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PubMed2003

Comparison between the results of the Symptom Checklist-90 in two different populations with temporal lobe epilepsy.

We performed a prospective psychopathological analysis of two distinct populations with temporal lobe epilepsy (TLE), medically treated patients (n=18) and patients surgically treated for mesial temporal sclerosis (n=19), and compared the psychopathology in the surgical population pre- and postoperatively. The Symptom Checklist-90 (SCL-90) was administered to both groups, with the surgical patients being tested before and 6 months after surgery. A multivariant comparison of the SCL-90 subscales was made between medically treated patients and patients before and after surgical treatment. Surgically treated patients had less psychopathology after surgery than before. The comparison of surgically treated patients with medically treated patients showed statistically significant differences in most subscales. Except for the subscale of Hostility, no statistically significant differences were found between medically treated patients and the surgical population before lobectomy.

Adult↗

PubMed2005

On the psychopathology of unilateral temporal lobe epilepsy.

Personality adjustment of patients with unilateral temporal lobe epilepsy (TLE) was investigated in the light of special characteristics of the epilepsy process, psychosocial stressors, and the cognitive status of the patients. Thirty-seven patients with medically intractable unilateral temporal lobe epilepsy (16-55 years of age; 20 right temporal and 17 left temporal foci) were examined with standardized personality inventories (FPI, STAI, IPC, TSK) supplemented by a rating scale evaluated by the neuropsychologist (GEWLE). Patients with left temporal lobe epilepsy were characterized by increased emotional dependency, less externally judged composedness, increased depressive drive and mood, increased nervousness, increased search for information and exchange of disease experience, and greater tendency to persevere (P < 0.05). Cognitive status and psychosocial status did not significantly differ. The evaluation of personality adjustment contributes to the lateralization of the epileptogenic focus and reveals interesting patterns in the preoperative diagnostic puzzle, and in addition provides a strategy to individualize psychotherapeutic strategies.

Adult↗

PubMed2001

Rhodopsin-transducin interface: studies with conformationally constrained peptides.

To probe the interaction between transducin (G(t)) and photoactivated rhodopsin (R*), 14 analog peptides were designed and synthesized restricting the backbone of the R*-bound structure of the C-terminal 11 residues of G(t)alpha derived by transferred nuclear Overhauser effect (TrNOE) NMR. Most of the analogs were able to bind R*, supporting the TrNOE structure. Improved affinities of constrained peptides indicated that preorganization of the bound conformation is beneficial. Cys347 was found to be a recognition site; particularly, the free sulfhydryl of the side chain seems to be critical for R* binding. Leu349 was another invariable residue. Both Ile and tert-leucine (Tle) mutations for Leu349 significantly reduced the activity, indicating that the Leu side chain is in intimate contact with R*. The structure of R* was computer generated by moving helix 6 from its position in the crystal structure of ground-state rhodopsin (R) based on various experimental data. Seven feasible complexes were found when docking the TrNOE structure with R* and none with R. The analog peptides were modeled into the complexes, and their binding affinities were calculated. The predicted affinities were compared with the measured affinities to evaluate the modeled structures. Three models of the R*/G(t)alpha complex showed strong correlation to the experimental data.

Arginine↗

PubMed1987

The effects of cholesterol on lateral diffusion and vertical fluctuations in lipid bilayers. An electron-electron double resonance (ELDOR) study.

Electron-electron double resonance (ELDOR) and saturation-recovery spectroscopy employing 14N:15N stearic acid spin-label pairs have been used to study the effects of cholesterol on lateral diffusion and vertical fluctuations in lipid bilayers. The 14N:15N continuous wave electron-electron double resonance (CW ELDOR) theory has been developed using rate equations based on the relaxation model. The collision frequency between 14N-16 doxyl stearate and 15N-16 doxyl stearate, WHex (16:16), is indicative of lateral diffusion of the spin probes, while the collision frequency between 14N-16 doxyl stearate and 15N-5 doxyl stearate, WHex (16:5), provides information on vertical fluctuations of the 14N-16 doxyl stearate spin probe toward the membrane surface. Our results show that: (a) cholesterol decreases the electron spin-lattice relaxation time Tle of 14N-16 doxyl stearate spin label in dimyristoylphosphatidylcholine (DMPC) and egg yolk phosphatidylcholine (egg PC). (b) Cholesterol increases the biomolecular collision frequency WHex (16:16) and decreases WHex (16:5), suggesting that incorporation of cholesterol significantly orders the part of the bilayer that it occupies and disorders the interior region of the bilayer. (c) Alkyl chain unsaturation of the host lipid moderates the effect of cholesterol on both vertical fluctuations and lateral diffusion of 14N-16 doxyl stearate. And (d), there are marked differences in the effects of cholesterol on lateral diffusion and vertical fluctuations between 0-30 mol% and 30-50 mol% of cholesterol that suggest an inhomogeneous distribution of cholesterol in the membrane.

Cholesterol↗

PubMed1988

Solution of the nitroxide spin-label spectral overlap problem using pulse electron spin resonance.

Short-pulse saturation-recovery (SR) electron spin resonance (ESR) methods have been used to measure the lateral diffusion of a nitroxide-labeled cholesterol analogue (3-spiro-[2'-(N-oxyl-4',4'-dimethyloxazoladine)]-cholestane, CSL) in multilamellar liposomal dispersions. SR experiments were performed on samples containing 14NCSL:15NCSL pairs, and recovery signals were analyzed for initial conditions and multiexponential time constants by computer simulation. Rate equations describing the system were written and solved. The time constants contain combinations of electron spin lattice relaxation times Tle for both isotopes and the Heisenberg exchange rate constant Kx. We have investigated the complication that occurs from overlap of ESR spectral fragments from 14N and 15N moieties. The time constants of the multiexponential signals are independent of ESR line shape and position. From Kx, lateral diffusion constants of CSL in dimyristoylphosphatidylcholine (DMPC) were calculated (D = 1.7 x 10(-8) at 27 degrees C and 2.7 x 10(-8) cm2/s at 37 degrees C). It is shown that short-pulse saturation-recovery methods are able to overcome the ESR spectral overlap problem that is encountered in conventional ESR and continuous wave electron-electron double resonance (CW ELDOR) studies of spin-spin interactions. The present method can be extended to more complex situations involving spin labels in different environments with physical and chemical exchange.

Cyclic N-Oxides↗

PubMed2006

Jumping to conclusions: "language loss" versus "language impairment".

This paper discusses the impact of different metaphors of language dysfunction, with particular notice taken of the contribution of Marshall's work. This is especially the case regarding the notable paper on semantic error patterns (Marshall and Newcombe, 1973), and his later commentary on Chomsky's Rules and Representations (1980) with his elaboration of the conceptual commitments of The New Organology (1980). Examples of language performance provided by two sets of studies are used to illustrate the view that talk of language "loss" is hard to differentiate from the effects of concomitant processing mechanisms such as working memory. These examples are taken from studies of English and Turkish dementia of the Alzheimer type (DAT) patients (March, 2004), and temporal lobe epilepsy (TLE) patients (Field, 2001). Much contemporary neuropsychological research seems focussed on issues which assume that we already know how to describe the behaviours and processes we are interested in, and thus we can now concentrate on how and where in the brain these processes are handled. This perspective is examined from the points of view both that we do not yet have a sufficiently precise application of descriptions which utilise Linguistic constructs, and also that the available models of such processes as memory do not yet allow us to interpret task effects independently of the theoretician's intuitions.

Dementia↗

PubMed2000

Enantiomeric and diastereomeric high-performance liquid chromatographic separation of cyclic beta-substituted alpha-amino acids on a teicoplanin chiral stationary phase.

High-performance liquid chromatographic (HPLC) separation of stereomeric cyclic beta-substituted or-quaternary alpha-amino acids was performed on a chiral stationary phase based on the glycopeptide antibiotic teicoplanin. The investigated amino acids are the 1-amino-2-methylcyclohexanecarboxylic acids, the 1-amino-2-hydroxycyclohexanecarboxylic acids, Ala, Cha, Phe and Tle. The effects of the mobile phase composition (type and content of organic modifier, pH) and of the temperature on the enantio- and diastereoselectivity were studied and the conditions were optimised to resolve the four stereomers of one amino acid in a single chromatographic run. The influence of the modifier concentration and the pH of the mobile phase reveal two enantiomeric and diastereomeric discrimination mechanisms based on different interactions with the stationary phase. For optimal separation of diastereomers the column has to be conditioned with an acidic eluent.

Amino Acids↗

PubMed2000

Update on the pathophysiology of the epilepsies.

The pathophysiology of convulsive and non-convulsive epilepsies is discussed in its primary generalised forms. Focal, clinical and experimental epilepsies, with emphasis placed on the temporal lobe epilepsies (TLE) and their pathophysiologies are also reviewed. Neurotransmitters and neuromodulators and between them, the second messenger systems are considered in the generation, maintenance or inhibition of the epileptic discharge. Action mechanisms of the more classic antiepileptic drugs are briefly summarized along with the therapeutic strategies that might achieve the final control of abnormal discharges, including genetic control as a promising alternative in the current state of research. We emphasized the study of all type of glutamate and GABA receptors and their relation with mRNA editing in the brain. Some of the genetic studies which have been so fruitful during the last ten years and which have brought new insights regarding the understanding of epileptic syndromes are summarized in this article.

Animals↗

PubMed1998

Granule cell dispersion is correlated with early epileptic events in human temporal lobe epilepsy.

Granule cell dispersion (GCD) into the dentate gyrus (DG) molecular layer was observed in hippocampal specimens in 10 out of 22 cases of human non-lesional temporal lobe epilepsy (TLE) and was associated with hippocampal sclerosis (HS). The presence of GCD was significantly linked to events of epileptic nature arising during the first 4 years of life but not with the durations of epilepsy, nor the number of seizures. Dispersion could be induced by seizure-linked structural plasticity occurring during a specific early permissive period.

Cell Death↗

PubMed2002

Deficits in executive functions and motor coordination in children with frontal lobe epilepsy.

Frontal lobe dysfunction in adults has been associated with impairments of planning abilities, working memory, impulse control, attention and certain aspects of motor coordination. However, very few studies have attempted to assess these functions in children suffering from frontal lobe epilepsy. The aim of the present study was to determine whether some or all of the components of the frontal lobe syndrome are present in children with this disorder. For this purpose, a neuropsychological test battery was administered to 32 unresected epileptic children, aged 8-16 years: 16 with frontal lobe epilepsy (FLE), eight with temporal lobe epilepsy (TLE) and eight with generalized epilepsy whose principal manifestations were typical absences (GEA). The performances of the three epileptic groups were further compared to normative data derived from 200 French-speaking, healthy children aged 7-16 years, except for standardized tests for which the norms provided in the manual were used. The three epilepsy groups did not differ with respect to conceptual shift and recency memory. However, the FLE children showed deficits in planning and impulse control. Furthermore, they had significantly more coordination problems and exhibited greater rigidity than the other epilepsy groups on the motor tests. These problems were more marked in younger FLE children (8-12 years). The latter were also more impaired on verbal fluency measures. No differences were observed with respect to gender, localization of the epileptic abnormality (unilateral versus bilateral) or medication (monotherapy versus polytherapy). The findings reveal similarities between the neuropsychological profiles of FLE children and adults with frontal lobe lesions.

Adolescent↗

PubMed2000

Confrontation naming after anterior temporal lobectomy is related to age of acquisition of the object names.

Decline in visual confrontation naming ability may occur as a postacute complication of left anterior temporal lobectomy (ATL) for the treatment of intractable mesial temporal lobe epilepsy. In this study of 26 left ATL patients who demonstrated postsurgery decline on a standardized naming measure, it was hypothesized that naming performance would be significantly associated with specific attributes of the object names. We investigated the relation between performance on the Boston Naming Test (BNT) and the following attributes of the test items: living versus nonliving category (L/NL), word length (WL), written word frequency (WF), and age of acquisition (AoA). Regression analyses revealed that AoA and WF were significant predictors of preoperative group performance. AoA was the only significant predictor of performance after left ATL. For the 17 individuals who demonstrated a statistically meaningful decline on the BNT, as indicated by a Reliable Change Index, individual logistic regressions demonstrated that AoA was the strongest and most consistent predictor of postoperative success/failure for items that had been named correctly preoperatively. Consistent with the literature on naming errors in elderly normals and patients with aphasia or semantic dementia, the results provide evidence that object names learned in late childhood are among the most vulnerable when there is a decline in object naming ability. Investigation of additional attributes and semantic knowledge for the concepts represented by the pictured objects will be necessary to determine whether the naming deficit associated with TLE and ATL reflects an impairment of phonological word-form retrieval, semantics, or both.

Adult↗

PubMed2004

A mitochondrial protein, Bit1, mediates apoptosis regulated by integrins and Groucho/TLE corepressors.

A delicate balance of signals regulates cell survival. One set of these signals is derived from integrin-mediated cell adhesion to the extracellular matrix (ECM). Loss of cell attachment to the ECM causes apoptosis, a process known as anoikis. In searching for proteins involved in cell adhesion-dependent regulation of anoikis, we identified Bit1, a mitochondrial protein that is released into the cytoplasm during apoptosis. Cytoplasmic Bit1 forms a complex with AES, a small Groucho/transducin-like enhancer of split (TLE) protein, and induces cell death with characteristics of caspase-independent apoptosis. Cell attachment to fibronectin counteracts the apoptotic effect of Bit1 and AES. Increasing Bit1 expression enhances anoikis, while suppressing the expression reduces it. Thus, we have elucidated an integrin-controlled pathway that is, at least in part, responsible for the cell survival effects of cell-ECM interactions.

Animals↗

PubMed2003

Identification of epilepsy-related genes by gene expression profiling in the hippocampus of genetically epileptic rat.

Ihara epileptic rat (IER) is an animal model of temporal lobe epilepsy (TLE) with genetically programmed microdysgenesis in the hippocampal formation. The neuronal microdysgenesis is thought to be a cause for recurrent spontaneous seizures. To identify differentially expressed genes in the hippocampus of IER in comparison to control Wistar rat, we performed serial analysis of gene expression (SAGE). As many as 21 differentially expressed genes were identified.

Animals↗

PubMed1997

Structural modifications of the N-terminal tetrapeptide segment of [D-Ala2]deltorphin I: effects on opioid receptor affinities and activities in vitro and on antinociceptive potency.

A series of deltorphin I analogs containing D- or L-N-methylalanine (MeAla), D- or L-proline (Pro), alpha-aminoisobutyric acid (Aib), sarcosine (Sar) or D-tert-leucine (Tle) in place of D-Ala2, or phenylalanine in place of Tyr1, was synthesized. The opioid activity profiles of these peptides were determined in mu and delta opioid receptor-representative binding assays and bioassays in vitro as well as in the rat tail flick test in vivo. In comparison with the deltorphin I parent, both the L- and the D-MeAla2-analog were slightly more potent delta agonists in the mouse vas deferens (MDV) assay, and the D-MeAla2-analog showed two-fold higher antinociceptive potency in the analgesic test. In view of the fact that deltorphin analogs with an unsubstituted L-amino acid residue in the 2-position generally lack opioid activity, the observed high delta opioid potency of [L-MeAla2]deltorphin I is postulated to be due to the demonstrated presence of a conformer with a cis Tyr1-MeAla2 peptide bond, since the cis conformer allows for a spatial arrangement of the pharmacophoric moieties in the N-terminal tripeptide segment similar to that in active deltorphin analogs containing a D-amino acid residue in the 2-position. Substitution of Aib in the 2-position led to a compound, H-Tyr-Aib-Phe-Asp-Val-Val-Gly-NH2, which displayed lower delta receptor affinity than the parent peptide but higher delta selectivity and, surprisingly, three times higher antinociceptive potency. The D- and L-Pro2-, Sar2- and D-Tle2-analogs showed much reduced delta receptor affinities and were inactive in the tail flick test. Replacement of Tyr1 in deltorphin I with Phe produced a 32-fold decrease in delta receptor affinity but only a 7-fold drop in antinociceptive potency.

Analgesics, Opioid↗

PubMed2003

Lateralized impairment of the emotional enhancement of verbal memory in patients with amygdala-hippocampus lesion.

This study investigated amygdala-hippocampus's functional asymmetry in the emotional modulation of memory for stories. Thirty-nine, right-handed, drug-resistant epilepsy patients who had been submitted to unilateral temporal lobectomy (19 left and 20 right) watched either an arousing or neutral version of a story presented audio-visually. The slide sequence was the same in the neutral and arousing version, the narratives were matched for structure and comprehensibility. The set and order of the 11 slide sequence were identical in both conditions. Free recall and recognition measures were taken 2h after story presentation. Subjects in the TLE group who watched the arousing version recalled more details than the subjects who watched the neutral version (t(37)=3.4,p<.001). The group who watched the arousing version recalled more details of the phase 2 of the story (t(37)=6.76,p<.001). Scores in both conditions did not differ between control subjects and temporal lobectomy patients. When the right and left lesioned groups' results were analyzed separately, it was observed that the two groups did not differ in their recall of the neutral version. The right lesioned group recalled more items of the arousal than the neutral version (Z=-3.55,p<.001). However the left lesioned group did not show the memory enhancement for the emotional version, in this group it was only found an enhanced recall of the more pictorial emotional segment of the narrative (Z=-3.11,p<.001). This illustrates that the right amygdala can influence retention of complex emotional stimuli with verbal and pictorial arousing properties. We concluded that an intact left amygdala-hippocampus is important for enhancement of memory related to emotionally arousing verbal material.

Acoustic Stimulation↗

PubMed1999

Selectivity of action of typical and atypical anti-psychotic drugs as antagonists of the behavioral effects of 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI).

1. There has been considerable research in the field of schizophrenia over the past few years with emphasis on the discovery of better drugs, particularly those with 5-HT2 antagonist activity. 2. In an effort to enhance identification of such compounds and to further understand the contribution of 5-HT2 activity to the effects of antipsychotic drugs, a series of conventional, atypical and purported antipsychotic compounds were assessed as antagonists of DOI-induced behaviors in rats. 3. DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride) is an hallucinogen having high affinity and selectivity as an agonist at 5-HT2A/2C receptors. Over a 30-min period after injection, DOI (0.3-10.0 mg/kg; i.p.) produced dose-related behavioral effects including head-and-body shakes, forepaw tapping and skin-jerks. Effects of the antipsychotic drugs and other compounds (30 min pretreatment; i.p.) were examined against a fixed dose of DOI (3.0 mg/kg). 4. In a dose-dependent manner, M100907 (MDL 100,907), risperidone, haloperidol, clozapine, iloperidone, olanzapine, amperozide, remoxipride, ritanserin and the neurotensin agonist NT1 (N alpha MeArg-Lys-Pro-Trp-Tle-Leu) antagonized each of the three behavioral effects of DOI. Drugs attenuating the head-and-body shakes were equally effective in blocking both forepaw tapping and skin-jerks indicating that these behaviors are mediated by similar mechanisms. The following compounds had either inconsistent or no effect on the DOI-induced behaviors: SB 200646A, citalopram, imipramine, fluoxetine, morphine, CP 99994, diazepam, ondansetron and SKF 97541. 5. The data show that antipsychotic agents, as a drug class, effectively block the effects of DOI. These actions are selective, as a series of nine non-antipsychotic and centrally-acting drugs were generally inactive in the procedure.

Animals↗

PubMed2000

Increased amygdala volumes in female and depressed humans. A quantitative magnetic resonance imaging study.

The amygdala are thought to play an important role in emotional information processing. First studies indicate a link between amygdala atrophy, fear and aggression and between amygdala hypertrophy and depression. To investigate a possible relationship between amygdala volumes, aggression and depression, we measured the amygdala of 62 patients with temporal lobe epilepsy (TLE) with and without aggressive behavior or depression and 20 healthy volunteers using quantitative magnetic resonance imaging (MRI). Amygdala volumes of female patients (n=26) were significantly larger than those of males (n=36) (left side: P=0.001; right side P=0.05). Depressed patients displayed significant enlargement of both amygdala (left side: P=0.008; right side: P=0.001) There was no significant finding relating to the factor aggression neither was there any significant interaction between aggression, dysthymia and gender.

Adolescent↗

PubMed2000

Reduction of A1 adenosine receptors in rat hippocampus after kainic acid-induced limbic seizures.

In a temporal lobe epilepsy (TLE) model induced by kainic acid (KA), we examined the effect of limbic seizures on A1 adenosine receptor distribution in hippocampus and cortex. By using quantitative autoradiography, we determined a progressive decrease in A1 receptor density in CA1 and CA3 regions of hippocampus, which coincided in time with the degenerating process of hippocampal pyramidal cells. This result indicates that a great amount of A1 receptors are located postsynaptically on pyramidal cell dendrites. No difference in A1 receptor density was observed in the inner compared to the outer molecular layer of dentate gyrus, or in the infrapyramidal band compared to the outer layer of stratum oriens of CA3. This could indicate that the newly sprouted mossy fiber glutamatergic terminals do not contain A1 receptors, thus lacking a restrain in the release of glutamate.

Adenosine↗