nerve conduction and EMG studies were compatible with a sensorimotor neuropathy; quantitative EMG of two patients suggested a myogenic process. Muscle mitochondrial enzyme analysis revealed a partial defect of cytochrome c oxidase activity in five patients; three had additional respiratory chain enzyme defects. Two patients had isolated complex I defects, and one had normal respiratory chain function. Southern blot analysis revealed multiple deletions of mitochondrial DNA in four of eight patients.

Adolescent↗
PubMed1994

Abnormalities in the expression of beta-spectrin in Duchenne muscular dystrophy.

We studied beta-spectrin using an immunologic probe in muscle samples from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), other disease controls, and normal controls. By immunohistochemistry in DMD samples, beta-spectrin showed reduced or interrupted staining of the entire cell surface or only patches of bright staining at the cell periphery. There were also alterations of beta-spectrin immunostain in fibers that were not degenerating or regenerating. By immunoblotting, the amount of beta-spectrin in muscle was reduced and varied from 52% to 78% of the normal controls. We found normal values of beta-spectrin in BMD and disease controls. These observations indicate that the expression of beta-spectrin in DMD is abnormal and that beta-spectrin immunolabeling is not a good marker for monitoring membrane integrity in DMD muscle.

Adolescent↗
PubMed1994

Manganese toxicity: free amino acids in the striatum and olfactory bulb of the mouse.

We studied the levels of twenty two free amino acids in the striatum and olfactory bulb of mice treated during nine weeks with daily intraperitoneal injections of manganese chloride at a concentration of 5.0 mg Mn+2/kg body weight. In the olfactory bulb the contents of alanine, alpha-amino-n-butyrate, arginine, asparagine, aspartate, citrulline, GABA, glutamate, glycine, isoleucine, leucine, methionine, phenylalanine, serine, threonine, tyrosine, and valine were diminished. No alterations were observed in the concentrations of free amino acids in the striatum of Mn-treated mice. The changes detected in the olfactory bulb merit a thorough evaluation in order to determine its importance on the pathophysiology of manganese poisoning.

Amino Acids↗
PubMed1993

Dystrophinopathy in two young boys with exercise-induced cramps and myoglobinuria.

Two young boys were referred for evaluation of metabolic myopathy because of elevated serum levels of creatine kinase, cramps and pigmenturia. Immunohistochemical studies of dystrophin in muscle biopsies showed reduced intensity of the stain with a patchy and discontinuous pattern in most fibers. In both patients dystrophin was undetectable by immunoblotting. DNA analysis of the dystrophin gene was not informative in one patient; in the other it revealed an in-frame deletion comprising exons 3-6. These observations suggest that the two patients are affected with an unusual phenotype of Becker muscular dystrophy. Dystrophin analysis should be included in the evaluation of patients with childhood-onset of recurrent myoglobinuria.

Child↗
PubMed1993

Determining malaria effects in rural Colombia.

Good health is an integral component of the quality of human life, a prerequisite for developing human potential and an important determinant of economic development. When a person is ill from a tropical disease in an agricultural economy, a complex interaction between the individual's welfare and the family's welfare is set in motion. So complex are these interactions that few empirical studies exist on this subject and even where they do, empirical quantification of these interactions and economic losses places the analyst in the minefield of valuing time, ability and contribution to economic welfare. Placing monetary values on these commodities is always a little unsatisfactory since dollar values do not adequately reflect the nature of the losses. Secondly, the ill person's struggle to minimize the economic effects of disease on family income will mask its true impact; thirdly, tropical diseases disproportionately affect low-income groups and therefore measuring the income effects of disease amongst these groups will only reach at the earnings effect, and underestimate the economic implications of tropical disease control. Despite these difficulties, quantification of the economic impact of disease is important from a public health point of view. This study is an attempt at such a task, and focuses on the intra-familial struggle to minimize economic losses due to malaria. Using a case-control approach, time-losses and labour reallocations within the household are examined in an attempt to understand the economic consequences of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1993

Atypical clinical presentations associated with the MELAS mutation at position 3243 of human mitochondrial DNA.

Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is commonly associated with an A-->G transition at position 3243 of the mitochondrial DNA. To determine the diversity of clinical syndromes associated with this mutation, 91 patients with mitochondrial encephalomyopathies that did not conform to the MELAS phenotype were screened. Twenty one patients with the 3243 mutation, most of whom had progressive external ophthalmoplegia (PEO) were found. Clinical features did not distinguish PEO patients with the 3243 mutation from those with large-scale deletions of mtDNA. However, most cases with single large-scale mtDNA deletions were sporadic, whereas most patients with the 3243 mutation had affected maternal relatives. Histochemical studies of muscle showed that cytochrome c oxidase (COX) deficiency was more severe in patients with PEO than in patients with typical MELAS, even though PEO patients had a lower percentage of mutant genomes in muscle. These data imply that the 3243 mutation is a major cause of familial PEO, and suggests that the threshold number of mtDNAs harboring the 3243 mutation necessary to affect a particular tissue vary in different patients. The proportion of mutant genomes in combination with other, still undefined, tissue-specific modulating factors seem to determine the overall clinical syndrome.

Adolescent↗
PubMed1993

Immunolocalization of heat shock proteins in ragged-red fibers of patients with mitochondrial encephalomyopathies.

Monoclonal antibodies against the 60 kDa heat shock protein (HSP-60) and against ubiquitin (UB) were used to study the expression of these proteins in muscle samples from patients with qualitative and quantitative alterations of mitochondrial DNA (mtDNA). We found an enhanced expression of HSP-60 and UB that was preferentially localized in ragged-red fibers (RRFs). HSP-60 may act as a protein repair enzyme catalyzing the refolding of misfolded proteins in the matrix of mitochondria of RRFs. On the other hand, UB could promote the elimination of abnormal proteins by its covalent interaction to substrates.

Antibodies, Monoclonal↗
PubMed1993

A mitochondrial tRNA anticodon swap associated with a muscle disease.

We have identified an unusual mitochondrial (mt) tRNA mutation in a seven year-old girl with a pure myopathy. This G to A transition at mtDNA position 15990 changed the anticodon normally found in proline tRNAs (UGG) to the one found in serine tRNAs (UGA), and is the first pathogenic anticodon alteration described in a higher eukaryote. The mutant mtDNA was heteroplasmic (85% mutant) in muscle but was undetectable in white blood cells from the patient and her mother. Analysis of single muscle fibres indicated that mutant mtDNAs severely impaired mitochondrial protein synthesis and respiratory chain activity, but only when present at greater than 90%. The recessive behaviour of this mtDNA alteration may explain the patient's relatively mild clinical phenotype.

Anticodon↗
PubMed1993

Cytochrome C oxidase deficiency and neuronal involvement in Menkes' kinky hair disease: immunohistochemical study.

Antibodies against subunits II and IV of cytochrome c oxidase (COX) and against complex III of the respiratory chain were used to study the expression of these proteins in the cerebellum, spinal cord, and other regions of the central nervous system in an autoptic case of Menkes' kinky hair disease (MKHD). We found a reduced expression of COX subunits in all examined areas whereas staining for complex III appeared normal. Immunostaining was altered in morphologically well-preserved neurons, suggesting that COX deficiency may have a pathogenetic role in the neuronal degeneration of MKHD.

Antibodies, Monoclonal↗
PubMed1993

Two novel pathogenic mitochondrial DNA mutations affecting organelle number and protein synthesis. Is the tRNA(Leu(UUR)) gene an etiologic hot spot?

We identified two patients with pathogenic single nucleotide changes in two different mitochondrial tRNA genes: the first mutation in the tRNA(Asn) gene, and the ninth known mutation in the tRNA(Leu(UUR)) gene. The mutation in tRNA(Asn) was associated with isolated ophthalmoplegia, whereas the mutation in tRNA(Leu(UUR)) caused a neurological syndrome resembling MERRF (myoclonus epilepsy and ragged-red fibers) plus optic neuropathy, retinopathy, and diabetes. Both mutations were heteroplasmic, with higher percentages of mutant mtDNA in affected tissues, and undetectable levels in maternal relatives. Analysis of single muscle fibers indicated that morphological and biochemical alterations appeared only when the proportions of mutant mtDNA exceeded 90% of the total cellular mtDNA pool. The high incidence of mutations in the tRNA(Leu(UUR)) gene suggests that this region is an "etiologic hot spot" in mitochondrial disease.

Adult↗
PubMed1993

Cryptosporidium infections in a suburban community in Maracaibo, Venezuela.

A point prevalence survey for Cryptosporidium was conducted in 212 subjects two months to 70 years of age in a suburban area with a low socioeconomic status in Maracaibo City, Venezuela. Single stool specimens were collected and modified Ziehl-Neelsen carbol-fuchsin staining of 10% formalin-preserved stool was used to identify Cryptosporidium oocysts. Direct wet mounts, iron-hematoxylin-stained smears and formalin-ether concentrates were examined to determine the presence of other intestinal parasites. Cryptosporidium infections were identified in 21 subjects (9.9%), with a high percentage of asymptomatic carriers (15 of 21, 71.4%). Six children (28.5%) had gastrointestinal symptoms and four of them were infants. Cryptosporidium was the single detectable potential pathogenic parasite in only five (23.8%) of 21 patients. The infection rate with one or more parasites was high (82%) and multiple infections, including pathogenic helminths and protozoa, were observed in the majority of patients who passed oocysts. Our findings suggest that although Cryptosporidium is an important pathogen, the proportion of asymptomatic carriers may be high in areas of low socioeconomic status in developing countries.

Adolescent↗
PubMed1992

Dystrophin deficiency in a case of congenital myopathy.

We studied a 5-year-old boy who had the "floppy infant syndrome" and a dystrophic pattern on muscle biopsy. According to the clinical presentation and the histopathological findings the diagnosis of congenital muscular dystrophy with associated intellectual retardation was made. Immunohistochemical and immunoblot studies using anti-dystrophin antibodies showed complete absence of the protein in the patient's muscle. DNA analysis using cDNA probes showed a deletion at the 5' end of the dystrophin gene. Our observations on this patient suggest a new phenotypical variant of Duchenne muscular dystrophy.

Child, Preschool↗
PubMed1992

Dystrophin at the plasma membrane of human muscle fibers shows a costameric localization.

We studied the distribution of dystrophin at the sarcolemma of normal human muscle fibers using high resolution immunofluorescence and confocal laser scanning optical microscopy (CLSOM). We found that the dystrophin lattice is organized at the muscle plasma membrane in an array of thick bands interconnected by a finer network. The bands encircle the muscle fiber perpendicular to the long axis of the fiber and they matched the sites of attachment of the sarcomeres to the plasma membrane. Dystrophin co-localized with vinculin, and dystrophin and vinculin co-localized with alpha-actinin at the region of the I-band. Dystrophin may be one of the proteins involved in the linkage of the sarcomeres to the extracellular matrix.

Actinin↗
PubMed1992

Transanorectal approach for the treatment of urogenital sinus: preliminary report.

The treatment of the urogenital sinus with normal rectum still represents a challenge. A perineal approach with or without a skin flap seems to be effective for those patients with a low implantation of the vagina. However, in patients with a high vaginal implantation, this treatment frequently fails to provide a good, functional vagina due to a narrow, strictured vaginal opening. Based on previous experience in the treatment of more than 80 patients with a persistent cloaca, a posterior sagittal transanorectal approach with a protective colostomy was performed in three patients with urogenital sinus and normal rectum. The pelvis was approached through a midsagittal posterior incision; the coccyx was split and the entire anorectal sphincteric mechanism was divided in the midline. The rectum was bivalved in the midline including both posterior and anterior rectal walls. This provided excellent exposure to the urogenital sinus. The vagina was then fully separated from the urogenital sinus (as described in cases of persistent cloacas), and then mobilized and sutured to the perineum. The rectum and sphincteric mechanism were meticulously reconstructed. A midline incision assures the preservation of anorectal innervation, and provides excellent exposure to the pelvis. Anal dilatations are not necessary to maintain a patent and supple anorectal opening because the rectum has two suture lines, one in front of the other. After the colostomy was closed, all patients had appropriate bowel control for their age; two of them are fully continent for urine and the third one still has a suprapubic cystostomy tube waiting for a repair of an additional urethral malformation.

Anal Canal↗
PubMed1992

Molecular analysis of the muscle pathology associated with mitochondrial DNA deletions.

Large-scale deletions of mitochondrial DNA (mtDNA) are associated with a subgroup of mitochondrial encephalomyopathies. We studied seven patients with Kearns-Sayre syndrome or isolated ocular myopathy who harboured a sub-population of partially-deleted mitochondrial genomes in skeletal muscle. Variable cytochrome c oxidase (COX) deficiencies and reduction of mitochondrially-encoded polypeptides were found in affected muscle fibres, but while many COX-deficient fibres had increased levels of mutant mtDNA, they almost invariably had reduced levels of normal mtDNA. Our results suggest that a specific ratio between mutant and wild-type mitochondrial genomes is the most important determinant of a focal respiratory chain deficiency, even though absolute copy numbers may vary widely.

Blotting, Southern↗
PubMed1992

Prevalence of Entamoeba histolytica and other intestinal parasites in a community from Maracaibo, Venezuela.

The prevalences of Entamoeba histolytica and other intestinal parasites were assessed in a suburban community of Maracaibo, Venezuela, by examination of a stool specimen from each of 342 individuals, using iron-haematoxylin stained faecal smears and formalin-ether concentration. The overall parasitic infection rate was 80.4%, and 65.8% of the population had multiple infections. The overall amoebic infection rate, which was highest in female adults, averaged 39.7%. The E. histolytica infection rate was 8.7% and most of those infected were passing cysts. Entamoeba polecki was observed in two samples. Amongst the protozoa, Entamoeba coli was observed most frequently (24.8%) and Giardia lamblia was the predominant pathogen (13.0%). Trichuris trichiura (71.9%) and Ascaris lumbricoides (54%) were the most common parasites, particularly in school-children. The high rates of parasitic and multiple infections reflect the low socio-economic status of the community studied.

Adolescent↗