Search PubMed⌕ Search

Biomedical subjects

E Bonilla

Publications and source records attributed to E Bonilla.

At least 73 records · Page 4Linked to original sources
PubMed1998

Clinical manifestations of mitochondrial DNA depletion.

OBJECTIVE: We studied five new patients with mitochondrial DNA (mtDNA) depletion to better define the clinical spectrum of this disorder. BACKGROUND: mtDNA depletion has been associated with myopathy or hepatopathy, or both, in infants and young children. Involvement of the CNS and peripheral nervous system has not been clearly established. METHODS: We reviewed the clinical course and performed morphologic, biochemical, and genetic analyses of muscle samples from five patients. RESULTS: Age at onset ranged from 3 months to 5 years, and one patient survived until age 10 1/2 years. Two patients had laboratory and clinical features reminiscent of dystrophinopathy, two had evidence of brain involvement, and two had peripheral neuropathy. Muscle biopsy specimens in all patients showed abundant ragged-red fibers. Biochemistry showed cytochrome c oxidase deficiency in all patients tested and decreased activities of other respiratory chain complexes in some. CONCLUSIONS: Inheritance appeared to be autosomal recessive, suggesting that mutations in nuclear DNA are responsible for mtDNA depletion. mtDNA depletion should be considered in children with mitochondrial disorders of uncertain etiology, and criteria for diagnosis are proposed.

Blotting, Southern↗
PubMed1998

Mitochondrial DNA depletion in a patient with long survival.

We studied a 29-year-old woman with myopathy since childhood with evidence of mitochondrial DNA (mtDNA) depletion. Muscle biopsy sample showed cytochrome c oxidase (COX)-negative fibers. Biochemistry showed COX deficiency. Southern blot analysis showed 76% depletion of mtDNA as compared with controls. This patient's clinical course suggests that long survival is possible in some patients with mtDNA depletion.

Adult↗
PubMed1997

Association of myopathy with large-scale mitochondrial DNA duplications and deletions: which is pathogenic?

We identified large-scale heteroplasmic mitochondrial DNA (mtDNA) rearrangements in a 50-year-old woman with an adult-onset progressive myopathy. The predominant mtDNA abnormality was a 21.2-kb duplicated molecule. In addition, a small population of the corresponding partially deleted 4.6-kb molecule was detected. Skeletal muscle histology revealed fibers that were negative for cytochrome c oxidase (COX) activity and had reduced mtDNA-encoded COX subunits. By single-fiber polymerase chain reaction analysis, COX-negative fibers contained a low number of wild-type or duplicated mtDNA molecules (ie, nondeleted). In situ hybridization demonstrated that the abnormal fibers contained increased amounts of mtDNA compared with normal fibers and that most of the genomes were deleted. We concluded that deleted mtDNA molecules were primarily responsible for the phenotype in this patient.

Base Sequence↗
PubMed1997

Melatonin protects mice infected with Venezuelan equine encephalomyelitis virus.

We investigated whether the administration of melatonin (MLT) reduces the death rate and evolution of the disease in mice infected with Venezuelan equine encephalomyelitis (VEE) virus. Our results show that, MLT protects mice infected with the virus. The mortality rate was reduced from 100% to 16% merely by increasing the dose from 0 to 1000 micrograms/MLT per kg body weight MLT significantly postponed the onset of the disease and death by several days. In surviving mice very high titres of VEE virus IgM antibodies were found seven weeks after virus inoculation. MLT significantly reduced VEE virus levels in blood and brain of infected mice and increased the survival rate when the length of pretreatment was augmented from 3 to 7 or 10 days before virus inoculation. Serum levels of interleukin-2 were not affected by MLT administration. In control mice receiving MLT as well as in infected mice treated or non-treated with MLT, interferon gamma levels in sera were increased. Interleukin-4 concentrations were found to be elevated in sera of non-infected mice receiving MLT, but did not differ from controls in infected mice treated or non-treated with the hormone. MLT reduced the degree of cell destruction produced by VEE virus in culture plates of chicken embryo fibroblasts. The protective effect of MLT warrants further investigation of the possibility of using this hormone for the treatment of humans and equines infected with VEE virus.

Animals↗
PubMed1997

In vitro fertilizing capacity of frozen-thawed boar semen.

We describe a porcine semen cryopreservation technique and assess the in vitro fertilizing capacity of the frozen-thawed spermatozoa. The thawed spermatozoa did not lose the physiological properties of motility, viability, and acrosome reaction or capacity to fertilize in vitro. Immediately after thawing, the spermatozoa showed 51% mean motility, 60% viability, and 5% induced acrosome reaction. After 2.5 h of incubation in TALP medium, the spermatozoa exhibited 61% motility, 63% viability and 40% induced acrosome reaction. The average in vitro fertilization capacity of thawed spermatozoa was 68% compared with that of spermatozoa from fresh semen (85%). The percentage of polyspermy was highly variable, with frozen-thawed samples ranging from 0 to 28% and fresh samples from 0 to 30%. The results obtained with frozen semen from 5 boars of different breeds did not show considerable variation. This suggests that the freezing-thawing technique is reproducible and adequate for in vitro fertilization.

Journal Article↗
PubMed1997

Motor activity and quantitative autoradiographic analysis of muscarinic receptors in the brain of rats subjected to the forced swimming test.

A cholinergic dysfunction has been involved in the neurobiological mechanisms of stress and depression. In the present study, we determined the autoradiographic distribution of muscarinic cholinergic receptors in the brain of rats subjected to the forced swimming test for 15 days. Motor activity was automatically analyzed daily before swimming. In the forced swimming test group, both total horizontal activity and ambulatory movements exhibited a significant decrease, when the data from 1st and 15th day were compared. Neither the affinity of [3H]-quinuclidinyl benzilate nor the maximal number of receptors were affected by the forced swimming test in the caudate-putamen, cortex, and hippocampus. The distribution of [3H]-quinuclidinyl benzilate binding sites did not show significant differences in the 30 analyzed areas. Further analysis of muscarinic receptor subtypes after forced swimming test would be necessary to discard any cholinergic involvement.

Animals↗
PubMed1997

Mitochondrial DNA mutations and pathogenesis.

Approximately there years ago, this journal published a review on the clinical and molecular analysis of mitochondrial encephalomyopathies, with emphasis on defects in mitochondrial DNA (mtDNA). At the time, approximately 30 point mutations associated with a variety of maternally-inherited (or rarely, sporadic) disorders had been described. Since that time, almost twenty new pathogenic mtDNA point mutations have been described, and the pace of discovery of such mutations shows no signs of abating. This accumulating body of data has begun to reveal some patterns that may be relevant to pathogenesis.

Cardiomyopathies↗
PubMed1997

A novel mitochondrial G8313A mutation associated with prominent initial gastrointestinal symptoms and progressive encephaloneuropathy.

We describe a childhood mitochondrial disorder in which the clinical symptoms began and remained confined to the gastrointestinal (GI) system during the first 4 y. Seizures heralded the onset of progressive encephalopathy at age 7. Peripheral neuropathy, retinitis pigmentosa, and neural deafness developed subsequently. Laboratory investigations disclosed elevated levels of plasma lactate, and a muscle biopsy revealed ragged red fibers lacking cytochrome c oxidase activity and diminished levels of respiratory chain enzyme complexes. Molecular genetic tests failed to show any of the previously reported pathogenic mitochondrial DNA (mtDNA) mutations. We therefore screened the whole mitochondrial genome by coupling restriction digestions with single-strand conformational polymorphism (SSCP) patterns. We identified a unique SSCP in the segment that encompassed the tRNA(Lys) gene, and direct sequencing of this segment revealed a G-->A transition at an evolutionarily conserved nucleotide at mtDNA position 8313. This G8313A transition was heteroplasmic in muscle and fibroblasts of the patient, but was absent in the white blood cells and platelets from his maternal relatives. This report illustrates how GI symptoms can be the initial manifestation in a mitochondrial disorder and suggests that mitochondrial dysfunction should be considered in differentials of unexplained chronic GI symptoms, especially when lactic acidosis or other unrelated clinical signs or symptoms are present.

Adolescent↗
PubMed1997

Mitochondrial encephalomyopathy with coenzyme Q10 deficiency.

Coenzyme Q10 (CoQ10) transfers electrons from complexes I and II of the mitochondrial respiratory chain to complex III. There is one published report of human CoQ10 deficiency describing two sisters with encephalopathy, proximal weakness, myoglobinuria, and lactic acidosis. We report a patient who had delayed motor milestones, proximal weakness, premature exertional fatigue, and episodes of exercise-induced pigmenturia. She also developed partial-complex seizures. Serum creatine kinase was approximately four times the upper limit of normal and venous lactate was mildly elevated. Skeletal muscle biopsy revealed many ragged-red fibers, cytochrome c oxidase-deficient fibers, and excess lipid. In isolated muscle mitochondria, impaired oxygen consumption was corrected by the addition of decylubiquinone. During standardized exercise, ventilatory and circulatory responses were compatible with a defect of oxidation-phosphorylation, which was confirmed by near-infrared spectroscopy analysis. Biochemical analysis of muscle extracts revealed decreased activities of complexes I+II and I+III, while CoQ10 concentration was less than 25% of normal. With a brief course of CoQ10 (150 mg daily), the patient reported subjective improvement. The triad of CNS involvement, recurrent myoglobinuria, and ragged-red fibers should alert clinicians to the possibility of CoQ10 deficiency.

Adult↗
PubMed1996

Chromosome 12-linked autosomal dominant scapuloperoneal muscular dystrophy.

Scapuloperoneal syndromes are characterized by their distribution of muscle weakness and wasting. The reported pattern of inheritance has been variable. Both neurogenic and myopathic forms of autosomally dominantly inherited scapuloperoneal syndrome have been described. It has been suggested that these are variants of other neuromuscular diseases. We examined 44 members from a family with 14 members affected with a scapuloperoneal syndrome. Physiological and histological analysis implied that this condition is predominantly myopathic. Linkage analysis was done to confirm the genetic etiology of the disease in this family and to evaluate the possibility that it is a allelic variant of other neuromuscular diseases. Genetic analysis demonstrated linkage of the disease to chromosome 12, which makes it genetically distinct from other loci known to cause neuromuscular disease. Muscle fibers with hyaline desmin-containing cytoplasmic inclusions in combination with focal myopathic changes may be a disease-specific morphological marker of the disease.

Adult↗
PubMed1996

Multiple mitochondrial DNA deletions in sporadic inclusion body myositis: a study of 56 patients.

Inclusion body myositis, a chronic inflammatory disorder, is the most common cause of myopathy in adults over the age of 50. Diagnosis is based on clinical features and distinctive morphological findings by both light and electron microscopy. The causes of inclusion body myositis are still unknown. Ultrastructural mitochondrial changes and ragged-red fibers are common in patients with sporadic inclusion body myositis, and multiple [correction of mutiple] mitochondrial DNA (mtDNA) deletions have been reported in 3 such patients, suggesting that mtDNA mutations may have a pathogenetic role. We studied 56 patients with sporadic inclusion body myositis, using a combination of clinical, morphological, biochemical, and molecular genetic analyses to determine the frequency and the distribution of mtDNA deletions. Using the polymerase chain reaction, we found multiple mtDNA deletions in 73% of patients, compared to 40% of normal age-matched control subjects and 47% of disease control subjects. The presence of deletions correlated with morphological evidence of ragged-red, cytochrome c oxidase-negative fibers, and with defects of complexes I and IV of the electron transport chain. Although aging may account for a proportion of mtDNA deletions in patients with sporadic inclusion body myositis and control subjects, mtDNA alterations may be accelerated in sporadic inclusion body myositis.

Adult↗
PubMed1996

Mitochondrial myopathy simulating spinal muscular atrophy.

A patient with a severe progressive neuromuscular disorder resembling spinal muscular atrophy is reported. The initial muscle biopsy was consistent with a denervating process. DNA analysis did not reveal deletions in exons 7 and 8 of the survival motor neuron gene. Histology, histochemistry, and biochemistry of a second muscle biopsy suggested mitochondrial myopathy accompanying the denervating features. Immunohistochemistry using anti-DNA antibodies revealed only nuclear staining in skeletal muscle, suggesting mitochondrial DNA depletion. In patients with clinical features of spinal muscular atrophy and no deletions in the survival motor neuron gene, mitochondrial DNA depletion should be considered.

Biopsy↗
PubMed1996

Ascaris lumbricoides infestation as a cause of intestinal obstruction in children: experience with 87 cases.

PURPOSE: The purpose of this study is to describe the occurrence and management of bowel obstruction caused by Ascaris lumbricoides, a common parasite in warm climates that affects children with limited socioeconomic means. METHODS: Eighty-seven patients with intestinal infestation owing to Ascaris lumbricoides were treated in the past 10 years (1984-1994). There were 48 (55.2%) girls and 39 (44.8%) boys. The mean age was 4.6 years, with peak occurrence at 2 years of age. Half the patients had a history of passing worms by mouth or anus. The majority of patients, 64 (73.5%), presented with a subacute clinical course; 23 (26.5%) had acute presentation, with severe abdominal pain, fever, dehydratation, vomiting, and abdominal distension and required vigorous fluid resuscitation and emergency surgical intervention. Diagnosis was achieved with plain abdominal roentgenograms, which showed a "whirlpool" pattern of intraluminal worms in most cases. RESULTS: Six patients had been incorrectly diagnosed as having appendicitis; two cases had appendicitis owing to Ascaris in the cecum and distal ileum. The majority of cases with a subacute presentation respond to medical (anthelmintic) management using oral administration of racine oil and piperazine. Of the 23 patients taken to the operating room, 11 required external "milking" of the obstructing bolus of worms from the ileum into the colon, six required intestinal resection and end-to-end anastomosis, six had an appendectomy, and three needed an enterotomy to manually extract the worms. In one case, initial management consisted of an ileostomy because of intraoperative instability owing to sepsis. Subsequently, after stabilization and treatment with anthelmintic agents, closure of the stoma with an end-to-end ileocolostomy was performed. There was no significant postoperative morbidity or mortality. CONCLUSION: These observations suggest that physicians should have a high index of suspicion for parasitic infestation in warm climates where economically deprived children present with symptoms of intestinal obstruction. Ascaris lumbricoides may be the cause of these events in endemic areas. Oral piperazine and racine oil can successfully resolve most subacute cases; however, aggressive resuscitation and prompt surgical intervention in patients with intestinal obstruction result in a satisfactory outcome.

Adolescent↗