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Biomedical subjects

G Scarlato

Publications and source records attributed to G Scarlato.

At least 289 records · Page 16Linked to original sources
PubMedDate not supplied

Myosin polymorphism in human skeletal muscles.

Myosins isolated from individual human muscles (primarily normal muscles) were investigated with respect to their structural and catalytic properties. The results indicate unexpected elements of uniformity shared by the several myosins, such as a three-banded, electrophoretic pattern of light chains in sodium dodecylsulfate (SDS) gels and a low degree of alkaline lability. The pH activity profile and the effect of KCl on myosin ATPase activities were also found to be the same for the myosins from predominantly fast (e.g., vastus lateralis and rectus abdominis) and slow (e.g,, soleus and pectoralis minor) muscles. Coelectrophoretic experiments lend further credence to the interrelationship between human myosin light chains and the light chains of rabbit fast-muscle myosin. However, several kinds of circumstantial evidence, such as that derived from the study of myosin in nemaline myopathy, suggest that one shoould exercise caution in interpreting these results. On the other hand, human muscle myosins, like those of other mammalian species, can be divided into two main categories according to the peptide composition of tryptic heavy meromyosin (HMM) and the banding pattern of light meromyosin (LMM) paracrystals. These results, which are indicative of differences in the primary structure of the heavy chains, allow us to identify these heavy chains as the main site of heterogeneity among myosins in human mucles.

Adenosine Triphosphatases↗
PubMedDate not supplied

Treatment of denervated muscle by gangliosides.

Short-duration cooling of the nerve to the extensor digitorum longus muscle of the rat in vivo induced partially reversible denervation of the muscle and atrophy in the type 2 muscle fibers. Increases in cyclic adenosine monophosphate, cyclic guanosine monophosphate phosphodiesterase, adenylate cyclase, and guanylate cyclase were observed in the denervated muscle. Treatment with gangliosides of the bovine brain cortex seemed to improve the excitability of the surviving motor units and to encourage recovery of neuromuscular trophic control, but it did not affect the nerve conduction velocity or the contractile properties of the denervated muscle.

Animals↗
PubMedDate not supplied

Idebenone induces oxygen consumption rate modifications in aged rat brain mitochondria.

Idebenone effects on oxygen consumption in brain mitochondria, obtained from young and aged rats, were evaluated. Sixty rats (3 and 20 months of age) were treated for 3 months with 30 mg/kg of idebenone and compared to a placebo group. Brain mitochondria oxygen consumption rate was measured by polarographic techniques in basal (State 4), ADP-stimulated (State 3) and uncoupled conditions. When Complex I substrates (pyruvate + malate) were used, aged non-treated rats showed a significant increase in State 4 (175%) and uncoupled (152%) O(2)-uptake rate; no difference was found in State 3 respiration and in ADP/O(2) ratio. Idebenone was able to reverse these age-related effects probably acting on lipid peroxidation and the mitochondrial respiratory chain. No differences were found in mitochondrial enzymatic activities.

Journal Article↗
PubMedDate not supplied

Glial activation in Alzheimer's disease: the role of Abeta and its associated proteins.

A common feature of Alzheimer's disease (AD) pathology is the abundance of reactive astrocytes and activated microglia in close proximity to neuritic plaques containing amyloid-beta protein (Abeta). The relationship between glial activation and neurodegeneration remains unclear, although several cytokines and inflammatory mediators produced by activated glia have the potential to initiate or exacerbate the progression of neuropathology. Assuming that glial activation plays a central role in the development and progression of AD, a prominent feature is to understand which stimuli drive this activation in senile plaques and to define their effects in vitro. There is a growing body of evidence to suggest that deposition of Abeta and expression of its associated molecules represent important trigger factors in glial activation leading to an inflammatory reaction in the brain. Thus, unraveling the mechanisms by which these proteins exert their effect on glial cells may provide significant insight into the pathophysiology of AD, and may lead to the identification of new strategies for AD treatment.

Alzheimer Disease↗
PubMedDate not supplied

Influence of different screening procedures on the stroke prevalence estimates: the Italian Longitudinal Study on Aging.

Stroke prevalence surveys are more and more needed for health care and facility planning. Prevalence estimates and costs of the definition procedure may vary depending on different screening strategies. We evaluated the impact of these different strategies on the overall diagnostic procedure and on stroke prevalence estimates in the Italian Longitudinal Study on Aging. A population sample of 5, 632 individuals aged 65-84 years was screened for stroke by a simple question on previous stroke diagnosis, questions on possible stroke symptoms and a simple neurological examination. Those screened positive by any of these procedures were fully examined by a neurologist for conclusive diagnosis. We determined the positive predictive value of each procedure on the final stroke diagnosis and calculated prevalence as if each procedure had been used separately. Using the three procedures combined, the prevalence rate was 6.0% (95% confidence interval, 5.4-6.7%). If each procedure had been used as the unique screening tool, the rates would have been 5.1% (4.5-5. 7%), 4.1% (3.6-4.7%) and 2.3% (1.9-2.7%), and positive predictive values 66.4, 55.2 and 45.1%, respectively. Different screening procedures can affect stroke prevalence estimates. Compared to more complex screening strategies, the use of a simple question about previous diagnosis as the unique screening tool leads to only a slight underestimation of stroke prevalence and avoids a 66% increase in the number of subjects to be examined in a second-level specialist evaluation, potentially reducing the costs of the overall diagnostic procedure.

Age Factors↗
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

A sporadic, atypical case of desminopathy: morphological and immunological characterization.

Recently, abnormal expression of cyclin-dependent kinases was proposed as a possible cause of desminopathy. We describe an atypical case clinically characterized by severe respiratory distress. Muscle biopsy showed subsarcolemmal and intracytoplasmic accumulation areas, which intensively stained with anti-desmin antibodies and contained electrondense filamentous material at ultrastructural level. WB analysis showed 30% increased desmin signal compared to controls. Positive immunostain for CDC2 kinase, CDK2 and emerin and nuclear matrix-associated protein were, found in desmin-positive fibres.

Adult↗
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

Maintained cellular function of adrenal medullary cells in parkinsonian dysautonomia.

Adrenal gland involvement in Parkinson's disease was reported by different authors. Further studies became relevant after adrenal was proposed as dopaminergic donor for neurotransplantation. Chromaffin cells were grown in culture and the effects of nerve growth factor (NGF) tested: no differences were observed between parkinsonian and control cells. The expression of the beta-NGF mRNA in the parkinsonian adrenal was analyzed: a specific cDNA was synthesized and a 168 bp portion amplified using PCR. The products were identified and the identity of the fragment was confirmed by sequencing. Quantitative PCR demonstrated a beta-NGF mRNA concentration exceeding 5 fg/micrograms of total adrenal RNA. These findings demonstrate the retained functional capacity of the parkinsonian adrenal to respond to NGF and express the beta-NGF mRNA.

Adrenal Medulla↗
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↗