Dissertations / Theses on the topic 'Lambert-Eaton'

Dans le systeme nerveux central, les canaux calcium dependant du potentiel assurent des fonctions essentielles comme, par exemple, le couplage excitation-secretion. Ils sont classes en quatre sous-types n, l, p et t, d'apres leurs proprietes electrophysiologiques et pharmacologiques. Le sous-type l ou recepteur dihydropyridine (dhp), qui est le plus abondant dans le muscle squelettique, est le mieux caracterise structuralement. Le sous-type n, ou recepteur de l'omega-conotoxine, est represente presque exclusivement dans le systeme nerveux central et sa caracterisation structurale fait l'objet de nombreux travaux actuellement. L'implication respective des trois sous-types n, l et p dans la liberation de neurotransmetteurs a ete demontree dans differents modeles neuronaux ou neuroendocrines. Le syndrome myasthenique de lambert-eaton (lems) est une perturbation de la transmission neuromusculaire, d'origine auto-immune, associee a une diminution de la liberation d'acetylcholine. Le cancer du poumon a petites cellules (sclc) est une tumeur frequemment associee au lems. Les immunoglobulines g (igg) des serums des patients lems induisent une diminution du nombre de canaux calcium fonctionnels et immunoprecipitent specifiquement le recepteur de l'omegaconotoxine. Les resultats les plus importants, presentes ici, peuvent se resumer en deux points. D'une part, nous avons demontre la presence d'autoanticorps, dans le serum des patients lems, diriges contre la synaptotagmine, une proteine des vesicules synaptiques. Nous avons egalement demontre, a l'aide d'un anticorps monoclonal anti-synaptotagmine, que la synaptotagmine est associee au recepteur de l'omegaconotoxine. Cette interaction doit etre importante pour l'amarrage des vesicules synaptiques a proximite de leur site de liberation dans les terminaisons presynaptiques. Nous proposons que l'interaction des auto-anticorps des patients lems avec la synaptotagmine soit impliquee dans l'etiologie du lems. D'autre part, nous avons demontre l'expression concomitante du recepteur de l'omegaconotoxine, de la synaptotagmine et de la syntaxine, une proteine specifique des terminaisons nerveuses, dans un certain nombre de lignees sclc. Nous faisons l'hypothese que l'expression de la synaptotagmine dans ce tissu neoplasique est a l'origine de la reponse autoimmune

Lambert-Eaton myasthenic syndrome is a rare paraneoplastic and autoimmune disorder affecting the presynaptic voltage gated calcium channels at the neuromuscular junction. The aim of this project was to isolate the genes coding for the α1 and α2 subunits of the voltage-gated calcium channel from hybrid neuronal cell lines including NG108-15 whose potassium stimulated ⁴⁵Ca²⁺ flux is reduced by IgG from patients with Lambert-Eaton myasthenic syndrome. The cDNA libraries were constructed in λgt10 from NG108-15 mRNA and screened with PCR products derived from the rabbit skeletal muscle α1 and α2-δ genes. A 2230 bp portion of the NG108-15 α2-δ gene homologous to bp 1000- 3304 of the rabbit gene has been isolated and sequenced. This shows 48% homology to the amino acid sequence of the rabbit gene and 56% nucleotide homology with particular conservation of the C-tenninal domains. The NG108-l5 α2 mRNA is 8.5 kb long and was found in the N18TG2 mouse neuroblastoma cell line from which NG108-15 is derived and in mouse brain. Rabbit α2-δ gene PCR primers were used to screen a rodent tissue cDNA panel to detect highly homologous sequences by PCR amplification. These products were detected only in mouse brain and lung and in rat skeletal muscle. The mouse brain and lung product amino acid sequences were 87% homologous to the rabbit gene while the rat skeletal muscle product was 81% homologous and both differed significantly from the homologous region of the NG108-15 gene. This suggests that some of the diversity of voltage gated calcium channels arises from the expression of different α2-δ subunits within the 5 subunit VGCC complex as well as from diversity in the other subunits.

Trabalho final de mestrado integrado em Medicina (Fisiopatologia), apresentado á Faculdade de Medicina da Universidade de Coimbra
Os tumores neuroendócrinos constituem um grupo heterogéneo de neoplasias com diferentes apresentações clínicas e taxas de crescimento. Estes tumores têm a capacidade de produzir e libertar moléculas bioativas e em cerca de 8% dos casos causam diferentes síndromes paraneoplásicos. Os síndromes paraneoplásicos surgem quando estão presentes sinais e sintomas não atribuíveis à compressão direta ou invasão do tumor e manifestam-se principalmente pela secreção ectópica de hormonas (síndromes hormonais) ou pela imunidade por reatividade cruzada entre o tumor e os tecidos normais do paciente (síndromes neurológicos). O desenvolvimento de um síndrome paraneoplásico não se correlaciona necessariamente com o estadio do tumor, dessa forma, o reconhecimento da presença destes síndromes pode levar ao diagnóstico precoce de uma neoplasia não suspeitada e permitir o tratamento em fases mais iniciais com provável melhor prognóstico para o doente. Além disso, os síndromes paraneoplásicos são úteis no seguimento e monitorização do curso clínico e da doença subjacente. Com a incidência destes tumores a aumentar a uma taxa de 3-10% por ano, é de esperar que a prevalência dos síndromes paraneoplásicos secundários aos tumores neuroendócrinos também aumente. A apresentação clínica, a cintigrafia com 111In-ocreótido e a cromogranina A têm contribuído substancialmente para a sua identificação. Este artigo de revisão relata os síndromes paraneoplásicos comuns e incomuns secundários a tumores neuroendócrinos, fornece informação sobre a sua fisiopatologia, apresentação clínica, métodos diagnósticos e prognóstico e identifica caraterísticas que os distinguem de síndromes de hipersecreção hormonal eutópica.
Neuroendocrine tumors comprise a heterogeneous group of neoplasms with various clinical presentations and growth rates. These tumors have the ability to synthetize and secrete bioactive molecules and in 8% of cases can cause different paraneoplastic syndromes. Paraneoplastic syndromes arise when signs and symptoms not attributable to direct compression or tumor invasion are present and are mainly expressed as an ectopic hormonal secretion (humoral syndromes) or as a result of autoantibodies elicited by malignant cells that cross-react with nerve cells (neurological syndromes). The development of a paraneoplastic syndrome does not necessarily correlate with cancer stage, so, recognizing the presence of these syndromes may lead to an early diagnosis of a previously unsuspected neoplasm and allow treatment in initial stages with probable better prognosis for the patient. Furthermore, paraneoplastic syndromes are useful in following and monitoring the clinical course of the underlying disease. With the incidence of these tumors increasing at a rate of 3-10% per year, it is expected that the prevalence of paraneoplastic syndromes related to neuroendocrine tumors also rise. Clinical presentation, 111In-ocreteotid scintigraphy and chromogranin A have substantially contributed to their identification. This review describes common and uncommon paraneoplastic syndromes related to neuroendocrine tumors, provides information regarding their physiopathology, clinical presentation, diagnostic tools and prognosis and identifies features that distinguish them from the eutopic hormonal secretion-related syndromes.