[Type 3 Gaucher disease, also an adult disease?] / Maladie de Gaucher de type 3, une maladie également de l'adulte ?

INTRODUCTION: Gaucher disease is a genetic lysosomal storage disorder due to a glucocerebrosidase deficiency. Type 3, including neurological impairment, may have a specific phenotype in the context of the D409H mutation. OBSERVATION: We report the case of a 22-year-old woman who presented with Gaucher disease. Enzyme replacement therapy by imiglucerase was followed by rapid clinical and biological improvement. However, communication difficulties, which were initially attributed to the language barrier, revealed neurological impairment. After complementary assessment, the diagnosis of type 3 Gaucher disease was suspected. Gene analysis of the glucocerebrosidase showed a homozygous D409H mutation. CONCLUSION: This mutation results in calcified heart valves, corneal opacities, alteration of oculomotricity and hydrocephalus. The mild manifestation at onset and the late neurological involvement in the medical history make the diagnosis more difficult. This particular clinical phenotype deserves to be known in adult medicine departments.

Correction to: Inhibition of cathepsin B by caspase-3 inhibitors blocks programmed cell death in Arabidopsis.

We thank D Nicholson for initial advice on caspase activity purification and B Turk for advice on recombinant cathepsin B. We thank N Atanasova for cell death assays. The Bioimaging Facility microscopes used in this study were purchased with grants from BBSRC, Wellcome Trust and the University of Manchester Strategic Fund. Special thanks go to D Knight in the Faculty Biomolecular Analysis facility. We thank P Birch and M Kim for improving the manuscript. The project was partially funded by BBSRC Grants 34/P14516, BB/K009478/1 and China National High-Tech Research and Development Programme(863 programme)NO. 2015AA020903.

Inhibition of cathepsin B by caspase-3 inhibitors blocks programmed cell death in Arabidopsis.

Programmed cell death (PCD) is used by plants for development and survival to biotic and abiotic stresses. The role of caspases in PCD is well established in animal cells. Over the past 15 years, the importance of caspase-3-like enzymatic activity for plant PCD completion has been widely documented despite the absence of caspase orthologues. In particular, caspase-3 inhibitors blocked nearly all plant PCD tested. Here, we affinity-purified a plant caspase-3-like activity using a biotin-labelled caspase-3 inhibitor and identified Arabidopsis thaliana cathepsin B3 (AtCathB3) by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Consistent with this, recombinant AtCathB3 was found to have caspase-3-like activity and to be inhibited by caspase-3 inhibitors. AtCathepsin B triple-mutant lines showed reduced caspase-3-like enzymatic activity and reduced labelling with activity-based caspase-3 probes. Importantly, AtCathepsin B triple mutants showed a strong reduction in the PCD induced by ultraviolet (UV), oxidative stress (H2O2, methyl viologen) or endoplasmic reticulum stress. Our observations contribute to explain why caspase-3 inhibitors inhibit plant PCD and provide new tools to further plant PCD research. The fact that cathepsin B does regulate PCD in both animal and plant cells suggests that this protease may be part of an ancestral PCD pathway pre-existing the plant/animal divergence that needs further characterisation.

UV-C radiation induces apoptotic-like changes in Arabidopsis thaliana.

With a view to studying programmed cell death in plants at the molecular level, we report here for the first time that apoptotic-like changes are induced by UV radiation in plant nuclei. In Arabidopsis thaliana seedlings a UV-C dose of 10-50 kJ/m2 induces an oligonucleosomal DNA fragmentation which is reminiscent of the apoptotic DNA ladder described in animal cells. This DNA fragmentation was also detected in situ in protoplast nuclei as soon as 2 h after UV-C treatment. Moreover, UV-C induced a nuclear morphology characteristic of animal apoptotic nuclei. We propose that UV-C induction constitutes a powerful tool to compare the cellular response to irreversible UV damage in plants to that in animals and to study programmed cell death in A. thaliana.

Paternally inherited transgenes are down-regulated but retain low activity during early embryogenesis in Arabidopsis.

We investigated the timing of transgene activation after fertilisation in Arabidopsis following crosses and using two transgenic promoters (from the AtCYCB1 and AtLTP1 genes). Using both a transactivation system and direct transcriptional fusion to drive beta-glucuronidase reporter expression, reciprocal crosses showed a lack of expression of the paternal components. This is consistent with a lack of paternal genome activity previously reported during early seed development in Arabidopsis [Viella-Calzada et al. (2000) Nature 404, 91-94]. However, transactivation experiments of the BARNASE gene gave evidence that at least some paternal loci retain transcriptional activity, though at a low level, during early embryogenesis.

The distribution of T-DNA in the genomes of transgenic Arabidopsis and rice.

Almost all the nuclear genes of four Gramineae (maize, wheat, barley, rice) and pea are located in DNA fractions covering only a 1-2% GC range and representing between 10 and 25% of the different genomes. These DNA fractions comprise large gene-rich regions (collectively called the 'gene space') separated by vast gene-empty, repeated sequences. In contrast, in Arabidopsis thaliana, genes are distributed in DNA fractions covering an 8% GC range and representing 85% of the genome. Here, we investigated the integration of a transferred DNA (T-DNA) in the genomes of Arabidopsis and rice and found different patterns of integration, which are correlated with the different gene distributions. While T-DNA integrates essentially everywhere in the Arabidopsis genome, integration was detected only in the gene space, namely in the gene-rich, transcriptionally active, regions of the rice genome. The implications of these results for the integration of foreign DNA are discussed.

A double blind randomized controlled trial of Maharishi Vedic vibration technology in subjects with arthritis.

To explore ancient Vedic medical techniques, one hundred and seventy-six subjects with arthritis participated in a controlled study through the non-pharmacologic approach known as the Maharishi Vedic Vibration Technology (MVVT). Using a double-blinded and randomized experimental design, the findings showed significant reductions of pain and stiffness, and improvement in range of motion in the study sample. One hundred percent relief of symptoms was the most commonly reported category of improvement due to treatment. For the group as a whole, differences in mean response of treatment and control conditions with respect to relief of pain, limitation of motion, and reduction in stiffness were highly significant: t values ranged from a low of 5.609 in stiffness to a high of 20.950 in pain, p = 0.000009 to <10-49 respectively. Analysis by sub-categories of peripheral arthritis, painful conditions of the spine, and rheumatoid arthritis likewise produced significant results. Mechanisms of action were proposed, drawing on Maharishi Vedic Science, developments in quantum field theory, and specifically the theories of chaos and self-organizing systems as they relate to physiological functioning. The instantaneous relief of pain and improvement in function in such a high proportion of subjects with chronic arthritis is unparalleled in modern medical science

Silver stained isoelectrophoresis of tears and cerebrospinal fluid in multiple sclerosis.

Cerebrospinal fluid (CSF) analysis aids in the diagnosis of multiple sclerosis. However, this examination is invasive. The aim of this study was to assess the potentials of a new method of tears isoelectrophoresis (IEF). Silver staining of IEF was used to examined tears and CSF from 123 patients including 60 patients with multiple sclerosis (MS), 50 other neurological patients and 13 patients with inflammatory neurological diseases. Tears were collected on a Shirmer strip placed in one eye, avoiding reflex secretion. This method of IEF with silver staining allowed the detection of oligoclonal bands in tears that were truly immunoglobulin G on immunofixation. The concordance rate between tears and CSF was 83%, meaning that CSF provided no more information than tears analysis in 83% of cases. Sensitivity in tears (72%) and CSF (75%) was very close as was specificity (respectively 84 % and 86 %). High concordance between tears and CSF is the first step in developing a non invasive test which could replace lumbar puncture, particularly when this procedure is not fearalele or is refused by the patient.

[The delusion of place: contribution of the measurement of cerebral deficit]. / Le délire des lieux: apport de la débitmétrie cérébrale.

The authors report the observation of a 61-year-old female patient who, following a right frontal-temporal ischemia, presented disorientation with respect to her surroundings. She was convinced during her hospital stay that her house had been transformed into a hospital. There was no evidence of intellectual confusion or deterioration, and the neuropsychological examination revealed visuo-spatial disturbances only. A low basal cerebral blood flow was found in the right anterior hemisphere which further decreased when the patient was asked where he was. It is hypothesized that confabulatory responses corresponded to a disinhibition of the left hemisphere from the control of the hemisphere dominant in dealing with visuo-spatial data.

[Diagnostic importance of middle latency auditory evoked potentials (MLAEP) in multiple sclerosis]. / Intérêt diagnostique des potentiels évoqués auditifs de latence moyenne (PEALM) dans la sclérose en plaques.

This study was aimed at assessing the interest of middle latency auditory evoked potentials (MLAEP) recordings in multiple sclerosis (MS). Brainstem auditory evoked potentials (BAEP) and MLAEP were recorded in 40 control subjects and 65 patients who had MS according to Poser's criteria. Na and Pa latencies were significantly delayed in the MS group. These abnormalities were detected in 60% of the patients. In 26% of the cases with normal BAEP, abnormalities of MLAEP were present. In 71% of the patients abnormalities of both BAEP and MLAEP were observed. These results suggest the ability of MLAEP recordings to detect lesions of the auditory pathways rostral to the pons and show the value of their combined recordings in MS patients.

[Skeletal and velar myoclonus with vision disorders. Efficacy of carbamazepine]. / Myoclonies squelettiques et du voile avec troubles visuels. Efficacité de la carbamazépine.

The authors report the case of a 71 year-old woman presenting right velopharyngo-laryngeal and skeletal rhythmic myoclonus, associated with visual and phasic disorders. They appeared four months after an infarct in the region of the left posterior cerebral artery. The ischemia was of temporo-occipital location, very probably extending to the region of the left red nucleus, thereby interrupting the dento-olivary pathway. Several drugs which are usually active in the treatment of myoclonus proved ineffective. But carbamazepine at a dose of 600 mg per day was effective from the third day and remained so after seven months. It would seem to act by inhibiting the occurrence of paroxystic discharges of an epileptic type in the olivary body disinhibited by the underlying lesion.

[Cortical and subcortical dementia. The value of long auditory evoked potentials]. / Démences corticales et sous-corticales. Intérêt des potentiels évoqués auditifs tardifs.

Long latency auditory evoked potentials were studied in 27 normal subjects, 19 patients with Alzheimer's Disease (A.D.) and 70 patients with Parkinson's Disease (P.D.). 17 patients with P.D. showed cognitive impairment measured by the "test rapide d'évaluation des fonctions cognitives - E.R.F.C.". The N2 and P3 peak latencies were prolonged in the demented group of P.D. compared to the non demented group P.D.. Between the electrophysiological parameters only the N1 latency prolongation distinguished the demented parkinsonian patients from the patients with A.D..

Variations of IL2, IL6, TNF alpha plasmatic levels in relapsing remitting multiple sclerosis.

We performed a longitudinal analysis of serum IL2, IL6 and TNF alpha concentrations in 40 relapsing remitting MS patients and 20 healthy subjects. Disease activity was quantified by Minimal Record of Disease (M.R.D.) for MS, every 2 or 3 months. IL2, IL6 TNF alpha production was analysed without and with PHA stimulation of whole blood for 2 hours at 37 degrees C. No significant change in IL2 level was found in MS serum. Individual TNF alpha production was significantly increased (P < 0.007) during relapses. The global spontaneous IL6 production was markedly higher in the relapse group than in the control group (P < 0.01) and than in the remission group (P < 0.002) without significant individual variations of cytokine levels regarding the disease activity. Productions of cytokines were enhanced by PHA stimulation, a condition that however suppressed the differences observed without mitogen stimulation. Our data suggest that TNF alpha could be a marker for relapses while IL6 might reflect the global activity of the immune system in MS.

[Disconnection and recognition of faces. A case with lesions of the left visual cortex and the splenium]. / Disconnexion et reconnaissance des visages. Un cas avec lésions du cortex visuel gauche et du splenium.

We report the clinical findings in a case of alexia without agraphia, due to a left posterior cerebral artery infarction, in which C.T. showed occipital and splenial lesions. There were in addition a right homonymous hemianopsia and agnosia for colors, objects and pictures, with both associative and disconnective aspects. The hypothesis of an occipito-occipital disconnection, depriving the left visual associative areas of inputs, could explain this agnosia. The most striking findings in this case was, besides an anomia for faces, a peculiar difficulty to recognize her own face. The patient seemed to recognize herself. The patient spoke about herself in the third person, giving genuine autobiographical details, without being able to say: "it is me". This phenomenon is discussed in terms of disconnection: the right hemisphere sending information from the semantic field evoked by her own face, through the anterior part of the corpus callosum, to the left hemisphere. We discuss the hemispheric contribution within cognitive experience, and the role of language concerning the conscious experience in man.

[Motor impersistance of the eyelids. Study of 93 cases and a discussion of pathogenic mechanisms]. / L'impersistance motrice palpébrale. Etude de 93 cas et discussion des mécanismes pathogéniques.

In a prospective study, 252 subjects were investigated for motor impersistence of the eyelids (MIE) by means of a protocol that evaluated its intensity and detected associated signs, notably other phenomena of motor impersistence. MIE was frequent, being found in 93 subjects. It was usually observed in diffuse brain lesions, then in lesions of the right hemisphere, particularly in the posterior and deep cortex. In right hemisphere lesions, MIE was significantly associated with constructional apraxia, visual neglect and Anton-Babinski syndrome. In diffuse cerebral lesions, MIE was accompanied by other phenomena of motor impersistence on a background of dementia. In these cases the P 300 wave latency was significantly prolonged. Three main mechanisms may be regarded as responsible for the occurrence of MIE: apraxia, disturbance of the interhemispheric balance (notably in lesions of the right hemisphere) and disorders of attention (predominant in diffuse lesions). Actually, in every case MIE should be inserted in a continuum the extremities of which are represented by the above mentioned mechanisms.

[Hemiballism caused by metastasis to Luys' body]. / Hémiballisme par métastase du corps de Luys.

A 66 year-old man suddenly developed a left-sided hemiballism. CT scan revealed 3 metastases, one of them in the area of the right subthalamic nucleus (corpus Luysii). A primary lung tumor was suspected. Haloperidol and tiapride were unsuccessful to control the hemiballism. The patient died 5 months later. Pathological examination confirmed the diagnosis. The pathophysiology of this case is discussed with regard to the pathological findings. Hemiballism secondary to a metastasis is rare, 9 cases have been reported during the past 65 years. Vascular lesions are the usual cause (75 per cent); on rare occasions degenerative disorders (14 per cent), destructive (tumors: 10 per cent or surgical lesions: 0,3-9 per cent) can also result in hemiballism.

[The gaze and functional hemispheric activation in normal subjects]. / Regard et activation fonctionnelle hémisphérique chez le sujet normal.

The aim of this work was to determine whether the study of lateral and vertical conjugated eye movement could serve as an indicator of the functional hemispheric activation. Questions of vocabulary, calculation, logic (V.C.L.) and visuo-spatial instructions, as well as music-listening (V.S.M.), were proposed to 60 control subjects (21 men, 39 women). They were divided in 4 groups of 15 according to their laterality (complete right handed, incomplete right handed, ambidextrous, left handed). Eye movements were recorded using a video system. Deviations of the eyes towards the right and left, upwards and downwards, as well as episodes of staring were noted. Concerning V.C.L. questions, there was a significant correlation between conjugated lateral eye movements and the contralateral hemisphere activation. The study of vertical eye movements revealed a correlation only in complete right-handed and left-handed subjects: deviation upwards during the left hemisphere activation, and downwards during the right hemisphere activation. This pattern of response was no longer found during V.S.M. questions which, in the 4 groups, evoked staring episodes in 56 to 72 per cent of the cases. The negative emotional stimuli (emotional words, non verbal stimuli, stressful situations) evoked preferentially, but independently of laterality, deviations towards the left and downwards in favor of the right hemisphere activation. This method of observation of eye movements seems therefore of significant interest in Neuropsychology, provided that methodologic rules are rigorously respected.

[Visual evoked potentials and face recognition. Influence of celebrity and emotional expression]. / Potentiels évoqués visuels et reconnaissance des visages: influence de la célébrité et de l'expression émotionnelle.

Visual evoked potentials (VEP) were recorded in the right and left parietal and occipital regions of 40 right-handed controls in a facial recognition task. VEP were studied first according to the renown of the faces, then according to their emotional expression. Asymmetry was noted between the hemispheres: P100 was of greater amplitude and longer latency in the left occipital region. Later components (P400 and P600) were of greater amplitude and longer latency in the right parietal region in all situations. P100 latency on the left side was shorter for renowned faces than for non-renowned faces (P = 0.05). P600 latency was shorter on the right (P < 0.03) and left (P < 0.05) sides for smiling than for non-smiling faces. When the subjects were asked to look for emotional expression of the face (smiling or non-smiling) P400 was very ample and P600 of little amplitude. When the subjects were asked to recognize the face (renowned or not renowned) P600 was very ample and P400 of little amplitude. Thus, there seems to be a differential treatment of information: automatic and rapid to detect emotion (P400), controlled, tardy (P600) and involving memory in the search for renown.

[Late auditory evoked potentials in subcortical cognitive deterioration]. / Potentiels évoqués auditifs tardifs dans les détériorations cognitives sous-corticales.

Late auditory evoked potentials (AEPs) were recorded by the odd-ball method in 55 non-deteriorated parkinsonians (NP) and in 27 parkinsonians with cognitive deterioration (CDP), compared with 20 controls (C) and 24 patients with Alzheimer-type senile dementia (ATSD). The latency of P 300 was prolonged in the CDP and ATSD groups (410.72 +/- 24.45 and 433.62 +/- 38.30 respectively; P less than 0.001. The latency of N 100 was prolonged only in the CDP group (106.6 +/- 4.82; P less than 0.001). Late AEPs were also studied in 63 subjects with possible or confirmed disseminated sclerosis (DS) compared with 33 controls of similar mean age. The ERFC test divided these patients into 38 with non-deteriorated DS (NDS) and 25 with deteriorated DS (DDS). The latency of P 300 was prolonged in both groups: NDS 331.14 +/- 25.89; DDS 376.64 +/- 29.51 (P less than 0.001). The latency of N 100 was prolonged in the NDS group (100.25 +/- 9.20) and the DDS group (104.43 +/- 9.01). Following a study of correlations between the degree of mental deterioration and the electrophysiological parameters in these populations, the significance of the N 100 latency as electrophysiological marker of subcortical dementia is discussed.

[Association of cerebral cysticercosis and multifocal glioma. Discussion of interactions]. / Association d'une cysticercose cérébrale et d'un gliome multifocal. Discussion des interactions.

Diagnosis in a case of cerebral parenchyma cysticercosis was based on conventional arguments described in the literature. The patient died after progression of the disease over 6 months, despite two courses of Praziquantel. Results of neuropathologic examination confirmed diagnosis of cysticercosis and the discovery of a multifocal astrocytic tumor involving mainly the periventricular regions. Possible interactions between parasitic infection and glioma are discussed but it is difficult to determine the precise role played by the parasitosis in the evolution of the tumor, the hypothesis of a simple coincidence being most likely. Periventricular images of an inflammatory nature observed after PZQ treatment should not be accepted unreservedly, and when an unfavorable course is apparent the periventricular histopathologic lesions should be compared with results of CT scan imaging qualified as periventricular in origin.