Assuntos
Comunicação Interventricular , Síndrome Hepatopulmonar , Dispositivo para Oclusão Septal , Dispneia/etiologia , Comunicação Interventricular/diagnóstico por imagem , Comunicação Interventricular/cirurgia , Síndrome Hepatopulmonar/diagnóstico por imagem , Síndrome Hepatopulmonar/etiologia , Humanos , Resultado do TratamentoRESUMO
Hypertrophic cardiomyopathy with left ventricular (LV) mid-cavity obstruction and LV apical aneurysm is associated with high morbidity and mortality rates. However, consensus is lacking on the treatment modality for LV mid-cavity obstruction and LV apical aneurysm. Here, we report a case of reduced LV mid-cavity pressure gradient and symptoms, treated using permanent pacing. The effect of permanent pacing on pressure gradient and symptoms lasted for 4 years. As pacing is relatively non-invasive compared to surgical therapy, permanent pacing is a good option, especially in the elderly patients with LV mid-cavity obstruction and apical aneurysm.
Assuntos
Estimulação Cardíaca Artificial , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/terapia , Aneurisma Cardíaco/complicações , Disfunção Ventricular Esquerda/complicações , Obstrução do Fluxo Ventricular Externo/complicações , Idoso , Cardiomiopatia Hipertrófica/diagnóstico , Feminino , Aneurisma Cardíaco/diagnóstico , Aneurisma Cardíaco/terapia , Humanos , Marca-Passo Artificial , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/terapia , Obstrução do Fluxo Ventricular Externo/diagnóstico , Obstrução do Fluxo Ventricular Externo/terapiaRESUMO
The presence of the geranylgeranyl diphosphate synthase (GGS) gene is a common feature of gene clusters for diterpene biosynthesis. We demonstrated identification of a diterpene gene cluster using homology-based PCR of GGS genes and the subsequent genome walking in the fungus Phomopsis amygdali N2. Structure determination of a novel diterpene hydrocarbon phomopsene provided by enzymatic synthesis with the recombinant terpene synthase PaPS and screening of fungal broth extracts with reference to characteristic NMR signals of phomopsene allowed us to isolate a new diterpene, methyl phomopsenonate. The versatility of the gene-based screening of unidentified diterpenes is discussed in regard to fungal genomic data.
Assuntos
Ascomicetos/genética , Ascomicetos/metabolismo , Diterpenos/análise , Diterpenos/metabolismo , Genes Fúngicos , Alquil e Aril Transferases/química , Alquil e Aril Transferases/metabolismo , Ascomicetos/enzimologia , Clonagem Molecular , Dimetilaliltranstransferase/metabolismo , Diterpenos/química , Genoma Fúngico/genética , Espectroscopia de Ressonância Magnética , Família Multigênica , Estrutura Terciária de Proteína , Análise de Sequência de DNARESUMO
Two diterpene biosynthesis gene clusters in the fusicoccin-producing fungus, Phomopsis amygdali, were identified by genome walking from PaGGS1 and PaGGS4 which encode the geranylgeranyl diphosphate (GGDP) synthases. The diterpene cyclase-like genes, PaDC1 and PaDC2, were respectively located proximal to PaGGS1 and PaGGS4. The amino acid sequences of these two enzymes were similar to those of fungal labdane-related diterpene cyclases. Recombinant PaDC1 converted GGDP mainly into phyllocladan-16 alpha-ol via (+)-copalyl diphosphate (CDP) and trace amounts of several labdane-related hydrocarbons which had been identified from the P. amygdali F6 mycelia. Since phyllocladan-16 alpha-ol had not been identified in P. amygdali F6 mycelia, we isolated phyllocladan-16 alpha-ol from the mycelia. Recombinant PaDC2 converted GGDP into (+)-CDP. Furthermore, we isolated the novel diterpenoid, phyllocladan-11 alpha,16 alpha,18-triol, which is a possible metabolite of phyllocladan-16 alpha-ol in the mycelia. We propose that genome walking offers a useful strategy for the discovery of novel natural products in fungi.