Search PubMed⌕ Search

Biomedical subjects

P Parchi

Publications and source records attributed to P Parchi.

54 records · Page 3Linked to original sources
PubMed1995

Truncated forms of the human prion protein in normal brain and in prion diseases.

The cellular form of the prion protein (PrPc) is a glycoprotein anchored to the cell membrane by a glycosylphosphatidylinositol moiety. An aberrant form of PrPc that is partially resistant to proteases, PrPres, is a hallmark of prion diseases, which in humans include Cruetzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia. We have characterized the major forms of PrP in normal and pathological human brains. A COOH-terminal fragment of PrPc, designated C1, is abundant in normal and CJD brains as well as in human neuroblastoma cells. Sequence analysis revealed that C1 contains alternative NH2 termini starting at His-111 or Met-112. Like PrPc, C1 is glycosylated, anchored to the cell membrane, and is heat-stable. Consistent with the lack of the NH2-terminal region of PrPc, C1 is more acidic than PrPc and does not bind heparin. An additional fragment longer than C1, designated C2, is present in substantial amounts in CJD brains. Like PrPres, C2 is resistant to proteases and is detergent-insoluble. Our data indicate that C1 is a major product of normal PrPc metabolism, generated by a cleavage that disrupts the neurotoxic and amyloidogenic region of PrP comprising residues 106-126. This region remains intact in C2, suggesting a role for C2 in prion diseases.

Adult↗
PubMed1995

Regional distribution of protease-resistant prion protein in fatal familial insomnia.

Protease-resistant prion protein, total prion protein, and glial fibrillary acidic protein were measured in various brain regions from 9 subjects with fatal familial insomnia. Six were homozygotes methionine/methionine at codon 129 (mean duration, 10.7 +/- 4 months) and 3 were heterozygotes methionine/valine (mean duration, 23 +/- 11 months). In all subjects, protease-resistant prion protein was detected in gray matter but not in white matter and peripheral organs. Its distribution was more widespread than that of the histopathological lesions, which were observed only in the presence of a critical amount of the abnormal protein. In the mediodorsal thalamic nucleus, however, a severe neuronal loss and astrogliosis were associated with relatively moderate amounts of protease-resistant prion protein, suggesting a higher vulnerability. There was no overall correlation between amount of protease-resistant prion protein and either glial fibrillary acidic protein or total prion protein. While protease-resistant prion protein was virtually limited to subcortical areas and showed a selective pattern of distribution in the subjects with disease of the shortest duration, it was more widespread in the subjects with a longer clinical course, indicating that with time the disease process spreads within the brain. The kinetics of the accumulation of protease-resistant prion protein varied among different brain regions: While in the neocortex and to a lesser extent in the limbic lobe and in the caudate nucleus, the amount increased with disease duration, in the mediodorsal thalamic nucleus and in the brainstem it was present in comparable amounts in all subjects regardless of the disease duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Creutzfeldt-Jakob disease after liver transplantation.

We report a 57-year-old woman who died from Creutzfeldt-Jakob disease 2 years after a liver transplantation. The liver donor had no history of neurological disease. In one albumin donor, possible Creutzfeldt-Jakob disease developed 3 years later. The patient initially had cerebellar symptoms. Neuropathology included "Kuru-type" plaques and prion protein (PrP) deposits involving the cerebellum predominantly. The patient was homozygote valine at codon 129 of the PrP gene while the liver was homozygote methionine. This observation raises the possibility of transmission of Creutzfeldt-Jakob disease by the graft itself or the associated albumin transfusions and, on a wider extent, by nonneural tissue.

Creutzfeldt-Jakob Syndrome↗
PubMed1995

Human prion diseases.

Major advances have been made in prion diseases. Recent data indicate that the prion protein is likely to be a synaptic protein with a functional role in synaptic transmission. An impressive body of evidence suggests that (1) the normal prion protein plays a central role in prion replication; (2) the replication process implies an interaction between the normal prion protein and the pathogenic prion protein; and (3) the pathogenic prion protein is the infectious agent, the infectivity of which is dependent on its abnormal conformation. Genetic and protein analyses have expanded the spectrum of prion diseases and have underlined the complexity of genotype-phenotype interactions.

Adult↗
PubMed1995

Fatal familial insomnia and familial Creutzfeldt-Jakob disease: clinical, pathological and molecular features.

Fatal familial insomnia (FFI) and a subtype of familial Creutzfeldt-Jakob disease (CJD178) are two prion diseases that have different clinical and pathological features, the same aspartic acid to asparagine mutation (D178N) at codon 178 of the prion protein (PrP) gene, but distinct genotypes generated by the methionine-valine polymorphism at codon 129 (129M or 129V) in the mutant allele of the PrP gene. The D178N, 129M allele segregates with FFI while the D178N, 129V allele segregates with CJD178. The proteinase K resistant PrP (PrPres) isoforms present in FFI and CJD178 differ in degree of glycosylation and size. Thus, the amino acid, methionine or valine, at position 129 of the mutant allele, in conjunction with D178N mutation results in significant alterations of PrPres in FFI and CJD178. The 129 polymorphic site also exerts influence through the normal allele: the course of the disease is shorter in the patients homozygous at codon 129 and other minor but consistent phenotypic differences occur between homozygous and heterozygous FFI patients. The comparative study of PrPres distribution in FFI homozygotes and heterozygotes at codon 129 has lead to the conclusion that the phenotypic differences observed between these two FFI patient populations may be the result of different rates of conversion of normal PrP into PrPres, at least in some brain regions.

Adult↗
PubMed1994

Fatal familial insomnia and familial Creutzfeldt-Jakob disease: different prion proteins determined by a DNA polymorphism.

Fatal familial insomnia and a subtype of Creutzfeldt-Jakob disease, two clinically and pathologically distinct diseases, are linked to the same mutation at codon 178 (Asp-178-->Asn) but segregate with different genotypes determined by this mutation and the methionine-valine polymorphism at codon 129 of the prion protein gene. The abnormal isoforms of the prion protein in these two diseases were found to differ both in the relative abundance of glycosylated forms and in the size of the protease-resistant fragments. The size difference was consistent with a different protease cleavage site, suggesting a different conformation of the protease-resistant prion protein present in the two diseases. These differences are likely to be responsible for the type and location of the lesions that characterize these two diseases. Therefore, the combination of the mutation at codon 178 and the polymorphism at codon 129 determines the disease phenotype by producing two altered conformations of the prion protein.

Codon↗
PubMed1994

Cardiovascular autonomic dysfunction in normotensive awake subjects with obstructive sleep apnoea syndrome.

Cardiovascular autonomic function in normotensive awake patients with obstructive sleep apnoea syndrome was studied in 21 normotensive (mean age 48 +/- 14 years), drug-free men with obstructive sleep apnoea syndrome. Cardiovascular reflex tests with continuous blood pressure monitoring and biochemical indices were performed the morning after a standard polygraphic sleep recording. A group of 20 age-matched (mean age 49 +/- 19 years) normal subjects was used as controls. The obstructive sleep apnoea syndrome patients showed higher heart rate and noradrenaline plasma levels (p < 0.05) at rest and a higher blood pressure response to head-up tilt (p < 0.01), suggesting sympathetic overactivity. Respiratory arrhythmia, baroreflex sensitivity index and Valsalva ratio were significantly lower in the obstructive sleep apnoea syndrome group (p < 0.01) whereas the decrease in heart rate induced by the cold face test was significantly higher (p < 0.05) showing a blunting of reflexes dependent on baroreceptor or pulmonary afferents with normal or increased cardiac vagal efferent activity. These abnormalities in autonomic regulation may predispose obstructive sleep apnoea syndrome patients to cardiovascular complications like hypertension and cardiac arrhythmias.

Adult↗
PubMed1994

31P-magnetic resonance spectroscopy in migraine without aura.

We investigated 22 patients with migraine without aura, all drug-free and in headache-free periods, by means of 31P-magnetic resonance spectroscopy (MRS) of brain and muscle. Brain 31P-MRS showed significantly low phosphocreatine, increased adenosine diphosphate, and decreased phosphorylation potential. There was a slow rate of phosphocreatine recovery after exercise in the muscle of 12 of 22 patients. Energy metabolism is abnormal in migraine without aura, as previously demonstrated in patients with migraine stroke and migraine with aura.

Adolescent↗
PubMed1994

Do autonomic cardiovascular reflexes predict the nocturnal rise in blood pressure in obstructive sleep apnea syndrome?

To investigate the relationship between nocturnal changes in blood pressure (BP) and diurnal cardiovascular reflexes we examined a group of 19 male normotensive obstructive sleep apnea syndrome (OSAS) patients. All patients underwent a full polysomnographic examination including BP monitoring by a finger arterial pressure device (Finapres) and a battery of cardiovascular reflex tests; plasma catecholamine levels at rest were also measured. During sleep, BP increased with an average difference of 15.4 +/- 7.5 mmHg for systolic and 8.3 +/- 4.6 mmHg for diastolic pressure. Compared with control subjects, OSAS patients had lower values of Valsalva ratio (VR) (1.75 +/- 0.4 vs 1.34 +/- 0.2, p = 0.0004), E/I ratio (1.35 +/- 0.2 vs 1.13 +/- 0.9, p = 0.0004) and baroreflex sensitivity index (BRSI) (5.4 +/- 2.1 vs 2.7 +/- 1.9 mms/mmg, p = 0.0006) and a higher systolic (p = 0.02) and diastolic (p = 0.002) pressure response to tilting-up test. Noradrenaline plasma levels were also significantly higher (345 +/- 125 vs 224 +/- 92 pg/ml, p = 0.001). No significant correlations were found between the nocturnal rise in BP and the pressure responses during sympathetic manoeuvres or rest levels of noradrenaline. The nocturnal changes in systolic blood pressure during the night were negatively dependent on the diurnal BRSI (r = -0.91, p = 0.0007) and VR (r = -0.70, p = 0.006). We conclude that the high levels of noradrenaline at rest and the altered sympathetic cardiovascular reflexes alone do not account for the nocturnal variation in blood pressure in OSAS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Isolated failure of noradrenergic transmission in a case with orthostatic hypotension and hyperactivity of gastro-colic reflex.

We describe a 37-year-old man with a long-standing history of impotence and urgency of defaecation. The latter invariably followed the ingestion of food. Studies of cardiovascular autonomic function disclosed asymptomatic orthostatic hypotension due to isolated sympathetic noradrenergic failure with intact cardiac vagal control. There were no other neurological abnormalities. Levels of plasma noradrenaline and urinary vanillylmandelic acid were very low but plasma dopamine and urinary homovanillic acid were normal. A low level of dopamine-beta-hydroxylase activity was detected in plasma. The patient's parents were first cousins. The parents, the brother and the sister were investigated and clinical and biochemical studies showed no abnormalities. We conclude that this is a further observation of orthostatic hypotension due to isolated adrenergic failure with clinical and biochemical features different from cases previously described.

Adult↗
PubMed1992

Autonomic nervous system function in myotonic dystrophy.

Symptoms suggestive of dysautonomia are often reported in Myotonic Dystrophy (MD) patients. 12 patients with MD underwent cardiovascular function testing with assay of plasma noradrenaline (NA) and adrenaline (A) in supine rest condition and after orthostatic and cold stimulus. Statistical analysis showed no differences between MD patients and an age and sex matched control group.

Adolescent↗
PubMed1991

Cardiovascular dysautonomia in fatal familial insomnia.

Autonomic control of the cardiovascular system was assessed in two patients with Fatal Familial Insomnia. The diagnosis was confirmed at autopsy in patient 1. In the resting state blood pressure and heart rate were higher than controls in patient 1; plasma noradrenaline levels were elevated in both patients. Evaluation of cardiovascular reflexes indicated intact baroreflex pathways but with exaggerated blood pressure and biochemical responses to certain stimuli (postural change, Valsalva manoeuvre, isometric handgrip). There was no pressor response to intravenously infused noradrenaline, an increased response to atropine and diminished depressor and sedative effects to clonidine. Overall these results are indicative of an unbalanced autonomic control with preserved parasympathetic and higher background and stimulated sympathetic activity. These physiological, biochemical and pharmacological data, together with known neuro-pathological findings in this disorder, emphasize the possible role played by the thalamus in regulating autonomic control of cardiovascular function in man.

Adult↗
PubMed1991

Autonomic nervous system function in migraine without aura.

Autonomic nervous system functions were studied in 13 females with migraine without aura during headache-free intervals, using physiological, pharmacological and biochemical methods. Heart-rate in the resting condition and blood pressure rises in the cold-face and isometric handgrip tests were higher than in controls. Normal cardiovascular responses to the Valsalva manoeuvre and to noradrenaline infusion suggest that the baroreflex arc is intact. Normal heart rate responses to the Valsalva manoeuvre, to the cold-face test and to deep breathing confirmed a normal cardiac parasympathetic function. Clonidine infusion showed a sedative and depressor effect and an inhibition of plasma NA similar to those occurring in controls, suggesting a normal central sympathetic tone. As a whole, the physiological, pharmacological and biochemical tests were consistent with a non-specific sympathetic hyperactivity, but do not confirm any impairment of the autonomic control of the cardiovascular system in migraine patients in headache-free intervals.

Adolescent↗
PubMed1991

Circadian hormonal rhythms in two new cases of fatal familial insomnia.

We used a chronobiological inferential statistical method to investigate circadian rhythms of hypophyseal hormones, cortisol, melatonin and catecholamines in two females of the same family affected by fatal familial insomnia. Case 1 (confirmed at autopsy) presented an absent or progressive loss of circadian rhythms of all hormones. In case 2 there was a loss of GH circadian rhythm and a less significant rhythm for melatonin, catecholamines and gonadotropins. These results confirm the role of the thalamus in regulating hormonal circadian rhythm.

Adult↗
PubMed1990

Daily changes of neuropeptide Y-like immunoreactivity in the suprachiasmatic nucleus of the rat.

Most of the biochemical, physiological and behavioural events in living organisms show diurnal fluctuations, normally synchronized with 24-h environmental rhythms, such as the light-dark cycle. The suprachiasmatic nucleus (SCN) of the hypothalamus is considered to be a pacemaker of the circadian rhythms in several mammals. The light-dark cycle is the primary synchronizing agent for many of the circadian rhythms which are regulated by the SCN. The photic information reaches the SCN also through a neuropeptide Y(NPY)-like immunoreactive pathway from the ventro-lateral geniculate nucleus. We found that in 12-h-dark and 12-h-light housed rats the NPY-like immunoreactive innervation of the ventro-lateral part of the SCN shows a 24 h rhythm with values rising gradually during the light phase and falling during the dark phase. Besides this rhythm, we found two peaks corresponding to the switching on and switching off of the light. The average level of NPY-like immunoreactivity, as assessed by means of semiquantitative immunocytochemistry and expressed in 'arbitrary units', is reduced in rats housed in total darkness for 2 weeks. These results confirm the physiological role of NPY in the timing of the circadian activity of the SCN.

Animals↗
PubMed1989

Iodinated-NPY binding sites: autoradiographic study in the rat brain.

Several authors have described the presence of iodinated neuropeptide-Y binding sites on membranes of the mammalian CNS. In the present study we show a mapping of iodinated-NPY binding sites in the rat brain using receptor autoradiography. The sections were incubated with 125I-Bolton-Hunter coupled NPY (0.5-03 nM), in the absence or presence of 1 microM cold NPY. Some autoradiograms are studied by means of an image analyzer (VDC 501 Tesak) equipped with the host computer PDP 11 Digital, in order to enhance the contrast of the labeling. A very high density of NPY receptors is present in the limbic regions (hippocampus, amygdaloid complex, septal nuclei), in the cortex, and in some thalamic nuclei, while in some hypothalamic regions (paraventricular nucleus and median eminence) we detected a lower amount of NPY receptors. At the mesencephalic level, the substantia nigra presents a very high density of NPY receptors.

Animals↗