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Biomedical subjects

N Bresolin

Publications and source records attributed to N Bresolin.

At least 145 records · Page 8Linked to original sources
PubMed1984

Disorders of glycogen metabolism of muscle.

This review will briefly outline the major steps of glycogen metabolism in muscle and the role of glycogen as a source of energy in different types of exercise. There are nine specific enzyme defects of glycogen metabolism or glycolysis affecting muscle. Each of the nine glycogenoses will be discussed in terms of typical and variant clinical presentation, genetic transmission, muscle biopsy and biochemical findings. The proposed pathophysiology of the various symptoms and signs will be presented and the many unsolved problems in this area will be discussed.

Biopsy↗
PubMed1983

Congenital myopathy due to phosphorylase deficiency.

A 4-year-old boy had delayed psychomotor development, proximal weakness, increased serum CK, and myopathic EMG. Muscle biopsy was normal, but histochemical stain for phosphorylase showed no reaction. The enzyme defect was confirmed biochemically and in studies of anaerobic glycolysis in vitro. Glycogen concentration was twice normal. Atypical presentations of myophosphorylase deficiency have included progressive weakness of late onset and fatal infantile myopathy. This patient represents another example of clinical heterogeneity.

Child, Preschool↗
PubMed1983

Muscle phosphoglycerate mutase (PGAM) deficiency: a second case.

Muscle phosphoglycerate mutase (PGAM) activity was markedly decreased (6% of the normal mean) in a 17-year-old girl with recurrent myoglobinuria after intense exercise. Muscle biopsy showed increased PAS stain; glycogen concentration was twice normal. Studies of anaerobic glycolysis in vitro showed decreased lactate production with glycogen, and with all hexose phosphate glycolytic intermediates, which was corrected by addition of purified PGAM to the reaction mixtures. A defect of the M subunit of PGAM was documented by electrophoretic, heat lability, and mercury inhibition studies. Intermediate PGAM activities (39 and 50% of normal) were found in muscle biopsies from the patient's asymptomatic parents. These data confirm the clinical, morphologic, and biochemical features described in the first patient with PGAM deficiency and suggest autosomal-recessive transmission of the trait.

Adolescent↗
PubMed1981

Carnitine palmityl transferase deficiency: clinical variability, carrier detection, and autosomal-recessive inheritance.

A 21-year-old man had recurrent myoglobinuria; his 28-year-old sister had symptoms of fatigability. During prolonged fasting, serum free fatty acid rose in both siblings, but only the sister produced ketone bodies and had elevated creatine phosphokinase activity. Carnitine palmityl transferase (CPT) activity was less than 30% of normal in muscle and platelets. Liver biopsy disclosed a low level of the enzyme in the brother. The parents had intermediate levels of the enzyme in platelets. CPT deficiency seems to have an autosomal-recessive pattern of inheritance and a variable phenotypic expression.

Acyltransferases↗
PubMed1981

Neuronal localization of benzodiazepine receptors in the murine cerebellum.

Selective genetic and chemical lesions which affect specific neuronal populations in the cerebellum were studied for changes in benzodiazepine receptors. Destruction of cerebellar climbing fibers with 3-acetylpyridine, did not affect cerebellar benzodiazepine receptors. Destruction of Purkinje, basket and stellate cells with intracerebellar kainic acid, caused moderate decreases in benzodiazepine receptor density. Destruction of Purkinje cells with chronic high doses of phenytoin also caused a significant decrease in benzodiazepine receptor density. In "weaver" mice, which have a severe loss of granule cells, benzodiazepine receptor density was unchanged, while the absolute number of benzodiazepine receptors decreased by 57%. In "staggerer" mice which have diminished Purkinje cells dendritic thickenings at their synapses with parallel fibers and subsequent granule cell loss, there was a 45% decrease in benzodiazepine receptor density and a 90% decrease in the absolute number of benzodiazepine receptors. These results suggest that benzodiazepine receptors exist on cerebellar Purkinje cells, that they probably also occur on cerebellar granule cells, and that they do not appear to be present on cerebellar glial cells or on climbing fibers.

Animals↗
PubMed1980

Multisystem triglyceride storage disorder with impaired long-chain fatty acid oxidation.

A five-year-old girl presented with congenital ichthyosis, hepatosplenomegaly, vacuolized granulocytes (Jordans' anomaly), and myopathy. Pathological, ultrastructural, and biochemical studies revealed nonlysosomal, multisystemic triglyceride storage. The cultured fibroblasts had increased uptake but decreased oxidation of labeled oleate. The patient failed to produce ketone bodies on fasting. A medium-chain triglyceride diet reversed the hepatomegaly. These studies are all consistent with a partial defect in the catabolism of long-chain fatty acids. This newly identified syndrome is presumably transmitted as an autosomal recessive trait.

Bone Marrow↗
PubMed1980

Sodium-dependent, high-affinity taurine transport into rat brain synaptosomes.

Taurine uptake into rat brain synaptosomal fractions appears to occur by two saturable transport processes and by bulk diffusion. The transport requires the presence of sodium ions. The dependence of the transport on temperature and cellular respiration implies that the uptake is an active process. The active process is specific for taurine and closely related amino acids. Brain regions differ in their ability to transport taurine. Uptake is not due to mitochondrial contamination of the synaptosomal fractions. However, glial contamination might partly contribute to the uptake. Kainic acid lesions of rat corpus striatum and cerebellum reduce taurine uptake implying that the uptake is, at least partly, into neurons.

Animals↗
PubMed1980

The benzodiazepine receptor of mammalian brain.

There exists a saturable, high-affinity, stereospecific, regionally and pharmacologically specific, neuronally localized benzodiazepine receptor in mammalian brain, which has a development profile similar to other neurotransmitter receptors. This receptor appears to be modulated by gamma-aminobutyric acid and selected divalent cations, and chloride ions increase the affinity of the receptor for benzodiazepines. Several benzodiazepines were shown to bind irreversibly to the receptor upon exposure to ultraviolet light and these agents can be used to facilitate solubilization and purification of the benzodiazepine receptor. Although several substances have been suggested to be the endogenous ligand, none has achieved the acceptance given to other neurotransmitters or neuromodulators, e.g., enkephalins and endorphins.

Affinity Labels↗
PubMedDate not supplied

Extracorporeal circulation as a new experimental pathway for myoblast implantation in mdx mice.

The deficiency of dystrophin, a sarcolemmal associated protein, is responsible for Duchenne muscular dystrophy (DMD). Gene replacement is attractive as a potential therapy. In this article, we describe a new method for myoblast transplantation and expression of dystrophin in skeletal muscle tissue of dystrophin-deficient mdx mouse through iliac vessels extracorporeal circulation. We evaluated the extracorporeal circulation as an alternative route of delivering myoblasts to the target tissue. Two series of experiments were performed with the extracorporeal circulation. In a first series, L6 rat myoblasts, transfected with LacZ reporter gene, were perfused in limbs of 15 rats. In the second series, the muscle limbs of three 6-8-week-old mdx were perfused with myoblasts of donor C57BL10J mice. Before these perfusions, the right tibialis anterior (TA) muscle of the rats and mdx was injected three times at several sites with bupivacaine (BPVC) and hyaluronidase. The ability of injected cells to migrate in the host tissue was assessed in rats by technetium-99m cell labeling. No radioactivity was detected in the lungs, bowels, and liver of animals treated with extracorporeal circulation. The tissue integration and viability of the myoblasts were ultimately confirmed by genetic and histochemical analysis of LacZ reporter gene. Following a single extracorporeal perfusion of myoblasts from donor C57BL10J, sarcolemmal expression of dystrophin was observed in clusters of myofibers in tibialis anterior muscles previously treated with BPVC and hyaluronidase. Furthermore, large clusters of dystrophin-positive fibers were observed in muscles up to 21 days after repeated treatments. These clusters represented an average of 4.2% of the total muscle fibers. These results demonstrate that the extracorporeal circulation allows selective myoblast-mediated gene transfer to muscles, opening new perspectives in muscular dystrophy gene therapy.

Animals↗
PubMedDate not supplied

Intramuscular migration of myoblasts transplanted after muscle pretreatment with metalloproteinases.

The effect of pretreatments of host muscles with metalloproteinases (MMPs) or with notexin on the migration of transplanted myoblasts was investigated. Transgenic TnILacZ mice in which the beta-galactosidase gene is under the control of a quail fast skeletal troponin I gene promoter were used as donors. A polyethylene microtube with four perforations was inserted in the tibialis anterior (TA) of CD1 mice. Both pretreatment substances and cells were slowly injected through that microtube. Muscles were pretreated 2 days before myoblast injection either with a mixture of collagenase, matrilysin, and notexin or with only collagenase and matrilysin or only notexin. As control for our experiments, TnILacZ and C2C12 myoblasts were also injected in TA muscles not pretreated. Comparison of short and long-term myoblast radial migration was performed using a dye (PKH26) and X-gal staining, respectively. The recipient mice were immunosuppressed with FK506. Two days after myoblast transplantation, the cell movement in muscles pretreated with collagenase, matrilysin, and notexin was slightly greater than in muscles pretreated only with collagenase and matrilysin but was about twice that observed in muscles treated with notexin alone. Almost no radial migration of TnILacZ myoblasts was observed in untreated muscles. The C2C12 myoblasts showed a four-to fivefold higher migration capacity than TnILacZ myoblasts. At 15 days after TnILacZ myoblast transplantation, the farthest positive beta-gal muscle fibers show a two- to threefold extension of the initial migration observed at 2 days, demonstrating the ability of myoblasts to continue the migration following all pretreatments and even in the untreated muscles. In addition, more muscle fibers expressed the beta-gal reporter gene in muscles pretreated only with MMPs. Our results clearly demonstrate that muscle pretreatments with MMPs increase myoblast migration and fusion with host muscle fibers after transplantation and that the C2C12 cell line producing MMPs has a higher migratory capacity.

Animals↗
PubMedDate not supplied

In vitro and in vivo tetracycline-controlled myogenic conversion of NIH-3T3 cells: evidence of programmed cell death after muscle cell transplantation.

Ex vivo gene therapy of Duchenne muscular dystrophy based on autologous transplantation of genetically modified myoblasts is limited by their premature senescence. MyoD-converted fibroblasts represent an alternative source of myogenic cells. In this study the forced MyoD-dependent conversion of murine NIH-3T3 fibroblasts into myoblasts under the control of an inducible promoter silent in the presence of tetracycline was evaluated. After tetracycline withdrawal this promoter drives the transcription of MyoD in the engineered fibroblasts, inducing their myogenesis and giving rise to beta-galactosidase-positive cells. MyoD-expressing fibroblasts withdrew from the cell cycle, but were unable to fuse in vitro into multinucleated myotubes. Five days following implantation of engineered fibroblasts in muscles of C57BL/10J mice we observed a sevenfold increase of beta-galactosidase-positive regenerating myofibers in animals not treated with antibiotic compared with treated animals. After 1 week the number of positive fibers decreased and several apoptotic myonuclei were detected. Three weeks following implantation of MyoD-converted fibroblasts in recipient mice, no positive "blue" fiber was observed. Our results suggest that transactivation by tetracycline of MyoD may drive an in vivo myogenic conversion of NIH-3T3 fibroblasts and that, in this experimental setting, apoptosis plays a relevant role in limiting the efficacy of engineered fibroblast transplantation. This work opens the question whether apoptotic phenomena also play a general role as limiting factors of cell-mediated gene therapy of inherited muscle disorders.

3T3 Cells↗
PubMedDate not supplied

[Expression of a defect in the respiratory chain in cultured human cells].

Large scale deletions of mitochondrial DNA (mtDNA) or altered inter-genomic regulation in skeletal muscle have been demonstrated in patients with mitochondrial encephalomyopathies due to Cytochrome C oxidase (COx) deficiency. We have analyzed by Southern blotting and Polymerase Chain Reaction (PCR) the mtDNA in primary muscle cultures (myoblast-myotube stages and at clonal densities) and in fibrogenic subclones obtained from 9 patients with partial COx deficiency who had in their muscle biopsy a subpopulation of mtDNA showing deletions of variable size (between 2.1 and 6.5 Kb). Only in the cultures from one patient, southern analysis revealed in myoblasts and myotubes a mtDNA almost identical to that found in the original muscle biopsy and persistence of deletion in muscle cells grown at clonal densities. The deletion was detectable in fibrogenic lineage only by PCR amplification. The deleted mtDNA molecules were detectable in myogenic or fibrogenic cultures from other patients only by PCR amplification. The different amounts of deleted mtDNA in the various tissues could be due either to an unequal distribution of the altered mtDNA during embryogenesis with amplification of deleted molecules in myogenic lineage or could result from negative selection against the altered mtDNA in rapidly proliferating cells, such as fibroblasts.

Blotting, Southern↗
PubMedDate not supplied

Central nervous system involvement in HCV-related mixed cryoglobulinemia.

An involvement of the peripheral nervous system is frequent in patients with HCV-related mixed cryoglobulinemia (HCV-MC), whereas central nervous system (CNS) impairment has been rarely reported. To investigate the possible CNS involvement in MC, we evaluated 18 patients by neurophysiological, neuroradiological and neuropsychological methods. Three patients (16.7%) had clinically evident neurological central signs, ten (55.5%) complained of mild symptoms, possibly indicative of CNS impairment, and five (27.8%) did not have any CNS symptom. Evoked potentials (EPs) were abnormal in 83% of the cases (SSEPs in 72%, VEPs in 44%, MEPs in 39% and BAERs in 22%). Brain magnetic resonance imaging (MRI) showed abnormal findings in 83% (small T2-weighted hyperintense lesions in 72%, focal or diffuse atrophy in 50%). Cognitive impairment was detected in 22% of the patients. A mild or subclinical CNS involvement is frequent in MC patients. Neuropsychological, neurophysiological and neuroradiological examination are useful to detect CNS involvement also in asymptomatic subjects.

Aged↗
PubMedDate not supplied

Muscle biopsy in Alzheimer's disease: morphological and biochemical findings.

Recent evidences of a predisposing genetic factor associated with Alzheimer's disease (DAT) suggests that important alterations may be expressed in tissues other than the brain. We present morphological and biochemical studies on muscle obtained from ten patients with Alzheimer's disease and coeval controls. Muscle biopsy examination showed an increased subsarcolemmal mitochondrial oxidative activity in three patients. The biochemical studies showed an increased oxidative enzyme activity only in the DAT group. The CoQ10 level, studied so far in three DAT patients, was greatly reduced (approximately 50%) compared with controls. Possible new peripheral markers in Alzheimer's disease will be discussed.

Aged↗