Biomedical subjects
M Guarnieri
Publications and source records attributed to M Guarnieri.
Superoxide dismutase 1 subunits with mutations linked to familial amyotrophic lateral sclerosis do not affect wild-type subunit function.
Mutations in superoxide dismutase 1 (SOD1) have been linked to familial amyotrophic lateral sclerosis, a dominantly inherited motor neuron disorder of midlife. Because SOD1 is a homodimeric enzyme, dimerization of mutant and wild-type SOD1 subunits could dominantly alter the activity, stability, or localization of wild-type SOD1 subunits. To explore these possibilities, we used transient and stable gene transfection to express high levels of either of two mutant human SOD1 subunits in the presence of limited levels of wild-type mouse and/or human SOD1 subunits. Although both mutant subunits displayed diminished half-lives and free radical scavenging activities, their presence caused no change in the half-life or activity of wild-type SOD1 subunits. Our data indicate that mutant subunits do not dominantly affect the function of wild-type SOD1 subunits. These findings, together with observations that many mutant SOD1 subunits retain significant stability and activity, suggest that motor neuron damage in familial amyotrophic lateral sclerosis is caused by the acquisition of injurious properties by mutant SOD1 subunits.
Superoxide dismutase 1 with mutations linked to familial amyotrophic lateral sclerosis possesses significant activity.
Familial amyotrophic lateral sclerosis (FALS) has been linked to mutations in the homodimeric enzyme Cu/Zn superoxide dismutase 1 (SOD1). Assay by transient expression in primate cells of six FALS mutant enzymes revealed a continuum of enzymatic activity bounded by the enzyme carrying the mutation Gly-85-->Arg, which was inactive, and mutant enzyme G37R carrying the Gly-37-->Arg change, which retained full specific activity but displayed a 2-fold reduction in polypeptide stability. The G37R mutant displayed similar properties in transformed lymphocytes from an individual heterozygous for the G37R and wild-type SOD1 genes; heterodimeric enzymes composed of mutant and wild-type subunits were detected, but there was no measurable diminution in the stability and activity of the wild-type subunits. Thus, for mutants such as G37R, either surprisingly modest losses in activity (involving only the mutant subunit) can yield motor neuron death, or alternatively, mutant SOD1 may acquire properties that injure motor neurons by one or more mechanisms unrelated to the metabolism of oxygen radicals.
Rapid anterograde axonal transport of the cellular prion glycoprotein in the peripheral and central nervous systems.
In prion diseases, the cellular prion protein (PrPc), abundant in neurons, is converted posttranslationally into an amyloid-forming scrapie prion protein (PrPSc), which accumulates in white matter tracts and nerve terminals. The trafficking of PrPc in neurons was investigated in vivo by injecting [35S]methionine into the L4 and L5 dorsal root ganglia and the entorhinal cortices of adult rats and by tracing the movement of radiolabeled PrPc. In both paradigms, labeled 33-35-kDa PrPc was transported, within 4 h, to distal axons and nerve terminals cofractionating with proteins in the fast component. Future studies using these methods may allow us to determine whether PrPc is converted into PrpSc during axonal transport and whether PrPSc is transported in animals with prion diseases.
The non-existent 'perfect' glove would be useful for diverse tasks.
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[ABACTO-SCREEN: a new system for the rapid screening of bacteriuria. Evaluation of the precision versus the traditional methods and compared with the Abbott MS-2].
ABACTO-SCREEN is an automated turbidimetric system for rapid screening of bacteriuria composed by a multichannel photometric instrument and an original disposable. In this study the system has shown good sensitivity (6.9% of false negative results on the true positives) and specificity (22.4% of false positive results on the true negatives) when on assuming 100,000 colony forming units (CFU)/ml as a threshold of positivity. Comparison with Abbott MS-2 has revealed better performances for sensitivity and comparable specificity. False negatives analysis has revealed probable influence of anaerobic bacteria in the plate counting or slowing in culture broth growth cause by antimicrobial substances in urine samples.
[Incidence of the manifestations of the so-called status varicosus of Curtius in subjects with idiopathic varices of the lower extremities].
Two groups of subjects have been studied: the first one affected by varicose veins in lower legs, the second one as control (both groups include 138 subjects, mostly corresponding about age, sex and general health conditions). Acrocyanosis, blue sclerae, juvenile spontaneous epistaxis, hand's primary osteoarthrosis, articular hypermobility, thin skin and hernia were present more frequently in the group affected by varicose veins, the difference being statistically very significant. We suggest that mechanical revealing factors lead to the development of varicose veins in subjects who have a constitutional and probably hereditary systemic weakness of connective tissue network.
The lipid composition of flight muscle mitochondria isolated from the blowfly, Phormia regina.
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Immunochemical measurement of myelin basic protein in developing rat brain: an index of myelin synthesis.
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Trypsin bound to sephadex beads. A tool for neuronal cell dissociation.
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A procedure for the bulk preparation of brain microsomes with low speed centrifugation.
A method is described for the rapid isolation of microsomes from brains of various species. The method depends on the interaction of calcium with microsomes. The procedure is limited because calcium inhibits certain microsomal enzymes. Magnesium and manganese may be substituted for calcium. However, the substitutions decrease the reliability and efficiency of the procedure.
Cells isolated from trypsin-treated brain contain trypsin.
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The antigenic region of the myelin basic protein is phylogenetically conservative.
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The effects of cell isolation techniques on neuronal membrane receptors.
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Reaction of anti-phosphatidyl inositol antisera with neural membranes.
Ca. 15% of the phosphatidyl inositol in myelin and microsomal membranes from rat brain was detectable by antiphosphatidyl inositol antibody. Antibody-detectable phosphatidyl inositol in myelin and microsomes readily increased when the membranes were incubated at 45 C with the antiserum. Synaptic membranes also had only a limited capacity to adsorb antibody. Quantitative binding studies with synaptic membranes and mitochondria were limited, because these membranes contain cardiolipin, which cross reacts with phosphatidyl inositol antisera. Moreover, highly purified synaptic and mitochondrial membranes contain appreciable amounts of other membrane fractions.
The reaction of myelin phospholipids with phospholipase C and D.
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A radioimmunoassay for myelin basic protein and its use for quantitative measurements.
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A rapid, simple method for the isolation of rat brain microsomes.
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