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Biomedical subjects

G Macchi

Publications and source records attributed to G Macchi.

At least 19 recordsLinked to original sources
PubMed1999

Prion protein glycotype analysis in familial and sporadic Creutzfeldt-Jakob disease patients.

Creutzfeldt-Jakob disease (CJD) and other transmissible spongiform encephalopathies (TSEs) are characterised by the accumulation of a pathological conformer of PrP, named PrPsc. Molecular weight and glycosylation of the protease-resistant core of PrPsc (PrP27-30) are heterogeneous in different forms of TSEs. We analysed PrP27-30 glycotypes in a large number of TSE-affected patients: 50 sporadic CJD (sCJD), 1 iatrogenic CJD, 1 Gerstmann-Sträussler-Scheinker syndrome (GSS) with the Pro102Leu mutation of PrP, 3 familial CJD (fCJD) with the Glu200Lys mutation and, for the first time, 7 fCJD with the Val210ll3e mutation. All patients were screened for the polymorphic codon 129 of the PrP gene. PrP27-30 deglycosylation and PrPsc immunohistochemistry were performed in selected cases. We found that two PrP27-30 glycotypes (type 1A and type 2A) are produced in sCJD. Type 1A is more frequently associated with methionine than valine in position 129. Type 1A is also formed in Val210lle fCJD. In Glu200Lys fCJD and GSS patients, we found that PrP27-30 has the same mobility of type 1 but different glycosylation ratios (type 1B). Our findings indicate that the polymorphic residue 129 of PrP has a leading role in determining the proteinase degradation site of PrPsc while mutant residues 102 or 200 influence only the glycosylation pattern.

Amino Acid Substitution↗
PubMed1999

Camillo Golgi: a clinical pathologist.

Camillo Golgi opened new avenues in histology and neurobiology as well as in clinical neurology and internal medicine. This is demonstrated by investigations Golgi performed during 1861-1876 on the etiology and pathology of mental diseases, on the neuropathology of Huntington's chorea (Golgi provided the first detailed description at the microscopic level of pathological changes in the basal ganglia and cerebral cortex of one case of chorea), on meningiomas and cerebral gliomas. In the period following these investigations, Golgi focused especially on infectious diseases. He pursued fundamental studies on malaria (which remain among the most important and original of his contributions) on rabies, as well as on smallpox and influenza. Thus, Camillo Golgi should be remembered for his discoveries of the black reaction and the Golgi apparatus, as well as for the modern impulse he was able to give to clinical neurology and internal medicine.

Communicable Diseases↗
PubMed1999

Is the "nonspecific" thalamus still "nonspecific"?

The classical concept of "nonspecific" thalamus, as distinguished from the principal thalamic nuclei (i.e. the primary sensory, motor and limbic relays) is here briefly revisited in the light of anatomical investigations performed in the last decades, and primarily those based on tract tracing techniques. Altogether these data pointed out that the so-called "nonspecific" thalamus is composed by a heterogeneous collection of nuclear masses, which display not only species differences, but also marked internuclear variations in their cytological and neurochemical features, connections, areal and laminar distribution upon the cortex, and functional properties. Thus, the "nonspecific" thalamus exerts a modulatory role on cortical activity, chiefly regulated at the intrathalamic level by the interplay between the thalamic reticular nucleus and the interneurons and projection neurons of the dorsal thalamus. However, each of the components that have been traditionally considered as "nonspecific" also subserves selective roles in the transfer of different kinds of information from the thalamus to the cerebral cortex and basal ganglia.

Animals↗
PubMed1998

Fatal familial insomnia: genetic, neuropathologic, and biochemical study of a patient from a new Italian kindred.

Fatal familial insomnia (FFI) is an inherited prion disease linked to a mutation at codon 178 of the PRNP gene that results in aspartic acid to asparagine substitution, in coupling phase with methionine at position 129. The disease is characterized clinically by insomnia with disturbances of the autonomic, endocrine, and motor systems and neuropathologically by selective degeneration of the thalamus. Phenotypic variability is well known and has been linked to homozygosity or heterozygosity at PRNP codon 129. We report the clinical, neuropathologic, and biochemical findings and genomic analysis of a patient with FFI from a new Italian kindred. Although homozygous for methionine at codon 129, this patient showed some clinical and pathologic features most commonly found in heterozygotes.

Blotting, Western↗
PubMed1997

Diffuse thalamic degeneration in fatal familial insomnia. A morphometric study.

A morphometric investigation disclosed most thalamic nuclei severely degenerated in two patients with fatal familial insomnia. Associative and motor nuclei lost 90% neurons, and limbic-paralimbic, intralaminar and reticular nuclei lost 60%. These findings point to the disorganization of most thalamic circuits as a condition necessary for the sleep-wake rhythm being affected.

Adult↗
PubMed1997

Toward an agreement on terminology of nuclear and subnuclear divisions of the motor thalamus.

The nomenclature most commonly applied to the motor-related nuclei of the human thalamus differs substantially from that applied to the thalamus of other primates, from which most knowledge of input-output connections is derived. Knowledge of these connections in the human is a prerequisite for stereotactic neurosurgical approaches designed to alleviate movement disorders by the placement of lesions in specific nuclei. Transfer to humans of connectional information derived from experimental studies in nonhuman primates requires agreement about the equivalence of nuclei in the different species, and dialogue between experimentalists and neurosurgeons would be facilitated by the use of a common nomenclature. In this review, the authors compare the different nomenclatures and review the cyto- and chemoarchitecture of the nuclei in the anterolateral aspect of the ventral nuclear mass in humans and monkeys, suggest which nuclei are equivalent, and propose a common terminology. On this basis, it is possible to identify the nuclei of the human motor thalamus that transfer information from the substantia nigra, globus pallidus, cerebellum, and proprioceptive components of the medial lemniscus to prefrontal, premotor, motor, and somatosensory areas of the cerebral cortex. It also becomes possible to suggest the principal functional systems involved in stereotactically guided thalamotomies and the functional basis of the symptoms observed following ischemic lesions in different parts of the human thalamus.

Afferent Pathways↗
PubMed1997

Toward an agreement on terminology of nuclear and subnuclear divisions of the motor thalamus.

The nomenclature most commonly applied to the motor-related nuclei of the human thalamus differs substantially from that applied to the thalamus of other primates, from which most knowledge of input-output connections is derived. Knowledge of these connections in the human is a prerequisite for stereotactic neurosurgical approaches designed to alleviate movement disorders by the placement of lesions in specific nuclei. Transfer to humans of connectional information derived from experimental studies in nonhuman primates requires agreement about the equivalence of nuclei in the different species, and dialogue between experimentalists and neurosurgeons would be facilitated by the use of a common nomenclature. In this review, the authors compare the different nomenclatures and review the cyto- and chemoarchitecture of the nuclei in the anterolateral aspect of the ventral nuclear mass in humans and monkeys, suggest which nuclei are equivalent, and propose a common terminology. On this basis, it is possible to identify the nuclei of the human motor thalamus that transfer information from the substantia nigra, globus pallidus, cerebellum, and proprioceptive components of the medial lemniscus to prefrontal, premotor, motor, and somatosensory areas of the cerebral cortex. It also becomes possible to suggest the principal functional systems involved in stereotactically guided thalamotomies and the functional basis of the symptoms observed following ischemic lesions in different parts of the human thalamus.

Afferent Pathways↗
PubMed1996

Trends in the anatomical organization and functional significance of the mammalian thalamus.

The last decade has witnessed major changes in the experimental approach to the study of the thalamus and to the analysis of the anatomical and functional interrelations between thalamic nuclei and cortical areas. The present review focuses on the novel anatomical approaches to thalamo-cortical connections and thalamic functions in the historical framework of the classical studies on the thalamus. In the light of the most recent data it is here discussed that: a) the thalamus can subserve different functions according to functional changes in the cortical and subcortical afferent systems; b) the multifarious thalamic cellular entities play a crucial role in the different functional states.

Animals↗
PubMed1996

Branched connections to the septum and to the entorhinal cortex from the hippocampus, amygdala, and diencephalon in the rat.

Neuronal cell populations giving origin to bifurcating projections to the septum and the entorhinal cortex were studied in the rat by means of double retrograde labeling using the fluorescent tracers Fast Blue and Diamidino Yellow. Double labeled pyramidal neurons were consistently detected in the temporal level of the CA1 area and subiculum of the hippocampal formation, where they represented at least 50% of the cells retrogradely labeled from the entorhinal injections. Double labeled neurons were also detected in the amygdala, where they prevailed in the basal complex. Scattered double labeled neurons were observed in a number of hypothalamic nuclei, with a slight predominance in the preoptic region. Finally, a few double labeled cells were detected in the midline thalamus, and especially in the thalamic paraventricular nucleus. In all these structures, double labeled neurons were located ispilaterally to the injection sites. The present data indicate that the septum and entorhinal cortex are tightly interconnected by axonal bifurcations deriving from a variety of telencephalic and diencephalic sources.

Amygdala↗
PubMed1996

Polymorphism at codon 129 or codon 219 of PRNP and clinical heterogeneity in a previously unreported family with Gerstmann-Sträussler-Scheinker disease (PrP-P102L mutation).

We present a new, large, Italian family affected by Gerstmann-Sträussler-Scheinker syndrome (GSS) associated with the Pro to Leu point mutation at codon 102 of the prion protein gene (PRNP). The affected members of this family show a remarkable phenotypic variability of the disease: three of them had a clinical picture characterized by dementia and a brief illness duration (less than 1 year), while the other five members presented an ataxic, slowly evolving syndrome (a clinical duration of 3 to 4 years) with no evidence of cognitive impairment. Despite these remarkable clinical differences among affected members, we found no correlation between the clinical presentation and the codon 129 or codon 219 genotypes. These data suggest that factors as yet unidentified may influence the clinical expression of the disease.

Aged↗
PubMed1995

Mapping subcortical extrarelay afferents onto primary somatosensory and visual areas in cats.

Projections from the claustrum (Cl) and the thalamic anterior intralaminar nuclei (AIN) to different representations within the primary somatosensory (S1) and visual (V1) areas were studied using the multiple retrograde fluorescent tracing technique. The injected cortical regions were identified electrophysiologically. Retrograde labeling in Cl reveals two different projection patterns. The first pattern is characterized by a clear topographic organization and is composed of two parts. The somatosensory Cl shows a dorsoventral progression of cells projecting to the hindpaw, forepaw, and face representations of S1. The visual Cl has cells projecting to the vertical meridian representation of V1 surrounded dorsally by neurons projecting to the representation of retinal periphery. A second pattern of Cl projections is composed of neurons that are distributed diffusely through the nucleus. In both somatosensory and visual sectors, these intermingle with the topographically projecting cells. Neurons retrogradely labeled from cortical injections are always present in the AIN. In the central medial nucleus, the segregation of modality is evident: The visual-projecting sector is dorsal, and the somatosensory is ventral. Projections from the central lateral nucleus display detectable somatotopic and retinotopic organization: Individual regions are preferentially connected with specific representations of S1 or V1. In the paracentral nucleus, no clear regional preferences are detectable. Also performed were comparisons of the proportions of neurons projecting to different sensory representations. Projections to V1 from both AIN and Cl are biased towards the retinal periphery representation. S1 projection preference is for the forepaw representation in Cl and for the hindpaw in the AIN. The quantitative analysis of multiply labeled cells reveals that, compared to Cl, the AIN contains a higher proportion of neurons branching between different representations of S1 or V1. The concept of topographic vs. diffuse projecting systems is reviewed and discussed, and functional implications of quantitative analysis are considered.

Afferent Pathways↗
PubMed1995

Nucleus reticularis thalami and neocortical paroxysms in the rat.

The role of the nucleus reticularis thalami in spike-wave discharges in rats with genetic absence epilepsy has already been demonstrated. This study further investigated the role of the nucleus reticularis thalami in paroxysmal synchronizations in Sprague-Dawley rats; this strain shows no propensity to epileptic activity. Electroencephalographic patterns were followed in chronically implanted, unrestrained rats. After both electrolytic and chemical unilateral lesions, stereotaxically placed in the anterolateral sectors of this nucleus (verified post mortem), abnormal electroencephalographic rhythms (high-voltage polyspikes and spike-wave complexes) were recorded from the frontoparietal cortex, primarily in the contralateral hemisphere. Stereotyped discharges at 3 Hz developed progressively from multiple spikes within the alpha frequency range through the lengthening of the wave component. The excessive synchronized activity recorded from the intact hemisphere was of greater amplitude and occurred slightly earlier than from the lesioned hemisphere. These EEG patterns were associated with behavioural manifestations closely resembling those seen during absence seizures in humans. Bilateral lesions did not induce paroxysmal activity, both hemispheres being characterized by dominant delta/theta activity without signs of EEG-synchronized sleep. The seizures may thus have been due to disinhibition of the contralateral reticularis nucleus, recently shown to project to the reticularis nucleus of the other side in rats. This working hypothesis is supported by callosal cuts. The results indicate that the reticular neurons exert a control over neocortical paroxysmal activity even in animals which do not present genetic absence epilepsy.

Animals↗
PubMed1994

Chemical compartmentation and relationships between calcium-binding protein immunoreactivity and layer-specific cortical caudate-projecting cells in the anterior intralaminar nuclei of the cat.

Neurons projecting to the parietal cortex or striatum and neurons showing immunoreactivity for the calcium-binding proteins parvalbumin and 28KD-calbindin were examined in the anterior intralaminar nuclei (IL) of the cat. Retrograde tracing from deep or superficial parietal cortical layers or from the caudate nucleus was coupled with immunohistochemistry to determine which of these proteins were expressed in the projection neurons. It was found that IL neurons project to deep as well as to superficial layers of the parietal cortex, that IL-cortical neurons could be differentiated into two populations according to their cortical projection pattern and their soma size, and that IL neurons projecting to the parietal cortex or to the striatum express 28KD calbindin immunoreactivity but not parvalbumin immunoreactivity. The distribution of immunoreactivity to 28KD calbindin and parvalbumin in the neuropil showed a consistent complementary distribution pattern in the IL. The compartments based on differential parvalbumin and 28KD calbindin expression may indicate the presence of functionally segregated units in IL.

Animals↗
PubMed1993

A new point mutation of the prion protein gene in Creutzfeldt-Jakob disease.

Complete sequencing of the prion protein open reading frame of a 68-year-old woman affected by a familial form of Creutzfeldt-Jakob disease (CJD) revealed a new mutation at codon 210 resulting in the substitution of isoleucine for valine. Moreover, a new 24-bp deletion encompassing codons 54 to 61 or 62 to 69 was found in the other allele. Four of the 17 asymptomatic relatives tested carry the 210 mutation. Two of them were 81 and 82 years old. Four of 22 patients with CJD whose recorded familial history was negative for demented illnesses, but none of 103 healthy control subjects, tested positive for the 210 mutation. These data suggest that the 210 mutation is associated with CJD, but that environmental factors or incomplete penetrance may contribute to the development of the disease. This finding also suggests that in Italy, familial CJD is more common than previously reported.

Aged↗
PubMed1993

Early MRI findings in Creutzfeldt-Jakob disease.

We describe the MRI changes preceding the onset of myoclonus in two patients whose post-mortem examination confirmed the diagnosis of Creutzfeldt-Jakob disease (CJD). MRI showed changes in the striatum early in the course of CJD (2-6 months after the onset of apathy, interpreted as depression, and 1-2 months before the onset of further clinical symptoms). Only in one patient did electroencephalography record the typical triphasic sharp-waves, 1 month after MRI.

Brain↗