RESUMEN
The ClC chloride channels control the ionic composition of the cytoplasm and the volume of cells, and regulate electrical excitability. Recently, it has been proposed that prokaryotic ClC channels are H+-Cl- exchange transporter. Although X-ray and molecular dynamics (MD) studies of bacterial ClC channels have investigated the filter open-close and ion permeation mechanism of channels, details have remained unclear. We performed MD simulations of ClC channels involving H+, Na+, K+, or H3O+ in the intracellular region to elucidate the open-close mechanism, and to clarify the role of H+ ion an H+-Cl- exchange transporter. Our simulations revealed that H+ and Na+ caused channel opening and the passage of Cl- ions. Na+ induced a bead-like string of Cl- -Na+-Cl--Na+-Cl- ions to form and permeate through ClC channels to the intracellular side with the widening of the channel pathway.
Asunto(s)
Permeabilidad de la Membrana Celular , Canales de Cloruro/química , Canales de Cloruro/fisiología , Cloruros/metabolismo , Modelos Biológicos , Proteínas Bacterianas/química , Proteínas Bacterianas/fisiología , Simulación por Computador , Transporte Iónico , Modelos Moleculares , Sodio/farmacocinética , Sodio/fisiologíaRESUMEN
Molecular dynamics analyses were performed to examine conformational changes in the C-domain of calmodulin and the N-domain of troponin C induced by binding of Ca(2+) ions. Analyses of conformational changes in calmodulin and troponin C indicated that the shortening of the distance between Ca(2+) ions and Ca(2+) binding sites of helices caused widening of the distance between Ca(2+) binding sites of helices on opposite sides, while the hydrophobic side chains in the center of helices hardly moved due to their steric hindrance. This conformational change acts as the clothespin mechanism.
Asunto(s)
Calcio/metabolismo , Calmodulina/química , Modelos Moleculares , Troponina C/química , Animales , Sitios de Unión , Calmodulina/metabolismo , Simulación por Computador , Interacciones Hidrofóbicas e Hidrofílicas , Cinética , Conformación Proteica , Estructura Secundaria de Proteína , Troponina C/metabolismo , Proteínas de Xenopus/química , Proteínas de Xenopus/metabolismoRESUMEN
A 23-year-old man was admitted to our hospital because of cough and sputum in April 2001. A chest roentgenogram revealed infiltrative shadow with cavity formation in the bilateral lung fields. He was treated with sensitive antituberculous drugs. After starting the antituberculous therapy with INH, RFP, EB and PZA, bilateral cervical lymphadenopathy developed. Three months later, pericostal abscess appeared in the left anterior chest wall. Microscopic examination of the specimen obtained by needle aspiration biopsy disclosed positive for acid-fast bacilli. Smears of the pus showed acidfast bacilli identified as Mycobacterium tuberculosis by DNA-DNA PCR method. He developed tuberculous bilateral cervical lymphadenopathy and pericostal abscess during the course of antituberculosis chemotherapy. Drug sensitivity test revealed that tubercle bacilli in this case were sensitive. One year after the administration of chemotherapy, cervical lymphadenopathy and pericostal abscess were improved. Both masses were discontinuous with pulmonary tuberculosis and the possibility of lymphogenous spread of organism was speculated as its etiology. We assumed that both masses were due to paradoxical response to the antituberculosis chemotherapy.
Asunto(s)
Absceso/etiología , Antituberculosos/efectos adversos , Costillas , Enfermedades Torácicas/etiología , Tuberculosis Ganglionar/etiología , Tuberculosis Pulmonar/complicaciones , Tuberculosis/etiología , Adulto , Antituberculosos/uso terapéutico , Quimioterapia Combinada , Humanos , Masculino , Resultado del Tratamiento , Tuberculosis Pulmonar/tratamiento farmacológicoRESUMEN
A 20-year-old woman was admitted to our hospital because of cough and dyspnea in April 2001. On admission, laboratory data showed positive inflammatory signs. A chest roentogenogram revealed infiltrated shadow in the bilateral lung fields. Sputum smear examination showed acid-fast bacilli identified as Mycobacterium tuberculosis by DNA-DNA PCR method. Four days after admission, she had an acute respiratory distress syndrome (ARDS) and serious liver dysfunction. Moreover, drug sensitivity test revealed that this case was multidrug-resistant tuberculosis (MDR-TB), and she was treated with sensitive anti-tuberculous drugs (PZA, SM, LVFX). Three months later, her sputa converted to negative for tubercle bacillis, however, a chest computed tomogram (CT) revealed multiple giant cysts in the bilateral lung fields, which developed during treatment. Pneumothorax of both sides was repeatedly observed, and it was difficult to treat. At present (1 year after admission), multiple giant cysts stopped its progression and treatment for tuberculosis is being continued.