RESUMO
Familial persistent hyperinsulinemic hypoglycemia of infancy is a disorder of glucose homeostasis and is characterized by unregulated insulin secretion and profound hypoglycemia. Loss-of-function mutations in the second nucleotide-binding fold of the sulfonylurea receptor, a subunit of the pancreatic-islet beta-cell ATP-dependent potassium channel, has been demonstrated to be causative for persistent hyperinsulinemic hypoglycemia of infancy. We now describe three additional mutations in the first nucleotide-binding fold of the sulfonylurea-receptor gene. One point mutation disrupts the highly conserved Walker A motif of the first nucleotide-binding-fold region. The other two mutations occur in noncoding sequences required for RNA processing and are predicted to disrupt the normal splicing pathway of the sulfonylurea-receptor mRNA precursor. These data suggest that both nucleotide-binding-fold regions of the sulfonylurea receptor are required for normal regulation of beta-cell ATP-dependent potassium channel activity and insulin secretion.
Assuntos
Transportadores de Cassetes de Ligação de ATP , Hiperinsulinismo/genética , Hipoglicemia/genética , Mutação Puntual/genética , Canais de Potássio Corretores do Fluxo de Internalização , Canais de Potássio/genética , Receptores de Droga/genética , Compostos de Sulfonilureia , Sequência de Aminoácidos , Sequência de Bases , Criança , DNA Complementar/genética , Humanos , Lactente , Dados de Sequência Molecular , Nucleotídeos/metabolismo , Pâncreas , Canais de Potássio/química , Processamento Pós-Transcricional do RNA/genética , Receptores de Droga/química , Homologia de Sequência de Aminoácidos , Receptores de SulfonilureiasRESUMO
Familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI), an autosomal recessive disorder characterized by unregulated insulin secretion, is linked to chromosome 11p14-15.1. The newly cloned high-affinity sulfonylurea receptor (SUR) gene, a regulator of insulin secretion, was mapped to 11p15.1 by means of fluorescence in situ hybridization. Two separate SUR gene splice site mutations, which segregated with disease phenotype, were identified in affected individuals from nine different families. Both mutations resulted in aberrant processing of the RNA sequence and disruption of the putative second nucleotide binding domain of the SUR protein. Abnormal insulin secretion in PHHI appears to be caused by mutations in the SUR gene.
Assuntos
Transportadores de Cassetes de Ligação de ATP , Hiperinsulinismo/genética , Hipoglicemia/genética , Pancreatopatias/genética , Canais de Potássio Corretores do Fluxo de Internalização , Canais de Potássio/genética , Receptores de Droga/genética , Sequência de Aminoácidos , Sequência de Bases , Mapeamento Cromossômico , Cromossomos Humanos Par 11 , Análise Mutacional de DNA , DNA Complementar/genética , Genótipo , Humanos , Lactente , Insulina/metabolismo , Secreção de Insulina , Dados de Sequência Molecular , Mutação , Fenótipo , Mutação Puntual , Canais de Potássio/química , Splicing de RNA , Receptores de Droga/química , Compostos de Sulfonilureia/metabolismo , Receptores de SulfonilureiasRESUMO
Authors report on results of the examination of a specially prepared shoe, therapeutically used by a faith-healer. The patients felt unexpected sensations caused by an electrical circuit built in the shoe and released by the doctors big toe. The faith-healer justified his method to be a special kind of "electrophysiological therapy". The public prosecutor withdrew the impeachment on trickery.
Assuntos
Campos Eletromagnéticos , Cura Mental , Charlatanismo , Sapatos , Prova Pericial/legislação & jurisprudência , Fraude/legislação & jurisprudência , Humanos , Charlatanismo/legislação & jurisprudênciaRESUMO
Two young men tried to stop a leaking patrol pipe of a private car in a workshop pit. One of them died from petrol-vapour-poisoning. Toxicological analyses by means of headspace gas chromatography permitted the identification of gasoline vapour. The other victim lost consciousness for a few hours and survived. By investigation of both victims alterations of skin were observed and interpreted as combustions with burns and blisters. Therefore the law-enforcement agency supposed an explosion or deflagration of gasoline vapour. In reality the experts on burnings could not gain any indication of an explosion and we proved the skin alterations to be a dermatotoxic effect of petrol.