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Biomedical subjects

E Bonilla

Publications and source records attributed to E Bonilla.

At least 127 records · Page 7Linked to original sources
PubMed1992

New morphological approaches to the study of mitochondrial encephalomyopathies.

Molecular genetics, biochemistry, immunology and morphology, are being applied in a coordinated fashion to unveil the molecular basis of the mitochondrial encephalomyopathies. Mutations of mitochondrial DNA (mtDNA) have been found in well characterized clinical groups of these disorders. New and old morphologic methods have been applied to investigate muscle biopsies from patients with mtDNA mutations. Important observations have been made on the cellular localization of normal and mutated mtDNA and on the expression of mtDNA-encoded polypeptides. These observations have provided insight into the pathogenesis of respiratory chain enzyme deficiency at the level of individual muscle fibers. Application of immunocytochemical and in situ hybridization techniques at the electron microscopic level will extend these studies to the level of individual mitochondria.

DNA, Mitochondrial↗
PubMed1992

Disorders associated with depletion of mitochondrial DNA.

Quantitative defects of mtDNA have been recently described in patients with fatal mitochondrial disease of early infancy or mitochondrial myopathy of childhood. There was variable tissue expression and depletion of up to 98% of mtDNA in affected tissues. Pedigree analysis was compatible with mendelian inheritance, suggesting faulty communication between nuclear and mitochondrial genomes, but the primary molecular lesion is unknown. In muscle, morphological studies allowed to correlate mtDNA depletion, absence of mtDNA-encoded peptides, mitochondrial proliferation, and loss of cytochrome c oxidase (COX) activity in individual fibers.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Mitochondrial myopathy of childhood associated with depletion of mitochondrial DNA.

We have studied five children with mitochondrial myopathy manifesting within or soon after the first year of life. Muscle biopsies showed ragged-red fibers and decreased respiratory chain activity. All five patients had a severe decrease (2 to 34% of normal) in the amount of muscle mitochondrial DNA (mtDNA). The depletion of mtDNA correlated with absence of mtDNA-encoded translation products and with loss of cytochrome c oxidase enzyme activity in individual muscle fibers. This mitochondrial myopathy of childhood illustrates one phenotypic expression of a novel pathogenetic mechanism in mitochondrial diseases, the specific depletion of mtDNA in affected tissues.

Blotting, Southern↗
PubMed1992

Acute quadriplegic myopathy: a complication of treatment with steroids, nondepolarizing blocking agents, or both.

We studied two patients who were given high-dose intravenous steroid therapy and were intubated for status asthmaticus. Both became quadriplegic and wasted within 2 weeks. EMG had myopathic abnormalities. Muscle biopsy revealed severe atrophy of most muscle fibers, with disorganization of myofibrils and selective loss of thick (myosin) filaments. Immunohistologic stains for myosin isoforms confirmed the decrease or absence of this protein. Both patients clinically improved over several months.

Acute Disease↗
PubMed1992

Dystrophinopathy in isolated cases of myopathy in females.

X-linked dystrophinopathy is the most common cause of isolated cases of myopathy in males. To investigate dystrophin abnormalities as a cause of myopathy in girls and women, we used dystrophin immunocytochemistry to study muscle biopsies from 505 girls and women with neuromuscular disease. Forty-six muscle biopsies showed a combination of fibers containing or lacking dystrophin; this mosaic immunostaining pattern denoted a carrier status. Twenty-one of 46 (45.6%) had a family history of Duchenne muscular dystrophy in males. Twenty-five of 46 (54.3%) were isolated cases, with no previous family history of neuromuscular disorder. The laboratory findings of the isolated cases were consistent with the familial cases; all showed myopathic histopathology and abnormal elevations of serum CK. The clinical presentations of the isolated cases varied but were consistent with the familial cases: 40% (10/25) of isolated cases showed proximal limb weakness before age 10, 24% (6/25) presented with myalgias or cramps, 24% (6/25) presented with incidental findings of grossly elevated CK levels, 8% (2/25) noted easy fatigue, and 4% (1/25) had slowly progressive proximal limb weakness beginning at age 45. From our data, the clinical criteria for consideration of an underlying dystrophinopathy in isolated female cases of myopathy are CK levels greater than 1,000 IU/l and myopathic histopathology. About 10% of the isolated cases of hyperCKemic myopathy (25/210) were proven by dystrophin analysis to have a dystrophinopathy as the cause of their disease (manifesting carriers of Duchenne dystrophy). However, we feel that this may be an underestimate. The correct diagnosis in these patients is imperative for appropriate genetic counseling to the patients and their families.

Adolescent↗
PubMed1992

Immunologic study of vinculin in Duchenne muscular dystrophy.

Using immunologic techniques, we studied vinculin, a cytoskeletal protein associated with the membrane-skeleton of the muscle fiber. We examined muscle biopsies from five patients with Duchenne muscular dystrophy (DMD), two with Becker's muscular dystrophy (BMD), three normal human muscle samples, and four biopsies from disease control patients. All DMD patients showed patchy and low-intensity immunostain at the sarcolemma of most fibers and, by immunoblot analysis, the content of vinculin was 42 to 61% of control values. There was no significant vinculin deficiency in samples from patients with BMD and other disease controls. The data suggest that vinculin content is reduced only in muscle where dystrophin is absent or sparse.

Adolescent↗
PubMed1992

Carrier detection of Duchenne and Becker muscular dystrophy using muscle dystrophin immunohistochemistry.

To ascertain whether dystrophin immunohistochemistry could improve DMD/BMD carrier detection, we analyzed 14 muscle biopsies from 13 DMD and one BMD probable and possible carriers. All women were also evaluated using conventional methods, including genetic analysis, clinical and neurological evaluation, serum CK levels, EMG, and muscle biopsy. In 6 cases, there was a mosaic of dystrophin-positive and dystrophin-deficient fibers that allowed to make the diagnosis of a carrier state. Comparing dystrophin immunohistochemistry to the traditional methods, it was noted that this method is less sensitive than serum CK measurements, but is more sensitive than EMG and muscle biopsy. The use of dystrophin immunohistochemistry in addition to CK, EMG and muscle biopsy. improved the accuracy of carrier detection. This method is also helpful to distinguish manifesting DMD carriers from patients with other neuromuscular diseases like limb-girdle muscular dystrophy and spinal muscular atrophy.

Adolescent↗
PubMed1992

[Spontaneous motor activity in mice overloaded with iron-dextran].

We studied the spontaneous motor activity and the levels of iron in brain (frontal cortex and striatum) and liver of mice overloaded with iron dextran. Two groups of mice injected intraperitoneally with two different doses of iron and the control group were used. We found a significant increase in the spontaneous motor activity only for the experimental group treated with the highest dose of iron. In frontal cortex and striatum the concentration of iron did not augment in the experimental groups. However, in liver we detected a highly significant rise in the iron content of both experimental groups. Our results suggest that the increase in the spontaneous motor activity observed in mice injected with the highest dose is not directly caused by changes in the iron concentration in the brain.

Animals↗
PubMed1992

[Retrospective diagnosis of a sample of patients discharged with a diagnosis of schizophrenia].

A retrospective diagnosis was obtained from a sample of 300 patients discharged from the Psychiatric Hospital of Maracaibo (Venezuela), with the clinical diagnosis of schizophrenia. These medical records were evaluated under DSM-III criteria, by two psychiatrists using structured formats. We found that 46.3% of the patients met the criteria corresponding to the schizophrenic disorder; from the remaining 53.6%, 19.6% did not have enough information to be included in this category, and 34.6% was classified under other psychiatric disorders. Of the patients with schizophrenic disorders, 61.2% were male, single, and Venezuelan citizens; 84.9% began their clinical manifestations during the second or third decade of their lives; 89.9% received education. The predominant symptomatology was impairment in social relations (93.5%), deterioration in hygiene and self- care (92.5%), impairment in functioning (87.1%), illogical thinking (86.3%), with predominant persecutory delusions, auditory hallucinations, dialogue hallucinations (84.6%), grandiose delusions (48.2%), and personal experiences of corporeal changes (45.3%). Affective symptomatology were present in all patients and the predominant subtype was the paranoid, that was observed in 80.6% of the cases. Positive signs of this disease in family history were present in 41 percent of the cases. Our findings confirm the necessity to unify criteria concerning the diagnosis of mental disorders, as it became evident that the variability in diagnosis, makes more difficult the psychiatric research in our country.

Adult↗
PubMed1992

The mitochondrial tRNA(Leu(UUR)) mutation in mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS): genetic, biochemical, and morphological correlations in skeletal muscle.

Mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) has recently been associated with an A----G transition at position 3243 within the mitochondrial tRNA(Leu(UUR)) gene. Besides altering the tRNA(Leu(UUR)) sequence, this point mutation lies within a DNA segment responsible for transcription termination of the rRNA genes. We have studied the distribution and expression of mutant mtDNAs in muscle biopsies from MELAS patients. Histochemical, immunohistochemical, and single-fiber PCR analysis showed that ragged-red fibers (RRF) are associated both with high levels of mutant mitochondrial genomes (greater than 85% mutant mtDNA) and with a partial cytochrome c oxidase deficiency. By quantitative in situ hybridization, the steady-state ratios of mRNAs:rRNAs were found to be similar to controls in six of eight patients studied. In two other patients the relative levels of heavy-strand mRNAs were slightly increased, but a patient with myoclonic epilepsy and RRF also exhibited a similar increase. These results directly correlate the A----G transition at mtDNA position 3243 with muscle mitochondrial proliferation, partial respiratory-chain impairment, decreased mitochondrially synthesized protein content, and no specific alterations in mitochondrial ratios of mRNAs:rRNAs.

Acidosis, Lactic↗
PubMed1992

[Clinical heterogeneity of the autistic syndrome: a study of 60 families].

Sixty families ascertained through a single proband, has helped to better define infantile autism as a heterogeneous group of disorders. Forty four patients showed a characteristic facio- auricular dysplasia. Twenty four of these, showed increased pyruvate and lactate and laboratory findings of metabolic acidosis i.e., anion gap above 18 mEq/L or serum bicarbonate below 21 mEq/L but only nine of these probands demonstrated reduction of plasma bicarbonate below 18 mEq/lt. Plasma amino acids in 17 probands and matched controls showed increased taurine with the rest of amino acids significantly (p less than 0.05) below the control level. Glutamate and aspartate were also significantly elevated (p less than 0.05; Student t-test). Segregation analysis in thirty four of these families which linked through at least one ancestral family name, suggested autosomal recessive inheritance (p = 0.20). Three out of eight probands who received megadoses of pyridoxine (Vitamin B6), subjectively gained in language abilities, affectivity and response to behavior modification therapy. Five autistic patients proved to have clinically defined syndromes: two with the Martin-Bell syndrome, and three girls affected respectively with the Rett syndrome, phenylketonuria and dicarboxylic aciduria.

Acidosis↗
PubMed1992

[Chronic manganese poisoning: autoradiographic quantification of cholinergic muscarinic receptors in mouse brain].

Chronic administration of manganese chloride (5 mg Mn/kg body weight/day) during nine weeks, did not affect the [3H]-quinuclidinyl benzilate binding to muscarinic cholinergic receptors in mouse brain. The quantitation and anatomical distribution of the receptors were determined by autoradiographic methods on coronal sections of midbrain and olfactory bulb. It is concluded that, in our experimental conditions, no alteration in the density of the muscarinic cholinergic receptors is produced in the brain of manganese intoxicated mouse.

Animals↗
PubMed1991

Serum ferritin deficiency in Huntington's disease patients.

This study was designed to investigate serum levels of iron, ferritin, vitamin B12 and folic acid in 18 Huntington's disease patients and 86 healthy control subjects. Serum iron, vitamin B12 and folic acid levels were normal. Ferritin concentrations were significantly diminished in the choreic patients. The importance of this finding in our attempt to understand the underlying biochemical defect and the chemical nature of the iron deposits found in several brain nuclei in Huntington's disease patients is unknown.

Adolescent↗
PubMed1991

Localization of mitochondrial DNA in normal and pathological muscle using immunological probes: a new approach to the study of mitochondrial myopathies.

We have studied the usefulness of anti-DNA antibodies to detect ragged-red fibers (RRF) in muscle biopsies from patients with mitochondrial myopathies. We have found that these antibodies are excellent probes for the localization of mitochondrial DNA (mtDNA) in RRF, and for the diagnosis of depletion of mtDNA in a newly described group of fatal myopathies of infancy.

Antibodies↗
PubMed1991

Appearance and localization of dystrophin in normal human fetal muscle.

We studied the localization of dystrophin in normal human fetal muscle by immunohistochemistry. Our results show the appearance of dystrophin at week 11 and a progressive organization of the protein along membrane in the following weeks of gestation. At week 22 almost all fibers show a clear membrane immunostaining. Concomitant analysis of muscle fiber-type composition reveals no correlation between progressive appearance of dystrophin and muscle fiber-type differentiation. Our findings suggest that synthesis and localization of dystrophin in developing human skeletal muscle is time-related and probably independent of neuronal influences.

Dystrophin↗
PubMed1991

Becker muscular dystrophy or spinal muscular atrophy?--Dystrophin studies resolve conflicting results of electromyography and muscle biopsy.

We studied a 29-year-old man with slowly progressive proximal leg weakness, calf hypertrophy, and high serum levels of creatine kinase activity. Clinically, it was not possible to identify his as a sporadic instance of Becker muscular dystrophy (BMD) or one of spinal muscular atrophy. The problem arose because electromyography and elevated creatine kinase suggested a myopathy whereas changes in the muscle biopsy resembled a neurogenic disorder. The diagnosis of BMD was made by DNA analysis which detected a deletion at Xp21 and by immunoelectrophoresis and immunohistochemical tests that identified an abnormal form of gene product, dystrophin. These studies were important for genetic counselling, identifying an X-linked disease instead of one that is autosomal recessive.

Adult↗
PubMed1991

Replication-competent human mitochondrial DNA lacking the heavy-strand promoter region.

We identified two patients with progressive external ophthalmoplegia, a mitochondrial disease, who harbored a population of partially deleted mitochondrial DNA (mtDNA) with unusual properties. These molecules were deleted from mtDNA positions 548 to 4,442 and encompassed not only rRNA sequences but the heavy-strand promoter region as well. A 13-bp direct repeat was found flanking the breakpoint precisely, with the repeat at positions 535 to 547 located within the binding site for mitochondrial transcription factor 1 (mtTF1). This is the second mtDNA deletion involving a 13-bp direct repeat reported but is at least 10 times less frequent in the patient population than the former one. In situ hybridization studies showed that transcripts under the control of the light-strand promoter were abundant in muscle fibers with abnormal proliferation of mitochondria, while transcripts directed by the heavy-strand promoter, whether of genes residing inside or outside the deleted region, were not. The efficient transcription from the light-strand promoter implies that the major heavy-and light-strand promoters, although physically close, are functionally independent, confirming previous in vitro studies.

Base Sequence↗