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N Romero

Publications and source records attributed to N Romero.

At least 55 records · Page 3Linked to original sources
PubMed1991

Genetic biochemical and pathophysiological characterization of a familial mitochondrial encephalomyopathy (MERRF).

Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome is a neuromuscular disorder characterized by mitochondrial myopathy and progressive myoclonus epilepsy. A heteroplasmic A to G transition mutation in the mitochondrial encoded tRNA(Lys) gene at nucleotide pair 8344 has been suggested to be linked to the MERRF-syndrome. We have investigated biochemically and histochemically muscle biopsies and studied the mitochondrial genomes of hair, blood and muscle tissue of a family including three cases of MERRF-syndrome as well as unaffected relatives within the maternal lineage. Sequence analysis of the mtDNAs, performed after amplification by the polymerase chain reaction (PCR), confirmed the A to G transition mutation in the tRNA(Lys) gene at position 8344. The additional point mutation at nucleotide pair 750 in the 12 S rRNA gene, which was also found by Shoffner et al. (1990), however, was absent in all investigated tissues. Quantitative analysis of the percentage of mutated mtDNA by mispairing PCR (Seibel et al., 1990) revealed variable contents in different tissues and individuals, including unaffected family members. Mitochondrial protein synthesis in cultured fibroblasts from MERRF patients revealed diminished incorporation of 35S-methionine into lysine-containing peptides.

Adolescent↗
PubMed1991

Autosomal dominant syndrome with strokelike episodes and leukoencephalopathy.

BACKGROUND AND PURPOSE: We conducted a prospective survey of a family presenting a new syndrome characterized mainly by recurrent strokelike episodes and neuroimaging evidence of leukoencephalopathy. SUMMARY OF REPORT: Forty-five members of a single family were studied clinically and with magnetic resonance imaging. Nine had strokelike episodes, including transient ischemic attacks, and minor or major strokes starting between the fourth and sixth decades, with neuroimaging evidence of small, deep infarcts and a widespread white matter disorder. Other symptoms included migraine (three), dementia (two), epilepsy (one), and hearing loss (one). In some patients, we found various immunologic anomalies and muscular lipidosis without ragged-red fibers. Eight other family members were clinically normal, but had identical neuroimaging signs of leukoencephalopathy. No abnormality was detected in the 28 other members of the family examined. Extensive investigations failed to reveal any known cause of cerebral ischemia. CONCLUSIONS: There appears to be a new syndrome in this family that is characterized by recurrent subcortical strokelike episodes, leukoencephalopathy, immunologic anomalies, muscular lipidosis, and an autosomal dominant pattern of transmission.

Adult↗
PubMed1991

[Clinical and electrophysiologic study of the peripheral nerve in 28 cases of mitochondrial disease].

Twenty-eight patients with mitochondrial disease were systematically investigated on clinical and electrophysiological grounds for peripheral neuropathy (PN): 25 had predominant ophthalmoplegia (including 4 with Kearns-Sayre syndrome) and 3 had predominant central nervous system involvement. There were 11 men and 17 women, mean age 43 years. Nine of the 28 patients had signs of sensory polyneuropathy involving mainly the lower limbs. These 9 patients and another asymptomatic patient had electrophysiological abnormalities: in the lower limbs, sensory potentials were absent or decreased in amplitude in all cases. In peroneal nerves, motor conduction nerve velocities were decreased in 4/10 cases. These data were consistent with an axonopathy. No correlation was found between the presence of PN and the clinical features of the mitochondrial diseases or with the respiratory chain defect (studied in 14 cases).

Action Potentials↗
PubMed1991

[Mitochondrial function and mitochondrial DNA in a series of 64 patients suspected of having mitochondrial myopathy].

Biochemical results concerning 64 patients suspected of mitochondrial myopathies are presented. Four clinical groups were studied including 21 encephalomyopathies, 42 ocular myopathies, 8 isolated myopathies and 3 cardiomyopathies. In 26 cases, the coexistence of a normal mitochondrial DNA and a mutated mitochondrial DNA (heteroplasmy) was found (19 simple deletions, 4 multiple deletions and 3 punctual mutations) and all cases presented with ocular disorders (excepted 2 cases with MERRF). Furthermore, 1 complex I deficiency (1 ocular myopathy), 1 complex IV deficiency (1 adult encephalomyopathy type Leigh), 3 complexes I + IV deficiencies (2 cases with a cardiomyopathy and 1 familial MELAS) and 2 pyruvate (1 adult from of Leigh's encephalomyopathy) dehydrogenase deficiencies (clinically and genetically different) did not show evidence of mitochondrial DNA mutation.

Blotting, Western↗
PubMed1990

Identification of point mutations by mispairing PCR as exemplified in MERRF disease.

The point mutation in the tRNA(Lys) gene of mitochondrial DNA (mtDNA) from patients with myoclonic epilepsy and ragged red fibers (MERRF) was quantitatively analyzed after digestion with the restriction endonuclease Nae I of the PCR amplified DNA. Since the point mutation is not part of a restriction site for a commonly available restriction endonuclease, the Nae I restriction site was introduced by PCR using a mispairing primer. The percentage of mutated mtDNA was determined in a few hairs of five members of an affected family by counting the radioactivity of the fragments after PCR amplification with labelled dATP.

Adolescent↗
PubMed1990

Immunohistochemical demonstration of fibre type-specific isozymes of cytochrome c oxidase in human skeletal muscle.

The immunohistochemical reaction of monoclonal as well as polyclonal antibodies against cytochrome c oxidase (COX) subunits with serial sections of normal human skeletal muscle was investigated. The stronger reactivity of polyclonal antibodies to COX subunits II-III and VIIbc with type I as compared to type II fibres, correlated well with the higher histochemical reactivity of NADH dehydrogenase, succinate dehydrogenase and cytochrome c oxidase in type I fibres. In contrast an almost exclusive reaction of a monoclonal antibody against subunit IV with type I fibre and a preponderant reaction of a polyclonal antibody against subunits Vab with type II fibres was obtained. Antibodies against subunits I, Vb and VIc did not reveal a fibre-type-specific reactivity. The data indicate in human muscle the occurrence of fibre type-specific isozymes of cytochrome c oxidase differing in subunits IV and Va or Vb.

Antibodies, Monoclonal↗
PubMed1990

Pearson's marrow-pancreas syndrome. A multisystem mitochondrial disorder in infancy.

Pearson's marrow-pancreas syndrome (McKusick No. 26056) is a fatal disorder of hitherto unknown etiology involving the hematopoietic system, exocrine pancreas, liver, and kidneys. The observation of high lactate/pyruvate molar ratios in plasma and abnormal oxidative phosphorylation in lymphocytes led us to postulate that Pearson's syndrome belongs to the group of mitochondrial cytopathies. Since rearrangements of the mitochondrial genome between direct DNA repeats were consistently found in all tissues tested, our results show that this disease is in fact a multisystem mitochondrial disorder, as suggested by the clinical course of the patients. Based on these observations, we would suggest giving consideration to the hypothesis of a defect of oxidative phosphorylation in elucidating the origin of other syndromes, especially those associated with an abnormal oxidoreduction status in plasma.

Anemia, Sideroblastic↗
PubMed1989

Mapping of heteroplasmic mitochondrial DNA deletions in Kearns-Sayre syndrome.

Kearns-Sayre syndrome (KSS) is a progressive neuromuscular disease characterised by ophtalmoplegia, cardiac bloc branch, pigmentary retinopathy associated with abnormal mitochondrial function. We have studied the mitochondrial DNA organization of patients presenting KSS and have found large deletions ranging from 3 to 8.5 kilobase pairs. DNA molecules containing deletion are accompanied by the presence of the normal sized mtDNA molecule forming heteroplasmic genomes. The deletions always map in the region which is potentially single stranded during mitochondrial DNA replication. The deletions differ in length and position between individuals but are similar within the different tissues of an individual suggesting that they arise during or before embryogenesis.

Biopsy↗
PubMed1989

Superoxide dismutase activity in some strains of lactobacilli: induction by manganese.

Dialyzed cell-free extract of lactobacilli was found to contain superoxide dismutase activity by using a test system in which superoxide ion is generated by xanthine oxidase. The specific activities of Lactobacillus acidophilus ATCC 4356, Lactobacillus murinus ATCC 35020, Lactobacillus acidophilus CRL 358, Lactobacillus plantarum ATCC 8014, Lactobacillus casei CRL 431, Lactobacillus plantarum CRL 353, Lactobacillus fermentum ATCC 9338, Lactobacillus buchneri NCDO 110, and Lactobacillus fermentum CRL 251 were between 0.06 and 0.43 U/mg protein. The presence of superoxide dismutase activity was demonstrated when the strains were grown in media containing Mn2+ ions. Superoxide dismutase of lactobacilli may be an Mn enzyme since it was not inhibited by either cyanide or azide ions. However, the cell-free extract of Lactobacillus murinus ATCC 35020 contains superoxide dismutase activity sensitive to both ions.

Enzyme Induction↗
PubMed1989

[Respiratory chain diseases in infancy. Clinical presentation and diagnosis].

Nineteen children with defects of the mitochondrial respiratory chain are described. First symptoms appeared during the first two years of their lives. Four types of clinical pictures were identified: 1/neonatal hypotonia. 2/cardiomyopathy. 3/progressive neurological deterioration. 4/multisystem disease. A study of pyruvate and fatty acids metabolism and a skeletal muscle biopsy were performed in all cases. Elevation of beta-hydroxybutyrate/acetoacetate and lactate were the most frequent biochemical abnormalities. Muscular biopsy in light microscopy showed in most cases abnormal lipid storage.

Biopsy↗
PubMed1988

Role of copper in the regulation and accumulation of superoxide dismutase and metallothionein in rat liver.

Weanling male Sprague-Dawley rats were fed one of four diets that varied in Cu, Zn or Cd content. To the control diet (I) Cu, Zn and Cd were added at 10, 100 and 0 mg/kg diet, respectively. Diets II and III also contained 10 mg/kg of dietary Cu, except that Zn was elevated to 1000 mg/kg for diet II, or Cd was added at 10 mg/kg for diet III. Diet IV was deficient in Cu (less than 1 mg/kg) with Zn at 100 mg/kg and no added Cd. At wk 6 postweaning, half of the rats fed diets I and IV were injected once with Cd acetate (5 mg Cd/kg body weight). The immediate response to Cd injection was an increase in metallothionein accumulation (three- to fourfold) and in Cu,Zn superoxide dismutase (SOD) accumulation (1.2- to 1.5-fold) in liver. SOD was estimated in an ELISA. These responses were not influenced by a change in Cu status (I vs. IV). However, in functional assays, SOD enzymatic activity was about half that of the control values. In this regard, SOD appears to be given high priority with respect to the utilization of cellular Cu, i.e., a 10-fold reduction in hepatic Cu only resulted in a twofold reduction in SOD activity and the amount of apoenzyme remained at normal levels.

Animals↗
PubMed1988

Effect of latissimus dorsi dynamic cardiomyoplasty on ventricular function.

In our approach to dynamic cardiomyoplasty, which consists of wrapping a skeletal muscle around the heart and stimulating the former in synchrony with heart contractions to augment ventricular contractility, we have transferred a latissimus dorsi muscle flap to the heart by way of a partial resection of the second rib and subsequently suturing the muscle flap around the ventricles. The muscle flap is stimulated by a Cardio-Myostimulator burst-pulse generator (Medtronic SP 1005) connected to intramuscular electrodes. In preclinical animal research, the latissimus dorsi muscle flap was shown to maintain adequate contractile force and to increase its fatigue resistance by gradual conversion of glycolytic-fatigue-sensitive-to-oxidative-fatigue-resistant muscular fibers (100%). Histochemical and biochemical studies of chronically stimulated muscles showed a total transformation of muscle fast myosin to slow myosin with characteristics similar to those of myocardium. Electron microscopy showed preserved myofibrillar cytoarchitecture and increased mitochondrial density in the cell. At 9 months, cardiac output and ultrasonic Doppler studies showed a significant increase in ventricular function (cardiac output, +21%; peak blood velocity, +40% -80%; and stroke volume, +98% -102%) during muscle stimulation. In the clinical situation, long-term (range of follow-up interval, 4-42 months) beneficial cardiac effects of cardiomyoplasty have been documented in eight patients with various pathologies (ventricular tumor, left ventricular aneurysm, ischemic disease, and dilated cardiomyopathy). Our current understanding of this process is that dynamic cardiomyoplasty acts in two ways: 1) it promotes more vigorous systolic contraction, and 2) it appears to limit heart dilatation.

Animals↗
PubMed1986

Tropoelastin production and tropoelastin messenger RNA activity. Relationship to copper and elastin cross-linking in chick aorta.

The elastin content of the chick thoracic aorta increases 2--3-fold during the first 3 weeks post-hatching. The deposition of elastin requires the covalent cross-linking of tropoelastin by means of lysine-derived cross-links. This process is sensitive to dietary copper intake, since copper serves as cofactor for lysyl oxidase, the enzyme that catalyses the oxidative deamination of the lysine residues involved in cross-link formation. Disruption of cross-linking alters tissue concentrations of both elastin and tropoelastin and results in a net decrease in aortic elastin content. Autoregulation of tropoelastin synthesis by changes in the pool sizes of elastin or tropoelastin has been suggested as a possible mechanism for the diminished aortic elastin content. Consequently, dietary copper deficiency was induced to study the effect of impaired elastin cross-link formation on tropoelastin synthesis. Elastin in aortae from copper-deficient chicks was only two-thirds to one-half the amount measured in copper-supplemented chicks, whereas copper-deficient concentrations of tropoelastin in aorta were at least 5-fold higher than normal. In spite of these changes, however, increased amounts of tropoelastin, copper deficiency and decreased amounts of elastin did not influence the amounts of functional elastin mRNA in aorta. Likewise, the production of tropoelastin in aorta explants was the same whether the explants were taken from copper-sufficient or -deficient birds. The lower accumulation of elastin in aorta from copper-deficient chicks appeared to be due to extracellular proteolysis, rather than to a decrease in the rate of synthesis. Electrophoresis of aorta extracts, followed by immunological detection of tropoelastin-derived products, indicated degradation products in aortae from copper-deficient birds. In extracts of aortae from copper-sufficient chicks, tropoelastin was not degraded and appeared to be incorporated into elastin without further proteolytic processing.

Animals↗
PubMed1986

Role of plasma and serum proteases in the degradation of elastin.

Accelerated proteolysis of tropoelastin and elastin occurs in the major arteries of chicks fed copper-deficient diets. Signs of elastin degradation are not obvious in normal arteries of copper-supplemented chicks. It is proposed that the sources of proteases that effect elastin degradation are from plasma and serum. Both calcium-dependent proteases and kallikrein were effective in degrading tropoelastin and partially crosslinked insoluble elastin into peptides similar to those detected in aortic extracts from copper-deficient chicks. As dietary copper deficiency progresses it is also possible to detect elastin peptides in plasma.

Animals↗
PubMed1985

Molsidomine in the treatment of acute heart failure.

In this report we present the results of hemodynamic monitoring with a Swan-Ganz balloon catheter in 14 patients with heart failure associated with acute myocardial infarction, before and during 8 hours after a single oral dose of molsidomine (6 mg). Molsidomine induced the following changes: heart rate was reduced between 1.6% and 4.7% (significant at 4 hours, p less than 0.05); systolic blood pressure decreased 8.4% at 1 hour (p less than 0.05); pulmonary capillary pressure decreased approximately 30% (significant and lasting until 8 hours after administration, p less than 0.002); cardiac index did not change significantly, although individual analysis showed an increase in 6 of 12 cases; stroke volume index increased by 6% (significant at 1 hour, p less than 0.025); and left ventricular stroke work index increased from 9.8% to 24.5% (significant at 1 and 4 hours, p less than 0.01 and 0.025). These findings show the beneficial hemodynamic effects of molsidomine in patients with heart failure complicating acute myocardial infarction.

Aged↗
PubMed1984

Haemodynamic effects of oral molsidomine in pump failure complicating myocardial infarction.

Haemodynamic monitoring, using a Swan-Ganz balloon catheter, was done in 14 patients with pump failure associated with acute myocardial infarction, before and for 8 h after single 6 mg oral dose of molsidomine. The following changes effects were found: HR fell by 1.6 to 4.7% (significant at 4th hour; p less than 0.05); SBP was 8.4% lower after 1 h (p less than 0.05); PCP was decreased by approximately 30%, a significant effect that lasted for 8 hours (p less than 0.002). CI did not change significantly, although individual analysis showed it to have increased in 6 out of 12 cases. Stroke volume index was increased by about 6% (significant after 1 h, p less than 0.025). The left ventricular stroke work index also increased from 9.8 to 24.5% (significant after 1 and 4 h, p less than 0.01 and 0.025). These findings show the beneficial haemodynamic effects of molsidomine in pump failure complicating acute myocardial infarction.

Aged↗