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R Guerrini

Publications and source records attributed to R Guerrini.

At least 73 records · Page 4Linked to original sources
PubMed1996

X-linked malformations of neuronal migration.

Malformations of neuronal migration such as lissencephaly (agyria-pachygyria spectrum) are well-known causes of mental retardation and epilepsy that are often genetic. For example, isolated lissencephaly sequence and Miller-Dieker syndrome are caused by deletions involving a lissencephaly gene in chromosome 17p13.3, while many other malformation syndromes have autosomal recessive inheritance. In this paper, we review evidence supporting the existence of two distinct X-linked malformations of neuronal migration. X-linked lissencephaly and subcortical band heterotopia (XLIS) presents with sporadic or familial mental retardation and epilepsy. The brain malformation varies from classical lissencephaly, which is observed in males, to subcortical band heterotopia, which is observed primarily in females. The XLIS gene is located in chromosome Xq22.3 based on the breakpoint of an X-autosomal translocation. Bilateral periventricular nodular heterotopia (BPNH) usually presents with sporadic or familial epilepsy with normal intelligence, primarily in females, although we have evaluated two boys with BPNH and severe mental retardation. The gene for BPNH has been mapped to chromosome Xq28 based on linkage studies in multiplex families and observation of a subtle structural abnormality in one of the boys with BPNH and severe mental retardation.

Adult↗
PubMed1995

Conformational analysis of potent and very selective delta opioid dipeptide antagonists.

The delta selectivity and antagonism of peptides containing L-tetrahydro-3-isoquinoline carboxylic acid (Tic) in second position can be attributed mainly to the Tyr-Tic unit. These properties can be further enhanced by substituting Tyr1 with 2,6-dimethyl-L-tyrosyl (Dmt). Dmt-Tic-NH2, Dmt-Tic-OH, Dmt-Tic-Ala-NH2 and Dmt-Tic-Ala-OH are all more active and/or selective than the corresponding [Tyr1]-parent peptides. In fact the selectivities of Dmt-Tic-OH and Dmt-Tic-Ala-OH are the highest ever recorded for opioid molecules. 1H NMR spectra in a DMSO/water mixture at 278 K reveal the presence of two similar conformers, characterised by a cis or trans Dmt-Tic bond, in all four peptides. A detailed conformational analysis in solution of Dmt-Tic-NH2 shows that these conformers have a shape very similar to that of the bioactive conformation of Tyr-Tic-NH2 and to that of naltrindole.

Dipeptides↗
PubMed1995

Calmodulin binding sites of the skeletal, cardiac, and brain ryanodine receptor Ca2+ channels: modulation by the catalytic subunit of cAMP-dependent protein kinase?

In this study, we define calmodulin binding sites of skeletal, cardiac, and brain ryanodine receptor (RYR) Ca2+ channels. Cardiac and brain RYR peptides corresponding to the calmodulin binding sites present in the skeletal RYR [Menegazzi, P., et al. (1994) Biochemistry 33, 9078-9084] were synthesized, and their interaction with calmodulin was monitored by fluorescent techniques. The central portions of the skeletal, cardiac, and brain RYR protomers display one high (CaM1; Kd ranging between 2.7 and 10.2 nM) and one low affinity (CaM2; Kd ranging between 116 and 142 nM) calmodulin binding site. Depending on the RYR model having 4 or 12 transmembrane segments, a third calmodulin binding site (CaM3) was identified a few residues upstream from the putative transmembrane segment M1 or M5. Its affinity for calmodulin varied between the RYR isoforms: the cardiac RYR CaM3 displays a high affinity (9.09 +/- 1.0 nM, n = 5), while the skeletal and brain RYR CaM3 have low affinity, the lowest affinity being displayed by the brain isoform (234 +/- 39 nM, n = 3). The RYRs calmodulin binding site CaM1 encompasses the sequence Arg-His-Arg-Val(Ile)-Ser-Leu, which is phosphorylated in vitro by the catalytic subunit of the cAMP-dependent protein kinase. Phosphorylation of RYR PM1 peptides occurs on the Ser, corresponding to amino acid number 2919, 3020, and 3055 of the brain, cardiac, and skeletal RYR protomers, respectively. We found that phosphorylation of the RYR PM1 peptides was inhibited by calmodulin binding and that the formation of the PM1 peptide-calmodulin complex was inhibited by peptide phosphorylation. These data indicate that the effect of calmodulin binding to RYR CaM1 may be regulated by the phosphorylation state of the Ser residue localized within the sequence Arg-His-Arg-Val(Ile)-Ser-Leu.

Amino Acid Sequence↗
PubMed1995

Effect of anchor residue modifications on the stability of HLA-A11/peptide complexes.

MHC class I antigens bind peptides derived from endogenous proteins and present them to cytotoxic T lymphocytes. This binding is selective and shows high allele specificity. Peptides binding to HLA-A11 contain a hydrophobic or a small polar amino acid at position 2 and a lysine at the carboxy terminus. Peptide analogues, derived from previously identified high affinity peptides and carrying amino acid substitutions in position 2, were used to determine the requirements for formation of stable HLA-A11/peptide complexes. By kinetic analysis we were able to discriminate among apparent and true binders. Only analogues carrying in position 2 the amino acids valine, threonine and isoleucine formed stable complexes with HLA-A11 with a half life > or = 72 hours.

Amino Acid Sequence↗
PubMed1995

Acid catalysis in the formation of dioxopiperazines from peptides containing tetrahydroisoquinoline-3-carboxylic acid at position 2.

The kinetics of the spontaneous formation of 2,5-dioxopiperazines from peptides containing the Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) residue in the 2-position of the sequence has been studied in DMSO and water solution. The reaction is first order in Tic-peptide and subject to general-acid catalysis. Moreover, only the fraction of peptide having the amino terminal group in the deprotonated state reacts with appreciable rate. In pure organic solvent, and in aqueous solution with low buffer concentration, the degradation reaction of Tic-peptides is very low; at 20 degrees C for the peptide H-Tyr-Tic-Phe-Phe-NH2, in DMSO and in neutral water in the absence of buffer, the half-lives (t1/2) are 3 x 10(4) and 1.2 x 10(4) h, respectively. The addition of carboxylic acids or buffers to the reaction solutions markedly increases the reaction rate; in 0.01 m HAc in DMSO and in 0.1 M phosphate buffer in water, pH 7.1, t1/2 values for the tetrapeptide are 61 and 121 h, respectively.

Acids↗
PubMed1995

Idiopathic photosensitive occipital lobe epilepsy.

We studied 10 neurologically normal patients (8 females, 2 males) aged 8-30 years (mean 17 years) who had recurrent episodes if visually induced occipital seizures. Television and computer screens were the main triggers. Seizure onset occurred between the ages of 5 and 17 years (mean 11 years). All seizures were stimulus related and began with elementary visual symptoms, followed in most patients by a slow clustering of cephalic pain, epigastric discomfort, and vomiting, with either normal of only mildly impaired responsiveness. EEG features included normal background activity, occipital spikes and waves, and a photoparoxysmal response which could be occipital, generalized, or both. Four patients also showed spontaneous generalized epileptiform abnormalities, and 3 had rolandic spikes. An Oz electrode was critical in identifying epileptiform activity in some patients. Complete seizure control was achieved in most patients with monotherapy, although occasional stimulus-related seizures occurred in 3 patients who showed a wider range of photosensitivity. These patients have an idiopathic localization-related epilepsy with age-related onset and specific mode of precipitation. Although this type of epilepsy has been reported previously, it has remained underrecognized, probably because it is difficult to differentiate clinically from migraine or from nonreflex childhood idiopathic occipital epilepsy.

Adolescent↗
PubMed1995

Panic attacks mistaken for relapse of epilepsy.

Panic attacks, a frequent type of pseudoepileptic seizures, occur more frequently in epilepsy patients than in the general population and are often misdiagnosed, leading to pseudosevere epilepsy. We evaluated 4 patients with a past history of epileptic seizures long in remission who were misdiagnosed as having relapsing seizures although they had fairly typical panic attacks. To avoid unnecessary and ineffective antiepileptic drug (AED) treatment, recurrence of seizures after long remission should be carefully evaluated to identify patients with a panic disorder who require specific treatment. In patients who unexpectedly exhibit seizures after long remission, an accurate retrospective diagnosis of the epileptic syndrome and a precise description of the attack symptomatology should be obtained, if possible with EEG-video monitoring.

Adolescent↗
PubMed1995

[Psychopathological risk in children with early onset of partial epilepsy].

In this study we compare the peculiarities of psychopathological risk in children with partial epilepsy versus children with chronic illness. Sixteen children affected by epilepsy with partial seizures, symptomatic or cryptogenetic (group A), are compared with 16 children affected by diabetes mellitus type 1 (group B) and with 16 early treated congenital hypothyroid children (group C). For the valuation we have used: 1) Rutter scales for parents; 2) questionnaire on maternal attitude towards epilepsy, modified for diabetes and hypothyroid children; 3) anamnestic interviews for epileptic patients; 4) individual observations. We have emphasized that: 1) the quality of life in children with epilepsy and their families is poorer compared to the ones of the other chronically ill children; 2) the attack is the most characterising factor of life quality of both group A and group B; 3) both group A and group B show an important anxiety for cognitive and behavioural disturbances; 4) in epilepsy families several factors contribute to the increased anxiety towards social life: occurrence of seizures, side effects of drugs, real or supposed underlying encephalopathy.

Age of Onset↗
PubMed1995

Delta opioidmimetic antagonists: prototypes for designing a new generation of ultraselective opioid peptides.

BACKGROUND: Tyr-Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) and Tyr-Tic-Ala were the first peptides with delta opioid antagonist activity lacking Phe, considered essential for opioid activity based on the N-terminal tripeptide sequence (Tyr-D-Xaa-Phe) of amphibian skin opioids. Analogs were then designed to restrain the rotational flexibility of Tyr by the substitution of 2,6-dimethyl-L-tyrosine (Dmt). MATERIALS AND METHODS: Tyr and Dmt peptides were synthesized by solid phase and solution methods using Fmoc technology or condensing Boc-Dmt-OH or Boc-Tyr(But)-OH with H-L-Tic-OBut or H-D-Tic-OBut, respectively. Peptides were purified (> 99%) by HPLC and characteristics determined by 1H-NMR, FAB-MS, melting point, TLC, and amino acid analyses. RESULTS: H-Dmt-Tic-OH had high affinity (Ki delta = 0.022 nM) and extraordinary selectivity (Ki mu/Ki delta = 150,000); H-Dmt-Tic-Ala-OH had a Ki delta = 0.29 nM and delta selectivity = 20,000. Affinity and selectivity increased 8700- and 1000-fold relative to H-Tyr-Tic-OH, respectively. H-Dmt-Tic-OH and H-Dmt-Tic-NH2 fitted one-site receptor binding models (eta = 0.939-0.987), while H-Dmt-Tic-ol, H-Dmt-Tic-Ala-OH and H-Dmt-Tic-Ala-NH2 best fitted two-site models (eta = 0.708-0.801, F 18.9-26.0, p < 0.0001). Amidation increased mu affinity by 10- to 100-fold and acted synergistically with D-Tic2 to reverse selectivity (delta-->mu). Dmt-Tic di- and tripeptides exhibited delta antagonist bioactivity (Ke = 4-66 nM) with mouse vas deferens and lacked agonist mu activity (> 10 microM) in guinea-pig ileum preparations. Dmt-Tic analogs weakly interacted with kappa receptors in the 1 to > 20 microM range. CONCLUSIONS: Dmt-Tic opioidmimetic peptides represent a highly potent class of opioid peptide antagonists with greater potency than the nonopioid delta antagonist naltrindole and have potential application as clinical and therapeutic compounds.

Amino Acid Sequence↗
PubMed1994

Conversion of enkephalin and dermorphin into delta-selective opioid antagonists by single-residue substitution.

The properties of di- and tri-peptides containing 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) in second position suggest that the message domain of opioid peptides can be composed of only two residues [Temussi, P. A., Salvadori, S., Amodeo, P., Guerrini, R., Tomatis, R., Lazarus, L. H., Picone, D. & Tancredi, T. (1994) Biochem. Biophys. Res. Commun. 198, 933-939]. As a crucial test of the possibility that the Tyr-Tic segment be a message domain in longer peptide sequences, we have inserted it in the sequences of two typical opioid peptides: [Leu]enkephalin, a non-selective agonist, and dermorphin, a selective mu agonist. Here we report the synthesis and biological activity of [L-Tic2]enkephalin, [L-Tic2]dermorphin, [L-Tic2]dermorphin carboxylic acid and [D-Tic2]dermorphin: all [L-Tic2]peptides were converted from agonists to delta-selective antagonists. The NMR conformational study in a dimethylsulfoxide/water cryoprotective mixture at low temperature shows diagnostic side-chain--side-chain NOEs in the spectra of all [L-Tic2]peptides and hints that the 90 degrees arrangement of the the two aromatic rings found in the cis-Tyr-L-Tic moiety, typical of N-methyl naltrindole and other delta-selective opiate antagonists, is responsible for the antagonist activity of all these peptides.

Amino Acid Sequence↗
PubMed1994

Identification and characterization of three calmodulin binding sites of the skeletal muscle ryanodine receptor.

In the present study, we have identified calmodulin binding sequences in the skeletal muscle ryanodine receptor Ca2+ release channel. Ligand overlays on RYR fusion proteins indicate that the skeletal muscle RYR contains three calmodulin binding regions defined by residues 2937-3225, 3546-3655, and 4425-4621. The RYR fusion protein PC28 (residues 2937-3225) bound calmodulin in the presence of EGTA and Ca2+, while RYR fusion protein PC26 (residues 3546-3655) exhibited strong calmodulin binding at 10 microM Ca2+. The RYR fusion protein PC15 (residues 4425-4621) did not bind calmodulin in the presence of either EGTA or 10-50 microM Ca2+. In the presence of 100-500 microM Ca2+, the RYR fusion protein PC15 exhibited an affinity for calmodulin of approximately 50 nM. Peptides RYR1 PM2 (residues 3610-3629) and RYR1 PM3 (4534-4552) encompassing putative RYR-calmodulin binding sites were synthesized. The synthetic peptides interacted directly with dansylcalmodulin as demonstrated by their capacity to affect the fluorescence emission of dansylcalmodulin. Missense mutation analysis indicates that the Lys and Arg residues are essential for calmodulin binding to the synthetic peptide RYR1 PM3. The RYR calmodulin binding site defined by peptide PM3 lies in the myoplasmic loop 2, a few residues upstream of the putative transmembrane segment M5; the other two calmodulin binding sites are next to the putative transmembrane segments M' and M''. Thus, the effect of calmodulin on Ca2+ release might involve the regulation of the putative transmembrane segments M5, M', and M''.

Amino Acid Sequence↗
PubMed1994

Selective opioid dipeptides.

The surprising change of selectivity induced by the change of chirality in peptides containing the tetrahydro-3-isoquinoline carboxylic acid (Tic) in second position, interpreted as a conformational preference induced on the Tyr-Xaa-Phe domain, can instead be attributed to the Tyr-Tic message domain. The relative spatial disposition of the aromatic ring of delta-selective non peptidic opiates is compatible with a message domain, in opioid peptides, of only two residues. This hypothesis was tested through the synthesis of Tyr-L-Tic-NH2, Tyr-D-Tic-NH2, Tyr-L-Tic-Ala-NH2, Tyr-L-Tic-Ala-OH and Tyr-D-Tic-Ala-NH2. Peptides containing Tyr-L-Tic- behave as very selective delta antagonists and those containing Tyr-DTic- as non selective agonists. This is the first case of opioid peptides containing a two-residue message domain and of opioid dipeptides with substantial opioid activity.

Amino Acid Sequence↗
PubMed1994

Band heterotopia: correlation of outcome with magnetic resonance imaging parameters.

The "band heterotopia" or "double cortex" is a brain anomaly that is presumed to result from a premature arrest of neuronal migration. Patients with this anomaly are reported to have a variable clinical course that has been, heretofore, unpredictable. The clinical records and magnetic resonance (MR) imaging studies of 27 patients with band heterotopia were retrospectively reviewed in an attempt to determine whether imaging findings are useful in predicting clinical outcome of affected patients. Statistical analyses revealed the following correlations: (1) severity of T2 prolongation in the brain with motor delay (p = 0.03); (2) degree of ventricular enlargement with the age of seizure onset (p = 0.04), and with development and intelligence (p = 0.04); (3) severity of pachygyria with the age of seizure onset (p = 0.01), seizure type (p = 0.03), and an abnormal neurologic examination (p = 0.002); (4) parietal involvement with delayed speech development (p = 0.05); (5) occipital involvement with age of seizure onset (p = 0.006); (6) age of seizure onset with development and intelligence (p = 0.03) and with an abnormal neurologic examination (p = 0.04); and (7) severity of the pachygyria and thickness of band with development of symptomatic generalized epilepsy (p = 0.002 and p = 0.02, respectively) and Lennox-Gastaut syndrome (p = 0.002 and p = 0.01, respectively).

Brain Diseases↗
PubMed1994

Infantile spasms: an early epileptic manifestation in some patients with the congenital bilateral perisylvian syndrome.

We report four patients with infantile spasms and the congenital bilateral perisylvian syndrome. Onset of spasms occurred during the first 6 months of life. Response to corticotropin treatment was prompt and resulted in resolution of seizures in all patients. Epilepsy developed in the four children after an interval of 2 to 12 years. Developmental outcome was variable; three were severely restricted and one was married and lived independently. Imaging studies revealed bilateral perisylvian lesions characteristic of polymicrogyria. Infantile spasms may be the presenting seizure type in some patients with the congenital bilateral perisylvian syndrome.

Adolescent↗
PubMed1994

Occipitotemporal seizures with ictus emeticus induced by intermittent photic stimulation.

We recorded occipitotemporal seizures induced by intermittent photic stimulation in three children with brain injuries, aged 10 to 13 years. All had a history of seizures and showed occipital spikes on EEG, but were seizure free and were not being treated at the time of investigation. In all, photic stimulation induced seizures in the right occipital lobe. They were followed by clinical and EEG signs suggesting infrasylvian spreading to ipsilateral mesiotemporal limbic structures and by vomiting, appearing at late stages of the attacks. Seizure spread was very slow in two patients in whom attacks lasted 16 and 25 minutes. Patients with occipital epileptiform abnormalities presenting with ictal vomiting are often diagnosed as having vague migraine-epilepsy syndromes. We conclude that vomiting can be a late ictal phenomenon resulting from temporal lobe spread of seizures originating in the occipital lobe.

Adolescent↗
PubMed1994

The epileptic spectrum in the congenital bilateral perisylvian syndrome. CBPS Multicenter Collaborative Study.

We studied the frequency, clinical and EEG characteristics, and outcome of the epileptic syndrome in 31 patients with a congenital neurologic syndrome characterized by pseudobulbar palsy, cognitive deficits, and bilateral perisylvian polymicrogyria. Seizures were present in 27 of 31 patients (87%) and usually began between the ages of 4 and 12 years; they commonly consisted of atypical absence, atonic/tonic, and generalized tonic-clonic seizures. Partial attacks were present in 26%. EEG demonstrated generalized spike and wave abnormalities and, less frequently, multifocal discharges, predominantly in centro-parietal regions. Seizures were poorly controlled in 65%, with the remaining patients well controlled. Seven patients underwent callosotomy, which resulted in seizure improvement. This study indicates that the epileptic spectrum in this syndrome is broad but follows predictable patterns. Callosotomy is a valuable treatment strategy in those with intractable drop attacks.

Adolescent↗
PubMed1993

Congenital bilateral perisylvian syndrome: study of 31 patients. The CBPS Multicenter Collaborative Study.

Advances in neuroimaging techniques have enabled the recognition of developmental malformations of the brain during life. Careful correlation of clinical and imaging features has identified several new syndromes. We have studied 31 patients with a congenital neurological syndrome characterised by pseudobulbar palsy, cognitive deficits, and bilateral perisylvian abnormalities on imaging studies. All patients had diplegia of the facial pharyngeal, and masticatory muscles, of variable severity. Some patients had slight dysarthria, whereas others were unable to speak. 85% of patients had mental retardation, ranging from mild to severe. Epilepsy was present in 27 (87%) and commonly consisted of atypical absence, atonic/tonic, tonic-clonic seizures, and, less frequently, partial attacks. Seizures were poorly controlled in 55%. Magnetic resonance imaging showed bilateral perisylvian cortical malformations consistent with polymicrogyria, confirmed at necropsy. Division of the corpus callosum in several patients resulted in seizure improvement. This congenital bilateral perisylvian syndrome can be clinically diagnosed and confirmed by imaging studies. Further studies are necessary to elucidate its cause.

Adolescent↗