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M A Verity

Publications and source records attributed to M A Verity.

At least 73 records · Page 4Linked to original sources
PubMed1985

Postnatal histochemical fiber type differentiation in normal and hypothyroid rat soleus muscle.

We have analyzed the effect of 6-propylthiouracil-induced hypothyroidism on neonatal fiber type differentiation in the rat soleus muscle. Body weight, total soleus fiber number, histochemical fiber type differentiation, and morphometry were determined at 7, 14, 21, and 28 days. Neonatal hypothyroidism (1) inhibits the apparent approximately 50% increase in soleus muscle fiber number occurring at 14-21 days, (2) blocks the transformation of type 2C to type 2A fibers occurring between 14 and 21 days, (3) preferentially inhibits the increase in type 2 fiber diameter, and (4) retards the development of sarcoplasmic reticulum. Immature muscle fibers reveal type 1 and type 2 fiber myosin adenosine triphosphatase (ATPase) differentiation at pH 10.3, which drops to pH 9.4 with maturation. No myosin ATPase differentiation was found at pH 9.4 in the hypothyroid animals, even at 28 days.

Aging↗
PubMed1985

Inhibition of RNA and protein synthesis in isolated cerebellar cells by in vitro and in vivo methyl mercury.

Cerebellar perikarya isolated from neonatal rats were exposed to 0-20 microM methyl mercury to simultaneously compare the effect on RNA and protein synthesis. Although 50% inhibition was found at approximately 8 microM for both [3H]uridine and [3H]phenylalanine incorporation, lower concentrations of methyl mercury produced 10-15% greater inhibition of RNA than protein synthesis. In vivo methyl mercury experiments also indicated a greater sensitivity of RNA synthesis in isolated cerebellar perikarya. The observed inhibition of RNA synthesis was not caused by a defect in cellular [3H]uridine uptake or by increased degradation of RNA. Both of these activities were altered by less than 10% at concentrations of methyl mercury that produced greater than 60% inhibition of RNA synthesis. Experiments showing that the specific activity of cerebellar cell RNA synthesis peaks and remains high between 4 and 10 d of age, whereas the specific activity of protein synthesis declines rapidly emphasize the potential importance of transcriptional perturbation in neonatal rats.

Animals↗
PubMed1985

Experimental methyl mercury neurotoxicity: locus of mercurial inhibition of brain protein synthesis in vivo and in vitro.

Brain cell-free protein synthesis is inhibited by methyl mercury chloride (MeHg) following in vivo or in vitro administration. In this report, we have identified the locus of mercurial inhibition of translation. Intraperitoneal injection of MeHg (40 nmol/g body wt) induced variable inhibition of amino acid incorporation into the post-mitochondrial supernatant (PMS) harvested from the brain of young (10-20-day-old) rats. No mercurial-induced disaggregation of brain polyribosomes nor change in the proportion of 80S monoribosomes was detected on sucrose density gradients. No difference in total RNA was found in the PMS. Initiation complex formation was stimulated by MeHg, as detected by radiolabelled methionine binding to 80S monoribosomes following continuous sucrose density gradient centrifugation. After micrococcal nuclease digestion of endogenous mRNA, both in vivo and in vitro MeHg inhibited polyuridylic acid-directed incorporation of [3H]phenylalanine. However, the in vivo inhibition was no longer observed when [3H]phenylalanyl-tRNAPhe replaced free [3H]phenylalanine in the incorporation assay. The formation of peptidyl[3H]puromycin revealed no difference from controls. There was significant mercurial inhibition of phenylalanyl-tRNA Phe synthetase activity in pH 5 enzyme fractions derived from brain PMS of MeHg-poisoned rats. These experiments revealed that the apparent MeHg inhibition of brain translation in vivo and in vitro is due primarily to perturbation in the aminoacylation of tRNA and is not associated with defective initiation, elongation, or ribosomal function.

Animals↗
PubMed1984

Emetine myopathy: two case reports with pathobiochemical analysis.

We report two female patients with a history of alcohol abuse presenting with proximal painful muscle weakness following aversion therapy with emetine hydrochloride. Muscle biopsy of Case 1 showed a reversible floccular-shaped loss of myosin ATPase and dehydrogenase, an accumulation of PAS positive material, and a normal lipid content. Repeat biopsy showed core change with no focal loss of myosin ATPase. In Case 2, muscle biopsy was taken 1 month after commencement of emetine therapy and revealed similar but milder changes to Case 1. Electron microscopy revealed Z-band streaming with a decrease or loss of mitochondria. Sarcotubular systems appeared normal in shape and size. Anaerobic glycolysis on homogenate from the initial biopsy of Case 1 showed generalized reduction of lactate formation, which returned to normal in the repeat biopsy.

Alcohol Deterrents↗
PubMed1983

Esophageal abnormalities and dysphagia in polymyositis and dermatomyositis.

Structural or functional abnormalities of the distal esophagus were demonstrated by cineradiography in 14 of 16 patients with polymyositis or dermatomyositis who had been incompletely responsive to high dose corticosteroids and, in some cases, immunosuppressive therapy, or who had adverse effects associated with these therapies. These distal abnormalities occurred in the absence of proximal esophageal skeletal muscle dysfunction in 70% of patients, usually were more frequent with increasing disease duration, and were functionally similar to abnormalities reported in scleroderma. Symptomatic improvement occurred to some patients with administration of antacids and measures designed to decrease esophageal reflux, but improved esophageal symptoms did not correlate with improvement in the myositis. In 18 autopsy subjects with similar histories, distal esophageal smooth muscle atrophy and fibrosis occurred in only 1 and 2 cases, respectively. Of 5 in whom distal esophageal dysmotility had been documented ante-mortem, only 1 had fibrosis and none had smooth muscle atrophy. These findings suggest that factors other than fibrosis and muscle atrophy may contribute to distal esophageal dysmotility in polymyositis and dermatomyositis.

Adult↗
PubMed1983

Failure of atractyloside to inhibit synaptosomal mitochondrial energy transduction.

Studies on synaptosome mitochondrial respiration are complicated by "free" mitochondria. Veratridine stimulation of synaptosomal respiration was due to increased Na+ cycling at the synaptosome membrane associated with increased oxidative phosphorylation of intraterminal ADP and was inhibited by oligomycin, ouabain or Na+ free medium. Atractylate or carboxyatractyloside failed to block veratridine-stimulated respiration but inhibited exogenous-ADP-stimulated respiration. Protein synthesis in the synaptosome fraction was inhibited by oligomycin, valinomycin or 2,4-dinitrophenol but was unaffected by excess atractylate. No change in synaptosomal adenine nucleotide content was found in the presence of atractylate, although a significant decrease in the [ATP]/[ADP] was found with oligomycin, veratridine or valinomycin. These findings show that atractylate does not modify intraterminal mitochondrial energy transduction and indirectly suggest an impermeability of the synaptosome membrane to atractylate.

Adenine Nucleotides↗
PubMed1983

Experimental methyl mercury neurotoxicity: similar in vivo and in vitro perturbation of brain cell-free protein synthesis.

Perturbation of brain protein synthesis by methyl mercury chloride (MeHg) was compared in vivo and in vitro. MeHg-stimulated and/or inhibited brain cell-free protein synthesis following in vivo or in vitro administration. Although pretreatment with GSH protected the postmitochondrial supernatant (PMS) from the in vitro inhibition, direct addition of -SH compounds did not reverse the in vivo or in vitro perturbations in synthesis induced by MeHg. Inhibition of synthesis induced by both in vivo and in vitro methyl mercury administration resulted in inactivation of component(s) in brain pH 5 enzymes. Stimulation of amino acid incorporation following in vivo administration of MeHg was apparently associated with the ribosome fraction, but in vitro preincubation of PMS with MeHg produced stimulation associated with the pH 5 enzyme fraction. A model of MeHg neurotoxicity was proposed providing a common molecular locus of interaction in vivo and in vitro.

Age Factors↗
PubMed1983

Delayed phytohemagglutinin-stimulated production of adenosine triphosphate by aged human lymphocytes: possible relation to mitochondrial dysfunction.

The decreased immune response associated with aging may, in part, reflect intrinsic age-related biochemical alterations in lymphocytes from older animals. We measured levels of lymphocyte adenosine triphosphate (ATP) and continuous [3H]thymidine incorporation in phytohemagglutinin-stimulated lymphocytes from young and old humans, and the effects thereon of inhibitors of mitochondrial oxidative phosphorylation and protein synthesis. No difference was found in adenine nucleotide content between young and old subjects. After 24 hours of culture there was a decrease in ATP, with recovery and 2--3-fold increase at 48 hours in young cells after phytohemagglutinin stimulation. We observed a clearcut delay in older lymphocytes of the increase in ATP and [3H]thymidine incorporation following phytohemagglutinin stimulation. We found no evidence for decreased viability or diminished number of responding units in aged cultures. The evidence suggests that mitochondrial dysfunction may play a role in the immunodeficiency of aging.

Adenine Nucleotides↗
PubMed1982

Morphology of developing cerebral cortical synaptosomal fractions isolated from eu- and hypothyroid rats.

Synaptosomal fractions isolated from the cerebrum of eu- and of hypothyroid rats during the neonatal period were analyzed by electron microscopy. This analysis revealed 3 main components: presynaptic endings, growth cones and unidentifiable structures that may be dendritic in origin. Since the size and the percentage of presynaptic endings were not altered by hypothyroidism but the size of the fraction in comparison to cerebrum weight was altered on postnatal day 14, it could be concluded that hypothyroidism results in a transient reduced synaptic density.

Age Factors↗
PubMed1982

Adult onset type II fiber centronuclear neuromyopathy with segmented demyelination.

We report a 54-year-old male with progressive, adult onset distal muscle weakness and intermittent paresthesia associated with preferential type II fiber centronuclear (myotubular) change and segmental demyelination in sural nerve. Morphometric analysis, single fiber teasing and graphic analysis of internode lengths confirms the segmental demyelination with no evidence of ongoing repetitive Schwann cell remyelination. Cases of adult onset centronuclear myopathy are reviewed. This cas provides evidence for a neurogenic component in the pathogenesis of the centronuclear neuromyopathies.

Demyelinating Diseases↗
PubMed1982

Stimulation of Na+-dependent, veratridine-sensitive synaptosomal amino acid uptakes by serum albumin.

Bovine serum albumin (BSA) is shown to stimulate selectively the synaptosomal uptakes of those amino acids that are dependent on external Na+ and that are inhibited by veratridine. Thus, the stimulation can be seen in the case of aspartic acid, glutamic acid, glycine, proline, and gamma-aminobutyric acid, but not with serine and threonine. Further, studies on the interaction of veratridine, valinomycin, and BSA on the uptake of proline suggest that the primary action of the albumin is to increase the influx of proline. Such an action could result as a consequence of stabilization of the Na+ gradient by increased endogenous levels of ATP. Intrasynaptosomal ATP was increased in the presence of BSA but significantly decreased by veratridine.

Amino Acids↗
PubMed1982

Congenital neuromuscular disease with type I fibre hypotrophy, ophthalmoplegia and myofibril degeneration.

We report a 7-year-old boy with progressive, early onset somatic and cranial muscle weakness associated with external ophthalmoplegia, facial weakness, type I fibre hypotrophy and myofibril degeneration. We separate this condition from congenital fibre type disproportion because of the facial weakness, ophthalmoplegia, central nucleation, and lysis in type I fibres. The case, which is similar to that described by Bender and Bender (1977), nosologically should be classified between the centronuclear myopathies and congenital fibre type disproportion, and most likely represents a congenital or neonatal disturbance of trophic interaction between nerve and muscle.

Blepharoptosis↗
PubMed1981

Studies on valinomycin inhibition of synaptosome-fraction protein synthesis.

The ionophore valinomycin inhibited adult and neonatal synaptosome fraction protein synthesis with half-maximal inhibition at approximately 10nM. Valinomycin had no effect on [3H]leucine uptake into synaptosomes at high or low external [K+]. Synaptosome-fraction protein synthesis was dependent on [K+]e reaching a maximum at 25mM-K+. Valinomycin inhibition of protein synthesis was not reversed at high [K+]e. Valinomycin failed to influence the intrasynaptosomal [K+] even at zero [K+]e. A significant increase in State-4 respiration of synaptosomal fractions was found at 5nM-valinomycin with a decrease in the respiratory control index. At these concentrations of valinomycin there was no inhibition of the ADP-stimulated (State 3) respiration rate. Valinomycin had no effect on cerebral microsomal protein synthesis in vitro, which was inhibited by puromycin (100 micrograms/ml) or the absence of ATP. Valinomycin, 2,4-dinitrophenol and KCN inhibition of protein synthesis was not reversed by added ATP, suggesting impermeability of the membrane to ATP. Valinomycin induced a rapid fall in synaptosome ATP content not observed with atractylate or ouabain. Valinomycin inhibition of protein synthesis under these conditions is secondary to uncoupling of mitochondrial oxidative phosphorylation with a subsequent decrease in intraterminal ATP necessary for translation.

Adenosine Triphosphate↗
PubMed1981

Presence of kynurenine hydroxylase in developing rat brain.

Kynurenine-3-hydroxylase, an enzyme that is part of the degradative pathway for tryptophan, was present in the cerebral cortex of neonatal rats and exhibited a Km for L-kynurenine close to that of the liver enzyme. This enzyme was enriched in mitochondrial fractions isolated from cerebral cortices of neonatal rats by Ficoll--sucrose gradient centrifugation, with some activity also present in synaptosomal fractions probably due to the mitochondrial content of synaptosomes since cytochrome c oxidase, another mitochondrial enzyme, had a similar distribution in the gradient. Kynurenine hydroxylase as well as monoamine oxidase, another mitochondrial enzyme, had increased specific activities in synaptosomal fractions isolated from 14-day-old rats compared to fractions from 8-day-old rats. Hypothyroidism, induced on the day of birth, resulted in increased activities of kynurenine hydroxylase and monoamine oxidase in synaptosomal fractions isolated from 14-day-old rats.

Animals↗
PubMed1980

Isolation of ribosome containing synaptosome subpopulation with active in vitro protein synthesis.

Subpopulations of synaptosomes harvested from neonatal rat brain cortices revealed a differential ability to synthesize protein in vitro. Incubation of synaptosomes with radiolabeled leucine, followed by continuous sucrose gradient centrifugation produced an asymmetric shift in the radioactivity toward the higher density sucrose fractions. The bulk of the mitochondrial cytochrome c-oxidase activity was also found in these fractions, however, subfractionation studies of osmotically-lysed synaptosomes suggested that the newly-synthesized proteins reside in an osmotically sensitive, non-mitochondrial compartment. The ability of each subpopulation of synaptosomes to synthesize protein in vitro was assessed after their isolation from linear continuous sucrose gradients. There was an enrichment of highly active protein synthesizing particles in the "heavy" subpopulations of neonatal synaptosomes. The inhibitory effects of chloramphenicol and cycloheximide on the protein synthesis in these particles were similar to those of the original synaptosome fraction. Electron microscopic analysis revealed an increase in the numbers of ribosome-containing structures resembling dendritic and axonal growth cones.

Animals↗