Sciatic pain in a young sportsman.
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Biomedical subjects
Publications and source records attributed to M Ceroni.
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Various neurological disorders have been related to Streptococcus pyogenes infection. Only recently, and for the first time, it has been suggested that acute disseminated encephalitis may also complicate a streptococcal infection. The case reported in this paper seems to confirm this hypothesis.
There is evidence of oxidative injury in postmortem brain, spinal cord, and CSF of patients with sporadic amyotrophic lateral sclerosis (SALS patients). We investigated the oxidative metabolism and calcium homeostasis in peripheral blood lymphocytes from such patients and did not find statistical differences in the basal oxygen consumption rate (QO2), cytochrome c oxidase activity, catalase activity, and lactate production. However the increase in QO2, induced by an uncoupler of oxidative phosphorylation, was depressed and the basal (resting) level of free cytosolic calcium ([Ca2+]in) was higher in lymphocytes from SALS patients (p < 0.01). Further increase in free [Ca2+]in challenged by a K+ channel blocker or by an uncoupler of oxidative phosphorylation was similar in SALS and control lymphocytes. The results show that systemic changes consistent with the presence of mitochondrial and of calcium metabolism dysfunction are present in SALS.
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Eighteen Italian patients presenting with sporadic, bilateral, simultaneous, or sequential optic neuritis (ON) were evaluated for 14 base changes in mitochondrial DNA (mtDNA) previously found associated with Leber's hereditary optic neuropathy (LHON), aiming to identify at a molecular level LHON cases with nontypical phenotypes. During a 36-month follow-up, 11 ON patients developed clinical or laboratory features allowing diagnosis of clinically definite multiple sclerosis (MS). None was positive for any of the "primary" LHON-associated mutations. However, single or multiple "secondary" LHON-associated sequence changes at 4216/ND1, 4917/ND2, and 13708/ND5 were detected in ON and ON-MS patients. MS controls without visual failure as well as healthy control subjects harbored the same base changes at similar frequencies. In addition, coexistence of three sequence changes was found in two cases (1 ON-MS patient and 1 MS control patient). We also report finding two new neutral sequence base changes in the ND-4 gene which were identified by SSCP and confirmed by automated DNA sequence analysis. The results suggests that these secondary mutations do not contribute to MS susceptibility in these patients, but rather represent neutral mitochondrial DNA polymorphisms. In addition, whether there are biochemical abnormalities related to single and multiple secondary mtDNA sequence changes remain to be demonstrated.
We report the case of a 34-year old patient who first complained of fever, confusion and transient ophthalmoplegia and then developed akinetic mutism, frontal lobe, pyramidal tract and extrapyramidal signs. Clinical and electrophysiological data support a diagnosis of encephalitis lethargica. Magnetic resonance imaging showed hyperintensive lesions in various brain regions. The patient responded to corticosteroid treatment. Two years after the onset of the first clinical signs he had recovered completely and today, after 5 years, he shows no sign of disease.
Interaction between immune cells and tumoral cells of a case of glioblastoma was studied. Tissue fragments obtained during neurosurgery from different areas of the tumor were examined before and after rIL-2 treatment in vitro. The same morphofunctional type of cells usually activated by rIL-2, which show antitumoral reactivity, was observed both in the glioblastoma imprints and in tumoral fragments cultured with rIL-2. This cytokine stimulated the proliferation of tumor infiltrating lymphocytes in vitro. This preliminary study shows that IL-2 potentiates the differentiation of HMS cells in peripheral blood which probably pass through the blood brain barrier and infiltrate the tumor.
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The utilization of denaturing methods for protein purification causes the irreversible loss of quaternary and tertiary structure together with consistent changes in the secondary structure. These modifications reflect on protein antigenicity. MBP is a myelin protein which is bound to membrane-phospholipids. Its tertiary structure is specific for this kind of interaction which determines its native conformation. MBP was obtained in two forms: denatured and non denatured. The latter has been purified using the non-ionic detergent beta-octil-D-glucopyranoside which is able to preserve protein tertiary structure separating it from the bilayer phospholipids. Non denaturated MBP could be useful in antibody and/or lymphocyte activity detection studies in various human pathological processes.
We report on the case of a patient presenting a muscle atrophy of the right hand and a left parietal neoplastic lesion rapidly progressing. EMG findings showed no signs of denervation nor sensory-motor conduction impairments. Parietal lesions might interrupt sensory control mechanisms of motor activity.
The inactivation of the scrapie agent in biologicals was evaluated on a scaled-down procedure currently in use on a large scale for the purification of gangliosides from bovine brain tissue. Residual infectivity was determined by an in vivo animal bio-assay using hamsters as the host species and the 263K strain as the reference agent. Infectivity was significantly diminished during the early stages of purification and infectivity was never detected in the final preparations. These results confirmed that a combination of chemicals or physical techniques known to affect the viability of the scrapie agent led to complete inactivation.
The extraction and purification of gangliosides from brains of animals infected with the scrapie agent was evaluated by scaling-down a large-scale procedure currently used with bovine brains. Inactivation experiments employed hamster brains infected with the 263 K strain of scrapie. Residual infectivity was determined at different points of the procedure and in the final preparation by an in vivo animal bioassay. The efficacy of single steps, which included chemicals or physical techniques known to affect the viability of the scrapie agent, was verified by spiking experiments where known amounts of infectivity were added just before each single step. Infectivity was significantly diminished at early stages of the purification, and no infectivity was detected in the final preparation containing purified gangliosides. The significant reduction of infectivity at intermediate steps and the total absence of detectable infectivity in the final product confirmed that a combination of heat and exposure to sodium hydroxide, even in the presence of organic solvents, completely inactivated the scrapie agent.
Thiamin-pyrophosphatase (TPPase) and thiamin-monophosphatase (TMPase) were determined using a spectrophotometric method at various pH values (5.5, 7.5, and 9.0) in brain tissue obtained at autopsy from amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) patients from Guam and from Guamanian patients who died from other diseases (controls). TPPase separation by thin-layer polyacrylamide gel isoelectric focusing (IEF) was also performed using both gray and white matter. TPPase content, chemically determined at pH 9.0, was found to be significantly reduced in the frontal cortex of ALS and PD patients compared to controls. TMPase content, on the contrary, was unchanged. IEF analysis showed 9 clear-cut bands with TPPase activity in the pH range 5.4-7.2 and a broad band at pH 4.7-5.2. The enzymatic activity was higher in gray than in white matter. In one patient the pattern was clearly different, with two additional bands observed at pH 7.1 and 6.7, and thought to be due to genetic microheterogeneity.
A 25-year-old male drug addict presented with a rapidly progressive ascending tetraplegia, requiring assisted ventilation. One month earlier he had fever (40 degrees C) and asthenia. Cerebrospinal fluid (CSF) examination showed elevated albumin level and albuminocytologic dissociation. HIV testing was positive in both serum and CSF. Plasma exchange therapy only partially improved the symptomatology. After five months the patient remained with a moderate tetraparesis. Differences between this and other cases of Guillain-Barré syndrome in HIV-seropositive patients reported in the literature are discussed.
The membrane interaction and hydrophobicity of the normal (PrPC) and infectious isoform (PrPSc/CJD) of scrapie and Creutzfeldt-Jakob disease amyloid precursor proteins was studied. The normal isoform of hamster and human scrapie amyloid precursor protein was found on the microsomal/synaptosomal membranes anchored solely by the C-terminal glycolipid. Glycolipid cleavage resulted in dissociation from the membranes and change of behavior from a highly hydrophobic to a hydrophilic protein, susceptible to proteases. In contrast, the PrPSc/CJD isoform was resistant to release by glycolipid-cleaving enzymes. A part of PrPSc/CJD was released from the membranes after prolonged trypsin treatment, yielding a further protease-resistant product of 27-30 kDa. The results demonstrate the proteolytic resistance of the membrane-bound PrPSc/CJD isoform and also indicate the presence of a different, apparently disease-induced mechanism of membrane interaction in the scrapie- and CJD-infected microsomal and synaptosomal membranes.
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