RESUMEN
OBJECTIVES: The primary objective of this study was to describe the accuracy of pneumonia diagnosis, both community-acquired pneumonia (CAP) and hospitalacquired pneumonia (HAP). Secondary objectives were describing the choice of antibiotics used, pathogens isolated, and predictive parameters in diagnosing pneumonia. METHODS: This was a prospective cross-sectional study to determine the accuracy of the diagnosis of CAP and HAP admitted to Hospital Tuanku Ja'afar. All patients aged ≥12 years admitted to the general medical ward with the diagnosis of CAP or HAP were included in the study. Chest radiograph interpretation was done by certified radiologists. An accurate diagnosis of pneumonia was defined by clinical signs and symptoms of pneumonia supported by radiographical evidence. RESULTS: A total of 159 patients were enrolled into the study from January 2018 to February 2018. Of these only 59(37.1%) cases were accurately diagnosed as pneumonia. Amongst those with pneumonia diagnosis made by the emergency department, medical officers and specialists of medical department; 65.4%, 60% and 47.3% respectively were not pneumonia. Amoxicillin with clavulanate and azithromycin were amongst the most common first choice of antibiotic used (46.5%). In this study, pathogens were isolated either by blood culture or sputum culture in only 20 (12.6%) patients. There was no significant predictive parameter identified in this study, which included white cell counts, Creactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and Pao2/FiO2 ratio. CONCLUSION: About two-thirds of patients diagnosed with pneumonia did not have a compatible radiological finding. Better tools and systems are needed to aid in the diagnosis of pneumonia.
Asunto(s)
Infecciones Comunitarias Adquiridas/diagnóstico , Errores Diagnósticos/prevención & control , Neumonía/diagnóstico , Centros de Atención Terciaria , Comorbilidad , Estudios Transversales , Diagnóstico por Imagen , Femenino , Humanos , Malasia , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Large-conductance Ca2+-dependent K+ (BK(Ca)) channels are activated by intracellular Ca2+ and membrane depolarization in an allosteric manner. We investigated the pharmacological and biophysical characteristics of a BK(Ca)-type K+ channel in androgen-dependent LNCaP (lymph node carcinoma of the prostate) cells with novel functional properties, here termed BK(L). K+ selectivity, high conductance, activation by Mg2+ or NS1619, and inhibition by paxilline and penitrem A largely resembled the properties of recombinant BK(Ca) channels. However, unlike conventional BK(Ca) channels, BK(L) channels activated in the absence of free cytosolic Ca2+ at physiological membrane potentials; the half-maximal activation voltage was shifted by about -100 mV compared with BK(Ca) channels. Half-maximal Ca2+-dependent activation was observed at 0.4 microM: for BK(L) (at -20 mV) and at 4.1 microM: for BK(Ca) channels (at +50 mV). Heterologous expression of hSlo1 in LNCaP cells increased the BK(L) conductance. Expression of hSlo-beta1 in LNCaP cells shifted voltage-dependent activation to values between that of BK(L) and BK(Ca) channels and reduced the slope of the P (open) (open probability)-voltage curve. We propose that LNCaP cells harbor a so far unknown type of BK(Ca) subunit, which is responsible for the BK(L) phenotype in a dominant manner. BK(L)-like channels are also expressed in the human breast cancer cell line T47D. In addition, functional expression of BK(L) in LNCaP cells is regulated by serum-derived factors, however not by androgens.
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Calcio/farmacología , Activación del Canal Iónico/efectos de los fármacos , Canales de Potasio de Gran Conductancia Activados por el Calcio/efectos de los fármacos , Potenciales de la Membrana/efectos de los fármacos , Neoplasias de la Próstata/fisiopatología , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Humanos , MasculinoRESUMEN
Collection of missense mutations in the SUP45 gene of Saccharomyces cerevisiae encoding translation termination factor eRF1 has been obtained by different approaches. It has been shown that most of isolated mutations cause amino acid substitutions in the N-terminal part of eRF1 and do not decrease the eRF1 amount. Most of mutations studied do not abolish eRF1-eRF3 interaction. The role of the N-terminal part of eRF1 in stop codon recognition is discussed.
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Codón de Terminación/genética , Mutación Missense/genética , Terminación de la Cadena Péptídica Traduccional/genética , Factores de Terminación de Péptidos/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos/genética , Datos de Secuencia Molecular , Factores de Terminación de Péptidos/análisis , Factores de Terminación de Péptidos/metabolismo , Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/análisis , Proteínas de Saccharomyces cerevisiae/metabolismo , Técnicas del Sistema de Dos HíbridosRESUMEN
Inwardly rectifying potassium channels require binding of phosphatidylinositol-4,5-bisphosphate (PIP2) for channel activity. Three independent sites (aa 175-206, aa 207-246, aa 324-365) were located in the C-terminal domain of Kir2.1 channels by assaying the binding of overlapping fragments to PIP2 containing liposomes. Mutations in the first site, which abolished channel activity, reduced PIP2 binding of this fragment but not of the complete C-terminus. Point mutations in the third site also reduced both, channel activity and PIP2 binding of this segment. The relevance of the third PIP2 binding site provides a basis for the understanding of constitutively active Kir2 channels.
Asunto(s)
Sitios de Unión , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Canales de Potasio de Rectificación Interna , Canales de Potasio/química , Proteínas de Saccharomyces cerevisiae , Factores de Transcripción/química , Factores de Transcripción/metabolismo , Animales , Bovinos , Pollos , Relación Dosis-Respuesta a Droga , Glutatión Transferasa/metabolismo , Liposomas/metabolismo , Ratones , Mutagénesis Sitio-Dirigida , Mutación , Oocitos/metabolismo , Mutación Puntual , Canales de Potasio/metabolismo , Unión Proteica , Estructura Terciaria de Proteína , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Xenopus laevisRESUMEN
The molecular nature of the sup45 respiratory deficient omnipotent suppressor, and of three reversions to respiratory competence which removed the suppressor effect of the initial mutation, was examined. All reversions were caused by secondary sup45 mutations which indicates a direct connection between sup45 "respiratory" and "translational" functions. Computer analysis showed the local changes of Sup45 protein characteristics in the suppressor strain and revertants in comparison to the wild-type protein. The distribution of mutant sites in relation to evolutionary conserved, and tentatively functional, regions in the Sup45 protein is discussed.