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Biomedical subjects

A Quattrini

Publications and source records attributed to A Quattrini.

At least 37 records · Page 2Linked to original sources
PubMed1999

Peripheral nerve dysmyelination due to P0 glycoprotein overexpression is dose-dependent.

We have previously shown that increased dosage of the mouse protein zero gene (Mpz) causes a dysmyelinating neuropathy in transgenic (Tg80) mice. To ask whether the dysmyelination is dose dependent, we inbred one of the Tg80 lines and compared the resulting phenotype in homozygous and heterozygous mice. Whereas heterozygous mice (30% overexpression) have only transient peripheral nerve hypomyelination at two weeks after birth and normal myelin at four weeks after birth, homozygous mice demonstrated more severely hypomyelinated nerves. In the latter, many Schwann cells had achieved a one-to-one relationship with large axons but formed no myelin at four weeks after birth. Expression analysis confirmed a doubling of Mpz overexpression in the sciatic nerves of the homozygous mice. Thus, a threshold exists for Mpz overexpression, above which dysmyelination results. These data have important implications for replacement therapy in Charcot-Marie-Tooth 1B neuropathies due to loss of P0 function.

Animals↗
PubMed1999

Docetaxel neuropathy: a distal axonopathy.

Docetaxel has been implicated as a causative agent in peripheral neuropathy, but pathological changes in peripheral nerve have not been described. During docetaxel treatment a 54-year-old man developed a sensorimotor polyneuropathy when the overall docetaxel dosage was 540 mg/m(2). Neurophysiological investigation revealed a sensorimotor axonal neuropathy. Fascicular sural nerve biopsy showed an axonal neuropathy with a preferentially loss of large myelinated fibers. There was evidence of considerable fiber regeneration. Sensory and motor symptoms progressively improved after docetaxel withdrawal.

Antineoplastic Agents, Phytogenic↗
PubMed1999

A novel P0 glycoprotein transgene activates expression of lacZ in myelin-forming Schwann cells.

P0 glycoprotein, the most abundant protein in peripheral nerve, is expressed specifically in the Schwann cell lineage. Upstream of the rat P0 gene 1.1 kb of DNA can activate expression of cDNAs specifically in Schwann cells in transgenic mice. However, the expression of P0 promoter-based transgenes has been inconsistent. As much as 9 kb of 5' flanking sequence fused to lacZ never yielded detectable levels of beta-galactosidase in multiple lines of mice. We describe transgenic mice that express lacZ in peripheral nerve, using the complete mouse P0 gene, including 6 kb of 5' flanking sequence, all exons and introns, and the natural polyadenylation signal. This vector activated lacZ expression specifically in cultured Schwann cells, and myelin-forming Schwann cells in four out of six transgenic lines. Transgene expression paralleled that of the endogenous P0 gene, both during development and after Wallerian degeneration. lacZ expression was lower than endogenous P0 expression, and was not detected in neural crest or Schwann cell precursors, where low levels of P0 mRNA are present. However, when the same vector contained a small myc tag instead of the 3.2-kb lacZ insert, the resulting transgenic mRNA was expressed at levels comparable to endogenous P0 mRNA. These data suggest that intragenic or 3' flanking sequences are necessary to generate the remarkable levels of endogenous P0 gene expression.

3T3 Cells↗
PubMed1999

Role of the corpus callosum in the somatosensory activation of the ipsilateral cerebral cortex: an fMRI study of callosotomized patients.

To verify whether the activation of the posterior parietal and parietal opercular cortices to tactile stimulation of the ipsilateral hand is mediated by the corpus callosum, a functional magnetic resonance imaging (fMRI, 1.0 tesla) study was performed in 12 control and 12 callosotomized subjects (three with total and nine with partial resection). Eleven patients were also submitted to the tactile naming test. In all subjects, unilateral tactile stimulation provoked a signal increase temporally correlated with the stimulus in three cortical regions of the contralateral hemisphere. One corresponded to the first somatosensory area, the second was in the posterior parietal cortex, and the third in the parietal opercular cortex. In controls, activation was also observed in the ipsilateral posterior parietal and parietal opercular cortices, in regions anatomically corresponding to those activated contralaterally. In callosotomized subjects, activation in the ipsilateral hemisphere was observed only in two patients with splenium and posterior body intact. These two patients and another four with the entire splenium and variable portions of the posterior body unsectioned named objects explored with the right and left hand without errors. This ability was impaired in the other patients. The present physiological and anatomical data indicate that in humans activation of the posterior parietal and parietal opercular cortices in the hemisphere ipsilateral to the stimulated hand is mediated by the corpus callosum, and that the commissural fibres involved probably cross the midline in the posterior third of its body.

Adult↗
PubMed1999

Callosal and cortical contribution to procedural learning.

Acallosal and callosotomized subjects usually show impairments on tasks requiring bilateral interdependent motor control. However, few studies have assessed the ability of these subjects to learn a skill that requires the simultaneous contribution of each hemisphere in its acquisition. The present study examined whether acallosal and callosotomized subjects could learn a visuomotor skill that involved a motor control from either both or a single hemisphere. Eleven adult patients, six acallosal and five callosotomized, participated in this study. Seven of these patients had epileptic foci located in the frontal and/or temporal areas and one of the acallosal patients showed bilateral prefrontal atrophy following surgical removal of an orbitofrontal cyst. The performance of the experimental subjects was compared with that of 11 matched control subjects, on a modified version of a serial reaction time task developed by Nissen and Bullemer (Cogn Psychol 1987; 19: 1-32). This skill acquisition task involved bimanual or unimanual key-pressing responses to a sequence of 10 visual stimuli that was repeated 160 times. A declarative memory task was then performed to assess explicit knowledge of the sequence. None of the experimental subjects learned the task in the bimanual condition. Patients with frontal epileptic foci or orbitofrontal damage also failed to learn the task in the unimanual condition when they were using the hand contralateral to the damaged hemisphere. All other subjects, including the acallosal and callosotomized patients with temporal foci, learned the visuomotor skill as well as their controls in the unimanual condition. In spite of the absence of transfer and interhemispheric integration of procedural learning, some of the acallosal and callosotomized patients were able to learn the sequence explicitly. These findings indicate that the corpus callosum and the frontal cortical areas are important for procedural learning of a visuomotor skill. They also confirm the dissociation described by Squire (Science 1986; 232: 1612-9 and J Cogn Neurosci 1992; 4: 232-43) between the declarative and procedural memory systems and extend this dissociation to processes involving simultaneous bihemispheric co-operation.

Adult↗
PubMed1999

Laminin receptor alpha6beta4 integrin is highly expressed in ENU-induced glioma in rat.

Laminins and their receptors influence neoplastic growth and invasiveness. We recently reported the abnormal expression of a laminin receptor, alpha6beta4 integrin, in human astrocytomas. To further investigate the role of alpha6beta4 in gliomas, we produced an experimental model of glioma in rat by transplacental ethylnitrosourea (ENU) administration. This animal model allowed us to study the timing of alpha6beta4 expression during tumor development and the topography of expression in the tumor and the surrounding tissue. Immunohistochemistry, in situ hybridization, and immunoprecipitation studies demonstrated that alpha6beta4 heterodimer forms in experimental gliomas, and confirmed that alpha6beta4 is expressed diffusely in neoplastic cells and reactive astrocytes, but not in normal glia surrounding the tumors. Interestingly, alpha6beta4 was expressed from the early phases of tumor development, and more highly expressed by cells in the proliferative centers of the tumors. Both neoplastic cells and reactive astrocytes also expressed the glial growth factor (neuregulin) receptors, Erb-B2 and Erb-B3. Finally, alpha6beta4 expression was reduced in a subset of tumor blood vessels. Thus, this study suggests a potential role for alpha6beta4 in the pathogenesis of gliomas. Furthermore, this is the first description of altered integrin expression in experimental gliomas; transplacental ENU-induced gliomas in rat will provide a useful model to study the role of altered adhesion in the pathogenesis of human gliomas.

Animals↗
PubMed1998

A minimal human MBP promoter-lacZ transgene is appropriately regulated in developing brain and after optic enucleation, but not in shiverer mutant mice.

Previous studies, both in vitro and in vivo, suggest that small portions of the mouse myelin basic protein (MBP) promoter are sufficient to activate regulated expression of MBP. To confirm our previous in vitro studies, we prepared transgenic mice with short regions of the human MBP promoter fused to the lacZ reporter gene. We found that 750 nucleotides of the proximal human MBP promoter is sufficient to activate oligodendrocyte-specific, developmentally regulated expression of lacZ in three independent lines. This promoter, however, does not activate expression of lacZ in Schwann cells in peripheral nerve or in adult mouse brain. The relative levels of beta-galactosidase specific activity, mRNA, and transcription parallel those of MBP mRNA during myelinogenesis. Thus, we exploited this transgene as a quantitative tool to evaluate the response to stimuli known to affect myelination. Transgene expression is reduced 75 % after optic enucleation, as previously reported for levels of MBP mRNA, indicating that axons signal to this portion of the proximal MBP promoter to fully activate MBP expression during myelinogenesis. Instead, in adult shiverer mice, another setting in which MBP transcription is modulated, transgene expression is not increased, in contrast to the increased transcriptional activation of MBP previously reported in these mice. These data suggest that the regulatory region that mediates transcriptional activation of the MBP gene is modular, since discrete subregions are required for activation in Schwann cells, during myelinogenesis in oligodendrocytes, during maintenance myelination in adult brain, and in the dysmyelinating mutant shiverer mouse.

Animals↗
PubMed1998

Light chain deposition disease neuropathy resembling amyloid neuropathy in a multiple myeloma patient.

A 65-year-old man with IgG lambda multiple myeloma developed severe polyneuropathy with prominent thermal-pain sensory impairment and autonomic failure. Although the clinical presentation suggested amyloid neuropathy, nerve biopsy showed the immunohistochemical and ultrastructural features typical of light chain deposition disease (LCDD). A precise morphologic and clinical description of LCDD neuropathy is given for the first time in the present report.

Aged↗
PubMed1998

Amyloid neuropathy simulating lower motor neuron disease.

We report a 57-year-old man with progressive symmetric weakness and fasciculation affecting the legs. Electromyography revealed fibrillations and neurogenic motor unit potentials in the leg muscles. Biopsy of a motor branch of the obturator nerve revealed axonal degeneration, loss of myelinated nerve fibers, and amyloidosis with deposits of lambda light chains. At 6-month follow-up, the patient manifested sensory and autonomic symptoms, and lambda light chains were first detected in the serum. In this case, diagnosis of amyloidosis remained elusive until motor nerve biopsy.

Amyloid Neuropathies↗
PubMed1997

Motor nerve biopsy studies in motor neuropathy and motor neuron disease.

The clinical presentation of motor neuropathy often resembles that of motor neuron disease, sometimes leading to an erroneous diagnosis. Moreover, the underlying pathological process in motor neuropathy has been rarely investigated and there are no systematic studies of the affected motor nerves. We describe a new motor nerve biopsy procedure, performed in 15 patients: 6 with motor neuropathy and 9 with motor neuron disease. The motor branch from the anterior division of the obturator nerve to the gracilis muscle in the thigh was biopsied. In both groups of patients the motor nerves exhibited depletion of myelinated nerve fibers. In motor neuropathy there was a significantly higher density of regenerative clusters of small myelinated fibers in comparison to motor nerves from patients with motor neuron disease. In addition, in 3 patients with motor neuropathy there was evidence for demyelination with thinly myelinated axons and small onion bulb formations. These pathological studies of motor nerve biopsies can help to differentiate motor neuropathy from motor neuron disease.

Adult↗
PubMed1997

Axonal neuropathy associated with interferon-alpha treatment for hepatitis C: HLA-DR immunoreactivity in Schwann cells.

A 44-year-old man developed a peripheral neuropathy during treatment with interferon-alpha for chronic hepatitis C. The onset was insidious, beginning symmetrically in the hands with paresthesia. Neurophysiological investigation revealed a predominantly sensory axonal neuropathy. A sural nerve biopsy confirmed primary axonal damage. Immunofluorescence studies showed increased expression of HLA-DR molecules prevalently on Schwann cells of non-myelin-forming type.

Adult↗
PubMed1997

Atypical hereditary neuropathy with liability to pressure palsies (HNPP): the value of direct DNA diagnosis.

We report two patients with suspected hereditary liability to pressure palsies. Neurophysiological studies showed a mixed axonal-demyelinating sensory-motor polyneuropathy with focal slowing of conduction velocities at the common sites of entrapment. Morphological studies on sural nerve biopsy from the proband showed active axonal regeneration without typical tomacula. Molecular analysis confirmed the presence of a deletion of chromosome 17p11.2 in both patients. Our observation confirms the heterogeneity of hereditary liability to pressure palsies and the relevance of DNA testing for the diagnosis of this hereditary neuropathy.

Adolescent↗
PubMed1997

The role of corpus callosum in experimental epileptogenesis. A brief survey of literature.

The authors briefly summarize the experimental papers dealing with the role of corpus callosum in experimental epileptogenesis published over more than half a century. On the whole, the experimental work concerns more electro-encephalographic findings than epileptic manifestations in animals. The papers taken into account are classified in two main groups: I) positive findings supporting the efficacy of callosotomy in preventing generalization of initially localized seizures. II) papers failing to demonstrate any positive effect of commissurotomy on the generalization of discharges. On these grounds, experimental studies lack of homogeneity and cannot constitute a reliable basis for making surgical decision in clinical practice. However some remarks of practical use can be derived: a) the usefulness of the corpus callosum division for the management of secondarily generalized epilepsies appears to be sufficiently demonstrated in most studies; b) then is also evidence that the corpus callosum conveys inhibitory and/or suppressive stimuli as well, the practical value of which is still to be established; d) the corpus callosum is the most important but not the only anatomic structure for spreading seizures. Anterior and posterior commissures, thalamus, tegmentum tectum may play the same role.

Animals↗
PubMed1997

Predictive factors of callosotomy in drug-resistant epileptic patients with a long follow-up.

Some possible factors to predict outcome after callosotomy were investigated in a personal series composed of 36 patients. Twenty-seven of them were submitted to anterior callosotomy, 1 to posterior callosotomy and the remaining 8 patients to two stage complete division of corpus callosum. All factors, either positive or negative, do not appear completely reliable; they can be envisaged only in relative terms and do not seem to be relevant to make surgical decision or to discard surgery. In author's series, dealing specifically with drop-attacks, it clearly appeared that abrupt falls to the ground unpreceded by other epileptic features did definitely better. This was the only statistically significant datum.

Adolescent↗
PubMed1997

EEG Patterns after callosotomy.

In 36 patients with drug-resistant epilepsy submitted to anterior callosotomy (27 cases), to two-stage total callosotomy (8 cases) and to posterior callosotomy (1 case) the EEG variations concerning background activity, focal activity and sharp-waves (SW) bisynchronous activity were evaluated. EEG modifications observed after callosotomy are the following: background rhythm tends to be better organised as spectral analysis demonstrated, this finding usually coincide with reduction of bisynchronous discharges. It appears that improvement in background activity cannot be correlated with outcome, but it seems to be to some extent since at the same time cognitive functions also seem to improve; however, this last aspect need to be checked in much larger series. The number and location of EEG foci do not change, but they appear to be more active; this is likely to depend only on the concomitant reduction of bisynchronous activity. No correlation seems to exist between the number and the location of foci, which are generally multiple. Lateralization of bisynchronous discharges as well as the reduction of their frequency and duration were observed. However, the clinical course is quite different: in some patients we have achieved good clinical responses in others postoperative results were poor. Lateralization of bisynchronous discharges is never absolute, on the grounds that in prolonged recordings bisynchronous discharges are nearly always present. Bisynchronous discharges in some cases are alternatively predominant in both hemispheres even within minutes or seconds. It was observed that after certain time, generally some months, lateralized discharges tend to generalize again, confirming that corpus callosum is replaced in discharge diffusion by other structures (brain-stem, diencephalon).

Adolescent↗
PubMed1997

Mutism in 36 patients who underwent callosotomy for drug-resistant epilepsy.

Thirty-six drug-resistant epileptic patients submitted to callosotomy were studied. Anterior callosotomy was performed in 27 patients, total two-stage callosotomy was performed in 8 patients and 1 patient had only posterior callosotomy. We found mutism in 10 patients (2 after complete callosotomy and 8 after anterior section). The patients did not speak, but the comprehension was present: they were able to carry out orders and to write. Their attitude to the environment was characterized by complete indifference. The mutism was always transient, lasting from 4 to 25 days (mean 7 days). Regression of mutism was always complete. We think that this complication should be chiefly attributed mainly to surgical manipulation, even if it is impossible to completely exclude a multi-factorial etiology.

Adolescent↗
PubMed1996

Beta 4 integrin and other Schwann cell markers in axonal neuropathy.

Schwann cell gene expression is dynamically regulated after peripheral nerve injury and during regeneration. We hypothesized that the changes in protein expression described after rat peripheral nerve injury could be used to identify single Schwann cell-axon units in human axonal neuropathy. Therefore, we performed immuno-fluorescence staining on sections of injured rat sciatic nerves compared with sections of neuropathic human sural nerves. We chose the markers beta 4 integrin, P0 glycoprotein, and glial fibrillary acidic protein (GFAP) to characterize Schwann cells, and neurofilament-heavy (NF-H) to recognize axons. Normal rat or human myelin-forming units demonstrated a sharp ring of beta 4 staining at their outer surface, P0 staining in the myelin sheath, and NF-H staining in the axon. Acutely denervated rat units transited from broken rings of beta 4 and P0 staining, to diffuse beta 4 and absent P0 and NF-H staining. Chronically denervated rat Schwann cells re-expressed beta 4 more highly, but in a diffuse, non-polarized pattern. In contrast, regenerating units re-expressed beta 4, P0, and NF-H; beta 4 staining was polarized to the outer surface of Schwann cells. Finally, GFAP staining increased progressively after injury and decreased during regeneration in the distal nerve stump. In neuropathic human sural nerves, we identified units exhibiting each of these beta 4, P0, and NF-H staining patterns; the proportion of each pattern correlated best with the extent and chronicity of axonal injury. Thus, synchronous injury of rat sciatic nerve predicts patterns of Schwann cell marker expression in human axonal neuropathy. In addition, the unique changes in the polarity of beta 4 integrin expression, in combination with changes in P0 and NF-H expression, may distinguish normal from denervated or reinnervated myelin-forming Schwann cells in human sural nerve biopsies.

Adult↗