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30 Pags.- 1 Tabl.- 6 Figs. The definitive version is available at: https://www.sciencedirect.com/science/journal/01401963, We investigated the phytotoxic effects of volatile and water soluble chemicals produced by the shrub Artemisia herba-alba Asso. We conducted a number of germination and early seedling growth bioassays on species that co-exist with A. herba-alba in natural semiarid plant communities (Salsola vermiculata L. Lygeum spartum L. Pinus halepensis Mill. and A. herba-alba itself). In addition, we assessed the phytotoxic effects of a mixture of phenols that were identified in the aqueous extract of A. herba-alba on the germination of such species. We found that volatile chemicals inhibited the germination of P. halepensis seeds, promoted the growth of P. halepensis seedlings and reduced the root biomass of S. vermiculata seedlings, while water soluble chemicals promoted the growth of L. spartum and P. halepensis seedlings. On the other hand, both volatile and water soluble compounds inhibited the germination of A. herba-alba seeds, highlighting its strong autotoxic nature. We did not find a phytotoxic effect of phenols identified (catechol, protocatechuic and vanillic acids) on species that co-exists with A. herba-alba, although they had a moderate autotoxic effect. Our results suggest that both the volatile and water soluble chemicals might be involved in chemical interactions among plants in semiarid environments., This research was supported by the Spanish Ministry of Education, Culture and Sport (AP-2012-4126 grant to A.I.A., FPU Program) and by the Spanish Ministry of Economy and Competitiveness (CGL-2012-37508 and CGL-2016-80783-R projects).

The study of plant-environment interactions has grown steadily during the past two decades. This trend will continue as many environmental changes impact the functioning of ecosystems. One aspect of studying the plant-environment interactions is to focus on the way plants react to abiotic or biotic stresses including chemical mediation between plants or plants-microorganisms (allelopathy) and plant reaction to pollutants. This chapter proposes to focus on carbon radiochemicals (14C) and stable carbon isotope tracers (13C). Indeed, they are powerful techniques in plant ecophysiological researches to describe the transfer and effects of allelochemicals and pollutants in plants and their environment.

Phenolic compounds have been identified previously as potentially responsible for allelopathic interferences in spruce forest at high altitude. They have now been analyzed in canopy leachates, snow, and soil solutions collected from the three layers of the podsolic soil: OA, E. and B. Leachates were characterized by high tanning capacity and by p-hydroxyacetophenone (found at 10−6 M) also detected as the major (10−7 M) monomeric compound in snow. At least 10 phenolic monomers, including vanillic, p-hydroxybenzoic, and protocatechuic acids were identified in capillary waters extracted from the OA layer with their sum reaching 2 × 10−6 M. These monomers were only a small part (1%) of the total phenolics. In soil solutions, significant decreases in phenolic concentrations with depth were observed between the E and B layers, with qualitative modifications of the phenolic pattern. Spruce leachates and soil solutions exhibited high temporal variability, resulting in transitory allelopathic potential towards both aerial and subterranean parts of spruce seedlings. The occurrence of various and soluble phenolic coumpounds in the whole forest system, including p-hydroxyacetophenone, which persist from green needles to soil solutions, suggests that they could be involved in complex and interactive processes occurring during organic matter accumulation on the coniferous forest floor.

The idiopathic inflammatory myopathies (IIM) are acquired muscle diseases characterized by muscle weakness and inflammation on muscle biopsy. Clinicoserologic classifications do not take muscle histology into account to distinguish the subsets of IIM. Our objective was to determine the pathologic features of each serologic subset of IIM and to correlate muscle biopsy results with the clinicoserologic classification defined by Troyanov et al, and with the final diagnoses. We retrospectively studied a cohort of 178 patients with clinicopathologic features suggestive of IIM with the exclusion of inclusion body myositis. At the end of follow-up, 156 of 178 cases were still categorized as IIM: pure dermatomyositis, n = 44; pure polymyositis, n = 14; overlap myositis, n = 68; necrotizing autoimmune myopathy, n = 8; cancer-associated myositis, n = 18; and unclassified IIM, n = 4. The diagnosis of IIM was ruled out in the 22 remaining cases. Pathologic dermatomyositis was the most frequent histologic picture in all serologic subsets of IIM, with the exception of patients with anti-Ku or anti-SRP autoantibodies, suggesting that it supports the histologic diagnosis of pure dermatomyositis, but also myositis of connective tissue diseases and cancer-associated myositis. Unspecified myositis was the second most frequent histologic pattern. It frequently correlated with overlap myositis, especially with anti-Ku or anti-PM-Scl autoantibodies. Pathologic polymyositis was rare and more frequently correlated with myositis mimickers than true polymyositis. The current study shows that clinicoserologic and pathologic data are complementary and must be taken into account when classifying patients with IIM patients. We propose guidelines for diagnosis according to both clinicoserologic and pathologic classifications, to be used in clinical practice.

For the last 50 years, Chamois (Rupicapra rupicapra) population exponentially increased in the French Alps. This herbivore faces a food shortage in the winter; its diet mainly includes woody species (Abies alba Mill.) and brambles (Rubus fruticosus). The physiological response following simulated herbivory of these two plants was assessed. More precisely, the effects of leaf clipping and ungulate saliva application on the epidermal flavonoids and chlorophyll contents were considered as an induced structural response. The chlorophyll fluorescence (Fv/Fm) was also measured to provide information on the photosynthesis status as an induced functional response. The non-invasive techniques used in this experiment highlighted an induced response, emerging during the days following the simulated herbivory. R. fruticosus was drastically affected, photosynthesis was disturbed (decreased Fv/Fm) and mortality began on day 5 reaching 100 % less than 1 week later. Physiological parameters were also affected in A. alba (slight decrease of Fv/Fm and lower content of flavonoids), but this species recovered and survived no matter what the stressing treatment was. These results did not point out an efficient repulsive-induced response of A. alba and R. fruticosus to herbivory. The existence of constitutive defences such as prickles (R. fruticosus) or low-digestible tannins (A. alba) is no more efficient to escape from ungulates consumption. Nevertheless, in spite of the increase of the ungulates exponential demography, these two plants do not face rarefaction problem in the French Alps. Thus, survival of A. alba stands is probably linked to the recovery ability of saplings, when R. fruticosus stands maintain themselves thanks to the strong resprouting capacity of this species.

A new method for germination bioassays in allelopathy was evaluated. Inspired by pharmacology, allelochemical quantity to test on different target seeds was calculated according to seeds biometry. The first step consisted in measuring volume, mass, surface and shape of Lactuca sativa and Raphanus sativus seeds. The radish seed mass, surface, volume and contact area biometric parameters were respectively 10, 2, 6 and 1.7 that of lettuce. Two germination bioassay sets were compared: (i) a conventional one, testing the same concentration of allelochemical (2-benzoxazolinone termed as “BOA”) on the two species and, (ii) a biometrics enhanced seed test (“BEST” method), employing quantities of the chemical that were calculated in proportion to seed biometry parameters. The conventional method indicated that 1 mM BOA slowed and decreased germination rate (radish 50 %, lettuce 10 %) whereas 10 and 0.1 μM did not induce any effect. The BEST method offered more differentiated results: applied BOA according to seed volume induced significant inhibition of radish germination (both quantities), while lettuce was only affected by the highest dose. The same occurred when considering grain surface and contact area. Thus, the BEST assay showed more clearly that radish was more sensitive to BOA than lettuce. Compared to a setup with identical test compound concentrations for all tested species, the BEST method provides more differentiated results contributing to a more realistic comparative susceptibility assessment.

Diffuse leucoencephalopathy with axonal spheroids (DLS) is a rare disease affecting the white matter leading to dementia and progressive motor impairment. The neuropathological hallmark includes axonal swelling and spheroids as well as myelin loss. We report a case of a 46-year-old man with memory deficit and behavioral changes followed by a rapid cognitive decline and pyramidal syndrome. Head magnetic resonance imaging showed cortical atrophy of the brain and symmetric corticospinal tract involvement. He died 4 years after the first symptoms. Autopsy was performed and the brain revealed cortical and corpus callosum atrophy, a grayish granular appearance of the white matter and ventricular enlargement. Myelin stains showed a significant demyelination of the centrum ovale and corticospinal tract. Such degeneration was accompanied by axonal loss, axonal swelling, and numerous spheroids. There was no pigment overload or inflammation. We discuss this new DLS case with bilateral, severe, and rapid cortical-spinal involvement.

Mutations in the nebulin gene are the main cause of autosomal recessive nemaline myopathy, with clinical presentations ranging from mild to severe disease. We have previously reported a nonspecific distal myopathy caused by homozygous missense mutations in the nebulin gene in six Finnish patients from four different families. Here we describe three non-Finnish patients in two unrelated families with distal nemaline myopathy caused by four different compound heterozygous nebulin mutations, only one of which is a missense mutation. One of the mutations has previously been identified in one family with the severe form of nemaline myopathy. We conclude that nemaline myopathy and distal myopathy caused by nebulin mutations form a clinical and histological continuum. Nemaline myopathy should be considered as a differential diagnosis in patients presenting with an early-onset predominantly distal myopathy.

Interest in Morvan's disease or syndrome has grown, owing to its close links with various potassium channelopathies. Potassium is crucial for gating mechanisms (channel opening and closing), and especially for repolarization. Defective potassium regulation can lead to neuronal hyperexcitability. There are three families of potassium channels: voltage-gated potassium channels or VGKC (Kv1.1-Kv1.8), inward rectifier K+ channels (Kir), and two-pore channels (K2p). VGK channels are the commonest, and especially those belonging to the Shaker group (neuromyotonia and Morvan's syndrome, limbic encephalitis, and type 1 episodic ataxia). Brain and heart K+ channelopathies are a separate group due to KCNQ1 mutation (severe type 2 long QT syndrome). Kv7 channel mutations (in KNQ2 and KCNQ3) are responsible for benign familial neonatal seizures. Mutation of the Ca+ activated K+ channel gene causes epilepsy and paroxysmal dyskinesia. Inward rectifier K+ channels regulate intracellular potassium levels. The DEND syndrome, a treatable channelopathy of the brain and pancreas, is due to KCNJ1 mutation. Andersen's syndrome, due to KCNJ2 mutation, is characterized by periodic paralysis, cardiac arrythmia, and dysmorphia. Voltage-insensitive K2p channelopathies form a final group.

RESUME L’encephalite limbique est une affection inflammatoire portant theoriquement sur le grand lobe limbique defini en 1878 par Broca, cependant tantot limitee a des lesions de l’hippocampe, tantot comportant des lesions a distance, limbiques ou extra limbiques. Elle se manifeste essentiellement par l’apparition soudaine de troubles de la memoire a court terme, de desordres cognitifs, de crises epileptiques temporales. Des lesions hippocampiques sont souvent detectees par l’imagerie cerebrale. Les causes en sont variees et se sont recemment multipliees. Les premieres connues ont ete des atteintes infectieuses comportant une participation limbique, surtout l’encephalite herpetique. Mais ces caracteres cliniques pathologiques evolutifs ne justifient pas une etude detaillee dans le cadre des encephalites limbiques. Le terme d’encephalite limbique a ete propose pour isoler les encephalites paraneoplasiques parmi les autres encephalites temporales notamment infectieuses. Ont ensuite ete decrits les anticorps onconeuraux, antiHu, ANNA3, antiMa2, antiCV2. Toutefois, ils n’etaient pas detectes dans 40 % des cas. Dans l’ensemble, le pronostic de ces formes etait peu favorable. Les canalopathies potassiques voltage-dependants sont dues a une depolarisation prolongee, elle-meme liee a un depot d’anticorps inactivant les canaux potassiques. Les mutations du gene des sous unites Kv11 et Kv12 sont a l’origine de syndromes entrant dans le groupe Shaker : neuromyotonie, maladie de Morvan, ataxie episodique de type 1, encephalite limbique caracterisee par des troubles psychiatriques, des crises d’epilepsie, une hyponatremie dont la correction associee a l’immunotherapie est tres efficace. Les formes dont les anticorps precedents n’ont pas ete detectes, ont ete alors consideres comme en relation avec les antigenes antineuropile de l’hippocampe. En particulier, la presence d’anticorps antirecepteurs de N-methyl D-aspartate s’accompagne d’une semiologie particuliere et apparait causee par un teratome de l’ovaire chez la femme jeune. Ainsi on a pu proposer la separation d’une part des formes a antigenes intracellulaires, par exemple paraneoplasiques, de mauvais pronostic d’autre part celles a antigenes reagissant avec les membranes cellulaires (canalopathies potassiques, anticorps antineuropile) sensibles a l’immunotherapie et de pronostic favorable. Enfin, les encephalites limbiques revelant une maladie d’Hodgkin sont authentifiees par un certain nombre d’observations dont une personnelle.

Dysferlinopathies belong to the heterogeneous group of autosomal recessive muscular dystrophies. Mutations in the gene encoding dysferlin (DYSF) lead to distinct phenotypes, mainly Limb Girdle Muscular Dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM). Here, we analysed the mutational data from the largest cohort described to date, a cohort of 134 patients, included based on clinical suspicion of primary dysferlinopathy and/or dysferlin protein deficiency identified on muscle biopsy samples. Data were compiled from 38 patients previously screened for mutations in our laboratory (Nguyen, et al., 2005; Nguyen, et al., 2007), and 96 supplementary patients screened for DYSF mutations using genomic DHPLC analysis, and subsequent sequencing of detected variants, in a routine diagnostic setting. In 89 (66%) out of 134 patients, molecular analysis identified two disease causing mutations, confirming the diagnosis of primary Dysferlinopathy on a genetic basis. Furthermore, one mutation was identified in 30 patients, without identification of a second deleterious allele. We are currently developing complementary analysis for patients in whom only one or no disease-causing allele could be identified using the genomic screening procedure. Altogether, 64 novel mutations have been identified in this cohort, which corresponds to approximately 25% of all DYSF mutations reported to date. The mutational spectrum of this cohort significantly shows a higher proportion of nonsense mutations, but a lower proportion of deleterious missense changes as compared to previous series. (c) 2008 Wiley-Liss, Inc.

Resume Introduction La maladie de Pompe atteint classiquement le nouveau-ne avec une evolution rapidement mortelle. Nous rapportons six cas de forme de l’adulte de maladie de Pompe issus de la region du Languedoc-Roussillon. Methode Il s’agit d’une etude retrospective, dans laquelle nous recensons les cas de maladie de Pompe de l’adulte, issus de la region du Languedoc-Roussillon, diagnostiques entre 1975 et 2006 dans les services de neurologie du CHU de Montpellier et de Nimes. Nous decrivons le mode de presentation, l’evolution clinique et la demarche diagnostique. Resultats L’âge moyen de debut etait de 44,3 ans (extreme : 36–60 ans). Les deux symptomes les plus frequemment revelateurs etaient un deficit de la ceinture pelvienne et une atteinte respiratoire. L’evolution a abouti au deces par insuffisance respiratoire dans trois cas. Le deficit en maltase acide fut constamment confirme sur la biopsie musculaire. Discussion La maladie de Pompe de l’adulte doit etre evoquee devant une myopathie des ceintures inexpliquee ou une insuffisance respiratoire inaugurale. La biopsie musculaire et l’analyse enzymatique permettent d’en confirmer le diagnostic. Conclusion Diagnostiquer la forme adulte de maladie de Pompe, cause de myopathie progressive des ceintures, permet de proposer aux patients une prise en charge adaptee, notamment sur le plan respiratoire. Le traitement par enzymotherapie substitutive pourrait etre prometteur dans les formes adultes, mais doit etre valide par des etudes randomisees.

Resume Introduction La paralysie supranucleaire progressive (PSP) se presente habituellement avec une ophtalmoplegie supranucleaire, des chutes, un syndrome parkinsonien, un syndrome pseudobulbaire et des troubles cognitifs. Des presentations atypiques ont ete decrites, sans ophtalmoplegie ou avec mouvements choreiques, mais jamais sans aucun des autres signes habituels de la maladie. Cas clinique Une femme, âgee de 60 ans, consulta pour une agitation nocturne et des mouvements choreiques. Des troubles de deglutition severes par achalasie du sphincter superieur de l’œsophage apparurent quelques mois plus tard, responsables d’episodes recurrents de detresse respiratoire, conduisant a la realisation d’une tracheotomie et d’une gastrostomie. Elle deceda deux ans apres le debut des troubles. L’examen autopsique du cerveau revela la presence d’une taupathie, avec depots de proteine tau phosphorylee anormale formant des fibres tortueuses dystrophiques et des degenerescences neurofibrillaires (DNF) dans le tronc cerebral, le noyau sous-thalamique et l’hippocampe. L’analyse en microscopie electronique des DNF revela la presence de paires de filaments droits, compatibles avec le diagnostic de PSP. Conclusion Ce cas illustre la diversite de presentations cliniques de la PSP. Une partie des symptomes peut etre expliquee par la distribution des anomalies neuropathologiques plus limitees qu’a l’habitude, probablement du fait du deces precoce de la patiente. Les anomalies neuropathologiques precoces de la PSP pourraient apparaitre dans la region dorsale du tronc cerebral.

Resume Introduction Les complications neurologiques aigues ou sub-aigues de l’alcoolisme chronique les plus frequentes sont le delirium tremens, l’encephalopathie hepatique et l’encephalopathie de Gayet-Wernicke. La sclerose laminaire de Morel en est une complication plus rare et mal connue, souvent associee a la maladie de Marchiafava-Bignami. Cas clinique Un homme de 57 ans, ethylique chronique, porteur d’une cirrhose alcoolique presenta dans les suites d’une intervention chirurgicale un syndrome confusionnel. Secondairement, apparurent des troubles mnesiques, des fausses reconnaissances et une crise convulsive, puis il devint mutique et grabataire. L’IRM cerebrale retrouva des anomalies temporo-parietales bilaterales. Le patient deceda 4 mois apres le debut des troubles neurologiques. L’examen neuropathologique retrouva une necrose laminaire corticale sans lesion calleuse, associee a une gliose d’Alzheimer de type II. Conclusion La necrose laminaire corticale peut etre secondaire a une anoxie cerebrale, une vascularite cerebrale ou un accident vasculaire cerebral. Chez l’ethylique chronique, de telles lesions ont ete rapportees sous le terme de sclerose laminaire de Morel. Certains aspects des donnees anatomopathologiques sont atypiques et seront discutes et confrontes aux donnees d’imagerie par IRM, jusque la non reportees dans la sclerose laminaire de Morel.

La presente etude a pour objectifs de connaitre les perceptions des professionnels de sante oeuvrant dans les contextes de fin de vie et de soins palliatifs, quant a l’exposition, la nature, la prevalence, la frequence, l’intensite, les causes, les enjeux, les effets et modes de resolution des conflits survenant dans leurs activites professionnelles ; et de formuler des propositions de politique de sante qui integrent les conflits comme un des determinants de la qualite de soins aux mourants, de la sante de soignants et d’une meilleure gestion des ressources. Une enquete transversale par questionnaire auto-administre a ete menee aupres de 460 professionnels de sante du Valais romand oeuvrant dans les hopitaux, les etablissements medico-sociaux, les centres medico-sociaux, les homes pour personnes âgees et les equipes de soins a domicile, via les directions de leurs institutions respectives. Deux cent trente trois (50.6 %) professionnels de sante ont repondu a l’enquete. Parmi eux, 82.4 % declarent avoir ete confrontes a des situations de conflits en periode de fin de vie. Pour deux tiers des repondants ces conflits ont ete plutot rares durant les douze derniers mois. Leur intensite est percue comme moyenne et haute aupres de 86.1 % de ce collectif. Les conflits de nature medicale et ceux d’ordre ethique apparaissent comme les plus courants selon 74.3 % et 63.6 % des repondants. Les parties qui s’opposent sont davantage les membres de famille entre eux (68.4 %), les infirmieres et les medecins (49.2 %) que les patients et medecins (16 %). A la base de ces conflits, on trouve les problemes de communication, l’ambivalence des acteurs, les differences des valeurs selon environ six et cinq sur dix repondants. Le gaspillage des energies et des ressources ainsi que l’epuisement physique et psychologique sont rapportes comme constituant les effets de ces conflits par 63 % et 52 % de l’echantillon. Les colloques interdisciplinaires, les supervisions internes et les partages d’experience sont les modes et strategies utilises pour resoudre les conflits. Ni l’âge, ni le sexe, ni le lieu de travail, ni encore l’experience professionnelle ou la formation aux soins palliatifs ne sont des discriminants de l’exposition des ces professionnels aux situations des conflits (p > 0.05). Le niveau d’exposition des professionnels de sante a des situations des conflits, la frequence et l’intensite de ceux-ci sont susceptibles d’affecter autant la qualite des soins aux patients, la prise en charge des familles, les objectifs des institutions et leur propre sante, induisant des couts economiques et sociaux eleves pour les communautes. Pour ces differents acteurs ces resultats montrent l’etendue, les effets des conflits et plaident pour une integration de leur prevention et gestion dans les politiques des systemes de sante et d’action sociale.

Introduction The aim of the study was to describe patterns of neuromuscular weakness using a combination of electromyography and histology, and to evaluate functional outcome in patients following complicated cardiovascular surgery. Methods Fifteen adults requiring long-term mechanical ventilation (>15 days) following cardiovascular surgery associated with postoperative complications were prospectively included. Electrophysiological and histological analyses (muscle and nerve) were performed when failure to wean from mechanical ventilation associated with peripheral neuromuscular weakness was noticed. Functional disability was evaluated 12 months after surgery. Results Six patients had a predominantly axonal neuropathy, six presented with myopathy, and three patients had a combination of axonal neuropathy and myopathy. All of them presented with acute tetraparesis and failure to wean from mechanical ventilation. All of the study patients who received corticosteroids exhibited a myopathic pattern (with or without axonopathic changes) but never an axonopathic pattern only. Only two of the eight survivors at 12 months were not ambulatory. These two patients had no detectable compound muscle action potential on electrophysiological examination. Conclusion The combination of electromyographic evaluation and neuromuscular histological abnormalities could help to identify the type and severity of neuromuscular weakness, in turn helping to evaluate the patient's potential functional prognosis.

The inflammatory myopathies include dermatomyositis (DM), polymyositis (PM), and sporadic inclusion-body myositis (s-IBM). In DM, the main immune effector response appears to be humoral and directed against the microvasculature, whereas in both PM and s-IBM, cytotoxic CD8+ T cells and macrophages invade and eventually destroy nonnecrotic muscle fibers expressing major histocompatibility complex class I. The need for more specific and safer therapies in inflammatory myopathies has prompted researchers to better decipher the molecular events associated with inflammation and muscle fiber loss in these diseases. The complex specific migration of leukocyte subsets to target tissues requires a coordinated series of events, namely activation of leukocytes, adhesion to the vascular endothelium, and migration. Cell adhesion molecules (CAM) and chemokines play a major role in this multistep process. In addition, cytokines by stimulating CAM expression and orchestrating T-cell differentiation also influence the immune response. This review focuses on recent advances in defining the molecular events involved in leukocyte trafficking in inflammatory myopathies. Specific topics include a concise summary of clinical features, pathological findings and immunopathology observed in inflammatory myopathies, background information about cytokines, chemokines and cell adhesion molecules, and the expression of these molecules in inflammatory myopathies.

Muscle biopsy findings in DM2 have been reported to be similar to those in DM1. The authors used myosin heavy chain immunohistochemistry and enzyme histochemistry for fiber type differentiation on muscle biopsies. Their results show that DM2 patients display a subpopulation of type 2 nuclear clump and other very small fibers and, hence, preferential type 2 fiber atrophy in contrast to type 1 fiber atrophy in DM1 patients.

Pituicytoma is a rare benign primary tumor of the neurohypophysis, occurring in the sellar and suprasellar spaces. We report here three new cases with immunohistochemical and electron microscopic study. Particular attention was paid to the expression of some cell adhesion molecules. These tumors were characterized by bundles of elongated cells strongly immunoreactive to anti-vimentin, S-100 protein, neural cell adhesion molecule and neuron-specific enolase antibodies. Glial fibrillary acidic protein (GFAP) was not recorded. It expressed the very late antigen alpha2 (VLAalpha2), but not VLAalpha5, and lacked epithelial markers expression (epithelial membrane antigen, E-cadherin), and specific neuronal markers (synaptophysin, chromogranin, neurofilament). Staining for pituitary hormones was negative. At the ultrastructural level, tumor/blood vessel basal lamina and cytoplasmic intermediate filaments were observed but desmosome or pericellular basal lamina were lacking. In one case few secretory granules were recorded. Differential diagnoses include granular cell tumors, pilocytic astrocytomas and spindle cell tumors such as solitary fibrous tumors, fibroblastic meningiomas and schwannomas. However, the unique pattern of antigenic expression and ultrastructural features of pituicytomas distinguish this rare tumor. As a subpopulation of pituicytes (which are distinctive glial cells of the neurophypophysis), some pituicytomas do not expressed GFAP. This suggests that pituicytomas presumably arise from pituicytes at various stages of their differentiation.

Over the past 10 years, the impact of modern microscopic pathology and molecular genetics on the knowledge of myopathies has been enormous. Dysferlinopathy is a good example. Dysferlin is a surface membrane protein without homology with known mammalian protein excepted otoferlin. It is encoded by a gene on chromosome 2. Miyoshi myopathy and limb girdle muscular dystrophy 2B have been reported to arise from defects in the same genetic locus (chromosome 2p 13). Some personal different examples are presented with typical features, high level of creatine kinase. Gene mutations, immunoblot and immunohistochemistry allow the diagnosis. Three clinical phenotypes are separated: distal myopathy, proximal myopathy, entire lower limbs posterior compartment amyotrophy. Structural changes are mild. Inflammation is not unusual and leads to the diagnosis of polymyositis. There are no correlation genotype-phenotype.

Colchicine, a microtubule polymerization inhibitor, can very occasionally induce myopathy. We report two cases of colchicine myopathy. Both patients presented with myalgia and proximal muscle weakness. The first patient, an 80-year-old woman, had chronic renal failure related to renal amyloidosis. She had been treated by colchicine for 4 months. The second, a 75-year-old man with normal renal function, suffering from gout, was treated by colchicine for 3 weeks. Muscle biopsies displayed the same alterations, but the degree of severity was different. Conventional histology revealed vacuolar changes characterized by acid phosphatase-positive vacuoles and myofibrillar disarray foci. The lesions were selective for type I fibers. Ultrastructural study demonstrated autophagic vacuoles. Most of the vacuoles expressed dystrophin but not merosin. Several fibers reacted with anti-MHC class I antibody and granular deposits of membrane attack complex were observed on the surface of numerous myofibers. Anti-αB-crystallin antibody strongly reacted with vacuolar content. Physiopathologically, microtubules are primordial for vesicle movements and colchicine induces autophagic vacuole accumulation by preventing their fusion with lysosomes. The selective type I involvement is probably due to the higher tubulin amount in type I fibers. αB-crystallin overexpression is related to its microtubule protection properties. Moreover, we suggest that vacuoles randomly floating in sarcoplasm might occasionally meet the plasma membrane and open in the extracellular space, leading to complement activation. Accurate diagnosis of colchicine myopathy is relevant because the treatment is based on colchicine interruption.

Intermediate filament (IF) proteins are constituents of the cytoskeleton, conferring resistance to mechanical stress, and are encoded by a dispersed multigene family. In man we have identified two isoforms (180 and 150 kDa) of the IF protein synemin. Synemin α and β have a very short N-terminal domain of 10 amino acids and a long C-terminal domain consisting of 1243 amino acids for the α isoform and 931 amino acids for the β isoform. An intronic sequence of the synemin β isoform is used as a coding sequence for synemin α. Both mRNA isoforms (6.5 and 7.5 kb) result from alternative splicing of the same gene, which has been assigned to human chromosome 15q26.3. Analyses by Northern and Western blot revealed that isoform β is the predominant isoform in striated muscles, whereas both isoforms (α and β) are present in almost equal quantities in smooth muscles. Co-transfection and immunolabeling experiments indicate that both synemin isoforms are incorporated with desmin to form heteropolymeric IFs. Furthermore synemin and desmin are found aggregated together in certain pathological situations.

We report the case of a young patient with neurocutaneous melanosis (NCM) who presented with temporary aphasia and right hemiparesis followed by progressive coma and death. To our knowledge, this is the first case of this disease examined by CT, MRI, angiography and in which an autopsy was performed to assert the diagnosis with histology. Besides, we discuss differential diagnoses and interest of MRI for early diagnosis.

Macrophagic myofasciitis (MMF) is an emerging condition of unknown cause, detected in patients with diffuse arthromyalgias and fatigue, and characterized by muscle infiltration by granular periodic acid-Schiff's reagent-positive macrophages and lymphocytes. Intracytoplasmic inclusions have been observed in macrophages of some patients. To assess their significance, electron microscopy was performed in 40 consecutive cases and chemical analysis was done by microanalysis and atomic absorption spectrometry. Inclusions were constantly detected and corresponded to aluminium hydroxide, an immunostimulatory compound frequently used as a vaccine adjuvant. A lymphocytic component was constantly observed in MMF lesions. Serological tests were compatible with exposure to aluminium hydroxide-containing vaccines. History analysis revealed that 50 out of 50 patients had received vaccines against hepatitis B virus (86%), hepatitis A virus (19%) or tetanus toxoid (58%), 3-96 months (median 36 months) before biopsy. Diffuse myalgias were more frequent in patients with than without an MMF lesion at deltoid muscle biopsy (P < 0.0001). Myalgia onset was subsequent to the vaccination (median 11 months) in 94% of patients. MMF lesion was experimentally reproduced in rats. We conclude that the MMF lesion is secondary to intramuscular injection of aluminium hydroxide-containing vaccines, shows both long-term persistence of aluminium hydroxide and an ongoing local immune reaction, and is detected in patients with systemic symptoms which appeared subsequently to vaccination.

[Ring-U14C] p-hydroxybenzoic acid (POH) translocation during radish germination and early seedling growth was studied to compare two culture conditions (sterile/non-sterile) and two modes of POH extraction (ethanol/oxidizing). Quantification of POH in organs was performed by grinding them in a mortar with ethanol or by combusting them in a biological oxidizer. Comparison of these extraction methods revealed that the oxidizer provides higher POH concentrations than grinding. Uptake and translocation of POH into radish seedlings occured in the first 24 hr with the highest accumulation in cotyledons. POH in cotyledons ranged from 8 to 12.4 μmol g−1 FW. Two forms of POH were found in seedlings, an ethanol-soluble one and a “bound” one. After 96 hr incubation, half of the recovered POH was “bound” in roots and hypocotyls. POH recovery in seedlings was also higher under axenic rather than non-axenic conditions. POH was degraded into 14CO2 by microorganisms under non-sterile cultures, its concentration in culture medium decreased from 10−3 to 10−4 M between the first and the fourth day of incubation. Choice between sterile and non-sterile culture conditions as a method depends on particular research objectives. Non-sterile methods can be used to reflect natural processes whereas sterile methods can be used if the objective is to determine allelochemical penetration and biological effects on target plants.

Aggressive or paradoxical behaviour may reflect an organic dementia. The most frequent is Alzheimer's disease, which results from an abnormal structural conformation of tubulin-associated protein (tau) and beta-amyloid protein that, respectively, aggregate in certain neurons as intracellular neurofibrillary tangles (NFTs) and in the extracellular environment as senile plaques. These lesions progress in the brain tissue according to the stages described by Braak and Braak. Staging of neurofibrillary pathology has proven anatomical and clinical correlation, which can be used in a medico-legal procedure. We report two cases demonstrating discrepancies between anatomical and clinical features, which should encourage medical expert to prudence when interpreting neuropathological reports.

Multiple mitochondrial DNA (mtDNA) deletions have been reported in patients with autosomal dominant and recessive disorders. We studied several affected and one non-affected individuals belonging to a pedigree in which the inheritance of the pathological trait was compatible with an autosomique dominant transmission. Affected members had late-onset multisystem disorders with multiple mtDNA deletions in skeletal muscle. But this family presented a striking difference from previously described cases, because none of the patients had progressive external ophthalmoplegia (PEO). We also studied one young boy with a no contributary family history. He had a cerebellar ataxia with PEO and multiple mtDNA deletions in muscle. Molecular analysis revealed that in the first family, repeated sequences were present at the breakpoint junctions, whereas such motifs were not found in the young patient's case. In the first family, we evidenced mtDNA point mutations in clones containing breakpoint junctions and a 9-bp motif triplication in the intergenic COII/tRNA(Lys) region, whereas this sequence is repeated twice in the wild type mtDNA. Our results suggest that multiple deletions observed in the two pedigrees result from different molecular mechanisms and point out the role of repeated sequences in the first pedigree. No mtDNA repair system has been described in mammals so far, but the molecular abnormalities found in the first family suggest that a defect in an mtDNA repair system, homologous to the E. coli MutHLS pathway, could be responsible for such a phenotype.

Plant-produced phenolic compounds inhibit soil microbial activity and are suspected to be involved in the failure of natural regeneration of French subalpine Norway spruce (Picea abies) forests. This work evaluated relationships between phenolic compounds and soil microorganisms in humus collected in spruce forest during winter and summer seasons. After having identified and quantified different phenolics from humus samples, we incubated another set of humus samples with 10 times the concentration of naturally occurring phenolics, and effects on the density of microorganisms were compared to humus with no addition of phenolic compounds. Furthermore, in order to follow the degradation of phenolic compounds by microbes, the concentration of phenolics in the incubated humus samples was determined by HPLC after three and six days of incubation. The results indicate that humus microorganisms use phenolics as a carbon source, since almost all phenolic compounds had disappeared after six days of incubation. Addition of phenolic compounds to the humus samples also affected the soil microbial populations so that bacteria were inhibited in the humus collected both in the winter and in the summer. However, there were differences between the experiments. Fungi and cellulose hydrolyzers were stimulated in the winter humus experiment, while fungi were unaffected and cellulose hydrolyzers were inhibited in the summer experiment. The addition of phenolic compounds stimulated ammonifiers in the summer experiment. We anticipate that the role of soil microorganisms in the problem of natural regeneration failure is probably more important than previously thought.

Allelopathy due to humus phenolics is a cause of natural regeneration deficiency in subalpine Norway spruce (Picea abies) forests. If inhibition of spruce germination and seedling growth due to allelochemicals is generally accepted, in contrast there is a lack of knowledge about phenolic effects on mycorrhizal fungi. Thus, this work tested effects of a humic solution and its naturally occurring phenolics on the growth and respiration of two mycorrhizal fungi: Hymenoscyphus ericae (symbiont of Vaccinium myrtillus, the main allelochemical-producing plant) and Hebeloma crustuliniforme (symbiont of P. abies, the target plant). Growth and respiration of H. crustuliniforme were inhibited by growth medium with the original humic solution (−6% and −30%), respectively, whereas the same humic solution did not affect growth but decreased respiration of H. ericae (−55%). When naturally occurring phenolics (same chemicals and concentrations in the original humic solution) were added to the growth medium, growth of H. crustuliniforme was not affected, whereas that of H. ericae significantly increased (+10%). We conclude that H. ericae is better adapted to the allelopathic constraints of this forest soil than H. crustuliniforme and that the dominance of V. myrtillus among understory species could be explained in this way.

Sorghum bicolor is an allelopathic crop that reduces the yield of succeeding crops. We have assessed its effect on the germination, emergence, and seedling growth of Arachis hypogea sown in soil that had had a prior sorghum cropping. A. hypogea was sown on rows and interrows of a previous sorghum crop in 1997 and 1998 in Senegal. Seedling establishment (germination rate and seedling weight) was better between rows than on rows of the previous crop. The highest concentrations of phenolic compounds occurred in the rows in 1998, while contents of row and interrow soils were similar in 1997. Vanillic acid was the main component of the six chemicals found in 1997 soils, whereas the 1998 soil samples contained mainly p-hydroxybenzoic acid, p-hydroxybenzaldehyde, vanillic, and p-coumaric acids (10 phenolics identified). The germination of peanut seeds in water (control), soil water extracts, and mixtures of pure phenolics (equivalent to those in 1997 and 1998 soil samples) was tested. All extracts inhibited germination compared to controls, but there was no significant difference among treatments, i.e., the inhibition was the same for seeds in soil solutions and those in the respective phenolic mixtures. Similarly, there were no significant differences among the germination rates in soil water extracts of rows and interrows or in the pure phenolic mixtures of rows and interrows. We propose a geometrical sowing pattern for peanuts between the rows of the previous sorghum crop to escape the latter's "allelopathic heritage."

Lethal injection of potassium chloride (KCl) can be used as a method of either suicide or homicide. As biological tests are still inadequate to differentiate endogenous from exogenous potassium, at the scene of death the cause can only be suspected. We wished to determine the usefulness of conventional pathological examination in this context and carried out a study in four fetuses after medical termination of pregnancy for serious disease. Pregnancy was terminated by KCl injection in two cases and by injection of lidocaine and sufentanil in the other two cases. In each of the two fetuses in which KCl injection was performed, macroscopic examination showed whitish deposits on the tissues and histological examination showed clumps of lanceolate crystals in the internal organs. In the two fetuses which received lidocaine and sufentanil injection, no deposits were visible on macroscopic examination and no crystals were seen on histological examination. These findings suggest that pathological study may have useful applications in forensic medicine when death by potassium injection is suspected.

We report a recent case of the severe congenital variant of glycogen storage disease type IV with prolonged survival. The patient was found to be a compound heterozygote for two novel mutations, a missense mutation in exon 5 (p.H188P, c.563A>C) and a severe mutation in intron 5 (c.691+2T>C). We propose that the genotype and the quality of medical care may account for the severe but non-lethal phenotype.

The idiopathic inflammatory myopathies (IIM), including dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM), are a group of autoimmune diseases characterized by the recruitment of lymphocytes and monocytes to the site of affection. The mechanism for recruitment of these cells likely involves chemokines. The monocyte chemoattractant protein-1 (MCP-1), a chemoattractant to T lymphocytes and monocytes, may play an important role in the pathogenesis of IIM. Frozen muscular tissues were obtained from eight cases of DM, five PM, and four IBM. We investigated the MCP-1 expression by the reverse transcription -PCR technique, immunohistochemistry and in situ hybridization. MCP-1 mRNA was markedly expressed in all the IIM cases. Greater amounts of MCP-1 mRNA were observed in DM, and in situ hybridization showed MCP-1 mRNA accumulation in perivascular mononuclear cells. Immunohistochemistry showed MCP-1 expression in vessels (endothelial cells and walls of veins and arteries) in all IIM cases. Very few mononuclear cells in DM perivascular infiltrates expressed MCP-1, whereas in PM and IBM, it was strongly expressed by mononuclear cells partially invading non-necrotic muscle fibers. These findings suggest that MCP-1 can contribute to the inflammatory response by attracting monocytes and T lymphocytes to sites of cell-mediated immune injury. The morphological characteristics and distribution of positive cells indicate that macrophages, lymphocytes, and endothelial cells previously reported to produce MCP-1, contribute to its production in IIM lesions.

Summary Background An unusual inflammatory myopathy characterised by an infiltration of non-epithelioid histiocytic cells has been recorded with increasing frequency in the past 5 years in France. We reassessed some of these cases. Methods We did a retrospective analysis of 18 such cases seen in five myopathology centres between May, 1993, and December, 1997. The myopathological changes were reassessed at a clinopathology seminar. Findings Detailed clinical information was available for 14 patients. The main presumptive diagnoses were polymyositis and polymyalgia rheumatica. Symptoms included myalgias in 12 patients, arthralgias in nine, muscle weakness in six, pronounced asthenia in five, and fever in four. Abnormal laboratory findings were occasionally observed, and included raised creatine kinase concentrations, increased erythrocyte sedimentation rate, and myopathic electromyography. Muscle biopsy showed infiltration of the subcutaneous tissue, epimysium, perimysium, and perifascicular endomysium by sheets of large macrophages, with a finely granular PAS-positive content. Also present were occasional CD8 T cells, and inconspicuous muscle-fibre damage. Epithelioid and giant cells, necrosis, and mitotic figures were not seen. The images were easily distinguishable from sarcoid myopathy and fasciitis-panniculitis syndromes. Whipple's disease, Mycobacterium avium intracellulare infection, and malakoplakia could not be confirmed. Ten patients were treated with various combinations of steroids and antibiotics; symptoms improved in eight patients, and stabilised in two. Interpretation A new inflammatory muscle disorder of unknown cause, characterised by a distinctive pathological pattern of macrophagic myofasciitis, is emerging in France.

Charcot-Marie-Tooth disease type 1A is most commonly caused by a duplication of a 1.5 Mb region of chromosome 17 which includes the peripheral myelin protein 22 gene (PMP22). Over-expression of this gene leads to a hypomyelinating/demyelinating neuropathy and to severely reduced nerve conduction velocity. Previous mouse and rat models have had relatively high levels of expression of the mouse or human PMP22 gene leading to severe demyelination. Here we describe five lines of transgenic mice carrying increasing copies of the human PMP22 gene (one to seven) and expressing increasing levels of the transgene. From histological and electrophysiological observations there appears to be a threshold below which expression of PMP22 has virtually no effect; below a ratio of human/mouse mRNA expression of approximately 0.8, little effect is observed. Between a ratio of 0.8 and 1.5, histological and nerve conduction velocity abnormalities are observed, but there are no behavioural signs of neuropathy. An expression ratio >1.5 leads to a severe neuropathy. A second observation concerns the histology of the different lines; the level of expression does not affect the type of demyelination, but influences the severity of involvement.

The Stüve-Wiedemann syndrome (SWS) comprises short stature, congenital bowing of the long bones, respiratory distress, and recurrent episodes of unexplained hyperthermia. The skeletal radiographic changes include short and broad long bones, large metaphyses, internal cortical thickening, and angulation primarily of tibiae and femora, but also of humeri and forearm bones. We report 3 cases of SWS from 2 different unrelated consanguineous gypsy families. All 3 cases fulfilled the clinical and radiological criteria of SWS. Two patients died shortly after birth, whereas the third one was alive at the age of one year. Besides hyperthermic episodes, one patient had hyperaminoaciduria, hepatic failure, and megaloblastic anemia which prompted us to investigate mitochondrial respiratory chain in 2 cases. Abnormal results consisting of decreased activities of complex I and IV were found in both. The simultaneous occurrence of both SWS phenotype and abnormal mitochondrial metabolism in two unrelated cases strongly supports the hypothesis of a pathogenetic relationship between the two events. These cases may also be related to recent reports on the effects of the mitochondrial respiratory chain defects on embryogenesis.

31-P MR spectroscopy has been used to investigate metabolic events surrounding muscular contraction in a patient with an unusual myopathy characterized by clinical signs of muscle stiffness and swelling after prolonged exercise. Histological assays demonstrated a predominance of type II fibers with tubular aggregates. These structures had low calcium content although calcium-ATPase protein was present. Metabolic measurements were normal at rest except for the presence of a marked signal in the phosphodiester region which could reflect membrane abnormalities. Exercise-induced PCr consumption was in the normal range but the extent of the related intracellular acidosis was abnormally large. Kinetics of PCr and PCr/Pi ratio post-exercise recovery were delayed, but were likely to reflect the effect of the very low end-of-exercise pH rather than an aerobic deficiency. Finally, proton efflux from muscle to bloodstream, measured during the initial recovery period, was delayed, indicating altered mechanisms of proton handling. The most prominent metabolic abnormality recorded is the large glycogenolysis-induced pH decrease which might be linked to either abnormal activation of glycogenolysis and/or impaired proton and lactate handling within the muscle. The association between tubular aggregates and hyperacidosis is of interest but the exact causal relationship remains to be elucidated.

CD24 is a glycoprotein with an unusual structure consisting of a small protein core extensively glycosylated and linked to the outer surface of the plasma membrane by a glycosylphosphatidylinositol (GPI) lipid anchor. Its murine homolog mCD24 is transiently expressed during the development and differentiation of the hematopoietic and neural cell lineages. We have searched for the expression of CD24 in the developing and in the mature human brain as well as in a wide range of neuroectodermal tumors. Neuroblastomas, a subgroup of tumors able to maturate from undifferentiated features towards mature ganglioneuromas, were more extensively studied. Immunohistochemical studies demonstrated that CD24 is transiently expressed by neurons during human brain development. In neuroectodermal tumors, CD24 is a marker of neuronal tumors. Furthermore, in neuroblastomas, CD24 expression decreases as tumors differentiate. In non-neuronal neuroectodermal tumors, CD24 expression is mostly absent. When present, it correlates with the emergence of anaplastic histological features. Reverse transcriptase -polymerase chain reaction (RT-PCR) demonstrated the presence of an unique transcript identical in both hematopoietic, developing and tumoral nervous tissue. RT-PCR and in situ hydridization techniques showed that CD24 expression is transcriptionally regulated. Interestingly, Western blot analysis demonstrated differential CD24 isoforms according to the tissue (hematopoietic versus nervous), the differentiation status, and the origin of neuroblastomas likely reflecting variations in the extent of glycosylation. This indicates an additional level of regulation of CD24 involving post-translational modifications.

Expression of some developmentally regulated cytoskeleton components (desmin, vimentin and myosin heavy chain isoforms) and cell surface proteins (including neural cell adhesion molecule (NCAM), its polysialylated (PSA) isoform and CD24) have been studied by immunohistochemical detection in a series of 23 infantile spinal muscular atrophies (SMA). According to the clinical classification established by Byers and Banker in 1961, 8 cases were type I SMA (Werdnig-Hoffmann's disease), 10 cases were type II (intermediate form), and 5 cases were type III (Kugelberg-Welander's disease). In 15 cases, the percentage of immunoreactive fibers with the various antibodies used has been quantified and the results correlated with clinical data. The aim of the study was to search for variations in the pattern of expression of the proteins to improve the accuracy of diagnosis and prognosis, and to gain an understanding of the pathological processes involved in SMA. The results showed that the pattern of expression of these cytoskeleton and cell surface proteins is abnormal in all types of SMA. However, it was strikingly different in type I and II SMA as opposed to type III. In type I and II SMA, strong NCAM and developmental myosin heavy chain (MHC) expression was observed in atrophic fibers. Numerous atrophic fibers co-expressed desmin and vimentin as well as slow and fast adult MHC. Very few of them expressed PSA NCAM, fetal MHC and CD24. In type III SMA, the number of fibers expressing NCAM, developmental MHC and co-expressing slow and fast adult MHC was low and virtually none of them expressed vimentin or desmin. These findings are in favor of a denervation process occurring very early in life, probably even in utero, in type I and II SMA and leading to a severe impairment of muscle fibers maturation. In contrast, in type III SMA, the process is initiated well after birth and affects mature muscle fibers. In all types of SMA, the ability of muscle fibers to regenerate is low, although some fibers may be reinnervated. Immunohistochemical data was not related to the patients follow-up and thus has no prognostic value.

Sirs: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently discovered inherited disorder that usually leads to cerebrovascular manifestations in mid-adulthood [9]. We report a late-onset sporadic case of genetically proven CADASIL with an atypical pattern of progressive cognitive deterioration. A 61-year-old right-handed male was referred with a five-year history of progressive neurological decline characterized by apathy, cognitive impairment, gait difficulties and urinary incontinence. He reported no history of migraine and had no cerebrovascular risk factor including high blood pressure. Family history was negative for migraine, stroke, dementing illness or epilepsy. His father died at age 90 from heart disease. His mother had suffered from an unspecified gait disorder and died at age 82 from a non-neurological cause. The patient had no siblings and was the father of a healthy 37 year-old woman. Clinical symptoms had begun 5 years before with cognitive slowing and personality changes marked by decreased interest and depression. Two years later, he was noted to have attentional difficulties, depressed mood and slight gait slowing. On neurological examination, gait was slow and unsteady. He showed mild facial and limb hypokinesia but no rigidity. Reflexes were brisk in upper and lower limbs, and cutaneous plantar responses were flexor. A global intellectual deterioration was observed (WAIS-R IQ: 69 with performance IQ: 57 and verbal IQ: 79) [11]. Detailed neuropsychological assessment (Table 1) revealed preserved episodic memory, attentional and executive functioning impairment and the presence of interhemispheric disconnection features. Examination of upper limbs ideomotor praxis revealed marked left hand impairment, while gestures were adequately performed with his right hand. He displayed left hand agraphia, which was characterized by scrawl or no response. Tactile naming of objects placed in his left hand was severely impaired and dichotic listening showed complete left ear extinction. Cranial MRI was performed with a 1.5 T unit (Siemens Magnetom Symphony). Images covered the whole brain and were obtained in the coronal plane for T1, T2 and FLAIR, and also in the sagittal plane for T1. Images were reviewed by two neurologists unaware of the clinical findings. Lesions equivalent to the signal characteristics of cerebrospinal fluid (CSF) on T1weighted images and > 3 mm in diameter, as well as wedge-shaped corticosubcortical lesions, were regarded as brain infarcts [6]. Brain MRI revealed no infarcts as had been suggested, in particular in the basal ganglia-thalami region. It showed diffuse, symmetric and confluent white matter hypersignals on T2-weighted images, contrasting with mild signal abnormalities on T1 images. The temporal poles were relatively spared, and the corpus callosum appeared abnormally thin. Diffuse cortical and subcortical atrophy was also evident (Fig. 1). Laboratory evaluation showed a normal chemistry survey, complete blood count, sedimentation rate, fibrinogen level, C-reactive protein, serum protein and lipoprotein electrophoresis, thyroid function tests, vitamin B12, folates and urinalysis. Human immunodeficiency virus, TPHA and VDRL testings, LETTER TO THE EDITORS

International audience; no abstract

Investigations were conducted to determine whether the allelopathic effect (inhibition of oxygen consumption) of mull- and mor-type humic solutions on ectomycorrhizal fungi was due to the solutions' phenolic contents. In the first experiment, two concentrations (10(-3) M and 10(-7) M) of binary equimolar phenolic mixtures were tested on the oxygen consumption ofLaccaria laccata andCenococcum graniforme. The high concentrations of most of the mixtures induced an increase of fungal respiration, whereas the 10(-7) M treatments all reduced the rate of respiration. In the second experiment, the effects on respiration of the phenolic mixture reproducing mull- and mortype humic solutions were compared with the effects of natural humic solutions. The resulting data suggest that allelopathic effect of humic solutions can at least in part be attributed to their phenolic contents.

Summary Growth of Cenococcum geophilum and Laccaria laccata was measured in presence of four phenolic acids. Main results showed that these phenols inhibited or stimulated the two fungi mycelial growth, according to the kind of substance and its concentration. L. laccata was more affected than C. geophilum.

International audience; MFN2 and OPA1 genes encode two dynamin-like GTPase proteins involved in the fusion of the mitochondrial membrane. They have been associated with Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy, respectively. We report a large family with optic atrophy beginning in early childhood, associated with axonal neuropathy and mitochondrial myopathy in adult life. The clinical presentation looks like the autosomal dominant optic atrophy 'plus' phenotype linked to OPA1 mutations but is associated with a novel MFN2 missense mutation (c.629A>T, p.D210V). Multiple mitochondrial DNA deletions were found in skeletal muscle and this observation makes MFN2 a novel gene associated with 'mitochondrial DNA breakage' syndrome. Contrary to previous studies in patients with Charcot-Marie-Tooth disease type 2A, fibroblasts carrying the MFN2 mutation present with a respiratory chain deficiency, a fragmentation of the mitochondrial network and a significant reduction of MFN2 protein expression. Furthermore, we show for the first time that impaired mitochondrial fusion is responsible for a deficiency to repair stress-induced mitochondrial DNA damage. It is likely that defect in mitochondrial DNA repair is due to variability in repair protein content across the mitochondrial population and is at least partially responsible for mitochondrial DNA instability.

A novel myopathy characterized by hexagonally cross-linked tubular arrays has been reported in five patients. We studied the clinical and histopathological features of five additional unrelated patients with this myopathy. Patients experienced exercise intolerance with exercise-induced myalgia and weakness, without rhabdomyolysis. One patient additionally presented mild permanent pelvic girdle muscle weakness. Age at onset varied between 13 and 56 years. The inclusions were eosinophilic on H and E, bright red with modified Gomori’s trichrome stains, present in type 2 fibers, and revealed immunoreactivity selectively for a caveolin-3-antibody. Ultrastructurally, the inclusions showed a highly organized, hexagonally cross-linked crystalloid structure. Mutations in the caveolin-3 encoding gene were excluded. Biochemical assessment of glycogenolysis in muscle was normal. Inherited or sporadic myopathy with hexagonally cross-linked tubular arrays is associated with a homogeneous clinical and histopathological phenotype. This myopathy should be included in the differential diagnosis of patients with exercise intolerance and myalgia.