Résumé
Since Willis described 'fatigable weakness' in 1672, most physicians consider it as a kind of hysteria due to the inconsistent fluctuation of symptoms. Erb presented three cases of 'bulbal palsy' in the 1870s, and Oppenheim and Hopper considered myasthenia gravis as a disease similar to curare poisoning and as a disease induced by attack of the motor centers by intrinsic toxins, respectively. In 1903, Elliot suggested that a 'chemical substance' mediates the nerve impulses at synapse. However, it was not until 1921 that this was demonstrated by Loewi, who provided evidence from the famous two-frog-hearts experiment. Dale later revealed the substance to be acetylcholine, and he also suggested that myasthenia gravis is due to a problem with the motor end plate. In 1934, Walker was prompted by the resemblance between myasthenia gravis and curare poisoning to apply physostigmine, a curare-poisoning antidote, to a patient, which produced a dramatic result. Since then the use of anticholinesterase inhibitors has been adopted for standard therapeutic modality. Some prominent surgeons have also applied thymectomy as a surgical modality. The most recent focus of myasthenia gravis has been immunological. In 1960, Simpson proposed the autoimmune hypothesis, and Chang et al. showed that snake venom contained a selective antagonist of the nicotinic acetylcholine receptor, alpha-bungarotoxin. The immunization of rabbits with acetylcholine receptor purified from the electrical organs of electric eels by Patrick et al. induced myasthenic symptoms and signs, and these were reversed by acetylcholinesterase inhibitors. The role of the autoimmune system has led to the introduction of an immunosuppressive modality and plasma exchange to the field of clinical neurology.
Sujets)
Humains , Lapins , Acétylcholine , Potentiels d'action , Bungarotoxines , Anticholinestérasiques , Curare , Electrophorus , Histoire de la médecine , Hystérie , Immunisation , Plaque terminale motrice , Myasthénie , Physostigmine , Échange plasmatique , Récepteurs nicotiniques , Venins de serpent , Synapses , ThymectomieRésumé
The binding of interleukin-6 (IL-6) cytokine family ligands to the gp130 receptor complex activates the Janus kinase (JAK)/ signal transducer and activator of transcription 3 (STAT3) signal transduction pathway, where STAT3 plays an important role in cell survival and tumorigenesis. Constitutive activation of STAT3 has been frequently observed in many cancer tissues, and thus, blocking of the gp130 signaling pathway, at the JAK level, might be a useful therapeutic approach for the suppression of STAT3 activity, as anticancer therapy. AG490 is a tyrphostin tyrosine kinase inhibitor that has been extensively used for inhibiting JAK2 in vitro and in vivo. In this study, we demonstrate a novel mechanism associated with AG490 that inhibits the JAK/STAT3 pathway. AG490 induced downregulation of gp130, a common receptor for the IL-6 cytokine family compounds, but not JAK2 or STAT3, within three hours of exposure. The downregulation of gp130 was not caused by enhanced degradation of gp130 or by inhibition of mRNA transcription. It most likely occurred by translation inhibition of gp130 in association with phosphorylation of the eukaryotic initiation factor-2alpha. The inhibition of protein synthesis of gp130 by AG490 led to immediate loss of mature gp130 in cell membranes, due to its short half-life, thereby resulting in reduction in the STAT3 response to IL-6. Taken together, these results suggest that AG490 blocks the STAT3 activation pathway via a novel pathway.
Sujets)
Humains , Membrane cellulaire , Survie cellulaire , Transformation cellulaire néoplasique , Régulation négative , Stress du réticulum endoplasmique , Période , Interleukine-6 , Kinase Janus-2 , Ligands , Phosphorylation , Phosphotransferases , Biosynthèse des protéines , Protein-tyrosine kinases , ARN messager , Transduction du signal , Facteur de transcription STAT-3 , TyrphostinesRésumé
BACKGROUND & PURPOSE: Subcortical aphasia is derived from infarction, hemorrhage or tumor in subcortical area, such as striatocpsular region, thalamus, paraventricualr white matter and corona radiata. To our knowledge, there have been few studies on subwrtical aphasia in Korea. OBJECTIVE: 1) To evaluate various lesion sites and clinical features associated with subcortical aphasia. 2) To evaluate type and characteristics of subcortical aphasia by Modified Western Aphasia Battery(MWAB) test. 3)To predict the mechanisms of subcortical aphasia and to relate type of aphasia to hypoperfusion are a ascertained by brain SPECT. METHODS: We analysed 19patients wing brain CT/MRI and neurolinguistical method of MWAB, who presented language disturbance of aphasic nature due to subcortical strokes. Cerebral blood flow was measured in 10 out of 19 patients using brain SPECT. RESULTS & CONCLUSION: 1) The lesion sites responsible for subcortical aphasia were caudate nucleus, putamen, internal capsule, thalamus, paraventricular white matter and corona radiata. Hemiparesis and dysarthria were more common in subcortical aphasia than in cortical one. 2) Subcortical aphasia was characterized by higher incidence of anomic type and more rapid recovery than cortical aphasia. Most subcortical aphasia following thalamic lesions revealed characteristic features of Preservation of repetition and prominent deficits in naming. 3) Ten cases of subcortical aphasia showed both cortical and subcortical hypoperfusion, suggesting that subcortical aphasia be derived from secondary hypoperfusion of the cortical language area. In most of the patients, the types and severity of subcortical aphasia correlated with the location and extent of cortical hypoperfusion area.
Sujets)
Humains , Aphasie , Encéphale , Noyau caudé , Dysarthrie , Hémorragie , Incidence , Infarctus , Capsule interne , Corée , Parésie , Putamen , Accident vasculaire cérébral , Thalamus , Tomographie par émission monophotoniqueRésumé
OBJECTIVE : We investigated the relationship between the severity of the disease and the abnormality of some ocular movements in parkinson's disease. BACKGROUND: Disorders of eye movements have been described in diseases of the basal ganglia for over a century and ocular motor deficits of the saccadic and pursuit system have been reported in parkinsonian patients. METHOD : We studied the electro-oculography of the eye tracking and saccadic movement in 26 patients (11 males, 15 females) with Parkinson's disease. The severity of the disease was divided into two groups by Hoehn & Yahr(H-Y) staging, H-Y stage 1, 2(group A) and H-Y stage 3, 4 (Group B). Some patients antiparkinsonian drugs of L-dopa, dopamine agonist and anticholinergics. RESULT : The velocity of smooth pursuit and the velocity and latency of saccade were calculated and compared between two groups. Eye tracking test revealed decreased pursuit velocity leading to catch-up saccades, but normal phase relationship between eye and target movement, while saccadic eye movement had increased latency. These results showed more profound severity in more advanced stages of the disease. CONCLUSION : We suggest that ocular movement be often chosen as a simple but relevant example of general motor function, as well as criteria for staging of Parkinson's disease and basal ganglia play significant role in ocular movement.
Sujets)
Humains , Mâle , Noyaux gris centraux , Antagonistes cholinergiques , Agonistes de la dopamine , Mouvements oculaires , Lévodopa , Maladie de Parkinson , Poursuite oculaire , SaccadesRésumé
Since cyanide poisoning is almost always fatal, reports of surviving patients to develop neurologic signs are rare. Systemic hypoxemia was not documented with arterial blood gases : however, significant tissue hypoxia most likely occurred from the action of cyanide. A38-year-old man ingested cyanide in a suicidal attempt. He was treated and survived the poisoning episode. But one week later, he showed classic extrapyramidal symptoms and signs, characterized by pit disturbance, bradykinesia, increased muscle tone, micrographia, tremor, apraxia of eyelid opening, palilalia. These symptoms and signs continued to progress, and response to levo-dopa and anticholinergics was poor, except apraxia of eyelid opening. About 3 months later, brain MRI showed abnormal signals (increas ed signal intensity on T2WI, decreased signal intensity on TIWI) in both globus pallidus and a part of putamen, but hippocompus and substantia nigra was normal. After 16 months, follow-up brain MRI showed the same findings. Although brainstem auditory evoked potential(BAEP) was normal, motor evoked potential(MEP) showed prolongation of central motor conduction time(CMCT) in right upper and lower extremities, then wecould suspect subtle changes in pyramidal tract. We report a patient as cyanide-induced parkinsonism by history, neuroimaging finding, and clinical parkinsonian symptoms and signs.
Sujets)
Humains , Hypoxie , Apraxies , Encéphale , Tronc cérébral , Antagonistes cholinergiques , Paupières , Études de suivi , Gaz , Globus pallidus , Hypocinésie , Membre inférieur , Imagerie par résonance magnétique , Neuroimagerie , Manifestations neurologiques , Syndromes parkinsoniens , Intoxication , Putamen , Tractus pyramidaux , Substantia nigra , TremblementRésumé
Ataxic hemiparesis is a stroke syndrome in which the main features are unusual combination of weakness and cerebellar-like ataxia involving the limb on the same side. We describe an analysis of 17 patients with ataxic hemiparesis who underwent magnetic resonance imaging or computed tomography. Ten patients had lacunar infarction in the contralateral pons. In six, lesions were found in the contralateral thalamus and the posterior limb of internal capsule. In one patient, infarct was located in the contralateral midbrain, They showed different clinical manifestations depending on the sites of lesion. This study may suggest that variable sites of lesion can cause ataxic hemiparesis and different clinical manifestations.
Sujets)
Humains , Ataxie , Membres , Capsule interne , Imagerie par résonance magnétique , Mésencéphale , Parésie , Pont , Accident vasculaire cérébral , Accident vasculaire cérébral lacunaire , ThalamusRésumé
Lacune is small infarct located in the deeper part of the brain and developed by occlusion of small branch of the large cerebral arteries. It occupies 10-30% of infarction in western countries but 53.1% in our study. We investigated 181 cases of lacunar infarction confirmed by clinical features and neuroimaging study. We analyzed lacunar stroke into 13 groups of symdrome based on the clinical features. The frequent lacunar syndromes were pure motor stroke (35.4%), sensori-motor stroke (26.5%), ataxic hemiparesis (11.6%), and pure sensory stroke (6.1%). The frequent sites for lacune were pons (25.4%), corona radiata (24.9%), and thalamus (18.2%). The major contributing risk factors were hypertension (65.8%) and diabetes (19.3%). The incidence of multiple lacune was 67.4%. The determining factor for clinical presentation of lacune was not the size of lesion but the location of lesion.